Lod scores for gene mapping in the presence of marker map uncertainty.

PubMed

Stringham, H M; Boehnke, M

2001-07-01

Multipoint lod scores are typically calculated for a grid of locus positions, moving the putative disease locus across a fixed map of genetic markers. Changing the order of a set of markers and/or the distances between the markers can make a substantial difference in the resulting lod score curve and the location and height of its maximum. The typical approach of using the best maximum likelihood marker map is not easily justified if other marker orders are nearly as likely and give substantially different lod score curves. To deal with this problem, we propose three weighted multipoint lod score statistics that make use of information from all plausible marker orders. In each of these statistics, the information conditional on a particular marker order is included in a weighted sum, with weight equal to the posterior probability of that order. We evaluate the type 1 error rate and power of these three statistics on the basis of results from simulated data, and compare these results to those obtained using the best maximum likelihood map and the map with the true marker order. We find that the lod score based on a weighted sum of maximum likelihoods improves on using only the best maximum likelihood map, having a type 1 error rate and power closest to that of using the true marker order in the simulation scenarios we considered. Copyright 2001 Wiley-Liss, Inc.

Heritability and clinical features of multigenerational families with obsessive-compulsive disorder and hoarding.

PubMed

Mathews, Carol A; Nievergelt, Caroline M; Azzam, Amin; Garrido, Helena; Chavira, Denise A; Wessel, Jennifer; Bagnarello, Monica; Reus, Victor I; Schork, Nicholas J

2007-03-05

To date, only one complete genome screen for obsessive-compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood-onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive-compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding. (c) 2007 Wiley-Liss, Inc.

Distribution of model-based multipoint heterogeneity lod scores.

PubMed

Xing, Chao; Morris, Nathan; Xing, Guan

2010-12-01

The distribution of two-point heterogeneity lod scores (HLOD) has been intensively investigated because the conventional χ(2) approximation to the likelihood ratio test is not directly applicable. However, there was no study investigating th e distribution of the multipoint HLOD despite its wide application. Here we want to point out that, compared with the two-point HLOD, the multipoint HLOD essentially tests for homogeneity given linkage and follows a relatively simple limiting distribution ½χ²₀+ ½χ²₁, which can be obtained by established statistical theory. We further examine the theoretical result by simulation studies. © 2010 Wiley-Liss, Inc.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

PubMed

Abreu, P C; Greenberg, D A; Hodge, S E

1999-09-01

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

Multi-Level Building Reconstruction for Automatic Enhancement of High Resolution Dsms

NASA Astrophysics Data System (ADS)

Arefi, H.; Reinartz, P.

2012-07-01

In this article a multi-level approach is proposed for reconstruction-based improvement of high resolution Digital Surface Models (DSMs). The concept of Levels of Detail (LOD) defined by CityGML standard has been considered as basis for abstraction levels of building roof structures. Here, the LOD1 and LOD2 which are related to prismatic and parametric roof shapes are reconstructed. Besides proposing a new approach for automatic LOD1 and LOD2 generation from high resolution DSMs, the algorithm contains two generalization levels namely horizontal and vertical. Both generalization levels are applied to prismatic model of buildings. The horizontal generalization allows controlling the approximation level of building footprints which is similar to cartographic generalization concept of the urban maps. In vertical generalization, the prismatic model is formed using an individual building height and continuous to included all flat structures locating in different height levels. The concept of LOD1 generation is based on approximation of the building footprints into rectangular or non-rectangular polygons. For a rectangular building containing one main orientation a method based on Minimum Bounding Rectangle (MBR) in employed. In contrast, a Combined Minimum Bounding Rectangle (CMBR) approach is proposed for regularization of non-rectilinear polygons, i.e. buildings without perpendicular edge directions. Both MBRand CMBR-based approaches are iteratively employed on building segments to reduce the original building footprints to a minimum number of nodes with maximum similarity to original shapes. A model driven approach based on the analysis of the 3D points of DSMs in a 2D projection plane is proposed for LOD2 generation. Accordingly, a building block is divided into smaller parts according to the direction and number of existing ridge lines. The 3D model is derived for each building part and finally, a complete parametric model is formed by merging all the 3D models of the individual parts and adjusting the nodes after the merging step. In order to provide an enhanced DSM, a surface model is provided for each building by interpolation of the internal points of the generated models. All interpolated models are situated on a Digital Terrain Model (DTM) of corresponding area to shape the enhanced DSM. Proposed DSM enhancement approach has been tested on a dataset from Munich central area. The original DSM is created using robust stereo matching of Worldview-2 stereo images. A quantitative assessment of the new DSM by comparing the heights of the ridges and eaves shows a standard deviation of better than 50cm.

Linkage analysis of primary open-angle glaucoma excludes the juvenile glaucoma region on chromosome 1q

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

Wirtz, M.K.; Acott, T.S.; Samples, J.R.

1994-09-01

The gene for one form of juvenile glaucoma has been mapped to chromosome 1q21-q31. This raises the possibility of primary open-angle glaucoma (POAG) also mapping to this region if the same defective gene causes both diseases. To ask this question linkage analysis was performed on a large POAG kindred. Blood samples or skin biopsies were obtained from 40 members of this family. Individuals were diagnosed as having POAG if they met two or more of the following criteria: (1) Visual field defects compatible with glaucoma on automated perimetry; (2) Optic nerve head and/or nerve fiber layer analysis compatible with glaucomatousmore » damage; (3) high intraocular pressures (> 20 mm Hg). Patients were considered glaucoma suspects if they only met one criterion. These individuals were excluded from the analysis. Of the 40 members, seven were diagnosed with POAG; four were termed suspects. The earliest age of onset was 38 years old, while the average age of onset was 65 years old. We performed two-point and multipoint linkage analysis, using five markers which encompass the region 1q21-q31; specifically, D1S194, D1S210, D1S212, D1S191 and LAMB2. Two-point lod scores excluded tight linkage with all markers except D1S212 (maximum lod score of 1.07 at theta = 0.0). In the multipoint analysis, including D1S210-D1S212-LAMB2 and POAG, the entire 11 cM region spanned by these markers was excluded for linkage with POAG; that is, lod scores were < -2.0. In conclusion, POAG in this family does not map to chromosome 1q21-q31 and, thus, they carry a gene that is distinct from the juvenile glaucoma gene.« less

Percentiles of the null distribution of 2 maximum lod score tests.

PubMed

Ulgen, Ayse; Yoo, Yun Joo; Gordon, Derek; Finch, Stephen J; Mendell, Nancy R

2004-01-01

We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p(2)(0) + (1 - p)(2)(v). The values of MMLS appear to fit the mixture 0.20(2)(0) + 0.80chi(2)(1.6). The mixture distribution 0.13(2)(0) + 0.87chi(2)(2.8). appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS. Copyright 2004 S. Karger AG, Basel

Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24.

PubMed

Sillén, Anna; Brohede, Jesper; Forsell, Charlotte; Lilius, Lena; Andrade, Jorge; Odeberg, Jacob; Kimura, Toru; Winblad, Bengt; Graff, Caroline

2011-01-01

We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD. We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LOD(max)-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families. Linkage analysis of a family subset having at least one autopsy-confirmed AD case showed a significant nonparametric single-point LOD score of 4.4 in 8q24. Fine-mapping under the linkage peak with 10 microsatellite markers yielded an increase in the multipoint (mpt) LOD score from 2.1 to 3.0. SNP genotyping was performed on 21 selected candidate transcripts of the LOD(max)-2 region. Both family-based association and linkage analysis were performed on extended material from 30 families, resulting in a suggestive linkage at peak marker rs6577853 (mpt LOD score = 2.4). The 8q24 region has been implicated to be involved in AD etiology. Copyright © 2011 S. Karger AG, Basel.

Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans.

PubMed

Kammerer, Candace M; Schneider, Jennifer L; Cole, Shelley A; Hixson, James E; Samollow, Paul B; O'Connell, Jeffrey R; Perez, Reina; Dyer, Thomas D; Almasy, Laura; Blangero, John; Bauer, Richard L; Mitchell, Braxton D

2003-12-01

We performed a genome scan using BMD data of the forearm and hip on 664 individuals in 29 Mexican-American families. We obtained evidence for QTL on chromosome 4p, affecting forearm BMD overall, and on chromosomes 2p and 13q, affecting hip BMD in men. The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families. We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available. We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women. These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. J Bone Miner Res 2003;18:2245-2252

Quadtree of TIN: a new algorithm of dynamic LOD

NASA Astrophysics Data System (ADS)

Zhang, Junfeng; Fei, Lifan; Chen, Zhen

2009-10-01

Currently, Real-time visualization of large-scale digital elevation model mainly employs the regular structure of GRID based on quadtree and triangle simplification methods based on irregular triangulated network (TIN). TIN is a refined means to express the terrain surface in the computer science, compared with GRID. However, the data structure of TIN model is complex, and is difficult to realize view-dependence representation of level of detail (LOD) quickly. GRID is a simple method to realize the LOD of terrain, but contains more triangle count. A new algorithm, which takes full advantage of the two methods' merit, is presented in this paper. This algorithm combines TIN with quadtree structure to realize the view-dependence LOD controlling over the irregular sampling point sets, and holds the details through the distance of viewpoint and the geometric error of terrain. Experiments indicate that this approach can generate an efficient quadtree triangulation hierarchy over any irregular sampling point sets and achieve dynamic and visual multi-resolution performance of large-scale terrain at real-time.

Multivariate estimation of the limit of detection by orthogonal partial least squares in temperature-modulated MOX sensors.

PubMed

Burgués, Javier; Marco, Santiago

2018-08-17

Metal oxide semiconductor (MOX) sensors are usually temperature-modulated and calibrated with multivariate models such as partial least squares (PLS) to increase the inherent low selectivity of this technology. The multivariate sensor response patterns exhibit heteroscedastic and correlated noise, which suggests that maximum likelihood methods should outperform PLS. One contribution of this paper is the comparison between PLS and maximum likelihood principal components regression (MLPCR) in MOX sensors. PLS is often criticized by the lack of interpretability when the model complexity increases beyond the chemical rank of the problem. This happens in MOX sensors due to cross-sensitivities to interferences, such as temperature or humidity and non-linearity. Additionally, the estimation of fundamental figures of merit, such as the limit of detection (LOD), is still not standardized in multivariate models. Orthogonalization methods, such as orthogonal projection to latent structures (O-PLS), have been successfully applied in other fields to reduce the complexity of PLS models. In this work, we propose a LOD estimation method based on applying the well-accepted univariate LOD formulas to the scores of the first component of an orthogonal PLS model. The resulting LOD is compared to the multivariate LOD range derived from error-propagation. The methodology is applied to data extracted from temperature-modulated MOX sensors (FIS SB-500-12 and Figaro TGS 3870-A04), aiming at the detection of low concentrations of carbon monoxide in the presence of uncontrolled humidity (chemical noise). We found that PLS models were simpler and more accurate than MLPCR models. Average LOD values of 0.79 ppm (FIS) and 1.06 ppm (Figaro) were found using the approach described in this paper. These values were contained within the LOD ranges obtained with the error-propagation approach. The mean LOD increased to 1.13 ppm (FIS) and 1.59 ppm (Figaro) when considering validation samples collected two weeks after calibration, which represents a 43% and 46% degradation, respectively. The orthogonal score-plot was a very convenient tool to visualize MOX sensor data and to validate the LOD estimates. Copyright © 2018 Elsevier B.V. All rights reserved.

Earth's rotation variations and earthquakes 2010-2011

NASA Astrophysics Data System (ADS)

Ostřihanský, L.

2012-01-01

In contrast to unsuccessful searching (lasting over 150 years) for correlation of earthquakes with biweekly tides, the author found correlation of earthquakes with sidereal 13.66 days Earth's rotation variations expressed as length of a day (LOD) measured daily by International Earth's Rotation Service. After short mention about earthquakes M 8.8 Denali Fault Alaska 3 November 2002 triggered on LOD maximum and M 9.1 Great Sumatra earthquake 26 December 2004 triggered on LOD minimum and the full Moon, the main object of this paper are earthquakes of period 2010-June 2011: M 7.0 Haiti (12 January 2010 on LOD minimum, M 8.8 Maule Chile 12 February 2010 on LOD maximum, map constructed on the Indian plate revealing 6 earthquakes from 7 on LOD minimum in Sumatra and Andaman Sea region, M 7.1 New Zealand Christchurch 9 September 2010 on LOD minimum and M 6.3 Christchurch 21 February 2011 on LOD maximum, and M 9.1 Japan near coast of Honshu 11 March 2011 on LOD minimum. It was found that LOD minimums coincide with full or new Moon only twice in a year in solstices. To prove that determined coincidences of earthquakes and LOD extremes stated above are not accidental events, histograms were constructed of earthquake occurrences and their position on LOD graph deeply in the past, in some cases from the time the IERS (International Earth's Rotation Service) started to measure the Earth's rotation variations in 1962. Evaluations of histograms and the Schuster's test have proven that majority of earthquakes are triggered in both Earth's rotation deceleration and acceleration. Because during these coincidences evident movements of lithosphere occur, among others measured by GPS, it is concluded that Earth's rotation variations effectively contribute to the lithospheric plates movement. Retrospective overview of past earthquakes revealed that the Great Sumatra earthquake 26 December 2004 had its equivalent in the shape of LOD graph, full Moon position, and character of aftershocks 19 years earlier in difference only one day to 27 December 1985 earthquake, proving that not only sidereal 13.66 days variations but also that the 19 years Metons cycle is the period of the earthquakes occurrence. Histograms show the regular change of earthquake positions on branches of LOD graph and also the shape of histogram and number of earthquakes on LOD branches from the mid-ocean ridge can show which side of the ridge moves quicker.

Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Dimitrov, Latchezar; Keaton, Jacob M; Tabb, Keri L; Sajuthi, Satria; Taylor, Kent D; Ng, Maggie C Y; Speliotes, Elizabeth K; Hawkins, Gregory A; Long, Jirong; Ida Chen, Yii-Der; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

2017-02-01

Linkage studies of complex genetic diseases have been largely replaced by genome-wide association studies, due in part to limited success in complex trait discovery. However, recent interest in rare and low-frequency variants motivates re-examination of family-based methods. In this study, we investigated the performance of two-point linkage analysis for over 1.6 million single-nucleotide polymorphisms (SNPs) combined with single variant association analysis to identify high impact variants, which are both strongly linked and associated with cardiometabolic traits in up to 1414 Hispanics from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of all 50 phenotypes yielded 83 557 000 LOD (logarithm of the odds) scores, with 9214 LOD scores ⩾3.0, 845 ⩾4.0 and 89 ⩾5.0, with a maximal LOD score of 6.49 (rs12956744 in the LAMA1 gene for tumor necrosis factor-α (TNFα) receptor 2). Twenty-seven variants were associated with P<0.005 as well as having an LOD score >4, including variants in the NFIB gene under a linkage peak with TNFα receptor 2 levels on chromosome 9. Linkage regions of interest included a broad peak (31 Mb) on chromosome 1q with acute insulin response (max LOD=5.37). This region was previously documented with type 2 diabetes in family-based studies, providing support for the validity of these results. Overall, we have demonstrated the utility of two-point linkage and association in comprehensive genome-wide array-based SNP genotypes.

Medium- and Long-term Prediction of LOD Change by the Leap-step Autoregressive Model

NASA Astrophysics Data System (ADS)

Wang, Qijie

2015-08-01

The accuracy of medium- and long-term prediction of length of day (LOD) change base on combined least-square and autoregressive (LS+AR) deteriorates gradually. Leap-step autoregressive (LSAR) model can significantly reduce the edge effect of the observation sequence. Especially, LSAR model greatly improves the resolution of signals’ low-frequency components. Therefore, it can improve the efficiency of prediction. In this work, LSAR is used to forecast the LOD change. The LOD series from EOP 08 C04 provided by IERS is modeled by both the LSAR and AR models. The results of the two models are analyzed and compared. When the prediction length is between 10-30 days, the accuracy improvement is less than 10%. When the prediction length amounts to above 30 day, the accuracy improved obviously, with the maximum being around 19%. The results show that the LSAR model has higher prediction accuracy and stability in medium- and long-term prediction.

Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity.

PubMed Central

Lester, D H; Inglehearn, C F; Bashir, R; Ackford, H; Esakowitz, L; Jay, M; Bird, A C; Wright, A F; Papiha, S S; Bhattacharya, S S

1990-01-01

Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome. Images Figure 2 Figure 3 Figure 4 PMID:2393026

TLS for generating multi-LOD of 3D building model

NASA Astrophysics Data System (ADS)

Akmalia, R.; Setan, H.; Majid, Z.; Suwardhi, D.; Chong, A.

2014-02-01

The popularity of Terrestrial Laser Scanners (TLS) to capture three dimensional (3D) objects has been used widely for various applications. Development in 3D models has also led people to visualize the environment in 3D. Visualization of objects in a city environment in 3D can be useful for many applications. However, different applications require different kind of 3D models. Since a building is an important object, CityGML has defined a standard for 3D building models at four different levels of detail (LOD). In this research, the advantages of TLS for capturing buildings and the modelling process of the point cloud can be explored. TLS will be used to capture all the building details to generate multi-LOD. This task, in previous works, involves usually the integration of several sensors. However, in this research, point cloud from TLS will be processed to generate the LOD3 model. LOD2 and LOD1 will then be generalized from the resulting LOD3 model. Result from this research is a guiding process to generate the multi-LOD of 3D building starting from LOD3 using TLS. Lastly, the visualization for multi-LOD model will also be shown.

Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree.

PubMed

Charlesworth, Jac C; Dyer, Thomas D; Stankovich, Jim M; Blangero, John; Mackey, David A; Craig, Jamie E; Green, Catherine M; Foote, Simon J; Baird, Paul N; Sale, Michèle M

2005-10-01

The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype. Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals. Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci. Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.

Ornithine aminotransferase (OAT): recombination between an X-linked OAT sequence (7.5 kb) and the Norrie disease locus.

PubMed

Ngo, J T; Bateman, J B; Spence, M A; Cortessis, V; Sparkes, R S; Kivlin, J D; Mohandas, T; Inana, G

1990-01-01

A human ornithine aminotransferase (OAT) locus has been mapped to the Xp11.2, as has the Norrie disease locus. We used a cDNA probe to investigate a 3-generation UCLA family with Norrie disease; a 4.2-kb RFLP was detected and a maximum lod score of 0.602 at zero recombination fraction was calculated. We used the same probe to study a second multigeneration family with Norrie disease from Utah. A different RFLP of 7.5 kb in size was identified and a recombinational event between the OAT locus represented by this RFLP and the disease loci was observed. Linkage analysis of these two loci in this family revealed a maximum load score of 1.88 at a recombination fraction of 0.10. Although both families have affected members with the same disease, the lod scores are reported separately because the 4.2- and 7.5-kb RFLPs may represent two different loci for the X-linked OAT.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed

Dizier, M H; Babron, M C; Clerget-Darpoux, F

1996-06-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed Central

Dizier, M. H.; Babron, M. C.; Clerget-Darpoux, F.

1996-01-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker. PMID:8651311

Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q

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

Tomfohrde, J.; Barnes, R.; Bowcock, A.

1994-05-20

A gene involved in psoriasis susceptibility was localized to the distal region of human chromosomes 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that is some families, psoriasis susceptibility ismore » due to variation at a single major genetic locus other than the human lymphocyte antigen locus. 28 refs., 2 figs., 1 tab.« less

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

PubMed Central

Simpson, Claire L; Cropp, Cheryl D; Wahlfors, Tiina; George, Asha; Jones, MaryPat S; Harper, Ursula; Ponciano-Jackson, Damaris; Tammela, Teuvo; Schleutker, Johanna; Bailey-Wilson, Joan E

2013-01-01

Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (ΔLOD=3.193, empirical P=0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD=2.541, ΔLOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, ΔLOD=2.36, P=0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families. PMID:22948022

Mapping of a possible X-linked form of familial developmental dysphasia (FDD) in a single large pedigree

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

Dunne, P.W.; Doody, R.S.; Epstein, H.F.

Children diagnosed with developmental dysphasia develop speech very late without exhibiting sensory or motor dysfunction, and when they do begin to speak their grammar is abnormal. A large three-generation British pedigree was recently identified in which 16 out of 30 members were diagnosed as dysphasic. Assuming a dominant mode of inheritance with homogeneous phenotypic expression and complete penetrance among affected members, we showed by simulation analysis that this pedigree has the power to detect linkage to marker loci with an average maximum LOD score of 3.67 at {theta}=0.1. Given the absence of male-to-male transmission and a ratio of female tomore » male affecteds (10/6) in this pedigree within the expected range for an X-linked dominant mode of inheritance, we decided to begin a genome-wide linkage analysis with microsatellite markers on the human X chromosome. Fifteen individuals (10 affected) from three generations were genotyped with 35 polymorphic STS`s (Research Genetics) which were approximately uniformly distributed along the X chromosome. Two-point linkage was assessed using the MLINK and ILINK programs from the LINKAGE package. Markers DXS1223, DXS987, DXS996 and DXS1060 on Xp22 showed consistent linkage to the disease locus with a maximum LOD score of 0.86 at a distance of 22 cM for DXS1060. If further analysis with additional markers and additional family members confirms X-linkage, such a localization would provide support for Lehrke`s hypothesis for X-linkage of major intellectual traits including verbal functioning.« less

Distribution and magnitude of type I error of model-based multipoint lod scores: implications for multipoint mod scores.

PubMed

Xing, Chao; Elston, Robert C

2006-07-01

The multipoint lod score and mod score methods have been advocated for their superior power in detecting linkage. However, little has been done to determine the distribution of multipoint lod scores or to examine the properties of mod scores. In this paper we study the distribution of multipoint lod scores both analytically and by simulation. We also study by simulation the distribution of maximum multipoint lod scores when maximized over different penetrance models. The multipoint lod score is approximately normally distributed with mean and variance that depend on marker informativity, marker density, specified genetic model, number of pedigrees, pedigree structure, and pattern of affection status. When the multipoint lod scores are maximized over a set of assumed penetrances models, an excess of false positive indications of linkage appear under dominant analysis models with low penetrances and under recessive analysis models with high penetrances. Therefore, caution should be taken in interpreting results when employing multipoint lod score and mod score approaches, in particular when inferring the level of linkage significance and the mode of inheritance of a trait.

Atmospheric and Oceanic Excitations to LOD Change on Quasi-biennial Time Scales

NASA Astrophysics Data System (ADS)

Ma, Li-Hua; Liao, De-Chun; Han, Yan-Ben

2006-12-01

We use wavelet transform to study the time series of the Earth's rotation rate (length-of-day, LOD), the axial components of atmospheric angular momentum (AAM) and oceanic angular momentum (OAM) in the period 1962--2005, and discuss the quasi-biennial oscillations (QBO) of LOD change. The results show that the QBO of LOD change varies remarkably in amplitude and phase. It was weak before 1978, then became much stronger and reached maximum values during the strong El Nino events in around 1983 and 1997. Results from analyzing the axial AAM indicate that the QBO signals in axial AAM are extremely consistent with the QBOs of LOD change. During 1963--2003, the QBO variance in the axial AAM can explain about 99.0% of that of the LOD, in other words, all QBO signals of LOD change are almost excited by the axial AAM, while the weak QBO signals of the axial OAM are quite different from those of the LOD and the axial AAM in both time-dependent characteristics and magnitudes. The combined effects of the axial AAM and OAM can explain about 99.1% of the variance of QBO in LOD change during this period.

Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for parallel biochemical single-end-point assays

PubMed Central

La, Moonwoo; Park, Sang Min; Kim, Dong Sung

2015-01-01

In this study, a multiple sample dispenser for precisely metered fixed volumes was successfully designed, fabricated, and fully characterized on a plastic centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays. The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C-MUFID) was designed with microfluidic structures based on the theoretical modeling about a centrifugal circumferential filling flow. The designed LODs were fabricated with a polystyrene substrate through micromachining and they were thermally bonded with a flat substrate. Furthermore, six parallel metering and dispensing assays were conducted at the same fixed-volume (1.27 μl) with a relative variation of ±0.02 μl. Moreover, the samples were metered and dispensed at different sub-volumes. To visualize the metering and dispensing performances, the C-MUFID was integrated with a serpentine micromixer during parallel centrifugal mixing tests. Parallel biochemical single-end-point assays were successfully conducted on the developed LOD using a standard serum with albumin, glucose, and total protein reagents. The developed LOD could be widely applied to various biochemical single-end-point assays which require different volume ratios of the sample and reagent by controlling the design of the C-MUFID. The proposed LOD is feasible for point-of-care diagnostics because of its mass-producible structures, reliable metering/dispensing performance, and parallel biochemical single-end-point assays, which can identify numerous biochemical. PMID:25610516

A study comparing precision of the maximum multipoint heterogeneity LOD statistic to three model-free multipoint linkage methods.

PubMed

Finch, S J; Chen, C H; Gordon, D; Mendell, N R

2001-12-01

This study compared the performance of the maximum lod (MLOD), maximum heterogeneity lod (MHLOD), maximum non-parametric linkage score (MNPL), maximum Kong and Cox linear extension (MKC(lin)) of NPL, and maximum Kong and Cox exponential extension (MKC(exp)) of NPL as calculated in Genehunter 1.2 and Genehunter-Plus. Our performance measure was the distance between the marker with maximum value for each linkage statistic and the trait locus. We performed a simulation study considering: 1) four modes of transmission, 2) 100 replicates for each model, 3) 58 pedigrees (with 592 subjects) per replicate, 4) three linked marker loci each having three equally frequent alleles, and 5) either 0% unlinked families (linkage homogeneity) or 50% unlinked families (linkage heterogeneity). For each replicate, we obtained the Haldane map position of the location at which each of the five statistics is maximized. The MLOD and MHLOD were obtained by maximizing over penetrances, phenocopy rate, and risk-allele frequencies. For the models simulated, MHLOD appeared to be the best statistic both in terms of identifying a marker locus having the smallest mean distance from the trait locus and in terms of the strongest negative correlation between maximum linkage statistic and distance of the identified position and the trait locus. The marker loci with maximum value of the Kong and Cox extensions of the NPL statistic also were closer to the trait locus than the marker locus with maximum value of the NPL statistic. Copyright 2001 Wiley-Liss, Inc.

Lod score curves for phase-unknown matings.

PubMed

Hulbert-Shearon, T; Boehnke, M; Lange, K

1996-01-01

For a phase-unknown nuclear family, we show that the likelihood and lod score are unimodal, and we describe conditions under which the maximum occurs at recombination fraction theta = 0, theta = 1/2, and 0 < theta < 1/2. These simply stated necessary and sufficient conditions seem to have escaped the notice of previous statistical geneticists.

Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods.

PubMed

d'Amato, T; Waksman, G; Martinez, M; Laurent, C; Gorwood, P; Campion, D; Jay, M; Petit, C; Savoye, C; Bastard, C

1994-05-01

In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.

The lod score method.

PubMed

Rice, J P; Saccone, N L; Corbett, J

2001-01-01

The lod score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential, so that pedigrees or lod curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders, where the maximum lod score (MLS) statistic shares some of the advantages of the traditional lod score approach but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the lod score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

Genotype × Adiposity Interaction Linkage Analyses Reveal a Locus on Chromosome 1 for Lipoprotein-Associated Phospholipase A2, a Marker of Inflammation and Oxidative Stress

PubMed Central

Diego, Vincent P.; Rainwater, David L.; Wang, Xing-Li; Cole, Shelley A.; Curran, Joanne E.; Johnson, Matthew P.; Jowett, Jeremy B. M.; Dyer, Thomas D.; Williams, Jeff T.; Moses, Eric K.; Comuzzie, Anthony G.; MacCluer, Jean W.; Mahaney, Michael C.; Blangero, John

2007-01-01

Because obesity leads to a state of chronic, low-grade inflammation and oxidative stress, we hypothesized that the contribution of genes to variation in a biomarker of these two processes may be influenced by the degree of adiposity. We tested this hypothesis using samples from the San Antonio Family Heart Study that were assayed for activity of lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of inflammation and oxidative stress. Using an approach to model discrete genotype×environment (G×E) interaction, we assigned individuals to one of two discrete diagnostic states (or “adiposity environments”): nonobese or obese, according to criteria suggested by the World Health Organization. We found a genomewide maximum LOD of 3.39 at 153 cM on chromosome 1 for Lp-PLA2. Significant G×E interaction for Lp-PLA2 at the genomewide maximum (P=1.16×10-4) was also found. Microarray gene-expression data were analyzed within the 1-LOD interval of the linkage signal on chromosome 1. We found two transcripts—namely, for Fc gamma receptor IIA and heat-shock protein (70 kDa)—that were significantly associated with Lp-PLA2 (P<.001 for both) and showed evidence of cis-regulation with nominal LOD scores of 2.75 and 13.82, respectively. It would seem that there is a significant genetic response to the adiposity environment in this marker of inflammation and oxidative stress. Additionally, we conclude that G×E interaction analyses can improve our ability to identify and localize quantitative-trait loci. PMID:17160904

Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q.

PubMed

Pieke-Dahl, S; Möller, C G; Kelley, P M; Astuto, L M; Cremers, C W; Gorin, M B; Kimberling, W J

2000-04-01

Usher syndrome is a group of autosomal recessive disorders that includes retinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is defined as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has been isolated and characterised. In 1993, a large Usher II family affected with a mild form of RP was found to be unlinked to 1q41 markers. Subsequent linkage studies of families in our Usher series identified several type II families unlinked to USH2A and USH3 on 3q25. After a second unlinked family with many affected members and a mild retinal phenotype was discovered, a genome search using these two large families showed another Usher II locus on 5q (two point lod = 3.1 at D5S484). To date, we have identified nine unrelated 5q linked families (maximum combined multipoint lod = 5.86) as well as three Usher II families that show no significant linkage to any known Usher loci. Haplotype analysis of 5q markers indicates that the new locus is flanked by D5S428 and D5S433. Review of ophthalmological data suggests that RP symptoms are milder in 5q linked families; the RP is often not diagnosed until patients near their third decade. Enamel hypoplasia and severe, very early onset RP were observed in two of the three unlinked families; dental anomalies have not been previously described as a feature of Usher type II.

Two quantitative trait loci affect ACE activities in Mexican-Americans.

PubMed

Kammerer, Candace M; Gouin, Nicolas; Samollow, Paul B; VandeBerg, Jane F; Hixson, James E; Cole, Shelley A; MacCluer, Jean W; Atwood, Larry D

2004-02-01

Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log of the odds [LOD]=4.57, genomic P=0.003) that a QTL for ACE activity is located on chromosome 17 near the ACE structural locus. We subsequently performed linkage analyses conditional on the effect of this QTL and obtained strong evidence (LOD=3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated the ACEIns/Del genotypes in our analyses and removed the evidence for the chromosome 17 QTL (maximum LOD=0.60); however, we retained our evidence for the QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked to ACE and is in strong disequilibrium with the insertion/deletion polymorphism, which is consistent with other reports. We also have evidence that an additional QTL affects ACE activity. Identification of this additional QTL might lead to alternate means of prophylaxis.

Intrinsic low pass filtering improves signal-to-noise ratio in critical-point flexure biosensors

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

Jain, Ankit; Alam, Muhammad Ashraful, E-mail: alam@purdue.edu

2014-08-25

A flexure biosensor consists of a suspended beam and a fixed bottom electrode. The adsorption of the target biomolecules on the beam changes its stiffness and results in change of beam's deflection. It is now well established that the sensitivity of sensor is maximized close to the pull-in instability point, where effective stiffness of the beam vanishes. The question: “Do the signal-to-noise ratio (SNR) and the limit-of-detection (LOD) also improve close to the instability point?”, however remains unanswered. In this article, we systematically analyze the noise response to evaluate SNR and establish LOD of critical-point flexure sensors. We find thatmore » a flexure sensor acts like an effective low pass filter close to the instability point due to its relatively small resonance frequency, and rejects high frequency noise, leading to improved SNR and LOD. We believe that our conclusions should establish the uniqueness and the technological relevance of critical-point biosensors.« less

The dynamic system corresponding to LOD and AAM.

NASA Astrophysics Data System (ADS)

Liu, Shida; Liu, Shikuo; Chen, Jiong

2000-02-01

Using wavelet transform, the authors can reconstruct the 1-D map of a multifractal object. The wavelet transform of LOD and AAM shows that at 20 years scale, annual scale and 2 - 3 years scale, the jump points of LOD and AAM accord with each other very well, and their reconstructing 1-D mapping dynamic system are also very similar.

A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.

PubMed

Qin, Wei; Shu, Anli; Qian, Xueqing; Gao, Jianjun; Xing, Qinghe; Zhang, Juan; Zheng, Yonglan; Li, Xingwang; Li, Sheng; Feng, Guoyin; He, Lin

2006-08-28

The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1). A detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with haplotype analysis was performed. Mutation screening was carried out in the candidate gene by sequencing of amplified products. A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome 2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a highly conserved Leu to Pro. This nucleotide alteration was neither seen in unaffected members of the family nor found in 50 unrelated control subjects. The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.

Localisation of the gene for cylindromatosis (turban tumor syndrome) to chromosome 9p12-13

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

Wooster, R.; Mangion, J.; Quirk, Y.

Cylindromatosis (multiple cylindromas, tomato syndrome syndrome, turban tumor syndrome) is a rare autosomal dominant disease characterized by the development of multiple, slow growing neoplasms of the skin appendages. The tumors, known as dermal cylindromas, exhibit histological features of eccrine or apocrine sweat glands and occur most commonly in the scalp area. Genetic linkage analysis of two families yielded a maximum two point LOD score of 3.2 at D9S169. Critical recombinants place the gene between D9S161 and IFN, a distance of approximately 9 cM. This region of chromosome 9 harbors a gene that encodes a 16 kD protein which is anmore » inhibitor of cyclin dependent kinase 4 (CDK-4) and which is somatically mutated in many classes of cancer. However, the observation of recombinants between the disease and a polymorphic microsatellite repeat CT29 close to this gene, suggests that the CDK-4 inhibitor gene is unlikely to be responsible for cylindromatosis.« less

Results of a SNP genome screen in a large Costa Rican pedigree segregating for severe bipolar disorder.

PubMed

Service, Susan; Molina, Julio; Deyoung, Joseph; Jawaheer, Damini; Aldana, Ileana; Vu, Thuy; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Fournier, Eduardo; Ramirez, Magui; Mathews, Carol A; Davanzo, Pablo; Macaya, Gabriel; Sandkuijl, Lodewijk; Sabatti, Chiara; Reus, Victor; Freimer, Nelson

2006-06-05

We have ascertained in the Central Valley of Costa Rica a new kindred (CR201) segregating for severe bipolar disorder (BP-I). The family was identified by tracing genealogical connections among eight persons initially independently ascertained for a genome wide association study of BP-I. For the genome screen in CR201, we trimmed the family down to 168 persons (82 of whom are genotyped), containing 25 individuals with a best-estimate diagnosis of BP-I. A total of 4,690 SNP markers were genotyped. Analysis of the data was hampered by the size and complexity of the pedigree, which prohibited using exact multipoint methods on the entire kindred. Two-point parametric linkage analysis, using a conservative model of transmission, produced a maximum LOD score of 2.78 on chromosome 6, and a total of 39 loci with LOD scores >1.0. Multipoint parametric and non-parametric linkage analysis was performed separately on four sections of CR201, and interesting (nominal P-value from either analysis <0.01), although not statistically significant, regions were highlighted on chromosomes 1, 2, 3, 12, 16, 19, and 22, in at least one section of the pedigree, or when considering all sections together. The difficulties of analyzing genome wide SNP data for complex disorders in large, potentially informative, kindreds are discussed.

The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36.

PubMed Central

Lubianca Neto, J F; Lu, L; Eavey, R D; Flores, M A; Caldera, R M; Sangwatanaroj, S; Schott, J J; McDonough, B; Santos, J I; Seidman, C E; Seidman, J G

1998-01-01

We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The clinical association of sensorineural hearing loss with pili torti (broken, twisted hairs) was described >30 years ago by Bjornstad; subsequently, several small families have been studied. We evaluated a large kindred with Bjornstad syndrome in which eight members inherited pili torti and prelingual sensorineural hearing loss as autosomal recessive traits. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum two-point LOD score = 4.98 at theta = 0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between loci D2S1371 and D2S163. We speculate that intermediate filament and intermediate filament-associated proteins are good candidate genes for causing Bjornstad syndrome. PMID:9545407

[18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

PubMed Central

Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

2008-01-01

Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

Two-locus maximum lod score analysis of a multifactorial trait: joint consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes.

PubMed

Cordell, H J; Todd, J A; Bennett, S T; Kawaguchi, Y; Farrall, M

1995-10-01

To investigate the genetic component of multifactorial diseases such as type 1 (insulin-dependent) diabetes mellitus (IDDM), models involving the joint action of several disease loci are important. These models can give increased power to detect an effect and a greater understanding of etiological mechanisms. Here, we present an extension of the maximum lod score method of N. Risch, which allows the simultaneous detection and modeling of two unlinked disease loci. Genetic constraints on the identical-by-descent sharing probabilities, analogous to the "triangle" restrictions in the single-locus method, are derived, and the size and power of the test statistics are investigated. The method is applied to affected-sib-pair data, and the joint effects of IDDM1 (HLA) and IDDM2 (the INS VNTR) and of IDDM1 and IDDM4 (FGF3-linked) are assessed with relation to the development of IDDM. In the presence of genetic heterogeneity, there is seen to be a significant advantage in analyzing more than one locus simultaneously. Analysis of these families indicates that the effects at IDDM1 and IDDM2 are well described by a multiplicative genetic model, while those at IDDM1 and IDDM4 follow a heterogeneity model.

Two-locus maximum lod score analysis of a multifactorial trait: joint consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes.

PubMed Central

Cordell, H J; Todd, J A; Bennett, S T; Kawaguchi, Y; Farrall, M

1995-01-01

To investigate the genetic component of multifactorial diseases such as type 1 (insulin-dependent) diabetes mellitus (IDDM), models involving the joint action of several disease loci are important. These models can give increased power to detect an effect and a greater understanding of etiological mechanisms. Here, we present an extension of the maximum lod score method of N. Risch, which allows the simultaneous detection and modeling of two unlinked disease loci. Genetic constraints on the identical-by-descent sharing probabilities, analogous to the "triangle" restrictions in the single-locus method, are derived, and the size and power of the test statistics are investigated. The method is applied to affected-sib-pair data, and the joint effects of IDDM1 (HLA) and IDDM2 (the INS VNTR) and of IDDM1 and IDDM4 (FGF3-linked) are assessed with relation to the development of IDDM. In the presence of genetic heterogeneity, there is seen to be a significant advantage in analyzing more than one locus simultaneously. Analysis of these families indicates that the effects at IDDM1 and IDDM2 are well described by a multiplicative genetic model, while those at IDDM1 and IDDM4 follow a heterogeneity model. PMID:7573054

The MEM of spectral analysis applied to L.O.D.

NASA Astrophysics Data System (ADS)

Fernandez, L. I.; Arias, E. F.

The maximum entropy method (MEM) has been widely applied for polar motion studies taking advantage of its performance on the management of complex time series. The authors used the algorithm of the MEM to estimate Cross Spectral function in order to compare interannual Length-of-Day (LOD) time series with Southern Oscillation Index (SOI) and Sea Surface Temperature (SST) series, which are close related to El Niño-Southern Oscillation (ENSO) events.

Improved methylene blue two-phase titration method for determining cationic surfactant concentration in high-salinity brine.

PubMed

Cui, Leyu; Puerto, Maura; López-Salinas, José L; Biswal, Sibani L; Hirasaki, George J

2014-11-18

The methylene blue (MB) two-phase titration method is a rapid and efficient method for determining the concentrations of anionic surfactants. The point at which the aqueous and chloroform phases appear equally blue is called Epton's end point. However, many inorganic anions, e.g., Cl(-), NO3(-), Br(-), and I(-), can form ion pairs with MB(+) and interfere with Epton's end point, resulting in the failure of the MB two-phase titration in high-salinity brine. Here we present a method to extend the MB two-phase titration method for determining the concentration of various cationic surfactants in both deionized water and high-salinity brine (22% total dissolved solid). A colorless end point, at which the blue color is completely transferred from the aqueous phase to the chloroform phase, is proposed as titration end point. Light absorbance at the characteristic wavelength of MB is measured using a spectrophotometer. When the absorbance falls below a threshold value of 0.04, the aqueous phase is considered colorless, indicating that the end point has been reached. By using this improved method, the overall error for the titration of a permanent cationic surfactant, e.g., dodecyltrimethylammonium bromide, in deionized (DI) water and high-salinity brine is 1.274% and 1.322% with limits of detection (LOD) of 0.149 and 0.215 mM, respectively. Compared to the traditional acid-base titration method, the error of this improved method for a switchable cationic surfactant, e.g., tertiary amine surfactant (Ethomeen C12), is 2.22% in DI water and 0.106% with LOD of 0.369 and 0.439 mM, respectively.

A practical approach to determination of laboratory GC-MS limits of detection.

PubMed

Underwood, P J; Kananen, G E; Armitage, E K

1997-01-01

Determination of limit of detection (LOD) values in a forensic laboratory serves a fundamental forensic requirement for assay performance. In addition to demonstrating assay capability, LOD values can also be used to fulfill certification requirements of a high-volume forensic drug laboratory. The LOD was defined as the lowest concentration of drug that the laboratory can detect in a specimen with forensic certainty at a minimum of 85% of the time. Overall batch acceptance criteria included acceptable quantitation of control materials (within 20% of target), acceptable chromatography (symmetry, peak integration, peak shape, peak, and baseline resolution), retention time within +/-1% of the extracted standard, and mass ion ratios within +/-20% of the extracted standard mass ion ratios. Individual specimen acceptance criteria were the same as the batch acceptance criteria excluding the quantitation requirement. Data were collected from all instruments on different runs. A minimum of ten data points was required for each certified instrument, and a minimum of 85% of data points was acceptable. Quantitation within +/-20% of the LOD concentration was not required, but acceptable mass ratios were required. Data points with poor chromatography (internal standard failed mass ratios; interference of the baseline, for example, shoulders; asymmetry; and baseline resolution) was omitted from the acceptable rate calculation. Data points with good chromatography with failed mass ion ratios were included in the acceptable rate calculation. With these criteria, we established the following LODs: 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid, 2 ng/mL; benzoylecgonine, 5 ng/mL; phencyclidine, 2.5 ng/mL; amphetamine, 150 ng/mL; methamphetamine, 100 ng/mL; codeine, 500 ng/mL; and morphine, 1000 ng/mL.

Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: potential genetic and phenotypic heterogeneity.

PubMed

Scott, W K; Grubber, J M; Conneally, P M; Small, G W; Hulette, C M; Rosenberg, C K; Saunders, A M; Roses, A D; Haines, J L; Pericak-Vance, M A

2000-03-01

Apolipoprotein E (APOE) is the only confirmed susceptibility gene for late-onset Alzheimer disease (AD). In a recent genomic screen of 54 families with late-onset AD, we detected significant evidence for a second late-onset AD locus located on chromosome 12 between D12S373 and D12S390. Linkage to this region was strongest in 27 large families with at least one affected individual without an APOE-4 allele, suggesting that APOE and the chromosome 12 locus might have independent effects. We have since genotyped several additional markers across the region, to refine the linkage results. In analyzing these additional data, we have addressed the issue of heterogeneity in the data set by weighting results by clinical and neuropathologic features, sibship size, and APOE genotype. When considering all possible affected sib pairs (ASPs) per nuclear family, we obtained a peak maximum LOD score between D12S1057 and D12S1042. The magnitude and location of the maximum LOD score changed when different weighting schemes were used to control for the number of ASPs contributed by each nuclear family. Using the affected-relative-pair method implemented in GENEHUNTER-PLUS, we obtained a maximum LOD score between D12S398 and D12S1632, 25 cM from the original maximum LOD score. These results indicate that family size influences the location estimate for the chromosome 12 AD gene. The results of conditional linkage analysis by use of GENEHUNTER-PLUS indicated that evidence for linkage to chromosome 12 was stronger in families with affected individuals lacking an APOE-4 allele; much of this evidence came from families with affected individuals with neuropathologic diagnosis of dementia with Lewy bodies (DLB). Taken together, these results indicate that the chromosome 12 locus acts independently of APOE to increase the risk of late-onset familial AD and that it may be associated with the DLB variant of AD.

A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1.

PubMed

Hughes, A E; Newton, V E; Liu, X Z; Read, A P

1994-08-01

Waardenburg syndrome (WS), an autosomal dominant syndrome of hearing loss and pigmentary disturbances, comprises at least two separate conditions. WS type 1 is normally caused by mutations in PAX3 located at chromosome 2q35 and is distinguished clinically by minor facial malformations. We have now located a gene for WS type 2. Two families show linkage to a group of microsatellite markers located on chromosome 3p12-p14.1. D3S1261 gave a maximum lod score of 6.5 at zero recombination in one large Type 2 family. In a second, smaller family the adjacent marker D3S1210 gave a lod of 2.05 at zero recombination. Interestingly, the human homologue (MITF) of the mouse microphthalmia gene, a good candidate at the phenotypic level, has recently been mapped to 3p12.3-p14.4.

Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

PubMed

Barbesino, G; Tomer, Y; Concepcion, E S; Davies, T F; Greenberg, D A

1998-09-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a candidate locus. We found a locus on Xq21.33-22 linked to GD that may help to explain the female predisposition to GD. Confirmation of these data in HT may require study of an extended number of families because of possible heterogeneity.

A gene for familial psoriasis susceptibility maps to the distal end of human chromosome 17q

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

Bowcock, A.; Tomfohrde, J.; Barnes, R.

1994-09-01

Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. A gene for psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome wide linkage-analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. With one large kindred a maximum two-point lod score with D17S784 was 5.70 at 15% recombination. Heterogeneity testing indicated that psoriasis susceptibility in 50% of the families was linked to distal 17q. Susceptibility to psoriasis has repeatedly been found to be associated with HLA-Cw6 and associated HLA alleles. We therefore genotyped the families for locimore » within and flanking HLA; these included PCR assays for susceptibility alleles. By lod score analysis no evidence of linkage of psoriasis susceptibility to HLA was detected. The distribution of HLA-Cw6 and HLA-Class II alleles showed that HLA-Cw6 was frequent among patients, particularly in 4 of the 5 unlinked families. All affected members of two of these unlinked families carried HLA-Cw6 (empirical P values of 0.027 and 0.004). In 2 other families 4 of 6 and 6 of 7 had HLA-Cw6. In some of these families, an inability to detect linkage to HLA may have been due to the occurrence of multiple haplotypes carrying the psoriasis associated allele, HLA-Cw6. Contrasting with these findings, we observed a lack of association between HLA-Cw6 and psoriasis in the 3 families in which 17q markers were linked to susceptibility. The ability to detect linkage to 17q confirms that some forms of familial psoriasis are due to molecular defects at a single major genetic locus other than HLA.« less

Impact of parental relationships in maximum lod score affected sib-pair method.

PubMed

Leutenegger, Anne-Louise; Génin, Emmanuelle; Thompson, Elizabeth A; Clerget-Darpoux, Françoise

2002-11-01

Many studies are done in small isolated populations and populations where marriages between relatives are encouraged. In this paper, we point out some problems with applying the maximum lod score (MLS) method (Risch, [1990] Am. J. Hum. Genet. 46:242-253) in these populations where relationships exist between the two parents of the affected sib-pairs. Characterizing the parental relationships by the kinship coefficient between the parents (f), the maternal inbreeding coefficient (alpha(m), and the paternal inbreeding coefficient (alpha(p)), we explored the relationship between the identity by descent (IBD) vector expected under the null hypothesis of no linkage and these quantities. We find that the expected IBD vector is no longer (0.25, 0.5, 0.25) when f, alpha(m), and alpha(p) differ from zero. In addition, the expected IBD vector does not always follow the triangle constraints recommended by Holmans ([1993] Am. J. Hum. Genet. 52:362-374). So the classically used MLS statistic needs to be adapted to the presence of parental relationships. We modified the software GENEHUNTER (Kruglyak et al. [1996] Am. J. Hum. Genet. 58: 1347-1363) to do so. Indeed, the current version of the software does not compute the likelihood properly under the null hypothesis. We studied the adapted statistic by simulating data on three different family structures: (1) parents are double first cousins (f=0.125, alpha(m)=alpha(p)=0), (2) each parent is the offspring of first cousins (f=0, alpha(m)=alpha(p)=0.0625), and (3) parents are related as in the pedigree from Goddard et al. ([1996] Am. J. Hum. Genet. 58:1286-1302) (f=0.109, alpha(m)=alpha(p)=0.0625). The appropriate threshold needs to be derived for each case in order to get the correct type I error. And using the classical statistic in the presence of both parental kinship and parental inbreeding almost always leads to false conclusions. Copyright 2002 Wiley-Liss, Inc.

Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa

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

Bunge, S.; Wedemann, H.; Samanns, C.

1993-07-01

Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 ([theta][sub max] = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, withmore » a maximum lod score of 13.447 directly at D3S20. 13 refs., 1 fig., 2 tabs.« less

The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q.

PubMed Central

Casaubon, L. K.; Melanson, M.; Lopes-Cendes, I.; Marineau, C.; Andermann, E.; Andermann, F.; Weissenbach, J.; Prévost, C.; Bouchard, J. P.; Mathieu, J.; Rouleau, G. A.

1996-01-01

Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN) is a devastating neurodegenerative disorder that is transmitted as an autosomal recessive trait. Genealogical studies in a large number of affected French Canadian individuals suggest that ACCPN results from a single founder mutation. A genomewide search using 120 microsatellite DNA markers in 14 French Canadian families allowed the mapping of the ACCPN gene to a 5-cM region on chromosome 15q13-q15 that is flanked by markers D15S1040 and D15S118. A maximum two-point LOD score of 11.1 was obtained with the marker D15S971 at a recombination fraction of 0. Haplotype analysis and linkage disequilibrium support a founder effect. These findings are the first step in the identification of the gene responsible for ACCPN, which may shed some light on the numerous conditions associated with the progressive peripheral neuropathy or agenesis of the corpus callosum. PMID:8554065

Combined contactless conductometric, photometric, and fluorimetric single point detector for capillary separation methods.

PubMed

Ryvolová, Markéta; Preisler, Jan; Foret, Frantisek; Hauser, Peter C; Krásenský, Pavel; Paull, Brett; Macka, Mirek

2010-01-01

This work for the first time combines three on-capillary detection methods, namely, capacitively coupled contactless conductometric (C(4)D), photometric (PD), and fluorimetric (FD), in a single (identical) point of detection cell, allowing concurrent measurements at a single point of detection for use in capillary electrophoresis, capillary electrochromatography, and capillary/nanoliquid chromatography. The novel design is based on a standard 6.3 mm i.d. fiber-optic SMA adapter with a drilled opening for the separation capillary to go through, to which two concentrically positioned C(4)D detection electrodes with a detection gap of 7 mm were added on each side acting simultaneously as capillary guides. The optical fibers in the SMA adapter were used for the photometric signal (absorbance), and another optical fiber at a 45 degrees angle to the capillary was applied to collect the emitted light for FD. Light emitting diodes (255 and 470 nm) were used as light sources for the PD and FD detection modes. LOD values were determined under flow-injection conditions to exclude any stacking effects: For the 470 nm LED limits of detection (LODs) for FD and PD were for fluorescein (1 x 10(-8) mol/L) and tartrazine (6 x 10(-6) mol/L), respectively, and the LOD for the C(4)D was for magnesium chloride (5 x 10(-7) mol/L). The advantage of the three different detection signals in a single point is demonstrated in capillary electrophoresis using model mixtures and samples including a mixture of fluorescent and nonfluorescent dyes and common ions, underivatized amino acids, and a fluorescently labeled digest of bovine serum albumin.

Application of LOD technology to the economic residence GIS for industry and commerce administration

NASA Astrophysics Data System (ADS)

Song, Yongjun; Feng, Xuezhi; Zhao, Shuhe; Yin, Haiwei; Li, Yulin; Cui, Hongxia; Zhang, Hui; Zhong, Quanbao

2007-06-01

The LOD technology has an impact upon the multi-scale representation of spatial database. This paper takes advantage of LOD technology to express the multi-scale geographical data, and establish the exchange of multi-scale electronic map, further attain the goal that the details of geographic features such as point, line and polygon can be displayed more and more clearly with the display scale being enlarged to be convenient for the personnel of all offices of industry and commerce administration to label the locations of the corporations or enterprises.

Another procedure for the preliminary ordering of loci based on two point lod scores.

PubMed

Curtis, D

1994-01-01

Because of the difficulty of performing full likelihood analysis over multiple loci and the large numbers of possible orders, a number of methods have been proposed for quickly evaluating orders and, to a lesser extent, for generating good orders. A new method is proposed which uses a function which is moderately laborious to compute, the sum of lod scores between all pairs of loci. This function can be smoothly minimized by initially allowing the loci to be placed anywhere in space, and only subsequently constraining them to lie along a one-dimensional map. Application of this approach to sample data suggests that it has promise and might usefully be combined with other methods when loci need to be ordered.

a Framework for Architectural Heritage Hbim Semantization and Development

NASA Astrophysics Data System (ADS)

Brusaporci, S.; Maiezza, P.; Tata, A.

2018-05-01

Despite the recognized advantages of the use of BIM in the field of architecture and engineering, the extension of this procedure to the architectural heritage is neither immediate nor critical. The uniqueness and irregularity of historical architecture, on the one hand, and the great quantity of information necessary for the knowledge of architectural heritage, on the other, require appropriate reflections. The aim of this paper is to define a general framework for the use of BIM procedures for architectural heritage. The proposed methodology consists of three different Level of Development (LoD), depending on the characteristics of the building and the objectives of the study: a simplified model with a low geometric accuracy and a minimum quantity of information (LoD 200); a model nearer to the reality but, however, with a high deviation between virtual and real model (LoD 300); a detailed BIM model that reproduce as much as possible the geometric irregularities of the building and is enriched by the maximum quantity of information available (LoD 400).

An extension of the Maximum Lod Score method to X-linked loci.

PubMed

Cordell, H J; Kawaguchi, Y; Todd, J A; Farrall, M

1995-10-01

The Maximum Lod Score method for affected relative-pair analysis, introduced by Risch, is a powerful method for detecting linkage between an autosomal marker locus and disease. In order to use the method to detect linkage to markers on the X-chromosome, some modification is necessary. Here we extend the method to be applicable to X-chromosomal data, and derive genetic restrictions on the haplotype-sharing probabilities analogous to the 'possible triangle' restrictions described by Holmans for the autosomal case. Size criteria are derived using asymptotic theory and simulation, and the power is calculated for a number of possible underlying models. The method is applied to data from 284 type 1 diabetic families and evidence is found for the presence of one or more diabetogenic loci on the X-chromosome.

Linkage of a gene for macular corneal dystrophy to chromosome 16.

PubMed Central

Vance, J. M.; Jonasson, F.; Lennon, F.; Sarrica, J.; Damji, K. F.; Stauffer, J.; Pericak-Vance, M. A.; Klintworth, G. K.

1996-01-01

Autosomal recessive macular corneal dystrophy (MCD) is a heterogeneous disorder leading to visual impairment. Sixteen American and Icelandic families (11 type I and 5 type II) were analyzed for linkage, by use of 208 polymorphic microsatellite markers. A significant maximum LOD score Zmax of 7.82 at a maximum recombination fraction (thetamax) of .06 was found with the 16q22 locus D16S518 for MCD type I. In addition, a peak LOD score of 2.50 at a recombination fraction of .00 was obtained for the MCD type II families, by use of the identical marker. These findings raise the possibility that MCD type II may be due to the same genetic locus that is involved in MCD type I. PMID:8644739

Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics.

PubMed

Mayeux, R; Lee, J H; Romas, S N; Mayo, D; Santana, V; Williamson, J; Ciappa, A; Rondon, H Z; Estevez, P; Lantigua, R; Medrano, M; Torres, M; Stern, Y; Tycko, B; Knowles, J A

2002-01-01

Linkage to chromosome 12p for familial Alzheimer disease (AD) has been inconsistent. Using 35 markers near the centromere of chromosome 12, we investigated 79 Caribbean Hispanic families with AD. Two-point linkage analysis using affected sib pairs yielded LOD scores of 3.15 at D12S1623 and 1.43 at D12S1042. The LOD score at D12S1623 decreased to 1.62 in families with late-onset (age >65 years) AD (LOAD), but the LOD score at D12S1042 was unchanged. Among families negative for the apolipoprotein E (APOE-epsilon 4) allele, the LOD score for D12S1623 was lower (1.01), whereas that for D12S1042 increased to 1.73. Among families positive for the APOE-epsilon 4 allele, none of the LOD scores reached 1. Multipoint affected-relative-pair analysis showed peaks at D12S1623 (nonparametric linkage [NPL] score 1.52; P=.028) and near D12S1042, at D12S1057 (NPL score 1.57; P=.027). NPL scores for both D12S1623 and D12S1057 increased in families affected with LOAD, but, in APOE-epsilon 4-negative families, only scores for the region flanking D12S1623 remained elevated (NPL score 1.74; P=.013). This study of Caribbean Hispanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the presence or absence of the APOE-epsilon 4 allele.

A Genomewide Linkage Scan of Cocaine Dependence and Major Depressive Episode in Two Populations

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R; Farrer, Lindsay A; Gelernter, Joel

2011-01-01

Cocaine dependence (CD) and major depressive episode (MDE) frequently co-occur with poorer treatment outcome and higher relapse risk. Shared genetic risk was affirmed; to date, there have been no reports of genomewide linkage scans (GWLSs) surveying the susceptibility regions for comorbid CD and MDE (CD–MDE). We aimed to identify chromosomal regions and candidate genes susceptible to CD, MDE, and CD–MDE in African Americans (AAs) and European Americans (EAs). A total of 1896 individuals were recruited from 384 AA and 355 EA families, each with at least a sibling-pair with CD and/or opioid dependence. Array-based genotyping of about 6000 single-nucleotide polymorphisms was completed for all individuals. Parametric and non-parametric genomewide linkage analyses were performed. We found a genomewide-significant linkage peak on chromosome 7 at 183.4 cM for non-parametric analysis of CD–MDE in AAs (lod=3.8, genomewide empirical p=0.016; point-wise p=0.00001). A nearly genomewide significant linkage was identified for CD–MDE in EAs on chromosome 5 at 14.3 cM (logarithm of odds (lod)=2.95, genomewide empirical p=0.055; point-wise p=0.00012). Parametric analysis corroborated the findings in these two regions and improved the support for the peak on chromosome 5 so that it reached genomewide significance (heterogeneity lod=3.28, genomewide empirical p=0.046; point-wise p=0.00053). This is the first GWLS for CD–MDE. The genomewide significant linkage regions on chromosomes 5 and 7 harbor four particularly promising candidate genes: SRD5A1, UBE3C, PTPRN2, and VIPR2. Replication of the linkage findings in other populations is warranted, as is a focused analysis of the genes located in the linkage regions implicated here. PMID:21849985

Mapping Quantitative Trait Loci (QTL) in sheep. III. QTL for carcass composition traits derived from CT scans and aligned with a meta-assembly for sheep and cattle carcass QTL.

PubMed

Cavanagh, Colin R; Jonas, Elisabeth; Hobbs, Matthew; Thomson, Peter C; Tammen, Imke; Raadsma, Herman W

2010-09-16

An (Awassi × Merino) × Merino single-sire backcross family with 165 male offspring was used to map quantitative trait loci (QTL) for body composition traits on a framework map of 189 microsatellite loci across all autosomes. Two cohorts were created from the experimental progeny to represent alternative maturity classes for body composition assessment. Animals were raised under paddock conditions prior to entering the feedlot for a 90-day fattening phase. Body composition traits were derived in vivo at the end of the experiment prior to slaughter at 2 (cohort 1) and 3.5 (cohort 2) years of age, using computed tomography. Image analysis was used to gain accurate predictions for 13 traits describing major fat depots, lean muscle, bone, body proportions and body weight which were used for single- and two-QTL mapping analysis. Using a maximum-likelihood approach, three highly significant (LOD ≥ 3), 15 significant (LOD ≥ 2), and 11 suggestive QTL (1.7 ≤ LOD < 2) were detected on eleven chromosomes. Regression analysis confirmed 28 of these QTL and an additional 17 suggestive (P < 0.1) and two significant (P < 0.05) QTL were identified using this method. QTL with pleiotropic effects for two or more tissues were identified on chromosomes 1, 6, 10, 14, 16 and 23. No tissue-specific QTL were identified.A meta-assembly of ovine QTL for carcass traits from this study and public domain sources was performed and compared with a corresponding bovine meta-assembly. The assembly demonstrated QTL with effects on carcass composition in homologous regions on OAR1, 2, 6 and 21.

An ion source for radiofrequency-pulsed glow discharge time-of-flight mass spectrometry

NASA Astrophysics Data System (ADS)

González Gago, C.; Lobo, L.; Pisonero, J.; Bordel, N.; Pereiro, R.; Sanz-Medel, A.

2012-10-01

A Grimm-type glow discharge (GD) has been designed and constructed as an ion source for pulsed radiofrequency GD spectrometry when coupled to an orthogonal time of flight mass spectrometer. Pulse shapes of argon species and analytes were studied as a function of the discharge conditions using a new in-house ion source (UNIOVI GD) and results have been compared with a previous design (PROTOTYPE GD). Different behavior and shapes of the pulse profiles have been observed for the two sources evaluated, particularly for the plasma gas ionic species detected. In the more analytically relevant region (afterglow), signals for 40Ar+ with this new design were negligible, while maximum intensity was reached earlier in time for 41(ArH)+ than when using the PROTOTYPE GD. Moreover, while maximum 40Ar+ signals measured along the pulse period were similar in both sources, 41(ArH)+ and 80(Ar2)+ signals tend to be noticeable higher using the PROTOTYPE chamber. The UNIOVI GD design was shown to be adequate for sensitive direct analysis of solid samples, offering linear calibration graphs and good crater shapes. Limits of detection (LODs) are in the same order of magnitude for both sources, although the UNIOVI source provides slightly better LODs for those analytes with masses slightly higher than 41(ArH)+.

A genome-wide linkage study of mammographic density, a risk factor for breast cancer

PubMed Central

2011-01-01

Introduction Mammographic breast density is a highly heritable (h2 > 0.6) and strong risk factor for breast cancer. We conducted a genome-wide linkage study to identify loci influencing mammographic breast density (MD). Methods Epidemiological data were assembled on 1,415 families from the Australia, Northern California and Ontario sites of the Breast Cancer Family Registry, and additional families recruited in Australia and Ontario. Families consisted of sister pairs with age-matched mammograms and data on factors known to influence MD. Single nucleotide polymorphism (SNP) genotyping was performed on 3,952 individuals using the Illumina Infinium 6K linkage panel. Results Using a variance components method, genome-wide linkage analysis was performed using quantitative traits obtained by adjusting MD measurements for known covariates. Our primary trait was formed by fitting a linear model to the square root of the percentage of the breast area that was dense (PMD), adjusting for age at mammogram, number of live births, menopausal status, weight, height, weight squared, and menopausal hormone therapy. The maximum logarithm of odds (LOD) score from the genome-wide scan was on chromosome 7p14.1-p13 (LOD = 2.69; 63.5 cM) for covariate-adjusted PMD, with a 1-LOD interval spanning 8.6 cM. A similar signal was seen for the covariate adjusted area of the breast that was dense (DA) phenotype. Simulations showed that the complete sample had adequate power to detect LOD scores of 3 or 3.5 for a locus accounting for 20% of phenotypic variance. A modest peak initially seen on chromosome 7q32.3-q34 increased in strength when only the 513 families with at least two sisters below 50 years of age were included in the analysis (LOD 3.2; 140.7 cM, 1-LOD interval spanning 9.6 cM). In a subgroup analysis, we also found a LOD score of 3.3 for DA phenotype on chromosome 12.11.22-q13.11 (60.8 cM, 1-LOD interval spanning 9.3 cM), overlapping a region identified in a previous study. Conclusions The suggestive peaks and the larger linkage signal seen in the subset of pedigrees with younger participants highlight regions of interest for further study to identify genes that determine MD, with the goal of understanding mammographic density and its involvement in susceptibility to breast cancer. PMID:22188651

LOD-climate Links: how the 2015-2016 El Niño Lengthened the Day by 0.8 ms, and Possible Rotational Forcing of Multidecadal Temperature Changes

NASA Astrophysics Data System (ADS)

Lambert, S. B.; de Viron, O.; Marcus, S.

2016-12-01

El Niño events are generally accompanied by significant changes in the Earth's length-of-day (LOD) that can be explained by two approaches. Considering the angular momentum conservation of the system composed by the solid Earth and the atmosphere, ENSO events are accompanied by a strengthening of the subtropical jet streams, and, therefore, a decrease of the Earth's rotation rate. Using the torque approach, the low pressure field of the Eastern Pacific, which is close to high mountain ranges along the Western American coasts, creates a negative torque of the atmosphere on the solid Earth which tends to slow down the Earth's rotation. The large 1983 event was associated with a lengthening of the day of about 1 ms. During the 2015-2016 winter season, a major ENSO event occurred, classified as very strong by meteorological agencies. This central Pacific event, for which the Nino 3.4 index is as high as in 1983, was also concurrent with positive phases of PDO, NAO, and AAO. It coincided with an excursion of the LOD as large as 0.8 ms over a few weeks reaching its maximum around 2016 New Year. We evaluate the mountain and friction torques responsible for the Earth's rotation variations during the winter season and compare to the mean situations and to previous strong ENSO events of 1983 and 1998. Especially, we noticed that the contribution from American mountain ranges is close to the value of 1983. The weaker LOD excursion comes from an inexistent torque over the Himalayas, a weaker contribution from Europe, and a noticeable positive contribution from Antarctica. On longer time scales, core-generated ms-scale LOD excursions are found to precede NH surface and global SST fluctuations by nearly a decade; although the cause of this apparent rotational effect is not known, reported correlations of LOD and tidal-orbital forcing with surface and submarine volcanic activity offer prospects to explain these observations in a core-to-climate chain of causality.

Posterior probability of linkage and maximal lod score.

PubMed

Génin, E; Martinez, M; Clerget-Darpoux, F

1995-01-01

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

Using lod scores to detect sex differences in male-female recombination fractions.

PubMed

Feenstra, B; Greenberg, D A; Hodge, S E

2004-01-01

Human recombination fraction (RF) can differ between males and females, but investigators do not always know which disease genes are located in genomic areas of large RF sex differences. Knowledge of RF sex differences contributes to our understanding of basic biology and can increase the power of a linkage study, improve gene localization, and provide clues to possible imprinting. One way to detect these differences is to use lod scores. In this study we focused on detecting RF sex differences and answered the following questions, in both phase-known and phase-unknown matings: (1) How large a sample size is needed to detect a RF sex difference? (2) What are "optimal" proportions of paternally vs. maternally informative matings? (3) Does ascertaining nonoptimal proportions of paternally or maternally informative matings lead to ascertainment bias? Our results were as follows: (1) We calculated expected lod scores (ELODs) under two different conditions: "unconstrained," allowing sex-specific RF parameters (theta(female), theta(male)); and "constrained," requiring theta(female) = theta(male). We then examined the DeltaELOD (identical with difference between maximized constrained and unconstrained ELODs) and calculated minimum sample sizes required to achieve statistically significant DeltaELODs. For large RF sex differences, samples as small as 10 to 20 fully informative matings can achieve statistical significance. We give general sample size guidelines for detecting RF differences in informative phase-known and phase-unknown matings. (2) We defined p as the proportion of paternally informative matings in the dataset; and the optimal proportion p(circ) as that value of p that maximizes DeltaELOD. We determined that, surprisingly, p(circ) does not necessarily equal (1/2), although it does fall between approximately 0.4 and 0.6 in most situations. (3) We showed that if p in a sample deviates from its optimal value, no bias is introduced (asymptotically) to the maximum likelihood estimates of theta(female) and theta(male), even though ELOD is reduced (see point 2). This fact is important because often investigators cannot control the proportions of paternally and maternally informative families. In conclusion, it is possible to reliably detect sex differences in recombination fraction. Copyright 2004 S. Karger AG, Basel

Effect of heterogeneity and assumed mode of inheritance on lod scores.

PubMed

Durner, M; Greenberg, D A

1992-02-01

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Interval mapping of high growth (hg), a major locus that increases weight gain in mice

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

Horvat, S.; Medrano, J.F.

1995-04-01

The high growth locus (hg) causes a major increase in weight gain and body size in mice. As a first step to map-based cloning of hg, we developed a genetic map of the hg-containing region using interval mapping of 403 F{sub 2} from a C57BL/6J-hghg x CAST/EiJ cross. The maximum likelihood position of hg was at the chromosome 10 marker D10Mit41 (LOD = 24.8) in the F{sub 2} females and 1.5 cM distal to D10Mit41 (LOD = 9.56) in the F{sub 2} males with corresponding LOD 2 support intervals of 3.7 and 5.4 cM, respectively. The peak LOD scores weremore » significantly higher than the estimated empirical threshold LOD values. The localization of hg by interval mapping was supported by a test cross of F{sub 2} mice recombinant between the LOD 2 support interval and the flanking marker. The interval mapping and test-cross indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study. The hg inheritance was recessive in females, although we could not reject recessive or additive inheritance in males. Possible causes for sex differences in peak LOD scores and for the distortion of transmission ratios observed in F{sub 2} males are discussed. The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals. 48 refs., 3 figs., 3 tabs.« less

Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12-q13.1: Part 1

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

Pulver, A.E.; Wolyniec, P.S.; Lasseter, V.K.

To identify genes responsible for the susceptibility for schizophrenia, and to test the hypothesis that schizophrenia is etiologically heterogeneous, we have studied 39 multiplex families from a systematic sample of schizophrenic patients. Using a complex autosomal dominant model, which considers only those with a diagnosis of schizophrenia or schizoaffective disorder as affected, a random search of the genome for detection of linkage was undertaken. Pairwise linkage analyses suggest a potential linkage (LRH = 34.7 or maximum lod score = 1.54) for one region (22q12-q13.1). Reanalyses, varying parameters in the dominant model, maximized the LRH at 660.7 (maximum lod score 2.82).more » This finding is of sufficient interest to warrant further investigation through collaborative studies. 72 refs., 5 tabs.« less

The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q

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

Casaubon, L.K.; Melanson, M.; Marineau, C.

1996-01-01

Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN) is a devastating neurodegenerative disorder that is transmitted as an autosomal recessive trait. Genealogical studies in a large number of affected French Canadian individuals suggest that ACCPN results from a single founder mutation. A genomewide search using 120 microsatellite DNA markers in 14 French Canadian families allowed the mapping of the ACCPN gene to a 5-cM region on chromosome 15q13-q15 that is flanked by markers D15S1040 and D15S118. A maximum two-point LOD score of 11.1 was obtained with the marker D15S971 at a recombination fraction of 0. Haplotype analysismore » and linkage disequilibrium support a founder effect. These findings are the first step in the identification of the gene responsible for ACCPN, which may shed some light on the numerous conditions associated with progressive peripheral neuropathy or agenesis of the corpus callosum. 28 refs., 2 figs., 3 tabs.« less

No clustering for linkage map based on low-copy and undermethylated microsatellites.

PubMed

Zhou, Yi; Gwaze, David P; Reyes-Valdés, M Humberto; Bui, Thomas; Williams, Claire G

2003-10-01

Clustering has been reported for conifer genetic maps based on hypomethylated or low-copy molecular markers, resulting in uneven marker distribution. To test this, a framework genetic map was constructed from three types of microsatellites: low-copy, undermethylated, and genomic. These Pinus taeda L. microsatellites were mapped using a three-generation pedigree with 118 progeny. The microsatellites were highly informative; of the 32 markers in intercross configuration, 29 were segregating for three or four alleles in the progeny. The sex-averaged map placed 51 of the 95 markers in 15 linkage groups at LOD > 4.0. No clustering or uneven distribution across the genome was observed. The three types of P. taeda microsatellites were randomly dispersed within each linkage group. The 51 microsatellites covered a map distance of 795 cM, an average distance of 21.8 cM between markers, roughly half of the estimated total map length. The minimum and maximum distances between any two bins was 4.4 and 45.3 cM, respectively. These microsatellites provided anchor points for framework mapping for polymorphism in P. taeda and other closely related hard pines.

A gene for cleidocranial dysplasia to the short arm of chromosome 6

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

Feldman, G.F.; Muenke, M.; Robin, N.H.

1995-04-01

Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia characterized by mild-to-moderate short stature, clavicular aplasia or hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth, a characteristic craniofacial appearance, and a variety of other skeletal anomalies. We have performed linkage studies in five families with CCD, with 24 affected and 20 unaffected individuals, using microsatellite markers spanning two candidate regions on chromosomes 8q and 6. The strongest support for linkage was with chromosome 6p microsatellite marker D6S282 with a two-point lod score of 4.84 ({theta} = .03). Furthermore, the multipoint lod score was 5.70 in the intervalmore » between D6S282 and D6S291. These data show that the gene for autosomal dominant CCD is located within a 19-cM interval on the short arm of chromosome 6, between D6S282 and D6S291. 25 refs., 3 figs., 1 tab.« less

Genomewide Scan for Nonsyndromic Cleft Lip and Palate in Multigenerational Indian Families Reveals Significant Evidence of Linkage at 13q33.1-34

PubMed Central

Radhakrishna, Uppala; Ratnamala, Uppala; Gaines, Mathew; Beiraghi, Soraya; Hutchings, David; Golla, Jeffrey; Husain, Syed A.; Gambhir, Prakash S.; Sheth, Jayesh J.; Sheth, Frenny J.; Chetan, Ghati K.; Naveed, Mohammed; Solanki, Jitendra V.; Patel, Uday C.; Master, Dilipkumar C.; Memon, Rafiq; Antonarakis, Gregory S.; Antonarakis, Stylianos E.; Nath, Swapan K.

2006-01-01

Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used ∼10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (α=100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of ∼20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families. PMID:16909398

Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h.

PubMed

Timsit, J F; Fosse, J P; Troché, G; De Lassence, A; Alberti, C; Garrouste-Orgeas, M; Azoulay, E; Chevret, S; Moine, P; Cohen, Y

2001-06-01

In most databases used to build general severity scores the median duration of intensive care unit (ICU) stay is less than 3 days. Consequently, these scores are not the most appropriate tools for measuring prognosis in studies dealing with ICU patients hospitalized for more than 72 h. To develop a new prognostic model based on a general severity score (SAPS II), an organ dysfunction score (LOD) and evolution of both scores during the first 3 days of ICU stay. Prospective multicenter study. Twenty-eight intensive care units (ICUs) in France. A training data-set was created with four ICUs during an 18-month period (893 patients). Seventy percent of the patients were medical (628) aged 66 years. The median SAPS II was 38. The ICU and hospital mortality rates were 22.7% and 30%, respectively. Forty-seven percent (420 patients) were transferred from hospital wards. In this population, the calibration (Hosmer-Lemeshow chi-square: 37.4, P = 0.001) and the discrimination [area under the ROC curves: 0.744 (95 % CI: 0.714-0.773)] of the original SAPS II were relatively poor. A validation data set was created with a random panel of 24 French ICUs during March 1999 (312 patients). The LOD and SAPS II scores were calculated during the first (SAPS1, LOD1), second (SAPS2, LOD2), and third (SAPS3, LOD3) calendar days. The LOD and SAPS scores alterations were assigned the value "1" when scores increased with time and "0" otherwise. A multivariable logistic regression model was used to select variables measured during the first three calendar days, and independently associated with death. Selected variables were: SAPS II at admission [OR: 1.04 (95 % CI: 1.027-1.053) per point], LOD [OR: 1.16 (95 % CI: 1.085-1.253) per point], transfer from ward [OR: 1.74 (95 % CI: 1.25-2.42)], as well as SAPS3-SAPS2 alterations [OR: 1.516 (95 % CI: 1.04-2.22)], and LOD3-LOD2 alterations [OR: 2.00 (95 % CI: 1.29-3.11)]. The final model has good calibration and discrimination properties in the training data set [area under the ROC curve: 0.794 (95 % CI: 0.766-0.820), Hosmer-Lemeshow C statistic: 5.56, P = 0.7]. In the validation data set, the model maintained good accuracy [area under the ROC curve: 0.826 (95 % CI: 0.780-0.867), Hosmer-Lemeshow C statistic: 7.14, P = 0.5]. The new model using SAPS II and LOD and their evolution during the first calendar days has good discrimination and calibration properties. We propose its use for benchmarking and evaluating the over-risk of death associated with ICU-acquired nosocomial infections.

Enhanced response of a proteinase K-based conductometric biosensor using nanoparticles.

PubMed

Nouira, Wided; Maaref, Abderrazak; Elaissari, Hamid; Vocanson, Francis; Siadat, Maryam; Jaffrezic-Renault, Nicole

2014-07-23

Proteinases are involved in a multitude of important physiological processes, such as protein metabolism. For this reason, a conductometric enzyme biosensor based on proteinase K was developed using two types of nanoparticles (gold and magnetic). The enzyme was directly adsorbed on negatively charged nanoparticles and then deposited and cross-linked on a planar interdigitated electrode (IDE). The biosensor was characterized with bovine serum albumin (BSA) as a standard protein. Higher sensitivity was obtained using gold nanoparticles. The linear range for BSA determination was then from 0.5 to 10 mg/L with a maximum response of 154 µs. These results are greater than that found without any nanoparticles (maximum response of 10 µs). The limit of detection (LOD) was 0.3 mg/L. An inter-sensor reproducibility of 3.5% was obtained.

Quantile-based permutation thresholds for quantitative trait loci hotspots.

PubMed

Neto, Elias Chaibub; Keller, Mark P; Broman, Andrew F; Attie, Alan D; Jansen, Ritsert C; Broman, Karl W; Yandell, Brian S

2012-08-01

Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key importance. One approach, randomly allocating observed QTL across the genomic locations separately by trait, implicitly assumes all traits are uncorrelated. Recently, an empirical test for QTL hotspots was proposed on the basis of the number of traits that exceed a predetermined LOD value, such as the standard permutation LOD threshold. The permutation null distribution of the maximum number of traits across all genomic locations preserves the correlation structure among the phenotypes, avoiding the detection of spurious hotspots due to nongenetic correlation induced by uncontrolled environmental factors and unmeasured variables. However, by considering only the number of traits above a threshold, without accounting for the magnitude of the LOD scores, relevant information is lost. In particular, biologically interesting hotspots composed of a moderate to small number of traits with strong LOD scores may be neglected as nonsignificant. In this article we propose a quantile-based permutation approach that simultaneously accounts for the number and the LOD scores of traits within the hotspots. By considering a sliding scale of mapping thresholds, our method can assess the statistical significance of both small and large hotspots. Although the proposed approach can be applied to any type of heritable high-volume "omic" data set, we restrict our attention to expression (e)QTL analysis. We assess and compare the performances of these three methods in simulations and we illustrate how our approach can effectively assess the significance of moderate and small hotspots with strong LOD scores in a yeast expression data set.

Photoacoustic infrared spectroscopy for conducting gas tracer tests and measuring water saturations in landfills

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

Jung, Yoojin; Han, Byunghyun; Mostafid, M. Erfan

2012-02-15

Highlights: Black-Right-Pointing-Pointer Photoacoustic infrared spectroscopy tested for measuring tracer gas in landfills. Black-Right-Pointing-Pointer Measurement errors for tracer gases were 1-3% in landfill gas. Black-Right-Pointing-Pointer Background signals from landfill gas result in elevated limits of detection. Black-Right-Pointing-Pointer Technique is much less expensive and easier to use than GC. - Abstract: Gas tracer tests can be used to determine gas flow patterns within landfills, quantify volatile contaminant residence time, and measure water within refuse. While gas chromatography (GC) has been traditionally used to analyze gas tracers in refuse, photoacoustic spectroscopy (PAS) might allow real-time measurements with reduced personnel costs and greater mobilitymore » and ease of use. Laboratory and field experiments were conducted to evaluate the efficacy of PAS for conducting gas tracer tests in landfills. Two tracer gases, difluoromethane (DFM) and sulfur hexafluoride (SF{sub 6}), were measured with a commercial PAS instrument. Relative measurement errors were invariant with tracer concentration but influenced by background gas: errors were 1-3% in landfill gas but 4-5% in air. Two partitioning gas tracer tests were conducted in an aerobic landfill, and limits of detection (LODs) were 3-4 times larger for DFM with PAS versus GC due to temporal changes in background signals. While higher LODs can be compensated by injecting larger tracer mass, changes in background signals increased the uncertainty in measured water saturations by up to 25% over comparable GC methods. PAS has distinct advantages over GC with respect to personnel costs and ease of use, although for field applications GC analyses of select samples are recommended to quantify instrument interferences.« less

Sensitivity of lod scores to changes in diagnostic status.

PubMed Central

Hodge, S E; Greenberg, D A

1992-01-01

This paper investigates effects on lod scores when one individual in a data set changes diagnostic or recombinant status. First we examine the situation in which a single offspring in a nuclear family changes status. The nuclear-family situation, in addition to being of interest in its own right, also has general theoretical importance, since nuclear families are "transparent"; that is, one can track genetic events more precisely in nuclear families than in complex pedigrees. We demonstrate that in nuclear families log10 [(1-theta)/theta] gives an upper limit on the impact that a single offspring's change in status can have on the lod score at that recombination fraction (theta). These limits hold for a fully penetrant dominant condition and fully informative marker, in either phase-known or phase-unknown matings. Moreover, log10 [(1-theta)/theta] (where theta denotes the value of theta at which Zmax occurs) gives an upper limit on the impact of a single offspring's status change on the maximum lod score (Zmax). In extended pedigrees, in contrast to nuclear families, no comparable limit can be set on the impact of a single individual on the lod score. Complex pedigrees are subject to both stabilizing and destabilizing influences, and these are described. Finally, we describe a "sensitivity analysis," in which, after all linkage analysis is completed, every informative individual in the data set is changed, one at a time, to see the effect which each separate change has on the lod scores. The procedure includes identifying "critical individuals," i.e., those who would have the greatest impact on the lod scores, should their diagnostic status in fact change. To illustrate use of the sensitivity analysis, we apply it to the large bipolar pedigree reported by Egeland et al. and Kelsoe et al. We show that the changes in lod scores observed there, on the order of 1.1-1.2 per person, are not unusual. We recommend that investigators include a sensitivity analysis as a standard part of reporting the results of a linkage analysis. PMID:1570835

Sensitivity of lod scores to changes in diagnostic status.

PubMed

Hodge, S E; Greenberg, D A

1992-05-01

This paper investigates effects on lod scores when one individual in a data set changes diagnostic or recombinant status. First we examine the situation in which a single offspring in a nuclear family changes status. The nuclear-family situation, in addition to being of interest in its own right, also has general theoretical importance, since nuclear families are "transparent"; that is, one can track genetic events more precisely in nuclear families than in complex pedigrees. We demonstrate that in nuclear families log10 [(1-theta)/theta] gives an upper limit on the impact that a single offspring's change in status can have on the lod score at that recombination fraction (theta). These limits hold for a fully penetrant dominant condition and fully informative marker, in either phase-known or phase-unknown matings. Moreover, log10 [(1-theta)/theta] (where theta denotes the value of theta at which Zmax occurs) gives an upper limit on the impact of a single offspring's status change on the maximum lod score (Zmax). In extended pedigrees, in contrast to nuclear families, no comparable limit can be set on the impact of a single individual on the lod score. Complex pedigrees are subject to both stabilizing and destabilizing influences, and these are described. Finally, we describe a "sensitivity analysis," in which, after all linkage analysis is completed, every informative individual in the data set is changed, one at a time, to see the effect which each separate change has on the lod scores. The procedure includes identifying "critical individuals," i.e., those who would have the greatest impact on the lod scores, should their diagnostic status in fact change. To illustrate use of the sensitivity analysis, we apply it to the large bipolar pedigree reported by Egeland et al. and Kelsoe et al. We show that the changes in lod scores observed there, on the order of 1.1-1.2 per person, are not unusual. We recommend that investigators include a sensitivity analysis as a standard part of reporting the results of a linkage analysis.

Production of a broad-specificity monoclonal antibody and application as a receptor to detection amatoxins in mushroom.

PubMed

He, Kuo; Mao, Qingwen; Zang, Xiuyuan; Zhang, Yanyu; Li, Hui; Zhang, Donghao

2017-09-01

In this study, we report the production of a monoclonal broad-specificity monoclonal antibody (mAb) specific for amatoxins and development of an indirect competitive immunoassay for detection of amatoxins in mushroom samples. In the assay, the complete antigen (α-amanitin-OVA) was used as coating antigen, and amatoxins as competitor competes with coating antigen to bind with mAb. Using this approach, The half-maximum inhibition concentrations (IC 50 ) of α-amanitin, β-amanitin and γ-amanitin, and limits of detection (LODs, IC 15 ) were 66.3, 97.4, 163.1 ng/mL and 0.91, 0.98, 0.89 ng/mL, respectively. The LODs for α-amanitin, β-amanitin and γ-amanitin in mushroom samples were 4.55, 4.9, and 4.45 ng/mL. The spiked results were also confirmed by HPLC, which showed a good correlation (R 2  = 0.996) between the two methods. The results indicated that the developed assay was reliable and suitable for the detection of amatoxins in mushroom samples. Copyright © 2017. Published by Elsevier Ltd.

Successional stage of biological soil crusts: an accurate indicator of ecohydrological condition

USGS Publications Warehouse

Belnap, Jayne; Wilcox, Bradford P.; Van Scoyoc, Matthew V.; Phillips, Susan L.

2013-01-01

Biological soil crusts are a key component of many dryland ecosystems. Following disturbance, biological soil crusts will recover in stages. Recently, a simple classification of these stages has been developed, largely on the basis of external features of the crusts, which reflects their level of development (LOD). The classification system has six LOD classes, from low (1) to high (6). To determine whether the LOD of a crust is related to its ecohydrological function, we used rainfall simulation to evaluate differences in infiltration, runoff, and erosion among crusts in the various LODs, across a range of soil depths and with different wetting pre-treatments. We found large differences between the lowest and highest LODs, with runoff and erosion being greatest from the lowest LOD. Under dry antecedent conditions, about 50% of the water applied ran off the lowest LOD plots, whereas less than 10% ran off the plots of the two highest LODs. Similarly, sediment loss was 400 g m-2 from the lowest LOD and almost zero from the higher LODs. We scaled up the results from these simulations using the Rangeland Hydrology and Erosion Model. Modelling results indicate that erosion increases dramatically as slope length and gradient increase, especially beyond the threshold values of 10 m for slope length and 10% for slope gradient. Our findings confirm that the LOD classification is a quick, easy, nondestructive, and accurate index of hydrological condition and should be incorporated in field and modelling assessments of ecosystem health.

Genomic scan for genes predisposing to schizophrenia

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

Coon, H.; Jensen. S.; Holik, J.

1994-03-15

We initiated a genome-wide search for genes predisposing to schizophrenia by ascertaining 9 families, each containing three to five cases of schizophrenia. The 9 pedigrees were initially genotyped with 329 polymorphic DNA loci distributed throughout the genome. Assuming either autosomal dominant or recessive inheritance, 254 DNA loci yielded lod scores less than -2.0 at {theta} = 0.0, 101 DNA markers gave lod scores less than -2.0 at {theta} = 0.05, while 5 DNA loci produced maximum lod scores greater than 1: D4S35, D14S17, D15S1, D22S84, and D22S55. Of the DNA markers yielding lod scores greater than 1, D4S35 and D22S55more » also were suggestive of linkage when the Affected-Pedigree-Member method was used. The families were then genotyped with four highly polymorphic simple sequence repeat markers; possible linkage diminished with DNA markers mapping nearby D4S35, while suggestive evidence of linkage remained with loci in the region of D22S55. Although follow-up investigation of these chromosomal regions may be warranted, our linkage results should be viewed as preliminary observations, as 35 unaffected persons are not past the age of risk. 90 refs., 3 tabs.« less

The variants of an LOD of a 3D building model and their influence on spatial analyses

NASA Astrophysics Data System (ADS)

Biljecki, Filip; Ledoux, Hugo; Stoter, Jantien; Vosselman, George

2016-06-01

The level of detail (LOD) of a 3D city model indicates the model's grade and usability. However, there exist multiple valid variants of each LOD. As a consequence, the LOD concept is inconclusive as an instruction for the acquisition of 3D city models. For instance, the top surface of an LOD1 block model may be modelled at the eaves of a building or at its ridge height. Such variants, which we term geometric references, are often overlooked and are usually not documented in the metadata. Furthermore, the influence of a particular geometric reference on the performance of a spatial analysis is not known. In response to this research gap, we investigate a variety of LOD1 and LOD2 geometric references that are commonly employed, and perform numerical experiments to investigate their relative difference when used as input for different spatial analyses. We consider three use cases (estimation of the area of the building envelope, building volume, and shadows cast by buildings), and compute the deviations in a Monte Carlo simulation. The experiments, carried out with procedurally generated models, indicate that two 3D models representing the same building at the same LOD, but modelled according to different geometric references, may yield substantially different results when used in a spatial analysis. The outcome of our experiments also suggests that the geometric reference may have a bigger influence than the LOD, since an LOD1 with a specific geometric reference may yield a more accurate result than when using LOD2 models.

A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.

PubMed

Kalay, E; de Brouwer, A P M; Caylan, R; Nabuurs, S B; Wollnik, B; Karaguzel, A; Heister, J G A M; Erdol, H; Cremers, F P M; Cremers, C W R J; Brunner, H G; Kremer, H

2005-12-01

Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1-25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at theta=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the -3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.

Effects of lodoxamide (LOD), disodium cromoglycate (DSCG) and N-acetyl-aspartyl-glutamate sodium salt (NAAGA) on ocular active anaphylaxis.

PubMed

Goldschmidt, P; Luyckx, J

1996-04-01

LOD, DSCG and NAAGA eye-drops were evaluated on experimentally-induced ocular active anaphylaxis in guinea pigs. Twelve animals per group were sensitized with egg albumin i.p. and challenged on the surface of the eye 14 days later. Two days before challenge, animals were treated with LOD, DSCG or NAAGA 4 times a day. Permeability indexes were calculated after intracardiac injection of Evans Blue. No effect on ocular active anaphylaxis was found with LOD nor with DSCG. NAAGA was able to significantly reduce blood-eye permeability indexes.

Sex-specific Linkage Scans in Opioid Dependence

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Palmer, Abraham A.; Gelernter, Joel

2017-01-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6000 single nucleotide polymorphism (SNP) markers were genotyped for 1758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD=3.29; point-wise p=0.00005; empirical autosome-wide p=0.042), which significantly differed from the linkage signal at the same location in EA women (empirical p=0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD=2.18), 104 cM on chromosome 11 (LOD=1.85), and 60.9 cM on chromosome 16 (LOD=1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD=2.32), 152.9 cM on chromosome 6 (LOD=1.86), 16.8 cM on chromosome 7 (LOD=1.95), and 36.1 cM on chromosome 17 (LOD=1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. PMID:27762075

LOD 1 VS. LOD 2 - Preliminary Investigations Into Differences in Mobile Rendering Performance

NASA Astrophysics Data System (ADS)

Ellul, C.; Altenbuchner, J.

2013-09-01

The increasing availability, size and detail of 3D City Model datasets has led to a challenge when rendering such data on mobile devices. Understanding the limitations to the usability of such models on these devices is particularly important given the broadening range of applications - such as pollution or noise modelling, tourism, planning, solar potential - for which these datasets and resulting visualisations can be utilized. Much 3D City Model data is created by extrusion of 2D topographic datasets, resulting in what is known as Level of Detail (LoD) 1 buildings - with flat roofs. However, in the UK the National Mapping Agency (the Ordnance Survey, OS) is now releasing test datasets to Level of Detail (LoD) 2 - i.e. including roof structures. These datasets are designed to integrate with the LoD 1 datasets provided by the OS, and provide additional detail in particular on larger buildings and in town centres. The availability of such integrated datasets at two different Levels of Detail permits investigation into the impact of the additional roof structures (and hence the display of a more realistic 3D City Model) on rendering performance on a mobile device. This paper describes preliminary work carried out to investigate this issue, for the test area of the city of Sheffield (in the UK Midlands). The data is stored in a 3D spatial database as triangles and then extracted and served as a web-based data stream which is queried by an App developed on the mobile device (using the Android environment, Java and OpenGL for graphics). Initial tests have been carried out on two dataset sizes, for the city centre and a larger area, rendering the data onto a tablet to compare results. Results of 52 seconds for rendering LoD 1 data, and 72 seconds for LoD 1 mixed with LoD 2 data, show that the impact of LoD 2 is significant.

A comparison of three organ dysfunction scores: MODS, SOFA and LOD for predicting ICU mortality in critically ill patients.

PubMed

Khwannimit, Bodin

2007-06-01

To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients. A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital. One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality. All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

PubMed

Huang, J; Jiang, Y

2001-01-01

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Mark Brown, W; Brown, Mark W; Ziegler, Julie T; Sandy An, S; An, Sandy S; Guo, Xiuqing; Ida Chen, Y-D; Chen, Ida Y-D; Taylor, Kent; Hawkins, Gregory A; Ng, Maggie C Y; Speliotes, Elizabeth K; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Wagenknecht, Lynne E; Langefeld, Carl D; Bowden, Donald W

2015-02-01

We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1,150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD = 20.98) and powerfully associated (p value = 8.1 × 10(-50)). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD > 3) but only four other SNPs in this region were associated with p values < 1.0 × 10(-4). When G45R was accounted for, the maximum LOD score across the interval dropped to 4.39 and the best p value was 1.1 × 10(-5). Linked and/or associated variants ranged in frequency (0.0018-0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r (2) < 0.20). In addition, the two-point linkage approach empirically outperformed multipoint microsatellite and multipoint SNP analysis. In the absence of data for rs200573126, family-based linkage analysis using a moderately dense SNP dataset, including both common and low-frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high-impact genetic variants.

Cycles, scaling and crossover phenomenon in length of the day (LOD) time series

NASA Astrophysics Data System (ADS)

Telesca, Luciano

2007-06-01

The dynamics of the temporal fluctuations of the length of the day (LOD) time series from January 1, 1962 to November 2, 2006 were investigated. The power spectrum of the whole time series has revealed annual, semi-annual, decadal and daily oscillatory behaviors, correlated with oceanic-atmospheric processes and interactions. The scaling behavior was analyzed by using the detrended fluctuation analysis (DFA), which has revealed two different scaling regimes, separated by a crossover timescale at approximately 23 days. Flicker-noise process can describe the dynamics of the LOD time regime involving intermediate and long timescales, while Brownian dynamics characterizes the LOD time series for small timescales.

Antifouling paint booster biocides (Irgarol 1051 and diuron) in marinas and ports of Bushehr, Persian Gulf.

PubMed

Saleh, Abolfazl; Molaei, Saeideh; Sheijooni Fumani, Neda; Abedi, Ehsan

2016-04-15

In the present study, antifouling paint booster biocides, Irgarol 1051 and diuron were measured in ports and marinas of Bushehr, Iran. Results showed that in seawater samples taken from ports and marinas, Irgarol was found at the range of less than LOD to 63.4ngL(-1) and diuron was found to be at the range of less than LOD to 29.1ngL(-1) (in Jalali marina). 3,4-dichloroaniline (3,4-DCA), as a degradation product of diuron, was also analyzed and its maximum concentration was 390ngL(-1). Results for analysis of Irgarol 1051 in sediments showed a maximum concentration of 35.4ngg(-1) dry weight in Bandargah marina. A comparison between the results of this study and those of other published works showed that Irgarol and diuron pollutions in ports and marinas of Bushehr located in the Persian Gulf were less than the average of reports from other parts of the world. Copyright © 2016 Elsevier Ltd. All rights reserved.

A review on current knowledge and future prospects of organohalogen contaminants (OHCs) in Asian birds.

PubMed

Abbasi, Naeem Akhtar; Malik, Riffat Naseem; Frantz, Adrien; Jaspers, Veerle Leontina Bernard

2016-01-15

The release of harmful chemicals in the Asian environment has recently increased dramatically due to rising industrial and agricultural activities. About 60% of the global human population is currently living on the Asian continent and may thus be exposed to a large range of different chemicals. Different classes of organohalogen chemicals have indeed been reported in various environmental compartments from Asia including humans and wildlife, but this issue has received less attention in birds. In this article, we reviewed the available literature on levels of legacy persistent organic pollutants (POPs) and various flame retardants (FRs) in Asian avifauna to analyze the existing pool of knowledge as well as to identify the gaps that should be addressed in future research. Furthermore, we discussed the variation in levels of organohalogens based on differences in regions, trophic level, dietary sources and migratory behaviors of species including distribution patterns in different tissues of birds. Although the mass of published literature is very low and even absent in many important regions of Asia, we deduced from the reported studies that levels of almost all classes of organohalogens (OHCs) including FRs were highest in East Asian countries such as Japan, China and South Korea, except for HCHs that were found at maximum levels in birds of South India. Concentrations (ng/g LW) of different OHCs in Asian birds ranged between

A gene defect causing a novel progressive epilepsy with mental retardation, EPMR, maps to chromosome 8p

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

Ranta, S.; Tahvanainen, E.; Karila, E.

1994-09-01

EPMR (progressive epilepsy with mental retardation) is a newly discovered autosomal recessively inherited disorder which occurs with high frequency in an isolated rural population in Finland. So far 25 patients have been identified, 21 of whom are alive. Twenty-three patients share a common ancestor from the 18th century. The main features of EPMR are: normal early development, tonic-clonic seizures with onset between ages 5 and 10, and mental retardation which begins approximately 2 years after the onset of epilepsy and soon leads to deepening mental retardation. Adult patients do not manage their daily life without help. The EEG is normalmore » at the onset of epilepsy but later progressive slowing of the background activity occurs. The etiology and pathogenesis of EPMR remain known. As this is a novel disease entity without any definitive diagnostic marker we wished to begin its elucidation by first defining its gene locus. A random search for linkage in four multiplex families (only 20 individuals tested) resulted in the finding of linkage to marker D8S264 with a lod score of 4.45 at zero recombination. The EPMR gene resides in a 7 centimorgan interval between marker loci AFM185xb2 and D8S262 with a maximum multipoint lod score of 7.03 at 1.8 centimorgans proximal to D8S264. Physically this region is very distal on 8p. Of the sixteen EPMR chromosomes haplotyped 15 were identical or almost identical. One chromosome, however, had a distinctly different haplotype raising the possibility of there being two different mutations or one very old mutation. These findings are a starting point toward isolating and characterizing the gene and its protein product. Physical mapping has been initiated by isolating nine YACs from the region.« less

Ultrasound assisted combined molecularly imprinted polymer for selective extraction of nicotinamide in human urine and milk samples: Spectrophotometric determination and optimization study.

PubMed

Asfaram, Arash; Ghaedi, Mehrorang; Dashtian, Kheibar

2017-01-01

Ultrasound-assisted dispersive solid phase microextraction followed by UV-vis spectrophotometer (UA-DSPME-UV-vis) was designed for extraction and preconcentration of nicotinamide (vitamin B 3 ) by HKUST-1 metal organic framework (MOF) based molecularly imprinted polymer (MIP). This new material was characterized by FTIR and FE-SEM techniques. The preliminary Plackett-Burman design was used for screening and subsequently the central composite design justifies significant terms and possible construction of mathematical equation which give the individual and cooperative contribution of variables like HKUST-1-MOF-NA-MIP mass, sonication time, temperature, eluent volume, pH and vortex time. Accordingly the optimum condition was set as: 2.0mg HKUST-1-MOF-NA-MIP, 200μL eluent and 5.0min sonication time in center points other variables were determined as the best conditions to reach the maximum recovery of the analyte. The UA-DSPME-UV-vis method performances like excellent linearity (LR), limits of detection (LOD), limits of quantification of 10-5000μgL -1 with R 2 of 0.99, LOD (1.96ngmL -1 ), LOQ (6.53μgL -1 ), respectively show successful and accurate applicability of the present method for monitoring analytes with within- and between-day precision of 0.96-3.38%. The average absolute recoveries of the nicotinamide extracted from the urine, milk and water samples were 95.85-101.27%. Copyright © 2016 Elsevier B.V. All rights reserved.

Extension of the lod score: the mod score.

PubMed

Clerget-Darpoux, F

2001-01-01

In 1955 Morton proposed the lod score method both for testing linkage between loci and for estimating the recombination fraction between them. If a disease is controlled by a gene at one of these loci, the lod score computation requires the prior specification of an underlying model that assigns the probabilities of genotypes from the observed phenotypes. To address the case of linkage studies for diseases with unknown mode of inheritance, we suggested (Clerget-Darpoux et al., 1986) extending the lod score function to a so-called mod score function. In this function, the variables are both the recombination fraction and the disease model parameters. Maximizing the mod score function over all these parameters amounts to maximizing the probability of marker data conditional on the disease status. Under the absence of linkage, the mod score conforms to a chi-square distribution, with extra degrees of freedom in comparison to the lod score function (MacLean et al., 1993). The mod score is asymptotically maximum for the true disease model (Clerget-Darpoux and Bonaïti-Pellié, 1992; Hodge and Elston, 1994). Consequently, the power to detect linkage through mod score will be highest when the space of models where the maximization is performed includes the true model. On the other hand, one must avoid overparametrization of the model space. For example, when the approach is applied to affected sibpairs, only two constrained disease model parameters should be used (Knapp et al., 1994) for the mod score maximization. It is also important to emphasize the existence of a strong correlation between the disease gene location and the disease model. Consequently, there is poor resolution of the location of the susceptibility locus when the disease model at this locus is unknown. Of course, this is true regardless of the statistics used. The mod score may also be applied in a candidate gene strategy to model the potential effect of this gene in the disease. Since, however, it ignores the information provided both by disease segregation and by linkage disequilibrium between the marker alleles and the functional disease alleles, its power of discrimination between genetic models is weak. The MASC method (Clerget-Darpoux et al., 1988) has been designed to address more efficiently the objectives of a candidate gene approach.

Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome

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

Willems, P.; Vits, L.; Buntinx, I.

1993-11-01

Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features. The MRX family reported here has been classified previously as MRX9. In this study, the authors performed linkage analysis of MRX9 with a panel of 43 polymorphic DNA markers dispersed over chromosome X. Two-point linkage analysis revealed lod scores of 3.52 and 3.82 at 0% recombination for OATL1 and MAOA, both located in Xp11.2-p11.4. Lod scores for linkage with PGK1P1, DXS106, and DXS132, all located in Xq11-q13, were 3.83, 3.82, and 3.52, respectively, all at 0% recombination. Multipoint linkage analysis showed two peaksmore » with MAOA and DXS132/DXS106, respectively. Analysis of recombinational events indicated a position of the MRX9 gene between DXS164 and DXS453. These findings are compatible with a location of the MRX9 gene in the pericentromeric region of the X chromosome at Xp21-q13. 26 refs., 3 figs., 2 tabs.« less

Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3.

PubMed

De Mars, G; Windelinckx, A; Huygens, W; Peeters, M W; Beunen, G P; Aerssens, J; Vlietinck, R; Thomis, M A I

2008-05-01

Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque-length relationship for knee flexors and extensors. In total, 283 informative male siblings (17-36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. The strongest evidence for linkage was found for the torque-length relationship of the knee flexors at 14q24.3 (LOD = 4.09; p<10(-5)). Suggestive evidence for linkage was found at 14q32.2 (LOD = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD = 2.57; p = 0.01) for isometric knee torque at 30 degrees flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD = 2.33, 2.69 and 2.21; p<10(-4) for all) for the torque-length relationship of the knee extensors and at 18p11.31 (LOD = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes.

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

PubMed

Asherson, P; Mant, R; Williams, N; Cardno, A; Jones, L; Murphy, K; Collier, D A; Nanko, S; Craddock, N; Morris, S; Muir, W; Blackwood, B; McGuffin, P; Owen, M J

1998-07-01

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity.

PubMed

Maeda, Kouji; Kaji, Ryuji; Yasuno, Katsuhito; Jambaldorj, Jamiyansuren; Nodera, Hiroyuki; Takashima, Hiroshi; Nakagawa, Masanori; Makino, Satoshi; Tamiya, Gen

2007-01-01

Hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) is an adult-onset peripheral neurodegenerative disorder which has been reported only in the Okinawa Islands, Japan. The disease locus of "Okinawa-type" HMSN-P has been previously mapped to 3q13.1, with all affected individuals sharing an identical haplotype around the locus, suggesting that the undiscovered causative mutation in HMSN-P originated from a single founder. We have newly found two large families from the western part of Japan within which multiple members developed symptoms similar to those exhibited by HMSN-P patients from Okinawa, with no record of affinal connection between the islands. Using these pedigrees with "Kansai-type" HMSN-P, we carried out a linkage study utilizing eight microsatellite markers and identified a candidate region on 3q13.1 cosegregating with the disease (maximum two-point LOD score of 8.44 at theta=0.0) overlapping with the Okinawa-type HMSN-P locus. However, the disease haplotype shared among all affected members in these families was different from that in the Okinawa kindred, suggesting allelic heterogeneity. Such allelic variation should aid in the identification of the disease-causative gene. Moreover, the allelic heterogeneity of HMSN-P in the Japanese population suggests that HMSN-P may be more common across other ethnic groups, but classified into other disease categories.

A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair.

PubMed

Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk; Irfanullah; Shahi, Shamim; Acharya, Anushree; Dai, Hang; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Santos-Cortez, Regie Lyn P; Ahmad, Wasim; Leal, Suzanne M

2015-10-01

Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth. In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1-q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at ϴ=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft. Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

LOD-based clustering techniques for efficient large-scale terrain storage and visualization

NASA Astrophysics Data System (ADS)

Bao, Xiaohong; Pajarola, Renato

2003-05-01

Large multi-resolution terrain data sets are usually stored out-of-core. To visualize terrain data at interactive frame rates, the data needs to be organized on disk, loaded into main memory part by part, then rendered efficiently. Many main-memory algorithms have been proposed for efficient vertex selection and mesh construction. Organization of terrain data on disk is quite difficult because the error, the triangulation dependency and the spatial location of each vertex all need to be considered. Previous terrain clustering algorithms did not consider the per-vertex approximation error of individual terrain data sets. Therefore, the vertex sequences on disk are exactly the same for any terrain. In this paper, we propose a novel clustering algorithm which introduces the level-of-detail (LOD) information to terrain data organization to map multi-resolution terrain data to external memory. In our approach the LOD parameters of the terrain elevation points are reflected during clustering. The experiments show that dynamic loading and paging of terrain data at varying LOD is very efficient and minimizes page faults. Additionally, the preprocessing of this algorithm is very fast and works from out-of-core.

Establishing an Appropriate Level of Detail (LoD) for a Building Information Model (BIM) - West Block, Parliament Hill, Ottawa, Canada

NASA Astrophysics Data System (ADS)

Fai, S.; Rafeiro, J.

2014-05-01

In 2011, Public Works and Government Services Canada (PWGSC) embarked on a comprehensive rehabilitation of the historically significant West Block of Canada's Parliament Hill. With over 17 thousand square meters of floor space, the West Block is one of the largest projects of its kind in the world. As part of the rehabilitation, PWGSC is working with the Carleton Immersive Media Studio (CIMS) to develop a building information model (BIM) that can serve as maintenance and life-cycle management tool once construction is completed. The scale and complexity of the model have presented many challenges. One of these challenges is determining appropriate levels of detail (LoD). While still a matter of debate in the development of international BIM standards, LoD is further complicated in the context of heritage buildings because we must reconcile the LoD of the BIM with that used in the documentation process (terrestrial laser scan and photogrammetric survey data). In this paper, we will discuss our work to date on establishing appropriate LoD within the West Block BIM that will best serve the end use. To facilitate this, we have developed a single parametric model for gothic pointed arches that can be used for over seventy-five unique window types present in the West Block. Using the AEC (CAN) BIM as a reference, we have developed a workflow to test each of these window types at three distinct levels of detail. We have found that the parametric Gothic arch significantly reduces the amount of time necessary to develop scenarios to test appropriate LoD.

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study

PubMed Central

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-01-01

Background High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Results Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Conclusion Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions. PMID:14975161

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

PubMed

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-12-31

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

Interactive distributed hardware-accelerated LOD-sprite terrain rendering with stable frame rates

NASA Astrophysics Data System (ADS)

Swan, J. E., II; Arango, Jesus; Nakshatrala, Bala K.

2002-03-01

A stable frame rate is important for interactive rendering systems. Image-based modeling and rendering (IBMR) techniques, which model parts of the scene with image sprites, are a promising technique for interactive systems because they allow the sprite to be manipulated instead of the underlying scene geometry. However, with IBMR techniques a frequent problem is an unstable frame rate, because generating an image sprite (with 3D rendering) is time-consuming relative to manipulating the sprite (with 2D image resampling). This paper describes one solution to this problem, by distributing an IBMR technique into a collection of cooperating threads and executable programs across two computers. The particular IBMR technique distributed here is the LOD-Sprite algorithm. This technique uses a multiple level-of-detail (LOD) scene representation. It first renders a keyframe from a high-LOD representation, and then caches the frame as an image sprite. It renders subsequent spriteframes by texture-mapping the cached image sprite into a lower-LOD representation. We describe a distributed architecture and implementation of LOD-Sprite, in the context of terrain rendering, which takes advantage of graphics hardware. We present timing results which indicate we have achieved a stable frame rate. In addition to LOD-Sprite, our distribution method holds promise for other IBMR techniques.

Ovarian surgery for symptom relief in women with polycystic ovary syndrome.

PubMed

Lepine, Sam; Jo, Junyoung; Metwally, Mostafa; Cheong, Ying C

2017-11-10

Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting approximately one in 10 women. PCOS is defined by two of three features: oligo- or anovulation, clinical or biochemical hyperandrogenism or both, or polycystic ovaries.Women with PCOS can have a wide range of health problems, including infrequent and irregular periods, unwanted hair growth and acne, and subnormal fertility. Long-term health concerns include an increased risk of heart disease, diabetes and the development of precancerous disease of the womb. To assess the effectiveness and harms of ovarian surgery as a treatment for symptomatic relief of hirsutism, acne and menstrual irregularity in PCOS. We searched the Cochrane Gynaecology and Fertility Group specialized register, CENTRAL, MEDLINE, Embase and PsycINFO (from inception to 17 October 2016). We handsearched citation lists, registers of ongoing trials and conference proceedings. We included randomized controlled trials (RCTs) of women undergoing ovarian drilling in comparison to no treatment, medical treatment, or other forms of surgical treatment for the symptoms of PCOS. We used standard methodological procedures recommended by Cochrane. The primary outcome measures were improvement in menstrual regularity and androgenic symptoms of PCOS (hirsutism, acne); the secondary outcome measures included harms, change of body mass index (BMI), waist circumference, androgen levels, metabolic measures and quality of life. We assessed the quality of the evidence using GRADE methods. We included 22 RCTs (2278 women analyzed) of participants with PCOS and symptoms of acne, hirsutism or irregular menstrual cycles, all of which included laparoscopic ovarian drilling (LOD) as an intervention.Two studies reported their funding source (Farquhar 2002 - supported in part by the Auckland Medical Research Foundation; Sarouri 2015 - the authors thank the Vice Chancellor for Research of Guilan University of Medical Sciences for funding this project).The quality of the evidence ranged from very low to moderate quality. The main limitations were imprecision associated with the low number of studies, inconsistency and risk of bias associated with the inability to blind participants. There were too few studies to assess risk of publication bias. Menstrual RegularityTwo studies compared LOD versus metformin (n=226) but no conclusions could be drawn with regard to menstrual regularity, as their findings were inconsistent and they were unsuitable for pooling. There appeared to be little or no difference in the rate of women reporting improvement in menstrual regularity when LOD was compared with medical treatment including metformin + clomiphene (OR 1.02, 95% CI 0.64 to 1.64, 2 studies, 332 women, I 2 = 13%, low-quality evidence), letrozole (OR 1.08, 95% CI 0.64 to 1.84, 1 study, 260 women, low-quality evidence), or metformin + letrozole (OR 0.95, 95% CI 0.49 to 1.81, 1 study, 146 women, low-quality evidence). However, one study reported that LOD was superior to gonadotrophin (OR 19.2, 95% CI 3.17 to 116.45, 1 study, 35 women, very low-quality evidence).There appeared to be little or no difference in the rate of women reporting improvement in menstrual regularity when bilateral unipolar LOD was compared to unilateral LOD (OR 1.51, 95% CI 0.62 to 3.71, 2 studies, 104 women, I 2 = 0%, moderate-quality evidence), transvaginal ultrasound-guided LOD (OR 1.23, 95% CI 0.64 to 2.37, 1 study, 147 women, low-quality evidence), LOD using adjusted thermal dose in accordance with the ovarian volume (OR 0.42, 95% CI 0.16 to 1.14, 1 study, 115 women, low-quality evidence) or bipolar LOD (OR 1.00, 95% CI 0.05 to 18.57, 1 study, 18 women, low-quality evidence).Four to five punctures per ovary may improve the rate of women reporting menstrual regularity compared with two or fewer (OR 16.04, 95% CI 4.19 to 61.34, 2 studies, 73 women, I 2 = 0%, low-quality evidence). Androgenic SymptomsThere was probably little or no difference in improvement in androgenic symptoms when LOD was compared to metformin (OR 1.00, 95% CI 0.42 to 2.37, 1 study, 126 women, moderate-quality evidence) or gonadotrophins; acne (OR 3.20, 95% CI 0.33 to 30.94, 1 study, 25 women, low-quality evidence), hirsutism (OR 2.31, 95% CI 0.22 to 23.89, 1 study, 25 women, low-quality evidence).There appeared to be little or no difference in improvement of androgenic symptoms when LOD was compared to transvaginal ultrasound-guided LOD, with respect to hirsutism (OR 1.09, 95% CI 0.30 to 3.91, 1 study, 39 women, low-quality evidence) or acne (OR 0.84, 95% CI 0.20 to 3.50, 1 study, 31 women, low-quality evidence). HarmsLOD was associated with fewer gastrointestinal side effects than metformin plus clomiphene (OR 0.05, 95% CI 0.01 to 0.36, 2 studies, 332 women, I 2 = 0%, moderate-quality evidence). One study suggested little or no difference in rates of ovarian hyperstimulation syndrome between LOD and gonadotrophins (OR 0.08, 95% CI 0.00 to 1.61, 1 study, 33 women, low-quality evidence).There were fewer adhesions with transvaginal hydrolaparoscopy compared to LOD (OR 0.10, 95% CI 0.05 to 0.18, 1 study, 246 women, moderate-quality evidence). There appeared to be little or no difference in adhesions when variable energy LOD was compared with standard LOD (OR 0.96, 95% CI 0.32 to 2.88, 1 study, 64 women, low-quality evidence). Another study (44 women) reported that none of the women who returned for surgery following either traditional or unilateral LOD were found to have adhesions. There was no clear evidence that LOD improves menstrual regularity or the androgenic symptoms of PCOS, compared to most of the medical treatments used in the included studies. LOD was associated with fewer gastrointestinal side effects compared to metformin and clomiphene.There was also no clear evidence of different effectiveness between types of LOD, except that LOD with four to five punctures per ovary may be more effective than two or fewer punctures. There was little evidence comparing LOD with different types of surgery, although one study concluded that transvaginal hydrolaparoscopy had a lower risk of adhesions than LOD.There was evidence from one small study of benefit from LOD compared to gonadotrophins for menstrual regulation. However, gonadotrophins are seldom used for this indication.

Combining presentation high-sensitivity cardiac troponin I and glucose measurements to rule-out an acute myocardial infarction in patients presenting to emergency department with chest pain.

PubMed

Greenslade, J H; Kavsak, P; Parsonage, W; Shortt, C; Than, M; Pickering, J W; Aldous, S; Cullen, L

2015-03-01

The use of high sensitivity troponin (hs-Tn) may enable early rule out of acute myocardial infarction (AMI) for patients presenting to the emergency department (ED) with chest pain. This study evaluated two approaches to the early rule out of AMI; a combination of a presentation hs-Tn <4ng/L and normal glucose at presentation (dual testing) and a presentation hs-Tn troponin below the limit of detection (LoD). We utilised prospectively collected data on adult patients presenting with suspected ACS in two EDs in Australia and New Zealand. Blood samples were taken on presentation and tested for glucose and high sensitivity troponin I. The primary endpoint was index AMI and the secondary endpoint was 30-day acute coronary syndrome (ACS). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of the dual testing and LoD approaches. Of the 1412 participants, 182 (12.9%) had index AMI. The LoD and the dual testing approach were 100% sensitive for index AMI. The specificity of the dual testing approach (25.2%) was slightly higher than that of the LoD (20.4%). Sensitivity for ACS was similar for the two approaches (96.5% for dual testing and 98.1% for the LoD). The dual testing and LoD approach identified all patients with index AMI and could be used to reduce the proportion of patients requiring lengthy assessment and inpatient admission. Further investigation is still required to rule out unstable angina pectoris in patients identified as low risk. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Autosomal Linkage Scan for Loci Predisposing to Comorbid Dependence on Multiple Substances

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Farrer, Lindsay A.; Elston, Robert C.; Gelernter, Joel

2014-01-01

Multiple substance dependence (MSD) trait comorbidity is common, and MSD patients are often severely affected clinically. While shared genetic risks have been documented, so far there has been no published report using the linkage scan approach to survey risk loci for MSD as a phenotype. A total of 1,758 individuals in 739 families [384 African American (AA) and 355 European American (EA) families] ascertained via affected sib-pairs with cocaine or opioid or alcohol dependence were genotyped using an array-based linkage panel of single-nucleotide polymorphism markers. Fuzzy clustering analysis was conducted on individuals with alcohol, cannabis, cocaine, opioid, and nicotine dependence for AAs and EAs separately, and linkage scans were conducted for the output membership coefficients using Merlin-regression. In EAs, we observed an autosome-wide significant linkage signal on chromosome 4 (peak lod = 3.31 at 68.3 cM; empirical autosome-wide P = 0.038), and a suggestive linkage signal on chromosome 21 (peak lod = 2.37 at 19.4 cM). In AAs, four suggestive linkage peaks were observed: two peaks on chromosome 10 (lod = 2.66 at 96.7 cM and lod = 3.02 at 147.6 cM] and the other two on chromosomes 3 (lod = 2.81 at 145.5 cM) and 9 (lod = 1.93 at 146.8 cM). Three particularly promising candidate genes, GABRA4, GABRB1, and CLOCK, are located within or very close to the autosome-wide significant linkage region for EAs on chromosome 4. This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations. PMID:22354695

Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome.

PubMed

Amer, S A; Li, T C; Metwally, M; Emarh, M; Ledger, W L

2009-01-01

Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545.

Evaluating Mass Analyzers as Candidates for Small, Portable, Rugged Single Point Mass Spectrometers for Analysis of Permanent Gases

NASA Technical Reports Server (NTRS)

Arkin, C. Richard; Ottens, Andrew K.; Diaz, Jorge A.; Griffin, Timothy P.; Follestein, Duke; Adams, Fredrick; Steinrock, T. (Technical Monitor)

2001-01-01

For Space Shuttle launch safety, there is a need to monitor the concentration of H2, He, O2 and Ar around the launch vehicle. Currently a large mass spectrometry system performs this task, using long transport lines to draw in samples. There is great interest in replacing this stationary system with several miniature, portable, rugged mass spectrometers which act as point sensors which can be placed at the sampling point. Five commercial and two non-commercial analyzers are evaluated. The five commercial systems include the Leybold Inficon XPR-2 linear quadrupole, the Stanford Research (SRS-100) linear quadrupole, the Ferran linear quadrupole array, the ThermoQuest Polaris-Q quadrupole ion trap, and the IonWerks Time-of-Flight (TOF). The non-commercial systems include a compact double focusing sector (CDFMS) developed at the University of Minnesota, and a quadrupole ion trap (UF-IT) developed at the University of Florida. The System Volume is determined by measuring the entire system volume including the mass analyzer, its associated electronics, the associated vacuum system, the high vacuum pump and rough pump. Also measured are any ion gauge controllers or other required equipment. Computers are not included. Scan Time is the time required for one scan to be acquired and the data to be transferred. It is determined by measuring the time required acquiring a known number of scans and dividing by said number of scans. Limit of Detection is determined first by performing a zero-span calibration (using a 10-point data set). Then the limit of detection (LOD) is defined as 3 times the standard deviation of the zero data set. (An LOD of 10 ppm or less is considered acceptable.)

Bisphenol A contamination in soft drinks as a risk for children's health in Italy.

PubMed

Fasano, Evelina; Esposito, Francesco; Scognamiglio, Gelsomina; Di Francesco, Fabio; Montuori, Paolo; Amodio Cocchieri, Renata; Cirillo, Teresa

2015-01-01

Bisphenol A (BPA) was determined in sugary carbonated, non-carbonated and milk-based beverages, through HLPC-fluorescence detection and confirmed by LC-MS/MS, in a selection of brands that are mostly consumed by Italian children. The daily intake was determined through the WHO budget method (BM). BPA was found at detectable levels in 57% of carbonated beverages, in 50% of non-carbonated and in 100% of milk-based beverages. The median concentrations were 1.24 µg l(-1) (range = < LOD-4.98 µg l(-1)) in canned carbonated beverages and 0.18 µg l(-1) (< LOD-1.78 µg l(-1)) in non-canned carbonated beverages. In non-carbonated beverages, median concentrations were 0.80 µg l(-1) (< LOD-2.79 µg l(-1)) and 0.18 µg l(-1) (< LOD-3.58 µg l(-1)), respectively, for canned and non-canned beverages; in milk-based products the BPA median concentration was 3.60 µg l(-1) (1.00-17.65 µg l(-1)). BPA daily intake from sugary drink consumption in children ranged from 0.008 to 1.765 µg kg(-1) bw day(-1). The median exposure values for the 'best' and 'worst' cases were 0.16% and 0.47% respectively of the EFSA t-TDI for BPA (4 µg kg(-1) bw day(-1)), and 10.59% and 35.30% of the t-TDI when the maximum levels were considered.

Looking Beyond Where Children Die: Determinants and Effects of Planning a Child’s Location of Death

PubMed Central

Dussel, Veronica; Kreicbergs, Ulrika; Hilden, Joanne M.; Watterson, Jan; Moore, Caron; Turner, Brian G.; Weeks, Jane C.; Wolfe, Joanne

2009-01-01

While dying at home may be the choice of many, where people die may be less important than argued. We examined factors associated with parental planning of a child’s location of death (LOD) and its effects on patterns of care and parent’s experience. In a cross-sectional study of 140 parents who lost a child to cancer at one of two tertiary level U.S. pediatric hospitals, 88 (63%) planned the child’s LOD and 97% accomplished their plan. After adjusting for disease and family characteristics, families whose primary oncologist clearly explained treatment options during the child’s end of life (EOL) and who had home care involved were more likely to plan LOD. Planning LOD was associated with more home deaths (72% versus 8% among those who did not plan, P<0.001) and fewer hospital admissions (54% versus 98%, P<0.001). Parents who planned were more likely to feel very prepared for the child’s EOL (33% versus 12%, P=0.007) and very comfortable with LOD (84% versus 40%, P<0.001), and less likely to have preferred a different LOD (2% versus 46%, P<0.001). Among the 73 non-home deaths, planning was associated with more deaths occurring in the ward than in the intensive care unit or other hospital (92% versus 33%, P<0.001), and fewer children being intubated (21% versus 48%, P=0.029). Comprehensive physician communication and home care involvement increase the likelihood of planning a child’s LOD. Opportunity to plan LOD is associated with outcomes consistent with high quality palliative care, even among non-home deaths, and thus may represent a more relevant outcome than actual LOD. PMID:18538973

STRP linkage studies in a new family with X-linked mental retardation: Tight linkage to DXS458

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

Lazzarini, A.; Stenroos, E.S.; Lehner, T.

1994-09-01

Isolated or non-specific mental retardation is defined as {open_quote}non-progressive intellectual handicap segregating in an X-linked manner without any consistent somatic or diagnostic features{close_quote}. The Human Gene Mapping Nomenclature Committee sequentially designates each newly reported MRX family, MRX1, MRX2,... etc. when a lod score of +2 is demonstrated between the MR locus and one or more X chromosome markers. A family, designated MRX20, was studied with nine short tandem repeat polymorphism (STRP) markers. Two-point lod scores above 3 were obtained with DXYS1 (Z = 3.02, {theta} = 0), DX3 (Z = 3.22, {theta} = 0), and DXS458 (Z = 3.31, {theta}more » = 0). A multipoint lod score of 3.66 was obtained with a peak between DXS3 and DXS458, 1.1cM distal to DXS3. A one-unit support interval is 16 cM between PGK1 and DXS458. This family represents the ninth of fourteen reported MRX families linked to markers in the region of DXYS1, perhaps reflecting a cluster of genes involved in brain function. The identification of genetic markers linked to the disease-causing gene has allowed gene carrier risk assessment for females in the family. Future research will concentrate on comparing the diversity of haplotypes containing the disease genes in different families, on physical mapping of the region, and on isolation of the MRX 20 gene.« less

A Study of a Two Stage Maximum Power Point Tracking Control of a Photovoltaic System under Partially Shaded Insolation Conditions

NASA Astrophysics Data System (ADS)

Kobayashi, Kenji; Takano, Ichiro; Sawada, Yoshio

A photovoltaic array shows relatively low output power density, and has a greatly drooping Current-Voltage (I-V) characteristic. Therefore, Maximum Power Point Tracking (MPPT) control is used to maximize the output power of the array. Many papers have been reported in relation to MPPT. However, the Current-Power (I-P) curve sometimes shows multi-local maximum points mode under non-uniform insolation conditions. The operating point of the PV system tends to converge to a local maximum output point which is not the real maximal output point on the I-P curve. Some papers have been also reported, trying to avoid this difficulty. However most of those control systems become rather complicated. Then, the two stage MPPT control method is proposed in this paper to realize a relatively simple control system which can track the real maximum power point even under non-uniform insolation conditions. The feasibility of this control concept is confirmed for steady insolation as well as for rapidly changing insolation by simulation study using software PSIM and LabVIEW. In addition, simulated experiment confirms fundament al operation of the two stage MPPT control.

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease

PubMed Central

Shanker, Jayashree; Perumal, Ganapathy; Rao, Veena S; Khadrinarasimhiah, Natesha B; John, Shibu; Hebbagodi, Sridhara; Mukherjee, Manjari; Kakkar, Vijay V

2008-01-01

Background The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history. Methods & results Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h2 48% – 70%; P < 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, P < 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (P < 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (P < 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (P < 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis. Conclusion The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians. PMID:18801202

Medium- and Long-term Prediction of LOD Change with the Leap-step Autoregressive Model

NASA Astrophysics Data System (ADS)

Liu, Q. B.; Wang, Q. J.; Lei, M. F.

2015-09-01

It is known that the accuracies of medium- and long-term prediction of changes of length of day (LOD) based on the combined least-square and autoregressive (LS+AR) decrease gradually. The leap-step autoregressive (LSAR) model is more accurate and stable in medium- and long-term prediction, therefore it is used to forecast the LOD changes in this work. Then the LOD series from EOP 08 C04 provided by IERS (International Earth Rotation and Reference Systems Service) is used to compare the effectiveness of the LSAR and traditional AR methods. The predicted series resulted from the two models show that the prediction accuracy with the LSAR model is better than that from AR model in medium- and long-term prediction.

Considerations on the determination of the limit of detection and the limit of quantification in one-dimensional and comprehensive two-dimensional gas chromatography.

PubMed

Krupčík, Ján; Májek, Pavel; Gorovenko, Roman; Blaško, Jaroslav; Kubinec, Robert; Sandra, Pat

2015-05-29

Methods based on the blank signal as proposed by IUPAC procedure and on the signal to noise ratio (S/N) as listed in the ISO-11843-1 norm for determination of the limit of detection (LOD) and quantitation (LOQ) in one-dimensional capillary gas chromatography (1D-GC) and comprehensive two-dimensional capillary gas chromatography (CG×GC) are described in detail and compared for both techniques. Flame ionization detection was applied and variables were the data acquisition frequency and, for CG×GC, also the modulation time. It has been stated that LOD and LOQ estimated according to IUPAC might be successfully used for 1D-GC-FID method. Moreover, LOD and LOQ decrease with decrease of data acquisition frequency (DAF). For GC×GC-FID, estimation of LOD by IUPAC gave poor reproducibility of results while for LOQ reproducibility was acceptable (within ±10% rel.). The LOD and LOQ determined by the S/N concept both for 1D-GC-FID and GC×GC-FID methods are ca. three times higher than those values estimated by the standard deviation of the blank. Since the distribution pattern of modulated peaks for any analyte separated by GC×GC is random and cannot be predicted, LOQ and LOD may vary within 30% for 3s modulation time. Concerning sensitivity, 1D-GC-FID at 2Hz and of GC×GC-FID at 50Hz shows a ca. 5 times enhancement of sensitivity in the modulated signal output. Copyright © 2015 Elsevier B.V. All rights reserved.

Nonsyndromic cleft lip with or without cleft palate: New BCL3 information

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

Amos, C.; Hecht, J.T.; Gasser, D.

1996-09-01

We did not previously provide LOD scores for linkage assuming heterogeneity, as suggested by Ott for the linkage analysis of cleft lip with or without cleft palate (CL/P) and BCL3, ApoC2, and D19S178 in the paper by Stein et al. The results from analysis using the HOMOG program, allowing for heterogeneity under the reduced penetrance model, gave a maximum LOD score of 1.85 for ApoC2, 0.41 for BCL3, 0.03 for D19S178, and 1.72 for multipoint analysis in the interval. For the affecteds-only model, the values are 1.96 for ApoC2, 0.41 for BCL3, 0.01 for D19S178, and 1.44 for the multipointmore » analysis. 8 refs.« less

Maximum power point tracker for photovoltaic power plants

NASA Astrophysics Data System (ADS)

Arcidiacono, V.; Corsi, S.; Lambri, L.

The paper describes two different closed-loop control criteria for the maximum power point tracking of the voltage-current characteristic of a photovoltaic generator. The two criteria are discussed and compared, inter alia, with regard to the setting-up problems that they pose. Although a detailed analysis is not embarked upon, the paper also provides some quantitative information on the energy advantages obtained by using electronic maximum power point tracking systems, as compared with the situation in which the point of operation of the photovoltaic generator is not controlled at all. Lastly, the paper presents two high-efficiency MPPT converters for experimental photovoltaic plants of the stand-alone and the grid-interconnected type.

Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3–14

PubMed Central

Warner, J; Nyholt, D R; Busfield, F; Epstein, M; Burgess, J; Stranks, S; Hill, P; Perry‐Keene, D; Learoyd, D; Robinson, B; Teh, B T; Prins, J B; Cardinal, J W

2006-01-01

Bachground Familial isolated hyperparathyroidism (FIHP) is an autosomal dominantly inherited form of primary hyperparathyroidism. Although comprising only about 1% of cases of primary hyperparathyroidism, identification and functional analysis of a causative gene for FIHP is likely to advance our understanding of parathyroid physiology and pathophysiology. Methods A genome‐wide screen of DNA from seven pedigrees with FIHP was undertaken in order to identify a region of genetic linkage with the disorder. Results Multipoint linkage analysis identified a region of suggestive linkage (LOD score 2.68) on chromosome 2. Fine mapping with the addition of three other families revealed significant linkage adjacent to D2S2368 (maximum multipoint LOD score 3.43). Recombination events defined a 1.7 Mb region of linkage between D2S2368 and D2S358 in nine pedigrees. Sequencing of the two most likely candidate genes in this region, however, did not identify a gene for FIHP. Conclusions We conclude that a causative gene for FIHP lies within this interval on chromosome 2. This is a major step towards eventual precise identification of a gene for FIHP, likely to be a key component in the genetic regulation of calcium homeostasis. PMID:16525030

No association between SNP rs498055 on chromosome 10 and late-onset Alzheimer disease in multiple datasets.

PubMed

Liang, Xueying; Schnetz-Boutaud, Nathalie; Bartlett, Jackie; Allen, Melissa J; Gwirtsman, Harry; Schmechel, Don E; Carney, Regina M; Gilbert, John R; Pericak-Vance, Margaret A; Haines, Jonathan L

2008-01-01

SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset >or= 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD.

Identification in Marinomonas mediterranea of a novel quinoprotein with glycine oxidase activity.

PubMed

Campillo-Brocal, Jonatan Cristian; Lucas-Elio, Patricia; Sanchez-Amat, Antonio

2013-08-01

A novel enzyme with lysine-epsilon oxidase activity was previously described in the marine bacterium Marinomonas mediterranea. This enzyme differs from other l-amino acid oxidases in not being a flavoprotein but containing a quinone cofactor. It is encoded by an operon with two genes lodA and lodB. The first one codes for the oxidase, while the second one encodes a protein required for the expression of the former. Genome sequencing of M. mediterranea has revealed that it contains two additional operons encoding proteins with sequence similarity to LodA. In this study, it is shown that the product of one of such genes, Marme_1655, encodes a protein with glycine oxidase activity. This activity shows important differences in terms of substrate range and sensitivity to inhibitors to other glycine oxidases previously described which are flavoproteins synthesized by Bacillus. The results presented in this study indicate that the products of the genes with different degrees of similarity to lodA detected in bacterial genomes could constitute a reservoir of different oxidases. © 2013 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

Estimation of the limit of detection using information theory measures.

PubMed

Fonollosa, Jordi; Vergara, Alexander; Huerta, Ramón; Marco, Santiago

2014-01-31

Definitions of the limit of detection (LOD) based on the probability of false positive and/or false negative errors have been proposed over the past years. Although such definitions are straightforward and valid for any kind of analytical system, proposed methodologies to estimate the LOD are usually simplified to signals with Gaussian noise. Additionally, there is a general misconception that two systems with the same LOD provide the same amount of information on the source regardless of the prior probability of presenting a blank/analyte sample. Based upon an analogy between an analytical system and a binary communication channel, in this paper we show that the amount of information that can be extracted from an analytical system depends on the probability of presenting the two different possible states. We propose a new definition of LOD utilizing information theory tools that deals with noise of any kind and allows the introduction of prior knowledge easily. Unlike most traditional LOD estimation approaches, the proposed definition is based on the amount of information that the chemical instrumentation system provides on the chemical information source. Our findings indicate that the benchmark of analytical systems based on the ability to provide information about the presence/absence of the analyte (our proposed approach) is a more general and proper framework, while converging to the usual values when dealing with Gaussian noise. Copyright © 2013 Elsevier B.V. All rights reserved.

Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3

PubMed Central

De Mars, G; Windelinckx, A; Huygens, W; Peeters, M W; Beunen, G P; Aerssens, J; Vlietinck, R; Thomis, M A I

2008-01-01

Background: Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque–length relationship for knee flexors and extensors. Methods: In total, 283 informative male siblings (17–36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. Results: The strongest evidence for linkage was found for the torque–length relationship of the knee flexors at 14q24.3 (LOD  = 4.09; p<10−5). Suggestive evidence for linkage was found at 14q32.2 (LOD  = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD  = 2.57; p = 0.01) for isometric knee torque at 30° flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD  = 2.33, 2.69 and 2.21; p<10−4 for all) for the torque–length relationship of the knee extensors and at 18p11.31 (LOD  = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. Conclusions: We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes. PMID:18178634

Further evidence for the increased power of LOD scores compared with nonparametric methods.

PubMed

Durner, M; Vieland, V J; Greenberg, D A

1999-01-01

In genetic analysis of diseases in which the underlying model is unknown, "model free" methods-such as affected sib pair (ASP) tests-are often preferred over LOD-score methods, although LOD-score methods under the correct or even approximately correct model are more powerful than ASP tests. However, there might be circumstances in which nonparametric methods will outperform LOD-score methods. Recently, Dizier et al. reported that, in some complex two-locus (2L) models, LOD-score methods with segregation analysis-derived parameters had less power to detect linkage than ASP tests. We investigated whether these particular models, in fact, represent a situation that ASP tests are more powerful than LOD scores. We simulated data according to the parameters specified by Dizier et al. and analyzed the data by using a (a) single locus (SL) LOD-score analysis performed twice, under a simple dominant and a recessive mode of inheritance (MOI), (b) ASP methods, and (c) nonparametric linkage (NPL) analysis. We show that SL analysis performed twice and corrected for the type I-error increase due to multiple testing yields almost as much linkage information as does an analysis under the correct 2L model and is more powerful than either the ASP method or the NPL method. We demonstrate that, even for complex genetic models, the most important condition for linkage analysis is that the assumed MOI at the disease locus being tested is approximately correct, not that the inheritance of the disease per se is correctly specified. In the analysis by Dizier et al., segregation analysis led to estimates of dominance parameters that were grossly misspecified for the locus tested in those models in which ASP tests appeared to be more powerful than LOD-score analyses.

Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study.

PubMed

Shearman, A M; Ordovas, J M; Cupples, L A; Schaefer, E J; Harmon, M D; Shao, Y; Keen, J D; DeStefano, A L; Joost, O; Wilson, P W; Housman, D E; Myers, R H

2000-05-22

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3-qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.

Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping.

PubMed Central

Kumar, S.; Kimberling, W. J.; Connolly, C. J.; Tinley, S.; Marres, H. A.; Cremers, C. W.

1994-01-01

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder associated with external-, middle-, and inner-ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss, and renal anomalies. The gene for BOR was mapped to the long arm of chromosome 8q. Several polymorphic dinucleotide repeat markers were investigated for linkage in two large BOR families, and the region of localization was refined. Two-point linkage analysis yielded the maximum lod scores of 7.44 at theta = .03 and 6.71 at theta = .04, with markers D8S279 and D8S260, respectively. A multipoint analysis was carried out to position the BOR gene with a defined region using markers D8S165, D8S285, PENK, D8S166, D8S260, D8S279, D8S164, D8S286, D8S84, D8S275, D8S167, D8S273, and D8S271. Haplotype analysis of recombination events at these polymorphic loci was also performed in multigeneration BOR kindreds. The linkage analysis and analysis of recombination events identified markers that clearly flank the BOR locus. The order was determined to be D8S260-BOR-D8S279 at odds > 10(3):1 over the other possible orders. This flanking markers provide a resource for high-resolution mapping toward cloning and characterizing the BOR gene. PMID:7977379

Grammar-Supported 3d Indoor Reconstruction from Point Clouds for As-Built Bim

NASA Astrophysics Data System (ADS)

Becker, S.; Peter, M.; Fritsch, D.

2015-03-01

The paper presents a grammar-based approach for the robust automatic reconstruction of 3D interiors from raw point clouds. The core of the approach is a 3D indoor grammar which is an extension of our previously published grammar concept for the modeling of 2D floor plans. The grammar allows for the modeling of buildings whose horizontal, continuous floors are traversed by hallways providing access to the rooms as it is the case for most office buildings or public buildings like schools, hospitals or hotels. The grammar is designed in such way that it can be embedded in an iterative automatic learning process providing a seamless transition from LOD3 to LOD4 building models. Starting from an initial low-level grammar, automatically derived from the window representations of an available LOD3 building model, hypotheses about indoor geometries can be generated. The hypothesized indoor geometries are checked against observation data - here 3D point clouds - collected in the interior of the building. The verified and accepted geometries form the basis for an automatic update of the initial grammar. By this, the knowledge content of the initial grammar is enriched, leading to a grammar with increased quality. This higher-level grammar can then be applied to predict realistic geometries to building parts where only sparse observation data are available. Thus, our approach allows for the robust generation of complete 3D indoor models whose quality can be improved continuously as soon as new observation data are fed into the grammar-based reconstruction process. The feasibility of our approach is demonstrated based on a real-world example.

Correlation of the earth's rotation rate and the secular change of the geomagnetic field. [power spectra/harmonic analysis

NASA Technical Reports Server (NTRS)

Jin, R. S.

1975-01-01

Power spectral density analysis using Burg's maximum entropy method was applied to the geomagnetic dipole field and its rate of change for the years 1901 to 1969. Both spectra indicate relative maxima at 0.015 cycles/year and its harmonics. These maxima correspond approximately to 66, 33, 22, 17, 13, 11, and 9-year spectral lines. The application of the same analysis techniques to the length-of-day (l.o.d) fluctuations for the period 1865 to 1961 reveal similar spectral characteristics. Although peaks were observed at higher harmonics of the fundamental frequency, the 22-year and 11-year lines are not attributed unambiguously to the solar magnetic cycle and the solar cycle. It is suggested that the similarity in the l.o.d fluctuations and the dipole field variations is related to the motion within the earth's fluid core during the past one hundred years.

Case-Deletion Diagnostics for Maximum Likelihood Multipoint Quantitative Trait Locus Linkage Analysis

PubMed Central

Mendoza, Maria C.B.; Burns, Trudy L.; Jones, Michael P.

2009-01-01

Objectives Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. Methods Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). Results Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. Conclusions The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation. PMID:19172086

Using Affordable Data Capturing Devices for Automatic 3d City Modelling

NASA Astrophysics Data System (ADS)

Alizadehashrafi, B.; Abdul-Rahman, A.

2017-11-01

In this research project, many movies from UTM Kolej 9, Skudai, Johor Bahru (See Figure 1) were taken by AR. Drone 2. Since the AR drone 2.0 has liquid lens, while flying there were significant distortions and deformations on the converted pictures of the movies. Passive remote sensing (RS) applications based on image matching and Epipolar lines such as Agisoft PhotoScan have been tested to create the point clouds and mesh along with 3D models and textures. As the result was not acceptable (See Figure 2), the previous Dynamic Pulse Function based on Ruby programming language were enhanced and utilized to create the 3D models automatically in LoD3. The accuracy of the final 3D model is almost 10 to 20 cm. After rectification and parallel projection of the photos based on some tie points and targets, all the parameters were measured and utilized as an input to the system to create the 3D model automatically in LoD3 in a very high accuracy.

Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree

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

Silverman, J.M.; Altstiel, L.D.; Siever, L.J.

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia-schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n =more » 2); the other 11 families were much smaller, less complete, and provided little additional information. Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophrenia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family. It may be of interest that over several generations, almost all the ancestors of family 17 could be traced back to a small, relatively isolated, hill region of Puerto Rico. 74 refs., 2 figs., 2 tabs.« less

Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi Jewish population using ordered subset analysis

PubMed Central

Simpson, Claire L.; Wojciechowski, Robert; Ibay, Grace; Stambolian, Dwight

2011-01-01

Purpose Despite many years of research, most of the genetic factors contributing to myopia development remain unknown. Genetic studies have pointed to a strong inherited component, but although many candidate regions have been implicated, few genes have been positively identified. Methods We have previously reported 2 genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish families that identified a locus on chromosome 22. Here we used ordered subset analysis (OSA), conditioned on non-parametric linkage to chromosome 22 to detect other chromosomal regions which had evidence of linkage to myopia in subsets of the families, but not the overall sample. Results Strong evidence of linkage to a 19-cM linkage interval with a peak OSA nonparametric allele-sharing logarithm-of-odds (LOD) score of 3.14 on 20p12-q11.1 (ΔLOD=2.39, empirical p=0.029) was identified in a subset of 20 families that also exhibited strong evidence of linkage to chromosome 22. One other locus also presented with suggestive LOD scores >2.0 on chromosome 11p14-q14 and one locus on chromosome 6q22-q24 had an OSA LOD score=1.76 (ΔLOD=1.65, empirical p=0.02). Conclusions The chromosome 6 and 20 loci are entirely novel and appear linked in a subset of families whose myopia is known to be linked to chromosome 22. The chromosome 11 locus overlaps with the known Myopia-7 (MYP7, OMIM 609256) locus. Using ordered subset analysis allows us to find additional loci linked to myopia in subsets of families, and underlines the complex genetic heterogeneity of myopia even in highly aggregated families and genetically isolated populations such as the Ashkenazi Jews. PMID:21738393

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster.

PubMed

Lilja, Heidi E; Soro, Aino; Ylitalo, Kati; Nuotio, Ilpo; Viikari, Jorma S A; Salomaa, Veikko; Vartiainen, Erkki; Taskinen, Marja-Riitta; Peltonen, Leena; Pajukanta, Päivi

2002-09-01

In patients with premature coronary heart disease, the most common lipoprotein abnormality is high-density lipoprotein (HDL) deficiency. To assess the genetic background of the low HDL-cholesterol trait, we performed a candidate gene study in 25 families with low HDL, collected from the genetically isolated population of Finland. We studied 21 genes encoding essential proteins involved in the HDL metabolism by genotyping intragenic and flanking markers for these genes. We found suggestive evidence for linkage in two candidate regions: Marker D1S2844, in the apolipoprotein A-II (APOA2) region, yielded a LOD score of 2.14 and marker D11S939 flanking the apolipoprotein A-I/C-III/A-IV gene cluster (APOA1C3A4) produced a LOD score of 1.69. Interestingly, we identified potential shared haplotypes in these two regions in a subset of low HDL families. These families also contributed to the obtained positive LOD scores, whereas the rest of the families produced negative LOD scores. None of the remaining candidate regions provided any evidence for linkage. Since only a limited number of loci were tested in this candidate gene study, these LOD scores suggest significant involvement of the APOA2 gene and the APOA1C3A4 gene cluster, or loci in their immediate vicinity, in the pathogenesis of low HDL.

Revisiting the hypothesis of equating the 6-year oscillation in the length-of-day to the mantle-inner core gravitational coupling

NASA Astrophysics Data System (ADS)

Chao, B. F.

2016-12-01

The steady 6-year oscillation observed in the length-of-day variation (ΔLOD) has been postulated to be, among others, an intrinsic oscillatory mode of the Earth's axial spin due to the mantle-inner core gravitational (MICG) coupling [Buffett and Mound, 2005]. Here I develop the general equation of motion of the 3-D MICG system from first principles in terms of multipole-multipole interactions (as in molecular electric field) under simple but realistic assumptions including the buoyancy effect of the fluid outer core. When specialized to the governing of the simple-harmonic oscillation in ΔLOD, the restoring force thereof is predominated, not surprisingly, by the [degree-2, order-2] density anomalies in the lower mantle and the upper inner core. Equating the corresponding "spring constant" to that belonging to the 6-year ΔLOD oscillation, one can estimate the difference between the two inner-core equatorial principal moments of inertia to be (BIC-AIC) ≈ 1.08 x 1031 kg m2 accurate perhaps to within a factor of 2, or a tri-axiality factor about 8 times larger than that of the whole Earth. Moreover, the orientation of the two principal axes can be identified in accordance with the timing of the 6-year ΔLOD oscillation. The physical excitation of the 6-year ΔLOD oscillation, ±0.12 ms in amplitude, is beyond the present scope.

Effects of forest harvesting on large organic debris in coastal streams

Treesearch

Christopher G. Surfleet; Robert R. Ziemer

1996-01-01

Abstract - Large organic debris (LOD) was inventoried in two coastal streams to assess the impacts of forest harvesting on LOD recruitment in 90-year-old, second-growth redwood and fir stands on the Jackson Demonstration State Forest in northern California. One stream, North Fork of Caspar Creek, drained a 508-ha watershed that had been 60% clear-cut, with riparian...

A locus for cerebral cavernous malformations maps to chromosome 7q in two families

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

Marchuk, D.A.; Gallione, C.J.; Morrison, L.A.

1995-07-20

Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seizure, intracranial hemorrhage, focal neurological deficit, and migraine. We have mapped a gene for this disorder in two families, one of Italian-American origin and one of Mexican-American origin, to markers on proximal 7q, with a combined maximum lod score of 3.92 ({theta} of zero) with marker D7S479. Haplotype analysis of these families places the locus between markers D7S502 proximally and D7S515 distally, an interval ofmore » approximately 41 cM. The location distinguishes this disorder from an autosomal dominant vascular malformation syndrome where lesions are primarily cutaneous and that maps to 9p21. 16 refs., 3 figs., 1 tab.« less

Potential linkage for schizophrenia on chromosome 22q12-q13: A replication study

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

Schwab, S.G.; Bondy, B.; Wildenauer, D.B.

1995-10-09

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al., we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Z{sub max} = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sibmore » pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al., is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point. 32 refs., 1 fig., 4 tabs.« less

LOD map--A visual interface for navigating multiresolution volume visualization.

PubMed

Wang, Chaoli; Shen, Han-Wei

2006-01-01

In multiresolution volume visualization, a visual representation of level-of-detail (LOD) quality is important for us to examine, compare, and validate different LOD selection algorithms. While traditional methods rely on ultimate images for quality measurement, we introduce the LOD map--an alternative representation of LOD quality and a visual interface for navigating multiresolution data exploration. Our measure for LOD quality is based on the formulation of entropy from information theory. The measure takes into account the distortion and contribution of multiresolution data blocks. A LOD map is generated through the mapping of key LOD ingredients to a treemap representation. The ordered treemap layout is used for relative stable update of the LOD map when the view or LOD changes. This visual interface not only indicates the quality of LODs in an intuitive way, but also provides immediate suggestions for possible LOD improvement through visually-striking features. It also allows us to compare different views and perform rendering budget control. A set of interactive techniques is proposed to make the LOD adjustment a simple and easy task. We demonstrate the effectiveness and efficiency of our approach on large scientific and medical data sets.

On computation of p-values in parametric linkage analysis.

PubMed

Kurbasic, Azra; Hössjer, Ola

2004-01-01

Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null hypothesis of no linkage when only one point (one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Zmax has no simple form when more than one marker is used (multipoint analysis). In fact, the distribution of Zmax depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Zmax leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (c) 2004 S. Karger AG, Basel.

Tumor necrosis factor alpha versus LH and androstendione as a reliable predictor of spontaneous ovulation after laparoscopic ovarian drilling for women with clomiphene citrate resistance polycystic ovarian disease.

PubMed

Seyam, Emaduldin; Hefzy, Enas

2018-03-01

Laparoscopic ovarian drilling (LOD) is still a controversial decision; due to the long term hazards; so short and long term predictors after the procedure should be taken in consideration. The aim of this work was to investigate the role of the serum level of tumor necrosis factor alpha (TNF-α) and other polycystic ovarian disease (PCOD) relevant clinical and biochemical factors as a predictor of spontaneous ovulation after laparoscopic ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic ovarian disease (CCR-PCOD). It was a prospective research work, where 150 infertile women with CCR-PCOD had been recruited. TNF-α serum level, which is an inflammatory biomarker, was investigated in addition to other PCOD relevant clinical and biochemical parameters as possible predictors of successful spontaneous ovulation and subsequent pregnancy after LOD. Recruited women with higher preoperative levels of TNF-α, LH, and androstenedione had significantly higher rates of spontaneous ovulation within the first three months follow up after LOD, in contrast to obese women with BMI ≥ 25 kg/m2, long duration of infertility ≥3 years, marked biochemical hyperandrogenism (testosterone levels ≥4.5 nmol/L, free androgen index ≥15), and high insulin resistance (IR). Ninty five (95 = 63.3%) women in between women regularly menstruated (105 = 70%) had spontaneous ovulation, and of those spontaneously ovulated, 35(36.8%) women got pregnant spontaneously during the first 3 months follow up. Extended follow up for 12 months period revealed that 61 women got pregnant, with cumulative pregnancy rate of 58%. Logistic regression showed that the best cut-off values for spontaneous ovulation after LOD were 65.1 pg/ml, 11.5 IU/l, and 3.1 ng/ml and with a sensitivity of 91%, 88%, 55%, and with a specificity of 85%, 79%, 78%, for TNF-α, LH, androstenedione serum level respectively. TNF-α, LH, and Androstenedione could be considered as reliable predictors to depend on for recruiting the ideal women candidates with CCR-PCOD; to have the maximum benefits after LOD treatment option. Copyright © 2018 Elsevier B.V. All rights reserved.

A Spatially-Registered, Massively Parallelised Data Structure for Interacting with Large, Integrated Geodatasets

NASA Astrophysics Data System (ADS)

Irving, D. H.; Rasheed, M.; O'Doherty, N.

2010-12-01

The efficient storage, retrieval and interactive use of subsurface data present great challenges in geodata management. Data volumes are typically massive, complex and poorly indexed with inadequate metadata. Derived geomodels and interpretations are often tightly bound in application-centric and proprietary formats; open standards for long-term stewardship are poorly developed. Consequently current data storage is a combination of: complex Logical Data Models (LDMs) based on file storage formats; 2D GIS tree-based indexing of spatial data; and translations of serialised memory-based storage techniques into disk-based storage. Whilst adequate for working at the mesoscale over a short timeframes, these approaches all possess technical and operational shortcomings: data model complexity; anisotropy of access; scalability to large and complex datasets; and weak implementation and integration of metadata. High performance hardware such as parallelised storage and Relational Database Management System (RDBMS) have long been exploited in many solutions but the underlying data structure must provide commensurate efficiencies to allow multi-user, multi-application and near-realtime data interaction. We present an open Spatially-Registered Data Structure (SRDS) built on Massively Parallel Processing (MPP) database architecture implemented by a ANSI SQL 2008 compliant RDBMS. We propose a LDM comprising a 3D Earth model that is decomposed such that each increasing Level of Detail (LoD) is achieved by recursively halving the bin size until it is less than the error in each spatial dimension for that data point. The value of an attribute at that point is stored as a property of that point and at that LoD. It is key to the numerical efficiency of the SRDS that it is under-pinned by a power-of-two relationship thus precluding the need for computationally intensive floating point arithmetic. Our approach employed a tightly clustered MPP array with small clusters of storage, processors and memory communicating over a high-speed network inter-connect. This is a shared-nothing architecture where resources are managed within each cluster unlike most other RDBMSs. Data are accessed on this architecture by their primary index values which utilises the hashing algorithm for point-to-point access. The hashing algorithm’s main role is the efficient distribution of data across the clusters based on the primary index. In this study we used 3D seismic volumes, 2D seismic profiles and borehole logs to demonstrate application in both (x,y,TWT) and (x,y,z)-space. In the SRDS the primary index is a composite column index of (x,y) to avoid invoking time-consuming full table scans as is the case in tree-based systems. This means that data access is isotropic. A query for data in a specified spatial range permits retrieval recursively by point-to-point queries within each nested LoD yielding true linear performance up to the Petabyte scale with hardware scaling presenting the primary limiting factor. Our architecture and LDM promotes: realtime interaction with massive data volumes; streaming of result sets and server-rendered 2D/3D imagery; rigorous workflow control and auditing; and in-database algorithms run directly against data as a HPC cloud service.

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

PubMed

Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

2008-07-01

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

Occurrences of Organochlorine Pesticides along the Course of the Buffalo River in the Eastern Cape of South Africa and Its Health Implications.

PubMed

Yahaya, Abdulrazaq; Okoh, Omobola O; Okoh, Anthony I; Adeniji, Abiodun O

2017-11-10

Most organochlorine pesticides (OCPs) which are increasingly used in agriculture and industry are not biodegradable and thereby persist in the environment for a very long period of time. They are capable of negatively impacting the health of humans and biota when present in a higher concentration than recommended. This study evaluated the concentrations of 17 OCPs in surface water samples collected from six sampling sites along the course of the Buffalo River in Eastern Cape, South Africa, between December 2015 and May 2016. The samples were subjected to solvent extraction, followed by florisil clean up, and analyzed using gas chromatography coupled with an electron capture detector. The individual concentrations of OCPs detected ranged from

A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8.

PubMed

Eidenschenk, Celine; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth

2006-04-01

We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus-driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans.

A Novel Primary Immunodeficiency with Specific Natural-Killer Cell Deficiency Maps to the Centromeric Region of Chromosome 8

PubMed Central

Eidenschenk, Céline; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth

2006-01-01

We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus–driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans. PMID:16532402

Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

PubMed Central

Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2016-01-01

Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

Chromosome 14 and late-onset familial alzheimer disease (FAD)

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

Schellenberg, G.D.; Anderson, L.; Nemens, E.

1993-09-01

Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analysis were used, in 49 families with a mean age at onset [>=]60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependentmore » penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score [>=]2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P<.02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset [>=]60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 37 refs., 1 fig., 6 tabs.« less

Glyphosate and Paraquat in Maternal and Fetal Serums in Thai Women.

PubMed

Kongtip, Pornpimol; Nankongnab, Noppanun; Phupancharoensuk, Ratanavadee; Palarach, Chonlada; Sujirarat, Dusit; Sangprasert, Supha; Sermsuk, Malasod; Sawattrakool, Namthip; Woskie, Susan Renee

2017-01-01

This longitudinal study measured the glyphosate and paraquat concentrations found in maternal and umbilical cord serum in 82 pregnant women who gave birth in three provinces of Thailand. Through questionnaires and biological samples collected at childbirth, factors such as personal characteristics, family members occupation, agricultural activities, and herbicide use in agricultural work were evaluated as predictors of glyphosate and paraquat levels in the pregnant women. Statistical analysis used univariate and binary multiple logistic regression, where the outcome was the probability of exposure to paraquat or glyphosate above the limit of detection associated with occupation and household factors. The glyphosate concentrations in the pregnant women's serum at childbirth (median: 17.5, range: 0.2-189.1 ng/mL) were significantly higher (P < .007) than those in the umbilical cord serum (median: 0.2, range: 0.2-94.9 ng/mL). However, the paraquat concentrations in the serum of the pregnant women at childbirth (83% ≤limit of detection [LOD], with maximum of 58.3 ng/mL) were similar to those in the umbilical cord serum (80% LOD in serum at childbirth were 11.9 times more likely to report work as an agriculturist (P < .001), 3.7 times more likely to live near agricultural areas (P = .006), and 5.9 times more likely to have a family member who worked in agriculture (P < .001). The only factors affecting paraquat exposures in pregnant women at childbirth were reporting the agricultural activity of digging in farm soil and working in the agricultural fields in the third trimester of pregnancy. These results show that pregnant women who work in agriculture or live in families that work in agriculture have higher exposures to the herbicides glyphosate and paraquat. The potential for long-term health impacts of these prenatal exposures to children should be evaluated, and greater regulation of the sale and use of herbicides should be considered in Thailand.

Genetic heterogeneity in families with non-epidermolytic palmar plantar keratosis

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

Spurr, N.K.; Kelshell, D.P.; Stevens, H.

1994-09-01

Following reports of linkage close to the keratin gene cluster in families with tylosis and the detection of mutations in the keratin 9 gene cosegregating in families with epidermolytic palmar plantar keratoderma (EPPK, and EPPK associated with breast and ovarian cancer), we have identified families with three phenotypically distinct forms of non-epidermolytic keratosis with either punctate, diffuse or focal keratoderma, one with diffuse lesions and one with punctate and malignancies. Initially we typed these families with 17q markers close to the keratin gene cluster; this included a dinucleotide repeat marker within the keratin 9 gene. Two point linkage analysis ofmore » the focal keratoderma family showed a positive lod score of 3.2 at a theta of 0 from the marker D17S855. The lod score for the diffuse family was -6.0 at a theta of 0.05 from the marker D17S776. The second focal keratoderma family showed a haplotype consistent with linkage to 17q close to the keratin gene cluster. A second keratin gene cluster has been mapped in humans on 12q, and we decided to test the unlinked diffuse and punctate keratoderma families with markers in that region. We used the markers: D12S87-D12S85-D12S368-D12S96-D12S90. Linkage analysis of the diffuse family gave a lod score of 3.1 at a theta of 0 from the marker D12S368. Currently studies are underway to look for mutations in specific keratin genes in the clusters on 17q and 12q that segregate with the observed phenotypes. The punctate keratoderma family gave lod scores of -3.9 at a theta of 0.55 with D17S855 and -6.0 at a theta of 0.05 with D12S90/D12S83. This would lead us to the conclusion that a separate susceptibility locus must exist for the punctate family associated with malignancy. Investigations of candidate regions are in progress.« less

Chronic and Recurrent Otitis Media: A Genome Scan for Susceptibility Loci

PubMed Central

Daly, Kathleen A.; Brown, W. Mark; Segade, Fernando; Bowden, Donald W.; Keats, Bronya J.; Lindgren, Bruce R.; Levine, Samuel C.; Rich, Stephen S.

2004-01-01

Otitis media (OM) is the most common childhood disease. Almost all children experience at least one episode, but morbidity is greatest in children who experience chronic/recurrent OM (COME/ROM). There is mounting evidence that COME/ROM clusters in families and exhibits substantial heritability. Subjects who had tympanostomy tube surgery for COME/ROM (probands) and their families were recruited for the present study, and an ear examination was performed, without knowledge of the subject’s history, to determine presence of OM sequelae. In addition, tympanometric testing was performed at three frequencies (226, 630 or 710, and 1,400 Hz) to detect abnormal middle-ear mechanics, and hearing was screened at 20 dB for the speech frequencies. Of these families, 121 had at least two individuals who had received the diagnosis of COME/ROM (364 affected and genotyped individuals), of whom 238 affected and informative relative pairs were used for analyses. Single-point nonparametric linkage analysis provided evidence of linkage of COME/ROM to chromosome 10q at marker D10S212 (LOD 3.78; P=3.0×10-5) and to chromosome 19q at marker D19S254 (LOD 2.61; P=5.3×10-4). Analyses conditional on support for linkage at chromosomes 10q and 19q resulted in a significant increase in LOD score support on chromosome 3p (between markers D3S4545 and D3S1259). These results suggest that risk of COME/ROM is determined by interactions between genes that reside in several candidate regions of the genome and are probably modulated by other environmental risk factors. PMID:15514890

Therapeutic effects of metformin and laparoscopic ovarian drilling in treatment of clomiphene and insulin-resistant polycystic ovary syndrome.

PubMed

Wang, Xiao-Hong; Wang, Jun-Qing; Xu, Yan; Huang, Li-Ping

2015-05-01

To compare the therapeutic effects of metformin (Met) and laparoscopic ovarian drilling (LOD) in clomiphene and insulin-resistant patients with polycystic ovary syndrome (CIRPCOS). A total of 110 patients were randomly divided into two groups. One group was administered Met (n = 55), while the other group underwent LOD (n = 55). Rates of ovulation, pregnancy, and abortion were compared between both groups. Rates of normal menstruation, ovulation, and pregnancy in the LOD group were higher than in the Met group: 76.4% (42/55) vs. 58.2% (32/55), P < 0.04; 50.8% (11/258) vs. 33.5% (94/281), P < 0.001; 38.2% (21/55) vs. 20.0% (11/55), P < 0.03. The difference in the early abortion rate between both groups was not statistically significant. Although Met can significantly improve a patient's insulin resistance, we found that in patients diagnosed with CIRCPOS, LOD can be much more effective in improving rates of normal menstruation, ovulation, and pregnancy.

Rapid Detection of Pathogenic Bacteria from Fresh Produce by Filtration and Surface-Enhanced Raman Spectroscopy

NASA Astrophysics Data System (ADS)

Wu, Xiaomeng; Han, Caiqin; Chen, Jing; Huang, Yao-Wen; Zhao, Yiping

2016-04-01

The detection of Salmonella Poona from cantaloupe cubes and E. coli O157:H7 from lettuce has been explored by using a filtration method and surface-enhanced Raman spectroscopy (SERS) based on vancomycin-functionalized silver nanorod array substrates. It is found that with a two-step filtration process, the limit of detection (LOD) of Salmonella Poona from cantaloupe cubes can be as low as 100 CFU/mL in less than 4 h, whereas the chlorophyll in the lettuce causes severe SERS spectral interference. To improve the LOD of lettuce, a three-step filtration method with a hydrophobic filter is proposed. The hydrophobic filter can effectively eliminate the interferences from chlorophyll and achieve a LOD of 1000 CFU/mL detection of E. coli O157:H7 from lettuce samples within 5 h. With the low LODs and rapid detection time, the SERS biosensing platform has demonstrated its potential as a rapid, simple, and inexpensive means for pathogenic bacteria detection from fresh produce.

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

PubMed

Dols, Annemiek; Bouckaert, Filip; Sienaert, Pascal; Rhebergen, Didi; Vansteelandt, Kristof; Ten Kate, Mara; de Winter, Francois-Laurent; Comijs, Hannie C; Emsell, Louise; Oudega, Mardien L; van Exel, Eric; Schouws, Sigfried; Obbels, Jasmien; Wattjes, Mike; Barkhof, Frederik; Eikelenboom, Piet; Vandenbulcke, Mathieu; Stek, Max L

2017-02-01

The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Cutaneous malignant melanoma and familial dysplastic nevi: evidence for autosomal dominance and pleiotropy.

PubMed Central

Bale, S J; Chakravarti, A; Greene, M H

1986-01-01

Segregation of familial cutaneous melanoma has been shown to be compatible with autosomal dominant transmission with incomplete penetrance. However, the combined phenotype of melanoma and a known melanoma-precursor lesion, the dysplastic nevus (DN), has not previously been found to fit a Mendelian model of inheritance using complex segregation analysis. Employing a life-table and disease-free survival analysis approach, we estimated the lifetime incidence of melanoma in the sibs and offspring of DN-affected individuals to be 46%, consistent with a highly penetrant, autosomal dominant mode of inheritance. To further elucidate the relationship between the two traits, we conducted a linkage analysis between the melanoma locus and a hypothetical DN locus, and obtained a maximum lod score of 3.857 at theta = .08. Furthermore, all families giving evidence for linkage were in the coupling phase and the maximum likelihood estimate of theta was not significantly different from 0 (P = .1). This provides evidence that the DN and melanoma traits may represent pleiotropic effects of a single, highly penetrant gene behaving in an autosomal dominant manner. PMID:3456198

Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1.

PubMed

Holmberg, M; Johansson, J; Forsgren, L; Heijbel, J; Sandgren, O; Holmgren, G

1995-08-01

We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated with retinal degeneration and anticipation. Common clinical signs in this family include ataxia, dysarthria and severely impaired vision with the phenotype ADCA type II. Different subtypes of ADCA have proven difficult to classify clinically due to extensive phenotypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also genetically. During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been identified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q), SCA4 (16q), and finally SCA5 (11). We performed a genome-wide search of the Swedish ADCA type II family using a total of 270 microsatellite markers. Positive lod scores were obtained with a number of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

PubMed

Bailey-Wilson, Joan E; Childs, Erica J; Cropp, Cheryl D; Schaid, Daniel J; Xu, Jianfeng; Camp, Nicola J; Cannon-Albright, Lisa A; Farnham, James M; George, Asha; Powell, Isaac; Carpten, John D; Giles, Graham G; Hopper, John L; Severi, Gianluca; English, Dallas R; Foulkes, William D; Mæhle, Lovise; Møller, Pål; Eeles, Rosalind; Easton, Douglas; Guy, Michelle; Edwards, Steve; Badzioch, Michael D; Whittemore, Alice S; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Dimitrov, Latchezar; Stanford, Janet L; Karyadi, Danielle M; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A; Wiley, Kathleen E; Isaacs, Sarah D; Walsh, Patrick C; Thibodeau, Stephen N; McDonnell, Shannon K; Hebbring, Scott; Lange, Ethan M; Cooney, Kathleen A; Tammela, Teuvo L J; Schleutker, Johanna; Maier, Christiane; Bochum, Sylvia; Hoegel, Josef; Grönberg, Henrik; Wiklund, Fredrik; Emanuelsson, Monica; Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier; Isaacs, William B

2012-06-19

Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

The Computer Image Generation Applications Study.

DTIC Science & Technology

1980-07-01

1059 7 T62 Tank 759 0 Lexington Carrier 1485 19 Sea Scape 600 1680 Fresnel Lens Optical Landing System (FLOLS) 20 0 Meatball 9 0 T37 Aircraft (LOD#3... Meatball T37 Aircraft NATO 4655 1914 33 new eye point. See also 7.1.5.5 for definition of monocular movement parallax. (g) Multiple Simulations

Investigation of cloud point extraction for the analysis of metallic nanoparticles in a soil matrix

PubMed Central

Hadri, Hind El; Hackley, Vincent A.

2017-01-01

The characterization of manufactured nanoparticles (MNPs) in environmental samples is necessary to assess their behavior, fate and potential toxicity. Several techniques are available, but the limit of detection (LOD) is often too high for environmentally relevant concentrations. Therefore, pre-concentration of MNPs is an important component in the sample preparation step, in order to apply analytical tools with a LOD higher than the ng kg−1 level. The objective of this study was to explore cloud point extraction (CPE) as a viable method to pre-concentrate gold nanoparticles (AuNPs), as a model MNP, spiked into a soil extract matrix. To that end, different extraction conditions and surface coatings were evaluated in a simple matrix. The CPE method was then applied to soil extract samples spiked with AuNPs. Total gold, determined by inductively coupled plasma mass spectrometry (ICP-MS) following acid digestion, yielded a recovery greater than 90 %. The first known application of single particle ICP-MS and asymmetric flow field-flow fractionation to evaluate the preservation of the AuNP physical state following CPE extraction is demonstrated. PMID:28507763

Comparison between Unilateral and Bilateral Ovarian Drilling in Clomiphene Citrate Resistance Polycystic Ovary Syndrome Patients: A Randomized Clinical Trial of Efficacy

PubMed Central

Zahiri Sorouri, Ziba; Sharami, Seyede Hajar; Tahersima, Zinab; Salamat, Fatemeh

2015-01-01

Background Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in polycystic ovary syndrome (PCOS) patients with clomiphene citrate (CC) resistant instead of gonadotropins. This study aimed to compare the efficacy of unilateral LOD (ULOD) versus bilateral LOD (BLOD) in CC resistance PCOS patients in terms of ovulation and pregnancy rates. Materials and Methods In a prospective randomized clinical trial study, we included 100 PCOS patients with CC resistance attending to Al-Zahra Hospital in Rasht, Guilan Province, Iran, from June 2011 to July 2012. Patients were randomly divided into two ULOD and BLOD groups with equal numbers. The clinical and biochemical responses on ovulation and pregnancy rates were assessed over a 6-month follow-up period. Results Differences in baseline characteristics of patients between two groups prior to laparoscopy were not significant (p>0.05). There were no significant differences between the two groups in terms of clinical and biochemical responses, spontaneous menstruation (66.1 vs. 71.1%), spontaneous ovulation rate (60 vs. 64.4%), and pregnancy rate (33.1 vs. 40%) (p>0.05). Following drilling, there was a significant decrease in mean serum concentrations of luteinizing hormone (LH) (p=0.001) and testosterone (p=0.001) in both the groups. Mean decrease in serum LH (p=0.322) and testosterone concentrations (p=0.079) were not statistically significant between two groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in two groups after LOD (p>0.05). Conclusion Based on results of this study, ULOD seems to be equally efficacious as BLOD in terms of ovulation and pregnancy rates (Registration Number: IRCT138903291306N2). PMID:25918587

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

PubMed

Paramu, Sobhana

2016-12-01

Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p<0.001). Women with AMH >8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

Tidal influence through LOD variations on the temporal distribution of earthquake occurrences

NASA Astrophysics Data System (ADS)

Varga, P.; Gambis, D.; Bizouard, Ch.; Bus, Z.; Kiszely, M.

2006-10-01

Stresses generated by the body tides are very small at the depth of crustal earth- quakes (~10^2 N/m2). The maximum value of the lunisolar stress within the depth range of earthquakes is 10^3 N/m2 (at depth of about 600 km). Surface loads, due to oceanic tides, in coastal areas are ~ 104 N/m2. These influences are however too small to affect the outbreak time of seismic events. Authors show the effect on time distribution of seismic activity due to ΔLOD generated by zonal tides for the case of Mf, Mm, Ssa and Sa tidal constituents can be much more effective to trigger earthquakes. According to this approach we show that the tides are not directly triggering the seismic events but through the generated length of day variations. That is the reason why in case of zonal tides a correlation of the lunisolar effect and seismic activity exists, what is not the case for the tesseral and sectorial tides.

A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

PubMed Central

Wiltshire, Steven; Hattersley, Andrew T.; Hitman, Graham A.; Walker, Mark; Levy, Jonathan C.; Sampson, Michael; O’Rahilly, Stephen; Frayling, Timothy M.; Bell, John I.; Lathrop, G. Mark; Bennett, Amanda; Dhillon, Ranjit; Fletcher, Christopher; Groves, Christopher J.; Jones, Elizabeth; Prestwich, Philip; Simecek, Nikol; Rao, Pamidighantam V. Subba; Wishart, Marie; Foxon, Richard; Howell, Simon; Smedley, Damian; Cardon, Lon R.; Menzel, Stephan; McCarthy, Mark I.

2001-01-01

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores ⩾1.18 (P⩽.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest. PMID:11484155

Does the Level of Graphical Detail of a Virtual Handball Thrower Influence a Goalkeeper’s Motor Response?

PubMed Central

Vignais, Nicolas; Bideau, Benoit; Craig, Cathy; Brault, Sébastien; Multon, Franck; Delamarche, Paul; Kulpa, Richard

2009-01-01

The authors investigated how different levels of detail (LODs) of a virtual throwing action can influence a handball goalkeeper’s motor response. Goalkeepers attempted to stop a virtual ball emanating from five different graphical LODs of the same virtual throwing action. The five levels of detail were: a textured reference level (L0), a non-textured level (L1), a wire-frame level (L2), a point-light-display (PLD) representation (L3) and a PLD level with reduced ball size (L4). For each motor response made by the goalkeeper we measured and analyzed the time to respond (TTR), the percentage of successful motor responses, the distance between the ball and the closest limb (when the stopping motion was incorrect) and the kinematics of the motion. Results showed that TTR, percentage of successful motor responses and distance with the closest limb were not significantly different for any of the five different graphical LODs. However the kinematics of the motion revealed that the trajectory of the stopping limb was significantly different when comparing the L1 and L3 levels, and when comparing the L1 and L4 levels. These differences in the control of the goalkeeper’s actions suggests that the different level of information available in the PLD representations (L3 and L4) are causing the goalkeeper to adopt different motor strategies to control the approach of their limb to stop the ball. Key points Virtual reality technology can be used to analyze sport performance because it enables standardization and reproduction of sport situations. Defining a minimal graphical level of detail of a virtual action could decrease the real time calculation of a virtual reality system. A Point Light Display graphical representation of a virtual throwing motion seems to influence the regulation of action of real handball goalkeepers. PMID:24149589

Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

PubMed

Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

1993-05-01

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

Detection and Resolution of Cryptosporidium Species and Species Mixtures by Genus-Specific Nested PCR-Restriction Fragment Length Polymorphism Analysis, Direct Sequencing, and Cloning ▿

PubMed Central

Ruecker, Norma J.; Hoffman, Rebecca M.; Chalmers, Rachel M.; Neumann, Norman F.

2011-01-01

Molecular methods incorporating nested PCR-restriction fragment length polymorphism (RFLP) analysis of the 18S rRNA gene of Cryptosporidium species were validated to assess performance based on limit of detection (LoD) and for detecting and resolving mixtures of species and genotypes within a single sample. The 95% LoD was determined for seven species (Cryptosporidium hominis, C. parvum, C. felis, C. meleagridis, C. ubiquitum, C. muris, and C. andersoni) and ranged from 7 to 11 plasmid template copies with overlapping 95% confidence limits. The LoD values for genomic DNA from oocysts on microscope slides were 7 and 10 template copies for C. andersoni and C. parvum, respectively. The repetitive nested PCR-RFLP slide protocol had an LoD of 4 oocysts per slide. When templates of two species were mixed in equal ratios in the nested PCR-RFLP reaction mixture, there was no amplification bias toward one species over another. At high ratios of template mixtures (>1:10), there was a reduction or loss of detection of the less abundant species by RFLP analysis, most likely due to heteroduplex formation in the later cycles of the PCR. Replicate nested PCR was successful at resolving many mixtures of Cryptosporidium at template concentrations near or below the LoD. The cloning of nested PCR products resulted in 17% of the cloned sequences being recombinants of the two original templates. Limiting-dilution nested PCR followed by the sequencing of PCR products resulted in no sequence anomalies, suggesting that this method is an effective and accurate way to study the species diversity of Cryptosporidium, particularly for environmental water samples, in which mixtures of parasites are common. PMID:21498746

Self-Referenced Smartphone-Based Nanoplasmonic Imaging Platform for Colorimetric Biochemical Sensing.

PubMed

Wang, Xinhao; Chang, Te-Wei; Lin, Guohong; Gartia, Manas Ranjan; Liu, Gang Logan

2017-01-03

Colorimetric sensors usually suffer due to errors from variation in light source intensity, the type of light source, the Bayer filter algorithm, and the sensitivity of the camera to incoming light. Here, we demonstrate a self-referenced portable smartphone-based plasmonic sensing platform integrated with an internal reference sample along with an image processing method to perform colorimetric sensing. Two sensing principles based on unique nanoplasmonics enabled phenomena from a nanostructured plasmonic sensor, named as nanoLCA (nano Lycurgus cup array), were demonstrated here for colorimetric biochemical sensing: liquid refractive index sensing and optical absorbance enhancement sensing. Refractive indices of colorless liquids were measured by simple smartphone imaging and color analysis. Optical absorbance enhancement in the colorimetric biochemical assay was achieved by matching the plasmon resonance wavelength with the chromophore's absorbance peak wavelength. Such a sensing mechanism improved the limit of detection (LoD) by 100 times in a microplate reader format. Compared with a traditional colorimetric assay such as urine testing strips, a smartphone plasmon enhanced colorimetric sensing system provided 30 times improvement in the LoD. The platform was applied for simulated urine testing to precisely identify the samples with higher protein concentration, which showed potential point-of-care and early detection of kidney disease with the smartphone plasmonic resonance sensing system.

An evaluation of several different classification schemes - Their parameters and performance. [maximum likelihood decision for crop identification

NASA Technical Reports Server (NTRS)

Scholz, D.; Fuhs, N.; Hixson, M.

1979-01-01

The overall objective of this study was to apply and evaluate several of the currently available classification schemes for crop identification. The approaches examined were: (1) a per point Gaussian maximum likelihood classifier, (2) a per point sum of normal densities classifier, (3) a per point linear classifier, (4) a per point Gaussian maximum likelihood decision tree classifier, and (5) a texture sensitive per field Gaussian maximum likelihood classifier. Three agricultural data sets were used in the study: areas from Fayette County, Illinois, and Pottawattamie and Shelby Counties in Iowa. The segments were located in two distinct regions of the Corn Belt to sample variability in soils, climate, and agricultural practices.

Linkage Analysis Using Co-Phenotypes in the BRIGHT Study Reveals Novel Potential Susceptibility Loci for Hypertension

PubMed Central

Wallace, Chris; Xue, Ming-Zhan; Newhouse, Stephen J.; Marçano, Ana Carolina B.; Onipinla, Abiodun K.; Burke, Beverley; Gungadoo, Johannie; Dobson, Richard J.; Brown, Morris; Connell, John M.; Dominiczak, Anna; Lathrop, G. Mark; Webster, John; Farrall, Martin; Mein, Charles; Samani, Nilesh J.; Caulfield, Mark J.; Clayton, David G.; Munroe, Patricia B.

2006-01-01

Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers’ previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD=4.24) and with parameters of renal function on chromosome 5p (maximum LOD=3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits. PMID:16826522

Linkage analysis using co-phenotypes in the BRIGHT study reveals novel potential susceptibility loci for hypertension.

PubMed

Wallace, Chris; Xue, Ming-Zhan; Newhouse, Stephen J; Marcano, Ana Carolina B; Onipinla, Abiodun K; Burke, Beverley; Gungadoo, Johannie; Dobson, Richard J; Brown, Morris; Connell, John M; Dominiczak, Anna; Lathrop, G Mark; Webster, John; Farrall, Martin; Mein, Charles; Samani, Nilesh J; Caulfield, Mark J; Clayton, David G; Munroe, Patricia B

2006-08-01

Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD = 4.24) and with parameters of renal function on chromosome 5p (maximum LOD = 3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.

Sensing cocaine in saliva with infrared laser spectroscopy

NASA Astrophysics Data System (ADS)

Hans, Kerstin M.-C.; Müller, Matthias; Gianella, Michele; Wägli, Ph.; Sigrist, Markus W.

2013-02-01

Increasing numbers of accidents caused by drivers under the influence of drugs, raise drug tests to worldwide interest. We developed a one-step extraction technique for cocaine in saliva and analyzed reference samples with laser spectroscopy employing two different schemes. The first is based on attenuated total reflection (ATR), which is applied to dried samples. The second scheme uses transmission measurements for the analysis of liquid samples. ATR spectroscopy achieved a limit of detection (LOD) of 3μg/ml. The LOD for the transmission approach in liquid samples is < 10 μg/ml. These LODs are realistic as such concentration ranges are encountered in the saliva of drug users after the administration of a single dose of cocaine. An improved stabilization of the set-up should lower the limit of detection significantly.

Improved LIBS limit of detection of Be, Mg, Si, Mn, Fe and Cu in aluminum alloy samples using a portable Echelle spectrometer with ICCD camera

NASA Astrophysics Data System (ADS)

Mohamed, Walid Tawfik Y.

2008-02-01

Laser-induced breakdown spectroscopy (LIBS) is a laser-based technique that can provide non-intrusive, qualitative and quantitative measurement of metals in various environments. LIBS uses the plasma generated by a high-energy laser beam to prepare and excite the sample in one step. In the present work, LIBS has been applied to perform elemental analysis of six trace elements simultaneously in aluminum alloy targets. The plasma is generated by focusing a pulsed Nd:YAG laser on the target in air at atmospheric pressure. LIBS limit of detection (LOD) is affected by many experimental parameters such as interferences, self-absorption, spectral overlap and matrix effect. We aimed to improve the LIBS LOD by optimizing these experimental parameters as possible. In doing so, a portable Echelle spectrometer with intensified CCD camera was used to detect the LIBS plasma emission. This advanced Echelle spectrometer provides a constant spectral resolution (CSR) of 7500 corresponding to 4 pixels FWHM over a wavelength range 200-1000 nm displayable in a single spectrum. Then, the calibration curves for iron, beryllium, magnesium, silicon, manganese and copper as minor elements were achieved with linear regression coefficients between 98-99% on average in aluminum standard sample alloys. New LOD values were achieved in the ppm range with high precision (RSD 3-8%). From the application view point, improving LIBS LOD is very important in the on-line industrial process control to follow-up multi-elements for the correct alloying in metals.

Meteorological interpretation of transient LOD changes

NASA Astrophysics Data System (ADS)

Masaki, Y.

2008-04-01

The Earth’s spin rate is mainly changed by zonal winds. For example, seasonal changes in global atmospheric circulation and episodic changes accompanied with El Nĩ os are clearly detected n in the Length-of-day (LOD). Sub-global to regional meteorological phenomena can also change the wind field, however, their effects on the LOD are uncertain because such LOD signals are expected to be subtle and transient. In our previous study (Masaki, 2006), we introduced atmospheric pressure gradients in the upper atmosphere in order to obtain a rough picture of the meteorological features that can change the LOD. In this presentation, we compare one-year LOD data with meteorological elements (winds, temperature, pressure, etc.) and make an attempt to link transient LOD changes with sub-global meteorological phenomena.

Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I

PubMed Central

Astuto, Lisa M.; Weston, Michael D.; Carney, Carol A.; Hoover, Denise M.; Cremers, Cor W. R. J.; Wagenaar, Mariette; Moller, Claes; Smith, Richard J. H.; Pieke-Dahl, Sandra; Greenberg, Jacquie; Ramesar, Raj; Jacobson, Samuel G.; Ayuso, Carmen; Heckenlively, John R.; Tamayo, Marta; Gorin, Michael B.; Reardon, Willie; Kimberling, William J.

2000-01-01

Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A–USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG χ2(1) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region. PMID:11060213

Genetic heterogeneity of Usher syndrome: analysis of 151 families with Usher type I.

PubMed

Astuto, L M; Weston, M D; Carney, C A; Hoover, D M; Cremers, C W; Wagenaar, M; Moller, C; Smith, R J; Pieke-Dahl, S; Greenberg, J; Ramesar, R; Jacobson, S G; Ayuso, C; Heckenlively, J R; Tamayo, M; Gorin, M B; Reardon, W; Kimberling, W J

2000-12-01

Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.

Structural analysis of three space crane articulated-truss joint concepts

NASA Technical Reports Server (NTRS)

Wu, K. Chauncey; Sutter, Thomas R.

1992-01-01

Three space crane articulated truss joint concepts are studied to evaluate their static structural performance over a range of geometric design parameters. Emphasis is placed on maintaining the four longeron reference truss performance across the joint while allowing large angle articulation. A maximum positive articulation angle and the actuator length ratio required to reach the angle are computed for each concept as the design parameters are varied. Configurations with a maximum articulation angle less than 120 degrees or actuators requiring a length ratio over two are not considered. Tip rotation and lateral deflection of a truss beam with an articulated truss joint at the midspan are used to select a point design for each concept. Deflections for one point design are up to 40 percent higher than for the other two designs. Dynamic performance of the three point design is computed as a function of joint articulation angle. The two lowest frequencies of each point design are relatively insensitive to large variations in joint articulation angle. One point design has a higher maximum tip velocity for the emergency stop than the other designs.

Malaria surveys using rapid diagnostic tests and validation of results using post hoc quantification of Plasmodium falciparum histidine-rich protein 2.

PubMed

Plucinski, Mateusz; Dimbu, Rafael; Candrinho, Baltazar; Colborn, James; Badiane, Aida; Ndiaye, Daouda; Mace, Kimberly; Chang, Michelle; Lemoine, Jean F; Halsey, Eric S; Barnwell, John W; Udhayakumar, Venkatachalam; Aidoo, Michael; Rogier, Eric

2017-11-07

Rapid diagnostic test (RDT) positivity is supplanting microscopy as the standard measure of malaria burden at the population level. However, there is currently no standard for externally validating RDT results from field surveys. Individuals' blood concentration of the Plasmodium falciparum histidine rich protein 2 (HRP2) protein were compared to results of HRP2-detecting RDTs in participants from field surveys in Angola, Mozambique, Haiti, and Senegal. A logistic regression model was used to estimate the HRP2 concentrations corresponding to the 50 and 90% level of detection (LOD) specific for each survey. There was a sigmoidal dose-response relationship between HRP2 concentration and RDT positivity for all surveys. Variation was noted in estimates for field RDT sensitivity, with the 50% LOD ranging between 0.076 and 6.1 ng/mL and the 90% LOD ranging between 1.1 and 53 ng/mL. Surveys conducted in two different provinces of Angola using the same brand of RDT and same study methodology showed a threefold difference in LOD. Measures of malaria prevalence estimated using population RDT positivity should be interpreted in the context of potentially large variation in RDT LODs between, and even within, surveys. Surveys based on RDT positivity would benefit from external validation of field RDT results by comparing RDT positivity and antigen concentration.

Flavoring exposure in food manufacturing.

PubMed

Curwin, Brian D; Deddens, Jim A; McKernan, Lauralynn T

2015-05-01

Flavorings are substances that alter or enhance the taste of food. Workers in the food-manufacturing industry, where flavorings are added to many products, may be exposed to any number of flavoring compounds. Although thousands of flavoring substances are in use, little is known about most of these in terms of worker health effects, and few have occupational exposure guidelines. Exposure assessment surveys were conducted at nine food production facilities and one flavor manufacturer where a total of 105 area and 74 personal samples were collected for 13 flavoring compounds including five ketones, five aldehydes, and three acids. The majority of the samples were below the limit of detection (LOD) for most compounds. Diacetyl had eight area and four personal samples above the LOD, whereas 2,3-pentanedione had three area samples above the LOD. The detectable values ranged from 25-3124 ppb and 15-172 ppb for diacetyl and 2,3-pentanedione respectively. These values exceed the proposed National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for these compounds. The aldehydes had the most detectable samples, with each of them having >50% of the samples above the LOD. Acetaldehyde had all but two samples above the LOD, however, these samples were below the OSHA PEL. It appears that in the food-manufacturing facilities surveyed here, exposure to the ketones occurs infrequently, however levels above the proposed NIOSH REL were found. Conversely, aldehyde exposure appears to be ubiquitous.

Evidence suggesting possible SCA1 gene involvement in schizophrenia

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

Diehl, S.R.; Wange, S.; Sun, C.

Several findings suggest a possible role for the SCA1 gene on chromosome 6p in some cases of schizophrenia. First, linkage analyses in Irish pedigrees provided LOD scores up to 3.0 for one model tested using microsatellites closely linked to SCA1. Reanalysis of these data using affected sibpair methods yielded a significant result (p = 0.01) for one marker. An attempt to replicate this linkage finding was made using 44 NIMH families (206 individuals, 80 affected) and 12 Utah families (120 individuals, 49 affected). LOD scores were negative in these new families, even allowing for heterogeneity, as were results using affectedmore » sibpair methods. However, one Utah family provided a LOD score of 1.3. We also screened the SCA1 trinucleotide repeat to search for expansions characteristic of this disorder in these families and in 38 additional unrelated schizophrenics. We found 1 schizophrenic with 41 repeats, which is substantially larger than the maximum size of 36 repeats observed in previous studies of several hundred controls. We are now assessing whether the distribution of SCA1 repeats differs significantly in schizophrenia versus controls. Recent reports suggest possible anticipation in schizophrenia (also characteristic of SCA1) and a few cases of psychiatric symptoms suggesting schizophrenia have been observed in the highly related disorder DRPLA (SCA2), which is also based on trinucleotide repeat expansion. These findings suggest that further investigations of this gene and chromosome region may be a priority.« less

Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications. PMID:22912817

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Determining the 95% limit of detection for waterborne pathogen analyses from primary concentration to qPCR.

PubMed

Stokdyk, Joel P; Firnstahl, Aaron D; Spencer, Susan K; Burch, Tucker R; Borchardt, Mark A

2016-06-01

The limit of detection (LOD) for qPCR-based analyses is not consistently defined or determined in studies on waterborne pathogens. Moreover, the LODs reported often reflect the qPCR assay alone rather than the entire sample process. Our objective was to develop an approach to determine the 95% LOD (lowest concentration at which 95% of positive samples are detected) for the entire process of waterborne pathogen detection. We began by spiking the lowest concentration that was consistently positive at the qPCR step (based on its standard curve) into each procedural step working backwards (i.e., extraction, secondary concentration, primary concentration), which established a concentration that was detectable following losses of the pathogen from processing. Using the fraction of positive replicates (n = 10) at this concentration, we selected and analyzed a second, and then third, concentration. If the fraction of positive replicates equaled 1 or 0 for two concentrations, we selected another. We calculated the LOD using probit analysis. To demonstrate our approach we determined the 95% LOD for Salmonella enterica serovar Typhimurium, adenovirus 41, and vaccine-derived poliovirus Sabin 3, which were 11, 12, and 6 genomic copies (gc) per reaction (rxn), respectively (equivalent to 1.3, 1.5, and 4.0 gc L(-1) assuming the 1500 L tap-water sample volume prescribed in EPA Method 1615). This approach limited the number of analyses required and was amenable to testing multiple genetic targets simultaneously (i.e., spiking a single sample with multiple microorganisms). An LOD determined this way can facilitate study design, guide the number of required technical replicates, aid method evaluation, and inform data interpretation. Published by Elsevier Ltd.

Determining the 95% limit of detection for waterborne pathogen analyses from primary concentration to qPCR

USGS Publications Warehouse

Stokdyk, Joel P.; Firnstahl, Aaron; Spencer, Susan K.; Burch, Tucker R; Borchardt, Mark A.

2016-01-01

The limit of detection (LOD) for qPCR-based analyses is not consistently defined or determined in studies on waterborne pathogens. Moreover, the LODs reported often reflect the qPCR assay alone rather than the entire sample process. Our objective was to develop an approach to determine the 95% LOD (lowest concentration at which 95% of positive samples are detected) for the entire process of waterborne pathogen detection. We began by spiking the lowest concentration that was consistently positive at the qPCR step (based on its standard curve) into each procedural step working backwards (i.e., extraction, secondary concentration, primary concentration), which established a concentration that was detectable following losses of the pathogen from processing. Using the fraction of positive replicates (n = 10) at this concentration, we selected and analyzed a second, and then third, concentration. If the fraction of positive replicates equaled 1 or 0 for two concentrations, we selected another. We calculated the LOD using probit analysis. To demonstrate our approach we determined the 95% LOD for Salmonella enterica serovar Typhimurium, adenovirus 41, and vaccine-derived poliovirus Sabin 3, which were 11, 12, and 6 genomic copies (gc) per reaction (rxn), respectively (equivalent to 1.3, 1.5, and 4.0 gc L−1 assuming the 1500 L tap-water sample volume prescribed in EPA Method 1615). This approach limited the number of analyses required and was amenable to testing multiple genetic targets simultaneously (i.e., spiking a single sample with multiple microorganisms). An LOD determined this way can facilitate study design, guide the number of required technical replicates, aid method evaluation, and inform data interpretation.

Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions

PubMed Central

Amin, Najaf; Hottenga, Jouke-Jan; Hansell, Narelle K; Janssens, A Cecile JW; de Moor, Marleen HM; Madden, Pamela AF; Zorkoltseva, Irina V; Penninx, Brenda W; Terracciano, Antonio; Uda, Manuela; Tanaka, Toshiko; Esko, Tonu; Realo, Anu; Ferrucci, Luigi; Luciano, Michelle; Davies, Gail; Metspalu, Andres; Abecasis, Goncalo R; Deary, Ian J; Raikkonen, Katri; Bierut, Laura J; Costa, Paul T; Saviouk, Viatcheslav; Zhu, Gu; Kirichenko, Anatoly V; Isaacs, Aaron; Aulchenko, Yurii S; Willemsen, Gonneke; Heath, Andrew C; Pergadia, Michele L; Medland, Sarah E; Axenovich, Tatiana I; de Geus, Eco; Montgomery, Grant W; Wright, Margaret J; Oostra, Ben A; Martin, Nicholas G; Boomsma, Dorret I; van Duijn, Cornelia M

2013-01-01

Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10−06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene. PMID:23211697

A phenotype-sensitizing Apoe-deficient genetic background reveals novel atherosclerosis predisposition loci in the mouse.

PubMed Central

Dansky, Hayes M; Shu, Pei; Donavan, M; Montagno, Jill; Nagle, Deborah L; Smutko, John S; Roy, Natalie; Whiteing, S; Barrios, Judith; McBride, T J; Smith, Jonathan D; Duyk, Geoffrey; Breslow, Jan L; Moore, Karen J

2002-01-01

Therapeutic intervention for atherosclerosis has predominantly concentrated on regulating cholesterol levels; however, these therapeutics are not efficacious for all patients, suggesting that other factors are involved. This study was initiated to identify mechanisms that regulate atherosclerosis predisposition in mice other than cholesterol level regulation. To do so we performed quantitative trait locus analysis using two inbred strains that each carry the atherosclerosis phenotype-sensitizing Apoe deficiency and that have been shown to have widely disparate predilection to atherosclerotic lesion formation. One highly significant locus on chromosome 10 (LOD = 7.8) accounted for 19% of the variance in lesion area independent of cholesterol. Two additional suggestive loci were identified on chromosomes 14 (LOD = 3.2) and 19 (LOD = 3.2), each accounting for 7-8% of the lesion variance. In all, five statistically significant and suggestive loci affecting lesion size but not lipoprotein levels were identified. Many of these were recapitulated in an independent confirmatory cross. In summary, two independently performed crosses between C57BL/6 and FVB/N Apoe-deficient mice have revealed several previously unreported atherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels. PMID:11973313

An LOD with improved breakdown voltage in full-frame CCD devices

NASA Astrophysics Data System (ADS)

Banghart, Edmund K.; Stevens, Eric G.; Doan, Hung Q.; Shepherd, John P.; Meisenzahl, Eric J.

2005-02-01

In full-frame image sensors, lateral overflow drain (LOD) structures are typically formed along the vertical CCD shift registers to provide a means for preventing charge blooming in the imager pixels. In a conventional LOD structure, the n-type LOD implant is made through the thin gate dielectric stack in the device active area and adjacent to the thick field oxidation that isolates the vertical CCD columns of the imager. In this paper, a novel LOD structure is described in which the n-type LOD impurities are placed directly under the field oxidation and are, therefore, electrically isolated from the gate electrodes. By reducing the electrical fields that cause breakdown at the silicon surface, this new structure permits a larger amount of n-type impurities to be implanted for the purpose of increasing the LOD conductivity. As a consequence of the improved conductance, the LOD width can be significantly reduced, enabling the design of higher resolution imaging arrays without sacrificing charge capacity in the pixels. Numerical simulations with MEDICI of the LOD leakage current are presented that identify the breakdown mechanism, while three-dimensional solutions to Poisson's equation are used to determine the charge capacity as a function of pixel dimension.

Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12.

PubMed

Pericak-Vance, M A; Bass, M P; Yamaoka, L H; Gaskell, P C; Scott, W K; Terwedow, H A; Menold, M M; Conneally, P M; Small, G W; Vance, J M; Saunders, A M; Roses, A D; Haines, J L

1997-10-15

Four genetic loci have been identified as contributing to Alzheimer disease (AD), including the amyloid precursor protein gene, the presenilin 1 gene, the presenilin 2 gene, and the apolipoprotein E gene, but do not account for all the genetic risk for AD. To identify additional genetic risk factors for late-onset AD. A complete genomic screen was performed (N=280 markers). Critical values for chromosomal regional follow-up were a P value of .05 or less for affected relative pair analysis or sibpair analysis, a parametric lod score of 1.0 or greater, or both. Regional follow-up included analysis of additional markers and a second data set. Clinic populations in the continental United States. From a series of multiplex families affected with late-onset (> or =60 years) AD ascertained during the last 14 years (National Insititute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria) and for which DNA has been obtained, a subset of 16 families (135 total family members, 52 of whom were patients with AD) was used for the genomic screen. A second subset of 38 families (216 total family members, 89 of whom were patients with AD) was used for the follow-up analysis. Linkage analysis results generated using both genetic model-dependent (lod score) and model-independent methods. Fifteen chromosomal regions warranted initial follow-up. Follow-up analyses revealed 4 regions of continued interest on chromosomes 4, 6, 12, and 20, with the strongest results observed forchromosome 12. Peak 2-point affecteds-only lod scores (n=54) were 1.3, 1.6, 2.7, and 2.2 and affected relative pairs P values (n=54) were .04, .03, .14, and .04 for D12S373, D12S1057, D12S1042, and D12S390, respectively. Sibpair analysis (n=54) resulted in maximum lod scores (MLSs) of 1.5, 2.6, 3.2, and 2.3 for these markers, with a peak multipoint MLS of 3.5. A priori stratification by APOE genotype identified 27 families that had at least 1 member with AD whose genotype did not contain an APOE*4 allele. Analysis of these 27 families resulted in MLSs of 1.0, 2.4, 3.7, and 3.3 and a peak multipoint MLS of 3.9. A complete genomic screen in families affected with late-onset AD identified 4 regions of interest after follow-up. Chromosome 12 gave the strongest and most consistent results with a peak multipoint MLS of 3.5, suggesting that this region contains a new susceptibility gene for AD. Additional analyses are necessary to identify the chromosome 12 susceptibility gene for AD and to follow up the regions of interest on chromosomes 4, 6, and 20.

Influence analysis in quantitative trait loci detection.

PubMed

Dou, Xiaoling; Kuriki, Satoshi; Maeno, Akiteru; Takada, Toyoyuki; Shiroishi, Toshihiko

2014-07-01

This paper presents systematic methods for the detection of influential individuals that affect the log odds (LOD) score curve. We derive general formulas of influence functions for profile likelihoods and introduce them into two standard quantitative trait locus detection methods-the interval mapping method and single marker analysis. Besides influence analysis on specific LOD scores, we also develop influence analysis methods on the shape of the LOD score curves. A simulation-based method is proposed to assess the significance of the influence of the individuals. These methods are shown useful in the influence analysis of a real dataset of an experimental population from an F2 mouse cross. By receiver operating characteristic analysis, we confirm that the proposed methods show better performance than existing diagnostics. © 2014 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.

PubMed

Li, Sisi; Xi, Quansheng; Zhang, Xiaoyu; Yu, Dong; Li, Lin; Jiang, Zhenyang; Chen, Qiuyun; Wang, Qing K; Traboulsi, Elias I

2018-06-01

We investigated an Amish family in which three siblings presented with an early-onset childhood retinal dystrophy inherited in an autosomal recessive fashion. Genome-wide linkage analysis identified significant linkage to marker D2S2216 on 2q11 with a two-point LOD score of 1.95 and a multi-point LOD score of 3.76. Whole exome sequencing was then performed for the three affected individuals and identified a homozygous nonsense mutation (c.C1813T, p.R605X) in the cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene located within the 2p14-2q14 Jalili syndrome locus. The initial assessment and collection of the family were performed before the clinical delineation of Jalili syndrome. Another assessment was made after the discovery of the responsible gene and the dental abnormalities characteristic of Jalili syndrome were retrospectively identified. The p.R605X mutation represents the first probable founder mutation of Jalili syndrome identified in the Amish community. The molecular mechanism underlying Jalili syndrome is unknown. Here we show that CNNM4 interacts with IQCB1, which causes Leber congenital amaurosis (LCA) when mutated. A truncated CNNM4 protein starting at R605 significantly increased the rate of apoptosis, and significantly increased the interaction between CNNM4 and IQCB1. Mutation p.R605X may cause Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of IQCB1 and apoptosis, or both. Our data, for the first time, functionally link Jalili syndrome gene CNNM4 to LCA gene IQCB1, providing important insights into the molecular pathogenic mechanism of retinal dystrophy in Jalili syndrome.

Two-point method uncertainty during control and measurement of cylindrical element diameters

NASA Astrophysics Data System (ADS)

Glukhov, V. I.; Shalay, V. V.; Radev, H.

2018-04-01

The topic of the article is devoted to the urgent problem of the reliability of technical products geometric specifications measurements. The purpose of the article is to improve the quality of parts linear sizes control by the two-point measurement method. The article task is to investigate methodical extended uncertainties in measuring cylindrical element linear sizes. The investigation method is a geometric modeling of the element surfaces shape and location deviations in a rectangular coordinate system. The studies were carried out for elements of various service use, taking into account their informativeness, corresponding to the kinematic pairs classes in theoretical mechanics and the number of constrained degrees of freedom in the datum element function. Cylindrical elements with informativity of 4, 2, 1 and θ (zero) were investigated. The uncertainties estimation of in two-point measurements was made by comparing the results of of linear dimensions measurements with the functional diameters maximum and minimum of the element material. Methodical uncertainty is formed when cylindrical elements with maximum informativeness have shape deviations of the cut and the curvature types. Methodical uncertainty is formed by measuring the element average size for all types of shape deviations. The two-point measurement method cannot take into account the location deviations of a dimensional element, so its use for elements with informativeness less than the maximum creates unacceptable methodical uncertainties in measurements of the maximum, minimum and medium linear dimensions. Similar methodical uncertainties also exist in the arbitration control of the linear dimensions of the cylindrical elements by limiting two-point gauges.

Speciated mercury at marine, coastal, and inland sites in New England - Part 1: Temporal variability

NASA Astrophysics Data System (ADS)

Mao, H.; Talbot, R.

2011-12-01

A comprehensive analysis was conducted using long-term continuous measurements of gaseous elemental mercury (Hgo), reactive mercury (RGM), and particulate phase mercury (HgP) at coastal (Thompson Farm, denoted as TF), marine (Appledore Island, denoted as AI), and elevated inland (Pac Monadnock, denoted as PM) sites from the AIRMAP Observatories. Decreasing trends in background Hgo were identified in the 7- and 5-yr records at TF and PM with decline rates of 3.3 parts per quadrillion by volume (ppqv) yr-1 and 6.3 ppqv yr-1, respectively. Common characteristics at these sites were the reproducible annual cycle of Hgo with its maximum in winter-spring and minimum in fall as well as a decline/increase trend in the warm/cool season. The coastal site TF differed from the other two sites with its exceptionally low levels (as low as below 50 ppqv) in the nocturnal inversion layer probably due to dissolution in dew water. Year-to-year variability was observed in the warm season decline in Hgo at TF varying from a minimum total seasonal loss of 20 ppqv in 2010 to a maximum of 92 ppqv in 2005, whereas variability remained small at AI and PM. Measurements of Hgo at PM, an elevated inland rural site, exhibited the smallest diurnal to annual variability among the three environments, where peak levels rarely exceeded 250 ppqv and the minimum was typically 100 ppqv. It should be noted that summertime diurnal patterns at TF and AI are opposite in phase indicating strong sink(s) for Hgo during the day in the marine boundary layer, which is consistent with the hypothesis of Hgo oxidation by halogen radicals there. Mixing ratios of RGM in the coastal and marine boundary layers reached annual maximum in spring and minimum in fall, whereas at PM levels were generally below the limit of detection (LOD) except in spring. RGM levels at AI were higher than at TF and PM indicating a stronger source strength(s) in the marine environment. Mixing ratios of HgP at AI and TF were close in magnitude to RGM levels and were mostly below 1 ppqv. Diurnal variation in HgP was barely discernible at TF and AI in spring and summer with higher levels during the day and smaller but above the LOD at night.

Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease

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

Hugot, J.P.; Laurent-Puig, P.; Gower-Rousseau, C.

1994-08-15

Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lodmore » score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than -2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. 37 refs., 2 figs., 2 tabs.« less

CA-LOD: Collision Avoidance Level of Detail for Scalable, Controllable Crowds

NASA Astrophysics Data System (ADS)

Paris, Sébastien; Gerdelan, Anton; O'Sullivan, Carol

The new wave of computer-driven entertainment technology throws audiences and game players into massive virtual worlds where entire cities are rendered in real time. Computer animated characters run through inner-city streets teeming with pedestrians, all fully rendered with 3D graphics, animations, particle effects and linked to 3D sound effects to produce more realistic and immersive computer-hosted entertainment experiences than ever before. Computing all of this detail at once is enormously computationally expensive, and game designers as a rule, have sacrificed the behavioural realism in favour of better graphics. In this paper we propose a new Collision Avoidance Level of Detail (CA-LOD) algorithm that allows games to support huge crowds in real time with the appearance of more intelligent behaviour. We propose two collision avoidance models used for two different CA-LODs: a fuzzy steering focusing on the performances, and a geometric steering to obtain the best realism. Mixing these approaches allows to obtain thousands of autonomous characters in real time, resulting in a scalable but still controllable crowd.

Animation Strategies for Smooth Transformations Between Discrete Lods of 3d Building Models

NASA Astrophysics Data System (ADS)

Kada, Martin; Wichmann, Andreas; Filippovska, Yevgeniya; Hermes, Tobias

2016-06-01

The cartographic 3D visualization of urban areas has experienced tremendous progress over the last years. An increasing number of applications operate interactively in real-time and thus require advanced techniques to improve the quality and time response of dynamic scenes. The main focus of this article concentrates on the discussion of strategies for smooth transformation between two discrete levels of detail (LOD) of 3D building models that are represented as restricted triangle meshes. Because the operation order determines the geometrical and topological properties of the transformation process as well as its visual perception by a human viewer, three different strategies are proposed and subsequently analyzed. The simplest one orders transformation operations by the length of the edges to be collapsed, while the other two strategies introduce a general transformation direction in the form of a moving plane. This plane either pushes the nodes that need to be removed, e.g. during the transformation of a detailed LOD model to a coarser one, towards the main building body, or triggers the edge collapse operations used as transformation paths for the cartographic generalization.

Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia

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

Shaikh, S.; Gill, M.; Collier, D.A.

1994-03-15

We report the results of a linkage study in 24 families multiply affected with schizophrenia using a polymorphic DNA sequence encoding the third cytoplasmic loop of the dopamine D4 receptor. Two-point LOD score analyses with a range of single gene models ranging from near dominant to near recessive revealed no evidence for linkage. In addition, we examined the data by non-parametric sib-pair analysis and found no excess sharing of alleles between affected sib-pairs. We therefore conclude that mutations within the dopamine D4 receptor gene do not have a major aetiological role in schizophrenia in our collection of pedigrees. 20 refs.,more » 2 tabs.« less

Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing

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

Georges, M.; Nielsen, D.; Mackinnon, M.

1995-02-01

We have exploited {open_quotes}progeny testing{close_quotes} to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of >150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score {ge} 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20.more » These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding. 44 refs., 4 figs., 3 tabs.« less

Physical and genetic mapping of the dipeptidase gene DPEP1 to 16q24. 3

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

Austruy, E.; Jeanpierre, C.; Junien, C.

1993-03-01

The authors report the subregional physical and genetic mapping on chromosome 16q of a cDNA clone selected as a potential tumor/growth suppressor sequence. By DNA sequencing and RNA expression pattern, this clone was identified as part of the renal dipeptidase gene (DPEP1). Using somatic cell hybrids carrying either different human chromosomes or chromosome 16 segments, they confirm and refine the physical mapping of DPEP1 to the chromosome 16 subregion q24.3. Two RFLPs, a biallelic polymorphism detected by TaqI and a VNTR detected by BamHI, EcoRI, and BglII, are described. Using the VNTR polymorphism, DPEP1 was shown to be linked tomore » D16S7 with a maximum lod score of 5.8 at a recombination fraction of 0.03. 14 refs., 2 figs., 2 tabs.« less

Combined metformin and clomiphene citrate versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Abu Hashim, Hatem; El Lakany, Naser; Sherief, Lotfy

2011-03-01

To compare the effect of combined metformin and clomiphene citrate (CC) with laparoscopic ovarian diathermy (LOD) meant for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS). Two-hundred and eighty-two anovulatory women with CC-resistant PCOS were selected in this randomized controlled trial. Patients (n = 138) received combined metformin-CC for up to six cycles or underwent LOD (n = 144) with six months follow up. The outcome measures were: ovulation rate, midcycle endometrial thickness, pregnancy and miscarriage rates. Ovulation occurred in 386/576 cycles (67%) in the combined metformin-CC group and 381/558 cycles (68.2%) in LOD group without a significant difference between the groups. Resumption of regular menstruation was similar in both groups. A significant increase in midcycle endometrial thickness was observed in the combined metformin-CC group (9.2 ± 1.2 mm vs 7.6 ± 1.1 mm) (P < 0.05). The pregnancy rate was similar in both groups (15.4% vs 17%), and there were no statistically significant differences regarding the miscarriage rate between both groups. Four twin pregnancies occurred in the metformin-CC group. No ovarian hyperstimulation occurred in either group. Combined metformin-CC and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Flavoring exposure in food manufacturing

PubMed Central

Curwin, Brian D.; Deddens, Jim A.; McKernan, Lauralynn T.

2015-01-01

Flavorings are substances that alter or enhance the taste of food. Workers in the food-manufacturing industry, where flavorings are added to many products, may be exposed to any number of flavoring compounds. Although thousands of flavoring substances are in use, little is known about most of these in terms of worker health effects, and few have occupational exposure guidelines. Exposure assessment surveys were conducted at nine food production facilities and one flavor manufacturer where a total of 105 area and 74 personal samples were collected for 13 flavoring compounds including five ketones, five aldehydes, and three acids. The majority of the samples were below the limit of detection (LOD) for most compounds. Diacetyl had eight area and four personal samples above the LOD, whereas 2,3-pentanedione had three area samples above the LOD. The detectable values ranged from 25–3124 ppb and 15–172 ppb for diacetyl and 2,3-pentanedione respectively. These values exceed the proposed National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for these compounds. The aldehydes had the most detectable samples, with each of them having >50% of the samples above the LOD. Acetaldehyde had all but two samples above the LOD, however, these samples were below the OSHA PEL. It appears that in the food-manufacturing facilities surveyed here, exposure to the ketones occurs infrequently, however levels above the proposed NIOSH REL were found. Conversely, aldehyde exposure appears to be ubiquitous. PMID:25052692

Multilocus lod scores in large pedigrees: combination of exact and approximate calculations.

PubMed

Tong, Liping; Thompson, Elizabeth

2008-01-01

To detect the positions of disease loci, lod scores are calculated at multiple chromosomal positions given trait and marker data on members of pedigrees. Exact lod score calculations are often impossible when the size of the pedigree and the number of markers are both large. In this case, a Markov Chain Monte Carlo (MCMC) approach provides an approximation. However, to provide accurate results, mixing performance is always a key issue in these MCMC methods. In this paper, we propose two methods to improve MCMC sampling and hence obtain more accurate lod score estimates in shorter computation time. The first improvement generalizes the block-Gibbs meiosis (M) sampler to multiple meiosis (MM) sampler in which multiple meioses are updated jointly, across all loci. The second one divides the computations on a large pedigree into several parts by conditioning on the haplotypes of some 'key' individuals. We perform exact calculations for the descendant parts where more data are often available, and combine this information with sampling of the hidden variables in the ancestral parts. Our approaches are expected to be most useful for data on a large pedigree with a lot of missing data. (c) 2007 S. Karger AG, Basel

Multilocus Lod Scores in Large Pedigrees: Combination of Exact and Approximate Calculations

PubMed Central

Tong, Liping; Thompson, Elizabeth

2007-01-01

To detect the positions of disease loci, lod scores are calculated at multiple chromosomal positions given trait and marker data on members of pedigrees. Exact lod score calculations are often impossible when the size of the pedigree and the number of markers are both large. In this case, a Markov Chain Monte Carlo (MCMC) approach provides an approximation. However, to provide accurate results, mixing performance is always a key issue in these MCMC methods. In this paper, we propose two methods to improve MCMC sampling and hence obtain more accurate lod score estimates in shorter computation time. The first improvement generalizes the block-Gibbs meiosis (M) sampler to multiple meiosis (MM) sampler in which multiple meioses are updated jointly, across all loci. The second one divides the computations on a large pedigree into several parts by conditioning on the haplotypes of some ‘key’ individuals. We perform exact calculations for the descendant parts where more data are often available, and combine this information with sampling of the hidden variables in the ancestral parts. Our approaches are expected to be most useful for data on a large pedigree with a lot of missing data. PMID:17934317

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

PubMed Central

2012-01-01

Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region. PMID:22712434

A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

PubMed Central

Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

2016-01-01

We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

Autosomal recessive mutilating sensory neuropathy with spastic paraplegia maps to chromosome 5p15.31-14.1.

PubMed

Bouhouche, Ahmed; Benomar, Ali; Bouslam, Naima; Ouazzani, Reda; Chkili, Taïeb; Yahyaoui, Mohamed

2006-02-01

Autosomal recessive ulcero-mutilating neuropathy with spastic paraplegia is a very rare disease since only few cases were described up to date. We report in this study a consanguineous Moroccan family with four affected males with this syndrome. The disease onset was in early infancy, with spastic paraplegia and sensory loss leading to mutilating acropathy. Electrophysiological studies revealed a severe axonal sensory neuropathy, magnetic resonance imaging ruled out compression of spinal cord and biological investigations showed decreased levels of Apo B, total cholesterol and triglycerides. A genomewide search was conducted in this family and linkage was found to chromosome 5p. Analysis of recombination events and LOD score calculation map the responsible gene in a 25 cM genetic interval between markers D5S2054 and D5S648. A maximum LOD score value of 3.92 was obtained for all markers located in this candidate interval. This study establishes the presence of a locus for autosomal recessive mutilating sensory neuropathy with spastic paraplegia on chromosome 5p15.31-14.1.

The research of selection model based on LOD in multi-scale display of electronic map

NASA Astrophysics Data System (ADS)

Zhang, Jinming; You, Xiong; Liu, Yingzhen

2008-10-01

This paper proposes a selection model based on LOD to aid the display of electronic map. The ratio of display scale to map scale is regarded as a LOD operator. The categorization rule, classification rule, elementary rule and spatial geometry character rule of LOD operator setting are also concluded.

Maximum power point tracking algorithm based on sliding mode and fuzzy logic for photovoltaic sources under variable environmental conditions

NASA Astrophysics Data System (ADS)

Atik, L.; Petit, P.; Sawicki, J. P.; Ternifi, Z. T.; Bachir, G.; Della, M.; Aillerie, M.

2017-02-01

Solar panels have a nonlinear voltage-current characteristic, with a distinct maximum power point (MPP), which depends on the environmental factors, such as temperature and irradiation. In order to continuously harvest maximum power from the solar panels, they have to operate at their MPP despite the inevitable changes in the environment. Various methods for maximum power point tracking (MPPT) were developed and finally implemented in solar power electronic controllers to increase the efficiency in the electricity production originate from renewables. In this paper we compare using Matlab tools Simulink, two different MPP tracking methods, which are, fuzzy logic control (FL) and sliding mode control (SMC), considering their efficiency in solar energy production.

Terrain modeling for real-time simulation

NASA Astrophysics Data System (ADS)

Devarajan, Venkat; McArthur, Donald E.

1993-10-01

There are many applications, such as pilot training, mission rehearsal, and hardware-in-the- loop simulation, which require the generation of realistic images of terrain and man-made objects in real-time. One approach to meeting this requirement is to drape photo-texture over a planar polygon model of the terrain. The real time system then computes, for each pixel of the output image, the address in a texture map based on the intersection of the line-of-sight vector with the terrain model. High quality image generation requires that the terrain be modeled with a fine mesh of polygons while hardware costs limit the number of polygons which may be displayed for each scene. The trade-off between these conflicting requirements must be made in real-time because it depends on the changing position and orientation of the pilot's eye point or simulated sensor. The traditional approach is to develop a data base consisting of multiple levels of detail (LOD), and then selecting for display LODs as a function of range. This approach could lead to both anomalies in the displayed scene and inefficient use of resources. An approach has been developed in which the terrain is modeled with a set of nested polygons and organized as a tree with each node corresponding to a polygon. This tree is pruned to select the optimum set of nodes for each eye-point position. As the point of view moves, the visibility of some nodes drops below the limit of perception and may be deleted while new points must be added in regions near the eye point. An analytical model has been developed to determine the number of polygons required for display. This model leads to quantitative performance measures of the triangulation algorithm which is useful for optimizing system performance with a limited display capability.

Bulk-modified modified screen-printing carbon electrodes with both lactate oxidase (LOD) and horseradish peroxide (HRP) for the determination of L-lactate in flow injection analysis mode.

PubMed

Ghamouss, Fouad; Ledru, Sophie; Ruillé, Nadine; Lantier, Françoise; Boujtita, Mohammed

2006-06-16

A screen-printed carbon electrode modified with both HRP and LOD (SPCE-HRP/LOD) has been developed for the determination of L-lactate concentration in real samples. The resulting SPCE-HRP/LOD was prepared in a one-step procedure, and was then optimised as an amperometric biosensor operating at [0, -100]mV versus Ag/AgCl for L-lactate determination in flow injection mode. A significant improvement in the reproducibility (coefficient variation of about 10%) of the preparation of the biosensors was obtained when graphite powder was modified with LOD in the presence of HRP previously oxidised by periodate ion (IO4-). Optimisation studies were performed by examining the effects of LOD loading, periodation step and rate of the binder on analytical performances of SPCE-HRP/LOD. The sensitivity of the optimised SPCE-HRP/LOD to L-lactate was 0.84 nAL micromol(-1) in a detection range between 10 and 180 microMol. The possibility of using the developed biosensor to determine L-lactate concentrations in various dairy products was also evaluated.

Lods, wrods, and mods: the interpretation of lod scores calculated under different models.

PubMed

Hodge, S E; Elston, R C

1994-01-01

In this paper we examine the relationships among classical lod scores, "wrod" scores (lod scores calculated under the wrong genetic model), and "mod" scores (lod scores maximized over genetic model parameters). We compare the behavior of these scores when the state of nature is linkage to their behavior when the state of nature is no linkage. We describe sufficient conditions for mod scores to be valid and discuss their use to determine the correct genetic model. We show that lod scores represent a likelihood-ratio test for independence. We explain the "ascertainment-assumption-free" aspect of using mod scores to determine mode of inheritance and we set this aspect into a well-established statistical framework. Finally, we summarize practical guidelines for the use of mod scores.

Flow injection analysis of organic peroxide explosives using acid degradation and chemiluminescent detection of released hydrogen peroxide.

PubMed

Mahbub, Parvez; Zakaria, Philip; Guijt, Rosanne; Macka, Mirek; Dicinoski, Greg; Breadmore, Michael; Nesterenko, Pavel N

2015-10-01

The applicability of acid degradation of organic peroxides into hydrogen peroxide in a pneumatically driven flow injection system with chemiluminescence reaction with luminol and Cu(2+) as a catalyst (FIA-CL) was investigated for the fast and sensitive detection of organic peroxide explosives (OPEs). The target OPEs included hexamethylene triperoxide diamine (HMTD), triacetone triperoxide (TATP) and methylethyl ketone peroxide (MEKP). Under optimised conditions maximum degradations of 70% and 54% for TATP and HMTD, respectively were achieved at 162 µL min(-1), and 9% degradation for MEKP at 180 µL min(-1). Flow rates were precisely controlled in this single source pneumatic pressure driven multi-channel FIA system by model experiments on mixing of easily detectable component solutions. The linear range for detection of TATP, HMTD and H2O2 was 1-200 µM (r(2)=0.98-0.99) at both flow rates, while that for MEKP was 20-200 µM (r(2)=0.97) at 180 µL min(-1). The detection limits (LODs) obtained were 0.5 µM for TATP, HMTD and H2O2 and 10 µM for MEKP. The detection times varied from 1.5 to 3 min in this FIA-CL system. Whilst the LOD for H2O2 was comparable with those reported by other investigators, the LODs and analysis times for TATP and HMTD were superior, and significantly, this is the first time the detection of MEKP has been reported by FIA-CL. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits

PubMed Central

Hinckley, Jesse D; Abbott, Diana; Burns, Trudy L; Heiman, Meadow; Shapiro, Amy D; Wang, Kai; Di Paola, Jorge

2013-01-01

We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. PMID:24058921

Pesticide extraction from table grapes and plums using ionic liquid based dispersive liquid-liquid microextraction.

PubMed

Ravelo-Pérez, Lidia M; Hernández-Borges, Javier; Herrera-Herrera, Antonio V; Rodríguez-Delgado, Miguel Angel

2009-12-01

Room temperature ionic liquids (RTILs) have been used as extraction solvents in dispersive liquid-liquid microextraction (DLLME) for the determination of eight multi-class pesticides (i.e. thiophanate-methyl, carbofuran, carbaryl, tebuconazole, iprodione, oxyfluorfen, hexythiazox, and fenazaquin) in table grapes and plums. The developed method involves the combination of DLLME and high-performance liquid chromatography with diode array detection. Samples were first homogenized and extracted with acetonitrile. After evaporation and reconstitution of the extract in water containing sodium chloride, a quick DLLME procedure that used the ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate ([C(6)MIM][PF(6)]) and methanol was developed. The RTIL dissolved in a very small volume of acetonitrile was directed injected in the chromatographic system. The comparison between the calibration curves obtained from standards and from spiked sample extracts (matrix-matched calibration) showed the existence of a strong matrix effect for most of the analyzed pesticides. A recovery study was also developed with five consecutive extractions of the two types of fruits spiked at three concentration levels. Mean recovery values were in the range of 72-100% for table grapes and 66-105% for plum samples (except for thiophanate-methyl and carbofuran, which were 64-75% and 58-66%, respectively). Limits of detection (LODs) were in the range 0.651-5.44 microg/kg for table grapes and 0.902-6.33 microg/kg for plums, representing LODs below the maximum residue limits (MRLs) established by the European Union in these fruits. The potential of the method was demonstrated by analyzing 12 commercial fruit samples (six of each type).

Positive and negative electrospray LC-MS-MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk.

PubMed

Durden, David A

2007-05-01

Avermectin endectocides are used for the treatment of cattle against a variety of nematode and arthropod parasites, and consequently may appear in milk after normal or off-label use. The compounds abamectin, doramectin, and ivermectin, contain only C, H and O and may be expected to be detected by LC-MS in negative ion mode. The others contain nitrogen in addition and would be expected to be preferentially ionized in positive mode. The use of positive ion and negative ion methods with electrospray LC-MS-MS were compared. Using negative ion the compounds abamectin, doramectin, ivermectin, emamectin, eprinomectin, and moxidectin gave a curvilinear response and were quantified in raw milk by LC-MS-MS with a triethylamine-acetonitrile buffer over the concentration range 1-60 ppb (microg/kg) using selamectin as the internal standard. The limits of detection (LOD) were between 0.19 ppb (doramectin) and 0.38 ppb (emamectin). The compounds gave maximum sensitivity with positive ionisation from a formic acid-ammonium formate-acetonitrile buffer and were detected in milk (LC-MS-MS) also with a curvilinear response over the range 0.5-60 ppb. Although the positive ion signals were larger, with somewhat lower limits of detection (LOD between 0.06 ppb (doramectin) and 0.32 ppb (moxidectin) the negative ion procedure gave a more linear response and more consistent results. Comparison of spiked samples in the range 2-50 ppb showed a high degree of correlation between the two methods.

Distribution in microbial genomes of genes similar to lodA and goxA which encode a novel family of quinoproteins with amino acid oxidase activity.

PubMed

Campillo-Brocal, Jonatan C; Chacón-Verdú, María Dolores; Lucas-Elío, Patricia; Sánchez-Amat, Antonio

2015-03-24

L-Amino acid oxidases (LAOs) have been generally described as flavoproteins that oxidize amino acids releasing the corresponding ketoacid, ammonium and hydrogen peroxide. The generation of hydrogen peroxide gives to these enzymes antimicrobial characteristics. They are involved in processes such as biofilm development and microbial competition. LAOs are of great biotechnological interest in different applications such as the design of biosensors, biotransformations and biomedicine. The marine bacterium Marinomonas mediterranea synthesizes LodA, the first known LAO that contains a quinone cofactor. LodA is encoded in an operon that contains a second gene coding for LodB, a protein required for the post-translational modification generating the cofactor. Recently, GoxA, a quinoprotein with sequence similarity to LodA but with a different enzymatic activity (glycine oxidase instead of lysine-ε-oxidase) has been described. The aim of this work has been to study the distribution of genes similar to lodA and/or goxA in sequenced microbial genomes and to get insight into the evolution of this novel family of proteins through phylogenetic analysis. Genes encoding LodA-like proteins have been detected in several bacterial classes. However, they are absent in Archaea and detected only in a small group of fungi of the class Agaromycetes. The vast majority of the genes detected are in a genome region with a nearby lodB-like gene suggesting a specific interaction between both partner proteins. Sequence alignment of the LodA-like proteins allowed the detection of several conserved residues. All of them showed a Cys and a Trp that aligned with the residues that are forming part of the cysteine tryptophilquinone (CTQ) cofactor in LodA. Phylogenetic analysis revealed that LodA-like proteins can be clustered in different groups. Interestingly, LodA and GoxA are in different groups, indicating that those groups are related to the enzymatic activity of the proteins detected. Genome mining has revealed for the first time the broad distribution of LodA-like proteins containing a CTQ cofactor in many different microbial groups. This study provides a platform to explore the potentially novel enzymatic activities of the proteins detected, the mechanisms of post-translational modifications involved in their synthesis, as well as their biological relevance.

A search for outflows from X-ray bright points in coronal holes

NASA Technical Reports Server (NTRS)

Mullan, D. J.; Waldron, W. L.

1986-01-01

Properties of X-ray bright points using two of the instruments on Solar Maximum Mission were investigated. The mass outflows from magnetic regions were modeled using a two dimensional MHD code. It was concluded that mass can be detected from X-ray bright points provided that the magnetic topology is favorable.

The optimum spanning catenary cable

NASA Astrophysics Data System (ADS)

Wang, C. Y.

2015-03-01

A heavy cable spans two points in space. There exists an optimum cable length such that the maximum tension is minimized. If the two end points are at the same level, the optimum length is 1.258 times the distance between the ends. The optimum lengths for end points of different heights are also found.

Prediction of UT1-UTC, LOD and AAM χ3 by combination of least-squares and multivariate stochastic methods

NASA Astrophysics Data System (ADS)

Niedzielski, Tomasz; Kosek, Wiesław

2008-02-01

This article presents the application of a multivariate prediction technique for predicting universal time (UT1-UTC), length of day (LOD) and the axial component of atmospheric angular momentum (AAM χ 3). The multivariate predictions of LOD and UT1-UTC are generated by means of the combination of (1) least-squares (LS) extrapolation of models for annual, semiannual, 18.6-year, 9.3-year oscillations and for the linear trend, and (2) multivariate autoregressive (MAR) stochastic prediction of LS residuals (LS + MAR). The MAR technique enables the use of the AAM χ 3 time-series as the explanatory variable for the computation of LOD or UT1-UTC predictions. In order to evaluate the performance of this approach, two other prediction schemes are also applied: (1) LS extrapolation, (2) combination of LS extrapolation and univariate autoregressive (AR) prediction of LS residuals (LS + AR). The multivariate predictions of AAM χ 3 data, however, are computed as a combination of the extrapolation of the LS model for annual and semiannual oscillations and the LS + MAR. The AAM χ 3 predictions are also compared with LS extrapolation and LS + AR prediction. It is shown that the predictions of LOD and UT1-UTC based on LS + MAR taking into account the axial component of AAM are more accurate than the predictions of LOD and UT1-UTC based on LS extrapolation or on LS + AR. In particular, the UT1-UTC predictions based on LS + MAR during El Niño/La Niña events exhibit considerably smaller prediction errors than those calculated by means of LS or LS + AR. The AAM χ 3 time-series is predicted using LS + MAR with higher accuracy than applying LS extrapolation itself in the case of medium-term predictions (up to 100 days in the future). However, the predictions of AAM χ 3 reveal the best accuracy for LS + AR.

Are LOD and LOQ Reliable Parameters for Sensitivity Evaluation of Spectroscopic Methods?

PubMed

Ershadi, Saba; Shayanfar, Ali

2018-03-22

The limit of detection (LOD) and the limit of quantification (LOQ) are common parameters to assess the sensitivity of analytical methods. In this study, the LOD and LOQ of previously reported terbium sensitized analysis methods were calculated by different methods, and the results were compared with sensitivity parameters [lower limit of quantification (LLOQ)] of U.S. Food and Drug Administration guidelines. The details of the calibration curve and standard deviation of blank samples of three different terbium-sensitized luminescence methods for the quantification of mycophenolic acid, enrofloxacin, and silibinin were used for the calculation of LOD and LOQ. A comparison of LOD and LOQ values calculated by various methods and LLOQ shows a considerable difference. The significant difference of the calculated LOD and LOQ with various methods and LLOQ should be considered in the sensitivity evaluation of spectroscopic methods.

Targeted Analyte Detection by Standard Addition Improves Detection Limits in MALDI Mass Spectrometry

PubMed Central

Eshghi, Shadi Toghi; Li, Xingde; Zhang, Hui

2014-01-01

Matrix-assisted laser desorption/ionization has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications. PMID:22877355

Targeted analyte detection by standard addition improves detection limits in matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Toghi Eshghi, Shadi; Li, Xingde; Zhang, Hui

2012-09-18

Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications.

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-07-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region.

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed Central

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-01-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region. PMID:1971992

Variants in Nebulin (NEB) Are Linked to the Development of Familial Primary Angle Closure Glaucoma in Basset Hounds

PubMed Central

Ahram, Dina F.; Grozdanic, Sinisa D.; Kecova, Helga; Henkes, Arjen; Collin, Rob W. J.; Kuehn, Markus H.

2015-01-01

Several dog breeds are susceptible to developing primary angle closure glaucoma (PACG), which suggests a genetic basis for the disease. We have identified a four-generation Basset Hound pedigree with characteristic autosomal recessive PACG that closely recapitulates PACG in humans. Our aim is to utilize gene mapping and whole exome sequencing approaches to identify PACG-causing sequence variants in the Basset. Extensive clinical phenotyping of all pedigree members was conducted. SNP-chip genotyping was carried out in 9 affected and 15 unaffected pedigree members. Two-point and multipoint linkage analyses of genome-wide SNP data were performed using Superlink-Online SNP-1.1 and a locus was mapped to chromosome 19q with a maximum LOD score of 3.24. The locus contains 12 Ensemble predicted canine genes and is syntenic to a region on chromosome 2 in the human genome. Using exome-sequencing analysis, a possibly damaging, non-synonymous variant in the gene Nebulin (NEB) was found to segregate with PACG which alters a phylogenetically conserved Lysine residue. The association of this variants with PACG was confirmed in a secondary cohort of unrelated Basset Hounds (p = 3.4 × 10-4, OR = 15.3 for homozygosity). Nebulin, a protein that promotes the contractile function of sarcomeres, was found to be prominently expressed in the ciliary muscles of the anterior segment. Our findings may provide insight into the molecular mechanisms that underlie PACG. The phenotypic similarities of disease presentation in dogs and humans may enable the translation of findings made in this study to patients with PACG. PMID:25938837

Variants in Nebulin (NEB) Are Linked to the Development of Familial Primary Angle Closure Glaucoma in Basset Hounds.

PubMed

Ahram, Dina F; Grozdanic, Sinisa D; Kecova, Helga; Henkes, Arjen; Collin, Rob W J; Kuehn, Markus H

2015-01-01

Several dog breeds are susceptible to developing primary angle closure glaucoma (PACG), which suggests a genetic basis for the disease. We have identified a four-generation Basset Hound pedigree with characteristic autosomal recessive PACG that closely recapitulates PACG in humans. Our aim is to utilize gene mapping and whole exome sequencing approaches to identify PACG-causing sequence variants in the Basset. Extensive clinical phenotyping of all pedigree members was conducted. SNP-chip genotyping was carried out in 9 affected and 15 unaffected pedigree members. Two-point and multipoint linkage analyses of genome-wide SNP data were performed using Superlink-Online SNP-1.1 and a locus was mapped to chromosome 19q with a maximum LOD score of 3.24. The locus contains 12 Ensemble predicted canine genes and is syntenic to a region on chromosome 2 in the human genome. Using exome-sequencing analysis, a possibly damaging, non-synonymous variant in the gene Nebulin (NEB) was found to segregate with PACG which alters a phylogenetically conserved Lysine residue. The association of this variants with PACG was confirmed in a secondary cohort of unrelated Basset Hounds (p = 3.4 × 10-4, OR = 15.3 for homozygosity). Nebulin, a protein that promotes the contractile function of sarcomeres, was found to be prominently expressed in the ciliary muscles of the anterior segment. Our findings may provide insight into the molecular mechanisms that underlie PACG. The phenotypic similarities of disease presentation in dogs and humans may enable the translation of findings made in this study to patients with PACG.

Linkage analysis of chromosome 22q12-13 in a United Kingdom/Icelandic sample of 23 multiplex schizophrenia families

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

Kalsi, G.; Read, T.; Butler, R.

A possible linkage to a genetic subtype of schizophrenia and related disorders has been reported on the long arm of chromosome 22 at q12-13. However formal statistical tests in a combined sample could not reject homogeneity and prove that there was linked subgroup of families. We have studied 23 schizophrenia pedigrees to test whether some multiplex schizophrenia families may be linked to the microsatellite markers D22S274 and D22S283 which span the 22q12-13 region. Two point followed by multipoint lod and non-parametric linkage analyses under the assumption of heterogeneity provided no evidence for linkage over the relevant region. 16 refs., 4more » tabs.« less

Detection of the significant geomagnetic field signals in the interannual variations of Length-of-Day using wavelet method

NASA Astrophysics Data System (ADS)

Liu, Genyou; Duan, Pengshuo; Hao, Xiaoguang; Hu, Xiaogang

2015-04-01

The previous studies indicated that the most of the interannual variations in Length-Of-Day (LOD) could be explained by the joint effects of ENSO (EI Nino-Southern Oscillations) and QBO (Quasi-Biennial Oscillation) phenomenon in the atmosphere. Due to the limit of the used methods, those results cannot give the 'time-frequency' coherence spectrum between ENSO and LOD, and cannot indicate in which specific periods the weak coherence occurred and difficult to give the reliable reason. This paper uses Daubechies wavelet with 10 order vanishing moment to analyze the LOD monthly time series from 1962 to 2011. Based on cross-wavelet and wavelet coherence methods, the analysis of the time-frequency correlations between ENSO and LOD series (1962-2011) on the 1.3~10.7 year scales is given. We have extracted and reconstructed the LOD signals on 1.3~10.7year scales. The result shows that there is obvious weak coherence on both biennial and 5~8 year scales after 1982 relative to before 1982. According to the previous works, the biennial weak coherence is due to QBO, but the weak coherence on 5~8 year scales cannot be interpreted by the effects of ENSO and QBO. In this study, the Geomagnetic field signals (can be characterized as Aa index) are introduced, we have further extracted and reconstructed the LOD, ENSO and Aa signals in 5-8.0 year band using wavelet packet analysis. Through analyzing the standardized series of the three signals, we found a linear time-frequency formula among the original observation series: LOD(t,f) =αENSO(t,f) +βAa(t,f). This study indicates that the LOD signals on 5.3~8.0 year scales can be expressed in term of linear combination of ENSO and Aa signals. Especially after 1982, the contributions of ENSO and Aa to LOD respectively reach about 0.95ms and 1.0ms.The results also imply that there is an obvious Geomagnetic field signal in interannual variations of LOD. Furthermore, after considering the geomagnetic field signal correction, the Pearson correlation coefficient between LOD and ENSO will increase from 0.51 to 0.98. Consequently, we can conclude that the weak coherence after 1982 on 5.3-8.0 year scales between LOD and ENSO is mainly due to the disturbance of Aa signal, and the observed LOD series is the result of the interaction between ENSO and geomagnetic field signals.

Methods for utilizing maximum power from a solar array

NASA Technical Reports Server (NTRS)

Decker, D. K.

1972-01-01

A preliminary study of maximum power utilization methods was performed for an outer planet spacecraft using an ion thruster propulsion system and a solar array as the primary energy source. The problems which arise from operating the array at or near the maximum power point of its 1-V characteristic are discussed. Two closed loop system configurations which use extremum regulators to track the array's maximum power point are presented. Three open loop systems are presented that either: (1) measure the maximum power of each array section and compute the total array power, (2) utilize a reference array to predict the characteristics of the solar array, or (3) utilize impedance measurements to predict the maximum power utilization. The advantages and disadvantages of each system are discussed and recommendations for further development are made.

Intermediate boundary conditions for LOD, ADI and approximate factorization methods

NASA Technical Reports Server (NTRS)

Leveque, R. J.

1985-01-01

A general approach to determining the correct intermediate boundary conditions for dimensional splitting methods is presented. The intermediate solution U is viewed as a second order accurate approximation to a modified equation. Deriving the modified equation and using the relationship between this equation and the original equation allows us to determine the correct boundary conditions for U*. This technique is illustrated by applying it to locally one dimensional (LOD) and alternating direction implicit (ADI) methods for the heat equation in two and three space dimensions. The approximate factorization method is considered in slightly more generality.

An Application to the Prediction of LOD Change Based on General Regression Neural Network

NASA Astrophysics Data System (ADS)

Zhang, X. H.; Wang, Q. J.; Zhu, J. J.; Zhang, H.

2011-07-01

Traditional prediction of the LOD (length of day) change was based on linear models, such as the least square model and the autoregressive technique, etc. Due to the complex non-linear features of the LOD variation, the performances of the linear model predictors are not fully satisfactory. This paper applies a non-linear neural network - general regression neural network (GRNN) model to forecast the LOD change, and the results are analyzed and compared with those obtained with the back propagation neural network and other models. The comparison shows that the performance of the GRNN model in the prediction of the LOD change is efficient and feasible.

Cloud point extraction-flame atomic absorption spectrometry for pre-concentration and determination of trace amounts of silver ions in water samples.

PubMed

Yang, Xiupei; Jia, Zhihui; Yang, Xiaocui; Li, Gu; Liao, Xiangjun

2017-03-01

A cloud point extraction (CPE) method was used as a pre-concentration strategy prior to the determination of trace levels of silver in water by flame atomic absorption spectrometry (FAAS) The pre-concentration is based on the clouding phenomena of non-ionic surfactant, triton X-114, with Ag (I)/diethyldithiocarbamate (DDTC) complexes in which the latter is soluble in a micellar phase composed by the former. When the temperature increases above its cloud point, the Ag (I)/DDTC complexes are extracted into the surfactant-rich phase. The factors affecting the extraction efficiency including pH of the aqueous solution, concentration of the DDTC, amount of the surfactant, incubation temperature and time were investigated and optimized. Under the optimal experimental conditions, no interference was observed for the determination of 100 ng·mL -1 Ag + in the presence of various cations below their maximum concentrations allowed in this method, for instance, 50 μg·mL -1 for both Zn 2+ and Cu 2+ , 80 μg·mL -1 for Pb 2+ , 1000 μg·mL -1 for Mn 2+ , and 100 μg·mL -1 for both Cd 2+ and Ni 2+ . The calibration curve was linear in the range of 1-500 ng·mL -1 with a limit of detection (LOD) at 0.3 ng·mL -1 . The developed method was successfully applied for the determination of trace levels of silver in water samples such as river water and tap water.

LOD estimation from DORIS observations

NASA Astrophysics Data System (ADS)

Stepanek, Petr; Filler, Vratislav; Buday, Michal; Hugentobler, Urs

2016-04-01

The difference between astronomically determined duration of the day and 86400 seconds is called length of day (LOD). The LOD could be also understood as the daily rate of the difference between the Universal Time UT1, based on the Earth rotation, and the International Atomic Time TAI. The LOD is estimated using various Satellite Geodesy techniques as GNSS and SLR, while absolute UT1-TAI difference is precisely determined by VLBI. Contrary to other IERS techniques, the LOD estimation using DORIS (Doppler Orbitography and Radiopositioning Integrated by satellite) measurement did not achieve a geodetic accuracy in the past, reaching the precision at the level of several ms per day. However, recent experiments performed by IDS (International DORIS Service) analysis centre at Geodetic Observatory Pecny show a possibility to reach accuracy around 0.1 ms per day, when not adjusting the cross-track harmonics in the Satellite orbit model. The paper presents the long term LOD series determined from the DORIS solutions. The series are compared with C04 as the reference. Results are discussed in the context of accuracy achieved with GNSS and SLR. Besides the multi-satellite DORIS solutions, also the LOD series from the individual DORIS satellite solutions are analysed.

Comparison of sensitivity to artificial spectral errors and multivariate LOD in NIR spectroscopy - Determining the performance of miniaturizations on melamine in milk powder.

PubMed

Henn, Raphael; Kirchler, Christian G; Grossgut, Maria-Elisabeth; Huck, Christian W

2017-05-01

This study compared three commercially available spectrometers - whereas two of them were miniaturized - in terms of prediction ability of melamine in milk powder (infant formula). Therefore all spectra were split into calibration- and validation-set using Kennard Stone and Duplex algorithm in comparison. For each instrument the three best performing PLSR models were constructed using SNV and Savitzky Golay derivatives. The best RMSEP values were 0.28g/100g, 0.33g/100g and 0.27g/100g for the NIRFlex N-500, the microPHAZIR and the microNIR2200 respectively. Furthermore the multivariate LOD interval [LOD min , LOD max ] was calculated for all the PLSR models unveiling significant differences among the spectrometers showing values of 0.20g/100g - 0.27g/100g, 0.28g/100g - 0.54g/100g and 0.44g/100g - 1.01g/100g for the NIRFlex N-500, the microPHAZIR and the microNIR2200 respectively. To assess the robustness of all models, artificial introduction of white noise, baseline shift, multiplicative effect, spectral shrink and stretch, stray light and spectral shift were applied. Monitoring the RMSEP as function of the perturbation gave indication of robustness of the models and helped to compare the performances of the spectrometers. Not taking the additional information from the LOD calculations into account one could falsely assume that all the spectrometers perform equally well which is not the case when the multivariate evaluation and robustness data were considered. Copyright © 2017 Elsevier B.V. All rights reserved.

LC-MS/MS determination of antiretroviral drugs in influents and effluents from wastewater treatment plants in KwaZulu-Natal, South Africa.

PubMed

Abafe, Ovokeroye A; Späth, Jana; Fick, Jerker; Jansson, Stina; Buckley, Chris; Stark, Annegret; Pietruschka, Bjoern; Martincigh, Bice S

2018-06-01

South Africa has the largest occurrence of the human immune deficiency virus (HIV) in the world but has also implemented the largest antiretroviral (ARV) treatment programme. It was therefore of interest to determine the presence and concentrations of commonly used antiretroviral drugs (ARVDs) and, also, to determine the capabilities of wastewater treatment plants (WWTPs) for removing ARVDs. To this end, a surrogate standard based LC-MS/MS method was optimized and applied for the detection of thirteen ARVDs used in the treatment and management of HIV/acquired immune deficiency syndrome (HIV/AIDS) in two major and one modular WWTP in the eThekwini Municipality in KwaZulu-Natal, South Africa. The method was validated and the detection limits fell within the range of 2-20 ng L -1 . The analytical recoveries for the ARVDs were mainly greater than 50% with acceptable relative standard deviations. The concentration values ranged from

Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE family study.

PubMed

Spielmann, Nadine; Leon, Arthur S; Rao, D C; Rice, Treva; Skinner, James S; Rankinen, Tuomo; Bouchard, Claude

2007-12-01

The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.

Sex-specific quantitative trait loci contribute to normal variation in bone structure at the proximal femur in men

PubMed Central

Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael J.

2006-01-01

Bone structure is an important determinant of osteoporotic fracture. In women bone structure is highly heritable and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed at establishing the heritability of bone structure at the proximal femur, identifying QTL contributing to normal variation in bone structure, and determining which QTL might be sex-specific. Bone structure at the proximal femur was measured in 205 pairs of brothers age 18–61. Heritability was calculated and linkage analysis performed on phenotypes at the proximal femur. Heritability estimates ranged from 0.99 to 0.39. A genome wide scan identified suggestive QTL (LOD>2.2) for femoral shaft width on chromosome 14q (LOD=2.69 at position 99cM), calcar femorale at chromosome 2p (LOD= 3.97 at position 194cM) and at the X chromosome (LOD= 3.01 at position 77cM), femoral neck width on chromosome 5p (LOD=2.28 at position 0 cM), femoral head width on chromosome 11q (LOD=2.30 at position 131 cM) and 15q (LOD=3.11 at position 90 cM), and pelvic axis length on chromosome 4q (LOD= 4.16 at 99cM) and 17q (LOD=2.80 at position 112 cM). Comparison with published data in 437 pairs of premenopausal sisters from the same geographical region suggested that 3 of the 7 autosomal QTL were male-specific. This study demonstrates that bone structure at the proximal femur in healthy men is highly heritable. The occurrence of sex-specific genes in humans for bone structure has important implications for the pathogenesis and treatment of osteoporosis. PMID:16046210

LODVIEW: a computer program for the graphical evaluation of lod score results in exclusion mapping of human disease genes.

PubMed

Hildebrandt, F; Pohlmann, A; Omran, H

1993-12-01

For linkage analysis projects aimed at mapping hereditary disease genes in humans, hundreds of highly polymorphic microsatellite markers which can be typed by PCR (PCR markers) have become available. With this technical improvement, the availability of a technique allowing for transparency in the handling of rapidly generated lod score data is becoming important. We present a computer program LODVIEW for the graphical representation of lod score data. It is designed for the input of lod score data generated with the LINKAGE package or similar programs. LODVIEW consists of 24 preformatted files, one for each chromosome. Each file contains a table for the input of lod score data and a file for the graphical representation of the data, which will show automatically any entry that is made in the respective input table. The program provides the user with published PCR marker information pre-entered into a table and graph at the correct positions corresponding to the genetic distances between markers. The graphical display of LODVIEW allows for the rapid evaluation of lod score results calculated from PCR markers on each chromosome. The following information can be obtained from the graphical display at one glance: (i) Regions of exclusion (Z(theta) < -2) and nonexclusion, (ii) markers with positive lod scores, (iii) the distribution of positive and negative lod scores among the families examined (indication of genetic heterogeneity), (iv) multipoint lod scores, and (v) the availability of PCR markers in regions of interest. The program is continually updated for novel PCR marker information from the literature. The program will help to efficiently monitor and direct the progress of exclusion mapping projects.

Systematic effects in LOD from SLR observations

NASA Astrophysics Data System (ADS)

Bloßfeld, Mathis; Gerstl, Michael; Hugentobler, Urs; Angermann, Detlef; Müller, Horst

2014-09-01

Beside the estimation of station coordinates and the Earth’s gravity field, laser ranging observations to near-Earth satellites can be used to determine the rotation of the Earth. One parameter of this rotation is ΔLOD (excess Length Of Day) which describes the excess revolution time of the Earth w.r.t. 86,400 s. Due to correlations among the different parameter groups, it is difficult to obtain reliable estimates for all parameters. In the official ΔLOD products of the International Earth Rotation and Reference Systems Service (IERS), the ΔLOD information determined from laser ranging observations is excluded from the processing. In this paper, we study the existing correlations between ΔLOD, the orbital node Ω, the even zonal gravity field coefficients, cross-track empirical accelerations and relativistic accelerations caused by the Lense-Thirring and deSitter effect in detail using first order Gaussian perturbation equations. We found discrepancies due to different a priories by using different gravity field models of up to 1.0 ms for polar orbits at an altitude of 500 km and up to 40.0 ms, if the gravity field coefficients are estimated using only observations to LAGEOS 1. If observations to LAGEOS 2 are included, reliable ΔLOD estimates can be achieved. Nevertheless, an impact of the a priori gravity field even on the multi-satellite ΔLOD estimates can be clearly identified. Furthermore, we investigate the effect of empirical cross-track accelerations and the effect of relativistic accelerations of near-Earth satellites on ΔLOD. A total effect of 0.0088 ms is caused by not modeled Lense-Thirring and deSitter terms. The partial derivatives of these accelerations w.r.t. the position and velocity of the satellite cause very small variations (0.1 μs) on ΔLOD.

Statins Reduces the Risk of Dementia in Patients with Late-Onset Depression: A Retrospective Cohort Study.

PubMed

Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng

2015-01-01

Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.

Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

PubMed

Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

1998-07-01

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.

Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

PubMed Central

Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

1998-01-01

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

Application of General Regression Neural Network to the Prediction of LOD Change

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Hong; Wang, Qi-Jie; Zhu, Jian-Jun; Zhang, Hao

2012-01-01

Traditional methods for predicting the change in length of day (LOD change) are mainly based on some linear models, such as the least square model and autoregression model, etc. However, the LOD change comprises complicated non-linear factors and the prediction effect of the linear models is always not so ideal. Thus, a kind of non-linear neural network — general regression neural network (GRNN) model is tried to make the prediction of the LOD change and the result is compared with the predicted results obtained by taking advantage of the BP (back propagation) neural network model and other models. The comparison result shows that the application of the GRNN to the prediction of the LOD change is highly effective and feasible.

Modeling, control, and simulation of grid connected intelligent hybrid battery/photovoltaic system using new hybrid fuzzy-neural method.

PubMed

Rezvani, Alireza; Khalili, Abbas; Mazareie, Alireza; Gandomkar, Majid

2016-07-01

Nowadays, photovoltaic (PV) generation is growing increasingly fast as a renewable energy source. Nevertheless, the drawback of the PV system is its dependence on weather conditions. Therefore, battery energy storage (BES) can be considered to assist for a stable and reliable output from PV generation system for loads and improve the dynamic performance of the whole generation system in grid connected mode. In this paper, a novel topology of intelligent hybrid generation systems with PV and BES in a DC-coupled structure is presented. Each photovoltaic cell has a specific point named maximum power point on its operational curve (i.e. current-voltage or power-voltage curve) in which it can generate maximum power. Irradiance and temperature changes affect these operational curves. Therefore, the nonlinear characteristic of maximum power point to environment has caused to development of different maximum power point tracking techniques. In order to capture the maximum power point (MPP), a hybrid fuzzy-neural maximum power point tracking (MPPT) method is applied in the PV system. Obtained results represent the effectiveness and superiority of the proposed method, and the average tracking efficiency of the hybrid fuzzy-neural is incremented by approximately two percentage points in comparison to the conventional methods. It has the advantages of robustness, fast response and good performance. A detailed mathematical model and a control approach of a three-phase grid-connected intelligent hybrid system have been proposed using Matlab/Simulink. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

NASA Astrophysics Data System (ADS)

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-07-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50-100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

PubMed Central

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-01-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50–100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering. PMID:27380889

Genome-wide Linkage and Positional Association Study of Blood Pressure Response to Dietary Sodium Intervention

PubMed Central

Mei, Hao; Gu, Dongfeng; Hixson, James E.; Rice, Treva K.; Chen, Jing; Shimmin, Lawrence C.; Schwander, Karen; Kelly, Tanika N.; Liu, De-Pei; Chen, Shufeng; Huang, Jian-feng; Jaquish, Cashell E.; Rao, Dabeeru C.; He, Jiang

2012-01-01

The authors conducted a genome-wide linkage scan and positional association analysis to identify the genetic determinants of salt sensitivity of blood pressure (BP) in a large family-based, dietary-feeding study. The dietary intervention was conducted among 1,906 participants in rural China (2003–2005). A 7-day low-sodium intervention was followed by a 7-day high-sodium intervention. Salt sensitivity was defined as BP responses to low- and high-sodium interventions. Signals of the logarithm of the odds to the base 10 (LOD ≥ 3) were detected at 33–42 centimorgans of chromosome 2 (2p24.3-2p24.1), with a maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium intervention. LOD scores were 2.35–2.91 for mean arterial pressure (MAP) and 0.80–1.49 for systolic blood pressure responses in this region, respectively. Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786 (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene (FAM84A)) in the linkage region was significantly associated with diastolic blood pressure (P = 0.0007) and MAP responses (P = 0.0007), and SNP rs16983422 (2.8 kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated with diastolic blood pressure (P = 0.005) and MAP responses (P = 0.005). An additive interaction between SNPs rs11674786 and rs16983422 was observed, with P = 7.00 × 10−5 and P = 7.23 × 10−5 for diastolic blood pressure and MAP responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1 might harbor functional variants for the salt sensitivity of BP. PMID:22865701

Mapping Genes that Contribute to Daunorubicin-Induced Cytotoxicity

PubMed Central

Duan, Shiwei; Bleibel, Wasim K.; Huang, Rong Stephanie; Shukla, Sunita J.; Wu, Xiaolin; Badner, Judith A.; Dolan, M. Eileen

2009-01-01

Daunorubicin is an anthracycline antibiotic agent used in the treatment of hematopoietic malignancies. Toxicities associated with this agent include myelosuppression and cardiotoxicity; however, the genes or genetic determinants that contribute to these toxicities are unknown. We present an unbiased genome-wide approach that incorporates heritability, whole-genome linkage analysis, and linkage-directed association to uncover genetic variants contributing to the sensitivity to daunorubicin-induced cytotoxicity. Cell growth inhibition in 324 Centre d’ Etude du Polymorphisme Humain lymphoblastoid cell lines (24 pedigrees) was evaluated following treatment with daunorubicin for 72 h. Heritability analysis showed a significant genetic component contributing to the cytotoxic phenotypes (h2 = 0.18–0.63at 0.0125, 0.025, 0.05, 0.1, 0.2, and 1.0 µmol/L daunorubicin and at the IC50, the dose required to inhibit 50% cell growth). Whole-genome linkage scans at all drug concentrations and IC50 uncovered 11 regions with moderate peak LOD scores (>1.5), including 4q28.2 to 4q32.3 with a maximum LOD score of 3.18. The quantitative transmission disequilibrium tests were done using 31,312 high-frequency single-nucleotide polymorphisms (SNP) located in the 1 LOD confidence interval of these 11 regions. Thirty genes were identified as significantly associated with daunorubicin-induced cytotoxicity (P ≤ 2.0 × 10−4, false discovery rate ≤ 0.1). Pathway and functional gene ontology analysis showed that these genes were overrepresented in the phosphatidylinositol signaling system, axon guidance pathway, and GPI-anchored proteins family. Our findings suggest that a proportion of susceptibility to daunorubicin-induced cytotoxicity may be controlled by genetic determinants and that analysis using linkage-directed association studies with dense SNP markers can be used to identify the genetic variants contributing to cytotoxicity. PMID:17545624

Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: a pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy.

PubMed

Giampaolino, Pierluigi; Morra, Ilaria; Della Corte, Luigi; Sparice, Stefania; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2017-01-01

Aim of the study was to asses and compare serum anti-Mullerian harmone (AMH) levels after laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL) ovarian drilling in clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients; secondary outcome was to evaluate postoperative pain to estimate the acceptability of procedures. A total of 246 patients with CC-resistant PCOS were randomized into two groups: 123 underwent LOD and 123 underwent THL ovarian drilling. AMH serum levels were evaluated before and after the procedure; moreover, women were asked to rate pain on a visual analog scale (VAS) from 0 (no pain, perfectly acceptable) to 10 (unbearable pain, completely unacceptable). In both groups, postoperative serum AMH levels were significantly reduced compared to preoperative levels (6.06 ± 1.18 and 5.84 ± 1.16 versus 5.00 ± 1.29 and 4.83 ± 1.10; p < 0.0001). Comparing postoperative serum AMH levels, no statistically significant difference was observed between the two surgical technique. After the procedure, mean pain VAS score was significantly higher for women who underwent LOD ovarian drilling in comparison to THL (3.26 ± 1.1 versus 1.11 ± 0.5; p < 0.0001). In conclusion, THL ovarian drilling is comparable to the LOD in terms of reduction in AMH, but it is preferred by patients in terms of acceptability. These results could support to use of THL ovarian drilling in the treatment of patients with CC- resistant PCOS.

Quantification of type I error probabilities for heterogeneity LOD scores.

PubMed

Abreu, Paula C; Hodge, Susan E; Greenberg, David A

2002-02-01

Locus heterogeneity is a major confounding factor in linkage analysis. When no prior knowledge of linkage exists, and one aims to detect linkage and heterogeneity simultaneously, classical distribution theory of log-likelihood ratios does not hold. Despite some theoretical work on this problem, no generally accepted practical guidelines exist. Nor has anyone rigorously examined the combined effect of testing for linkage and heterogeneity and simultaneously maximizing over two genetic models (dominant, recessive). The effect of linkage phase represents another uninvestigated issue. Using computer simulation, we investigated type I error (P value) of the "admixture" heterogeneity LOD (HLOD) score, i.e., the LOD score maximized over both recombination fraction theta and admixture parameter alpha and we compared this with the P values when one maximizes only with respect to theta (i.e., the standard LOD score). We generated datasets of phase-known and -unknown nuclear families, sizes k = 2, 4, and 6 children, under fully penetrant autosomal dominant inheritance. We analyzed these datasets (1) assuming a single genetic model, and maximizing the HLOD over theta and alpha; and (2) maximizing the HLOD additionally over two dominance models (dominant vs. recessive), then subtracting a 0.3 correction. For both (1) and (2), P values increased with family size k; rose less for phase-unknown families than for phase-known ones, with the former approaching the latter as k increased; and did not exceed the one-sided mixture distribution xi = (1/2) chi1(2) + (1/2) chi2(2). Thus, maximizing the HLOD over theta and alpha appears to add considerably less than an additional degree of freedom to the associated chi1(2) distribution. We conclude with practical guidelines for linkage investigators. Copyright 2002 Wiley-Liss, Inc.

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

PubMed

Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

2003-12-31

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

Mapping quantitative trait loci for fear-like behaviors in mice.

PubMed

Gershenfeld, H K; Paul, S M

1997-11-15

Two mouse models developed for screening anxiolytic drugs were selected for genetic analysis, namely "wall-seeking" tendency in an open field ("thigmotaxis") and the light-to-dark transition (LD) paradigm, a conflict test. These tests measure differences in naturalistic tendencies of mice to explore a novel environment and to avoid a bright light or the center of an open field. In an F2 intercross of two strains of mice (A/J and C57BL/6J) that differ markedly in these behaviors, we estimated a broad sense heritability ranging from 0.3 to 0.59. With this intercross (n = 518), we have mapped several quantitative trait loci (QTL) for these behaviors by performing a genome-wide search. A significant QTL on chromosome 10 (near D10Mit237; LOD of 9.3) that affects LD behavior was identified, and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6, 15, 19, and X. For center time behaviors, QTL were identified on chromosome 1 (LOD of 7.7 and 4.0 for the initial 5-min epoch and the first trial average of the next two 5-min epochs, respectively), and suggestive QTL (LOD > 2.8) were mapped to chromosomes 6 and 14. These QTL individually explain from 2.3 to 8.4% of the phenotypic variance. Collectively, the multiple independent QTL explain from 3.5 to 26.5% of the F2 population's phenotypic variance, depending on the trait. The complexity and heterogeneity of the genetic factors underlying these fear-like behaviors are illustrated by the lack of shared QTL between paradigms and by mapping different QTL for repeated trials of behavior. The identification of QTL affecting individual differences in fear-like behavior may lead to the identification of new gene products and pathways that modulate behavior, providing targets for rational drug design.

Laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome.

PubMed

Flyckt, Rebecca L; Goldberg, Jeffrey M

2011-03-01

Laparoscopic ovarian drilling (LOD) is an alternative to ovulation induction with gonadotropins for polycystic ovarian syndrome (PCOS) patients unresponsive to clomiphene. It is quick and easy to perform, although the number of punctures and energy doses has not been standardized. The mechanism of LOD is unclear, but it is likely mediated by a reduction in intraovarian androgen production. Serum luteinizing hormone and testosterone levels are rapidly normalized, and these changes are sustained over long-term follow-up. Studies have shown that ovulation and pregnancy rates are comparable between ovulation induction with gonadotropins and LOD, but LOD avoids the risks of multiple pregnancy and ovarian hyperstimulation syndrome. LOD is also more cost effective and better tolerated than gonadotropin therapy. Concerns regarding clinically significant adhesion formation and premature ovarian failure are not supported by the available data. Transvaginal hydrolaparoscopy and ultrasound guidance are less invasive techniques for performing ovarian drilling and may encourage LOD earlier in the course of treatment for PCOS. © Thieme Medical Publishers.

Measurement of methionine level with the LC-ESI-MS/MS method in schizophrenic patients.

PubMed

Kulaksizoglu, S; Kulaksizoglu, B; Ellidag, H Y; Eren, E; Yilmaz, N; Baykal, A

2016-01-01

The purpose of this study was to evaluate plasma methionine levels by using liquid chromatography electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS) in schizophrenic patients. A twelve-point standard graph was drawn, and the recovery rate, the intra-day and inter-day coefficients of variation (CV), the limit of detection (LOD), and the limit of quantification (LOQ) were evaluated. The y and R2 values of the standard graph equation were determined as 0.011x + 0.0179 and 0.9989, respectively, and the graph remained linear until the 200 µmol/l level. The intra-day coefficients of variation of the samples (n = 10) containing 8, 28, and 58 µmol/l methionine were determined as 2.68, 3.10, and 3.79%, respectively; while their inter-day coefficients of variation were determined as 2.98, 3.19, and 3.84%. The LOD and LOQ values were determined as 0.04 and 0.1 µmol/l, respectively, while the mean recovery rates were determined as 101.7 and 99.3%. Plasma methionine values were measured as 21.5 (19.5-24,6) µmol/l for the patient group, 17.8 (16.3-20.1) µmol/l for the control group, and the difference between the two groups was statistically significant (p = 0.03). LC-ESI-MS/MS method represents a fairly sensitive, economic, and rapid analysis that requires very little sample and is suitable for measuring methionine levels in schizophrenic patients.

78 FR 35001 - Applications for New Awards; Charter Schools Program (CSP) Grants to Non-State Educational Agency...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... applications (NIA) announces competitions for two different grants: (1) Planning, Program Design, and Initial... on how well the application meets Competitive Preference Priority 1, up to an additional two points... respond to one, two, or three of the priority areas but, in order to receive the maximum available points...

UV filters analyzed by isotope diluted TurboFlow-LC-MS/MS in urine from Danish children and adolescents.

PubMed

Frederiksen, Hanne; Nielsen, Ole; Skakkebaek, Niels E; Juul, Anders; Andersson, Anna-Maria

2017-03-01

Experimental studies indicate that some chemicals with UV blocking properties (known as UV filters) can act as endocrine disruptors. UV filters are used in sunscreens and other cosmetic- and personal care products, as well as in other consumer products such as food packaging, clothing and furniture textiles to protect the products against UV radiation. Here we present the urinary excretion of suspected endocrine active UV filters in Danish children and adolescents recruited from the general population. The content of benzophenone (BP), benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), 5-chloro-2- hydroxybenzophenone (BP-7), 4-hydroxybenzophenone (4-HBP), 4-methyl-benzophenone (4-MBP), 3-(4- methylbenzylidene)-camphor (4-MBC) and 3-benzylidene camphor (3-BC) were monitored in 24h urine and two consecutive first morning samples from 129 healthy Danish children and adolescents (6-21 yrs). All 387 samples were collected during the autumn (Nov. 2007) and were analyzed by a new on-line TurboFlow-LC-MS/MS method developed for simultaneous biomonitoring of these nine UV filters in urine. BP-3 and BP-1 were detected in more than 80% of the 24h samples and were significantly correlated (R 2 =0.815). BP, 4-HBP and BP-2 were found in 43, 15 and 5% of the samples, respectively. The median (range) concentrations of the UV-filters in 24-h urine were as follows: BP-3, 0.92 (LOD-115); BP-1, 0.54 (LOD-44.6); BP,

Post-operative ovarian adhesion formation after ovarian drilling: a randomized study comparing conventional laparoscopy and transvaginal hydrolaparoscopy.

PubMed

Giampaolino, Pierluigi; Morra, Ilaria; Tommaselli, Giovanni Antonio; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2016-10-01

To compare conventional laparoscopic ovarian drilling (LOD) with transvaginal hydrolaparoscopy (THL) ovarian drilling in terms of ovarian adhesion formation, evaluated using office THL during follow-up in CC-resistant anovulatory patients affected by PCOS. Prospective randomized study on 246 CC-resistant women with PCOS. The patients enrolled were divided into two groups, 123 were scheduled to undergo LOD and 123 to undergo THL ovarian drilling. Six months after the procedure all patients were offered office transvaginal hydrolaparoscopy (THL) follow-up, under local anesthesia to evaluate adhesion formation. Duration of the procedure was significantly shorter in the THL group in comparison with LOD group (p < 0.0001). No intra- or post-operative complication was observed in any of the patients in both groups. Post-operative THL follow-up after 6 months showed that 15 (15.5 %) patients in the THL group and 73 (70.2 %) in the LOD group showed the presence of ovarian adhesion. This difference was highly significant with a p value <0.0001 and a relative risk of 0.22 [95 % IC 0.133-0.350]. This study seems to indicate that THL ovarian drilling may reduce the risk of ovarian adhesion formation and could be used as a safe and effective option to reduce ovarian adhesion formation in patients undergoing ovarian drilling.

High-frequency variations in Earth rotation and the planetary momentum budget

NASA Technical Reports Server (NTRS)

Rosen, Richard D.

1995-01-01

The major focus of the subject contract was on helping to resolve one of the more notable discrepancies still existing in the axial momentum budget of the solid Earth-atmosphere system, namely the disappearance of coherence between length-of-day (l.o.d.) and atmospheric angular momentum (AAM) at periods shorter than about a fortnight. Recognizing the importance of identifying the source of the high-frequency momentum budget anomaly, the scientific community organized two special measurement campaigns (SEARCH '92 and CONT '94) to obtain the best possible determinations of l.o.d. and AAM. An additional goal was to analyze newly developed estimates of the torques that transfer momentum between the atmosphere and its underlying surface to determine whether the ocean might be a reservoir of momentum on short time scales. Discrepancies between AAM and l.o.d. at sub-fortnightly periods have been attributed to either measurement errors in these quantities or the need to incorporate oceanic angular momentum into the planetary budget. Results from the SEARCH '92 and CONT '94 campaigns suggest that when special attention is paid to the quality of the measurements, better agreement between l.o.d. and AAM at high frequencies can be obtained. The mechanism most responsible for the high-frequency changes observed in AAM during these campaigns involves a direct coupling to the solid Earth, i.e, the mountain torque, thereby obviating a significant oceanic role.

Detecting adulterants in milk with lower cost mid-infrared and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Changwon; Wang, Wenbo; Wilson, Benjamin K.; Connett, Marie; Keller, Matthew D.

2018-02-01

Adulteration of milk for economic gains is a widespread issue throughout the developing world that can have far-reaching health and nutritional impacts. Milk analysis technologies, such as infrared spectroscopy, can screen for adulteration, but the cost of these technologies has prohibited their use in low resource settings. Recent developments in infrared and Raman spectroscopy hardware have led to commercially available low-cost devices. In this work, we evaluated the performance of two such spectrometers in detecting and quantifying the presence of milk adulterants. Five common adulterants - ammonium sulfate, melamine, sodium bicarbonate, sucrose, and urea, were spiked into five different raw cow and goat milk samples at different concentrations. Collected MIR and Raman spectra were analyzed using partial least squares regression. The limit of detection (LOD) for each adulterant was determined to be in the range of 0.04 to 0.28% (400 to 2800 ppm) using MIR spectroscopy. Raman spectroscopy showed similar LOD's for some of the adulterants, notably those with strong amine group signals, and slightly higher LOD's (up to 1.0%) for other molecules. Overall, the LODs were comparable to other spectroscopic milk analyzers on the market, and they were within the economically relevant concentration range of 100 to 4000 ppm. These lower cost spectroscopic devices therefore appear to hold promise for use in low resource settings.

Clinical and genetic linkage analysis of a large Venezuelan kindred with Usher syndrome.

PubMed

Keogh, Ivan J; Godinho, R N; Wu, T Po; Diaz de Palacios, A M; Palacios, N; Bello de Alford, M; De Almada, M I; MarPalacios, N; Vazquez, A; Mattei, R; Seidman, C; Seidman, J; Eavey, R D

2004-08-01

To undertake a comprehensive investigation into the very high incidence of congenital deafness on the Macano peninsula of Margarita Island, Venezuela. Numerous visits were made to the isolated island community over a 4-year-period. During these visits, it became apparent that a significant number of individuals complained of problems with hearing and vision. Socioeconomic assessments, family pedigrees and clinical histories were recorded on standard questionnaires. All individuals underwent thorough otolaryngologic and ophthalmologic examinations. Twenty milliliters of peripheral venous blood was obtained from each participant. A genome-wide linkage analysis study was performed. Polymorphic microsatellite markers were amplified by polymerase chain reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to separate fragments and LOD scores were calculated by using published software. Twenty-four families were identified, comprising 329 individuals, age range 1-80 years, including 184 children. All families were categorized in the lower two (least affluent) socioeconomic categories. A high incidence of consanguinity was detected. Fifteen individuals (11 adults, 4 children) had profound congenital sensorineural hearing loss, vestibular areflexia and retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are consistent with a diagnosis of Usher syndrome 1B for those with hearing and vision problems. We report 15 Usher syndrome 1B individuals from a newly detected Latin American socio-demographic origin, with a very high prevalence of 76 per 100,000 population.

Pseudoautosomal linkage of Hodgkin disease.

PubMed

Horwitz, M; Wiernik, P H

1999-11-01

Heritable factors appear to account for much of the risk for Hodgkin disease (HD). There is evidence for an HLA-linked gene, but other predisposing loci remain unaccounted for. The observation of a family coinheriting both HD and Leri-Weill dyschondrosteosis (LWD) suggests that a gene conferring risk for HD resides adjacent to the LWD locus. The gene responsible for LWD, SHOX, localizes to the short-arm pseudoautosomal region (PAR) of the X and Y chromosomes. A unique segregation pattern for PAR-linked genes has been predicted-that affected sibs will tend to be same sex. An excess of sex-concordant affected sib pairs with HD has been noted but has been attributed to an environmental etiology. These two observations-sex concordance in sib pairs with HD and cosegregation of HD and LWD-impelled a test of the hypothesis that there is a PAR-localized gene for HD. By first scoring recombinations dissociating sex from phenotype in individuals from pedigrees with LWD, we determined a male maximum recombination frequency (thetamax) of.405. This places SHOX near the short-arm telomeres of the sex chromosome and supports the prediction that PAR recombination is obligatory for spermatogenesis. By inferring recombinations between HD and sexual phenotype in sib pairs, we predict, for the postulated HD gene, a male thetamax as high as .254, which places it in proximity to SHOX. Morton's nonparametric affected-sib-pair "beta" model was used in the evaluation of linkage between HD and phenotypic sex and gave a LOD score of 2.41. Using this approach, we reevaluated evidence for HLA linkage in HD in haplotyped sib pairs and found a LOD score of 2.00. The resulting beta values indicate that the putative PAR- and HLA-linked loci account for 29% and 40%, respectively, of the heritability of HD in an American population.

Improving data quality in the linked open data: a survey

NASA Astrophysics Data System (ADS)

Hadhiatma, A.

2018-03-01

The Linked Open Data (LOD) is “web of data”, a different paradigm from “web of document” commonly used today. However, the huge LOD still suffers from data quality problems such as completeness, consistency, and accuracy. Data quality problems relate to designing effective methods both to manage and to retrieve information at various data quality levels. Based on review from papers and journals, addressing data quality requires some standards functioning to (1) identification of data quality problems, (2) assessment of data quality for a given context, and (3) correction of data quality problems. However, mostly the methods and strategies dealing with the LOD data quality were not as an integrative approach. Hence, based on those standards and an integrative approach, there are opportunities to improve the LOD data quality in the term of incompleteness, inaccuracy and inconsistency, considering to its schema and ontology, namely ontology refinement. Moreover, the term of the ontology refinement means that it copes not only to improve data quality but also to enrich the LOD. Therefore, it needs (1) a standard for data quality assessment and evaluation which is more appropriate to the LOD; (2) a framework of methods based on statistical relational learning that can improve the correction of data quality problems as well as enrich the LOD.

Temperature initiated passive cooling system

DOEpatents

Forsberg, Charles W.

1994-01-01

A passive cooling system for cooling an enclosure only when the enclosure temperature exceeds a maximum standby temperature comprises a passive heat transfer loop containing heat transfer fluid having a particular thermodynamic critical point temperature just above the maximum standby temperature. An upper portion of the heat transfer loop is insulated to prevent two phase operation below the maximum standby temperature.

Hardware Implementation of Maximum Power Point Tracking for Thermoelectric Generators

NASA Astrophysics Data System (ADS)

Maganga, Othman; Phillip, Navneesh; Burnham, Keith J.; Montecucco, Andrea; Siviter, Jonathan; Knox, Andrew; Simpson, Kevin

2014-06-01

This work describes the practical implementation of two maximum power point tracking (MPPT) algorithms, namely those of perturb and observe, and extremum seeking control. The proprietary dSPACE system is used to perform hardware in the loop (HIL) simulation whereby the two control algorithms are implemented using the MATLAB/Simulink (Mathworks, Natick, MA) software environment in order to control a synchronous buck-boost converter connected to two commercial thermoelectric modules. The process of performing HIL simulation using dSPACE is discussed, and a comparison between experimental and simulated results is highlighted. The experimental results demonstrate the validity of the two MPPT algorithms, and in conclusion the benefits and limitations of real-time implementation of MPPT controllers using dSPACE are discussed.

The New Xpert MTB/RIF Ultra: Improving Detection of Mycobacterium tuberculosis and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing

PubMed Central

Simmons, Ann Marie; Rowneki, Mazhgan; Parmar, Heta; Cao, Yuan; Ryan, Jamie; Banada, Padmapriya P.; Deshpande, Srinidhi; Shenai, Shubhada; Gall, Alexander; Glass, Jennifer; Krieswirth, Barry; Schumacher, Samuel G.; Nabeta, Pamela; Tukvadze, Nestani; Rodrigues, Camilla; Skrahina, Alena; Tagliani, Elisa; Cirillo, Daniela M.; Davidow, Amy; Denkinger, Claudia M.; Persing, David; Kwiatkowski, Robert; Jones, Martin

2017-01-01

ABSTRACT The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M. tuberculosis H37Rv or Mycobacterium bovis BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For M. tuberculosis H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for M. bovis BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated M. tuberculosis rpoB mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection. PMID:28851844

[Preliminary linkage analysis of a Chinese family with benign familial infantile convulsion].

PubMed

Xiong, Ge; Deng, Fei-yan; Xiao, Bo; Yang, Xiao-su; Ning, Jing-chun; Wu, Zhi-guo; Wang, Kang; Deng, Hong-wen

2004-06-01

Benign familial infantile convulsions (BFIC) is a recently recognized autosomal dominant inherited disorder. This epileptic syndrome typically begins between 3 and 12 months of age with clusters of partial seizures in most cases and carries a good prognosis. So far, three loci have been linked to chromosome 19q12.1-13.1, chromosome 2q24 and chromosome 16p12-q12. The authors performed linkage analysis on this pedigree. A four-generation Chinese family was investigated. The total number of members was 32 in this family and two neurologists in Xiangya Hospital gave systemic physical examinations and interictal neurological examinations to nineteen members of this family. Venous blood samples were taken for genetic analysis. DNA was extracted from peripheral blood leukocytes using phenol-chloroform method. Seventeen microsatellite markers spanning the critical regions on chromosomes 19q12-13.1, 2q24, and 16p12-q12 were genotyped. These markers included D19S49, D19S250, D19S414, D19S416 and D19S245 for the 19q region, D2S2380, D2S399, D2S111, D2S2195, D2S2330 and D2S2345 for the 2q region, D16S401, D16S3131, D16S3093, D16S517, D16S3120 and D16S415 for the 16p-q region. The DNA from each sample was amplified for the 17 markers. After polymerase chain reactions (PCR), PCR products of chromosome 19 with markers D19S49, D19S250, D19S414, D19S416 and D19S245 were subjected to electrophoresis on 8% denatured polyacrylamide gel for at least 2 hours and 20 minutes. Then the length of the PCR products was judged in the Strategene Eagle Eye II automated gel image analyzer. For the markers from chromosome 2 and 16, PCR products were scanned at ABI 377 autosequencer. The data of PCR products were analyzed using the software Genescan v3.1, Genetyper v2.1 (Applied Biosystem, CA. USA) and GenoDB v1.0. After Mendelian checking, the eligible genotyping data were used for linkage analysis. LOD scores were calculated by using MLINK program of LINKAGE v5.1, under an assumption of autosomal dominant inheritance and the estimated penetrance was 0.9. The allele frequencies of each marker were assumed to be equal and the disease-allele frequencies were designated to be 1/10,000. The LOD scores were calculated at combination rate (theta) 0.0, 0.1, 0.2, 0.3, and 0.4. Among the 17 selected microsatellite markers, which cover the previously reported regions, seven markers' data (D16S3131, D16S517, D16S3120, D16S3093, D2S2380, D19S250 and D19S414) were omitted due to failed genotyping, low genetic heterogeneity, or failure to pass Mendelian checking. Omission of these markers was to ensure the reliability of our raw data. The two-point LOD scores were below zero for all the markers and the maximum LOD scores at theta = 0.0 were less than -2 for markers D19S49, D19S416, D19S245, D16S401, D16S415, D2S399, D2S111, D2S2195, D2S2330 and D2S2345. Thus, the linkage result showed no evidence that the disease locus is linked to any of these selected markers, which excludes the previously reported candidate regions found in other ethnic families. There is no evidence that this Chinese family was linked to one of the following loci: 19q12.1-13.1, 16p12-q12 and 2q24. The results indicated that BFIC showed genetic heterogeneity and the Chinese BFIC families might be mapped on another new locus.

A Centrifugal Volcanism Mechanism for the AMO

NASA Astrophysics Data System (ADS)

Pratt, V. R.

2016-12-01

The Atlantic Multidecadal Oscillation has proved hard to isolate from both (i) global warming and (ii) faster oscillations. For (i), we showed [1] that by filtering all harmonics of a 63-year period, what remained could be explained remarkably accurately by the expected contribution of greenhouse warming along with the interesting increase in TSI during 1900-1950, leading to considerable confidence that global surface temperature averaged over 2069-2131 will be very close to 3 C above preindustrial. For (ii), principal component analysis of HadCRUT4 since 1850, Central England Temperature since 1659, and various other land and sea time series all show a distinct 21-year oscillation the start of whose downward swing is well synchronized with the maximum solar activity of the odd-numbered solar cycles, persisting even through the Maunder Minimum. After these are removed there remains a well-defined signal that has been associated with the so-called Atlantic Multidecadal Oscillation. There are two schools of thought, the AMO is of either radiative (RAD) or internal (INT) origin. RAD is explained in terms of aerosol fluctuations of volcanic origin. In [2] we gave what we felt was a knockdown argument against RAD. INT so far has been explained mainly in terms of instabilities in ocean currents such as the Atlantic Meridional Overturning Current. An interesting correlation between the AMO and Earth's Length of Day (LOD) has been noted by several authors. Missing is a plausible mechanism explaining this correlation. The mechanism we propose here is that magma welling up through ocean ridges is in a quasi-equilibrium that even small fluctuations in LOD can disturb significantly. Heat from emerging magma is carried up to the oceanic mixed layer in very large thermals. A simple model of this process leads to a correlation that is excellent except for the period 1940-1950. We propose to explain this difference in terms of a lifting of the crust by the excess magma developed during the long increase in LOD from 1880 to 1910. [1] Pratt, V.R., Model Complexity of Global Climate: Could Arrhenius have foreseen the hiatus? Session GC43C, AGUFM2015. [2] Pratt, V.R., Reconciling multidecadal land-sea global temperature with rising CO2. GC53C, AGUFM2013.

The null distribution of the heterogeneity lod score does depend on the assumed genetic model for the trait.

PubMed

Huang, J; Vieland, V J

2001-01-01

It is well known that the asymptotic null distribution of the homogeneity lod score (LOD) does not depend on the genetic model specified in the analysis. When appropriately rescaled, the LOD is asymptotically distributed as 0.5 chi(2)(0) + 0.5 chi(2)(1), regardless of the assumed trait model. However, because locus heterogeneity is a common phenomenon, the heterogeneity lod score (HLOD), rather than the LOD itself, is often used in gene mapping studies. We show here that, in contrast with the LOD, the asymptotic null distribution of the HLOD does depend upon the genetic model assumed in the analysis. In affected sib pair (ASP) data, this distribution can be worked out explicitly as (0.5 - c)chi(2)(0) + 0.5chi(2)(1) + cchi(2)(2), where c depends on the assumed trait model. E.g., for a simple dominant model (HLOD/D), c is a function of the disease allele frequency p: for p = 0.01, c = 0.0006; while for p = 0.1, c = 0.059. For a simple recessive model (HLOD/R), c = 0.098 independently of p. This latter (recessive) distribution turns out to be the same as the asymptotic distribution of the MLS statistic under the possible triangle constraint, which is asymptotically equivalent to the HLOD/R. The null distribution of the HLOD/D is close to that of the LOD, because the weight c on the chi(2)(2) component is small. These results mean that the cutoff value for a test of size alpha will tend to be smaller for the HLOD/D than the HLOD/R. For example, the alpha = 0.0001 cutoff (on the lod scale) for the HLOD/D with p = 0.05 is 3.01, while for the LOD it is 3.00, and for the HLOD/R it is 3.27. For general pedigrees, explicit analytical expression of the null HLOD distribution does not appear possible, but it will still depend on the assumed genetic model. Copyright 2001 S. Karger AG, Basel

Three decades after Gjönnaess's laparoscopic ovarian drilling for treatment of PCOS; what do we know? An evidence-based approach.

PubMed

Abu Hashim, Hatem; Al-Inany, Hesham; De Vos, Michel; Tournaye, Herman

2013-08-01

The introduction of laparoscopic ovarian drilling (LOD) by Gjönnaess in 1984 as a substitute for ovarian wedge resection created opportunities for extensive research given its worldwide application for ovulation induction in women with polycystic ovary syndrome (PCOS). To critically evaluate and summarize the current body of literature regarding the role of LOD for the management of PCOS entailing its different preoperative, operative and postoperative aspects. In addition, long-term efficacy, cost-effectiveness, patient preference and health-related quality of life issues will be evaluated together with other available alternatives of ovulation induction treatments. A PubMed search was conducted looking for the different trials, reviews and various guidelines relating to the role of LOD in the management of PCOS. LOD whether unilateral or bilateral is a beneficial second-line treatment in infertile women with clomiphene citrate (CC)-resistant PCOS. It is as effective as gonadotrophin treatment but without the risk of multiple pregnancy or ovarian hyperstimulation and does not require intensive monitoring. Increased responsiveness of the ovary to CC especially in patients who remain anovulatory following LOD is another advantage. Recent evidence suggests that relatively novel oral methods of ovulation induction, e.g. CC plus metformin, CC plus tamoxifen, rosiglitazone plus CC and aromatase inhibitors represent a successful alternative to LOD in CC-resistant PCOS. Meanwhile current evidence does not support LOD as a first-line approach in PCOS-related anovulation or before IVF. LOD is currently recommended as a successful and economical second-line treatment for ovulation induction in women with CC-resistant PCOS.

75 FR 53730 - Culturally Significant Object Imported for Exhibition Determinations: “The Roman Mosaic from Lod...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... DEPARTMENT OF STATE [Public Notice 7145] Culturally Significant Object Imported for Exhibition Determinations: ``The Roman Mosaic from Lod, Israel'' SUMMARY: Notice is hereby given of the following... object to be included in the exhibition ``The Roman Mosaic from Lod, Israel,'' imported from abroad for...

The Use and Abuse of Limits of Detection in Environmental Analytical Chemistry

PubMed Central

Brown, Richard J. C.

2008-01-01

The limit of detection (LoD) serves as an important method performance measure that is useful for the comparison of measurement techniques and the assessment of likely signal to noise performance, especially in environmental analytical chemistry. However, the LoD is only truly related to the precision characteristics of the analytical instrument employed for the analysis and the content of analyte in the blank sample. This article discusses how other criteria, such as sampling volume, can serve to distort the quoted LoD artificially and make comparison between various analytical methods inequitable. In order to compare LoDs between methods properly, it is necessary to state clearly all of the input parameters relating to the measurements that have been used in the calculation of the LoD. Additionally, the article discusses that the use of LoDs in contexts other than the comparison of the attributes of analytical methods, in particular when reporting analytical results, may be confusing, less informative than quoting the actual result with an accompanying statement of uncertainty, and may act to bias descriptive statistics. PMID:18690384

Temporal and multiple quantitative trait loci analyses of resistance to bacterial wilt in tomato permit the resolution of linked loci.

PubMed

Mangin, B; Thoquet, P; Olivier, J; Grimsley, N H

1999-03-01

Ralstonia solanacearum is a soil-borne bacterium that causes the serious disease known as bacterial wilt in many plant species. In tomato, several QTL controlling resistance have been found, but in different studies, markers spanning a large region of chromosome 6 showed strong association with the resistance. By using two different approaches to analyze the data from a field test F3 population, we show that at least two separate loci approximately 30 cM apart on this chromosome are most likely involved in the resistance. First, a temporal analysis of the progression of symptoms reveals a distal locus early in the development of the disease. As the disease progresses, the maximum LOD peak observed shifts toward the proximal end of the chromosome, obscuring the distal locus. Second, although classical interval mapping could only detect the presence of one locus, a statistical "two-QTL model" test, specifically adapted for the resolution of linked QTL, strongly supported the hypothesis for the presence of two loci. These results are discussed in the context of current molecular knowledge about disease resistance genes on chromosome 6 and observations made by tomato breeders during the production of bacterial wilt-resistant varieties.

Temporal and multiple quantitative trait loci analyses of resistance to bacterial wilt in tomato permit the resolution of linked loci.

PubMed Central

Mangin, B; Thoquet, P; Olivier, J; Grimsley, N H

1999-01-01

Ralstonia solanacearum is a soil-borne bacterium that causes the serious disease known as bacterial wilt in many plant species. In tomato, several QTL controlling resistance have been found, but in different studies, markers spanning a large region of chromosome 6 showed strong association with the resistance. By using two different approaches to analyze the data from a field test F3 population, we show that at least two separate loci approximately 30 cM apart on this chromosome are most likely involved in the resistance. First, a temporal analysis of the progression of symptoms reveals a distal locus early in the development of the disease. As the disease progresses, the maximum LOD peak observed shifts toward the proximal end of the chromosome, obscuring the distal locus. Second, although classical interval mapping could only detect the presence of one locus, a statistical "two-QTL model" test, specifically adapted for the resolution of linked QTL, strongly supported the hypothesis for the presence of two loci. These results are discussed in the context of current molecular knowledge about disease resistance genes on chromosome 6 and observations made by tomato breeders during the production of bacterial wilt-resistant varieties. PMID:10049932

Substituting Sodium Hydrosulfite with Sodium Metabisulfite Improves Long-Term Stability of a Distributable Paper-Based Test Kit for Point-of-Care Screening for Sickle Cell Anemia.

PubMed

Torabian, Kian; Lezzar, Dalia; Piety, Nathaniel Z; George, Alex; Shevkoplyas, Sergey S

2017-09-20

Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness of laboratory-based SCA screening programs. To address this limitation our laboratory previously developed a low-cost, equipment-free, point-of-care, paper-based SCA test. Here, we improved the stability and performance of the test by replacing sodium hydrosulfite (HS), a key reducing agent in the hemoglobin solubility buffer which is not stable in aqueous solutions, with sodium metabisulfite (MS). The MS formulation of the test was compared to the HS formulation in a laboratory setting by inexperienced users ( n = 3), to determine visual limit of detection (LOD), readout time, diagnostic accuracy, intra- and inter-observer agreement, and shelf life. The MS test was found to have a 10% sickle hemoglobin LOD, 21-min readout time, 97.3% sensitivity and 99.5% specificity for SCA, almost perfect intra- and inter-observer agreement, at least 24 weeks of shelf stability at room temperature, and could be packaged into a self-contained, distributable test kits comprised of off-the-shelf disposable components and food-grade reagents with a total cost of only $0.21 (USD).

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

PubMed

Malhotra, Alka; Igo, Robert P; Thameem, Farook; Kao, W H Linda; Abboud, Hanna E; Adler, Sharon G; Arar, Nedal H; Bowden, Donald W; Duggirala, Ravindranath; Freedman, Barry I; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Knowler, William C; Kohn, Orly; Leehey, David; Meoni, Lucy A; Nelson, Robert G; Nicholas, Susanne B; Parekh, Rulan S; Rich, Stephen S; Chen, Yii-Der I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Taylor, Kent D; Thornley-Brown, Denyse; Zager, Philip G; Horvath, Amanda; Hanson, Robert L

2009-11-01

Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Wavelet analysis of interannual LOD, AAM, and ENSO: 1997-98 El Niño and 1998-99 La Niña signals

NASA Astrophysics Data System (ADS)

Zhou, Y. H.; Zheng, D. W.; Liao, X. H.

2001-05-01

On the basis of the data series of the length of day (LOD), the atmospheric angular momentum (AAM) and the Southern Oscillation Index (SOI) for January 1970-June 1999, the relationship among Interannual LOD, AAM, and the EL Niño/Southern Oscillation (ENSO) is analyzed by the wavelet transform method. The results suggest that they have similar time-varying spectral structures. The signals of 1997-98 El Niño and 1998-99 La Niña events can be detected from the LOD or AAM data.

Magnetic field variation caused by rotational speed change in a magnetohydrodynamic dynamo.

PubMed

Miyagoshi, Takehiro; Hamano, Yozo

2013-09-20

We have performed numerical magnetohydrodynamic dynamo simulations in a spherical shell with rotational speed or length-of-day (LOD) variation, which is motivated by correlations between geomagnetic field and climatic variations with ice and non-ice ages. The results show that LOD variation leads to magnetic field variation whose amplitude is considerably larger than that of LOD variation. The heat flux at the outer sphere and the zonal flow also change. The mechanism of the magnetic field variation due to LOD variation is also found. The keys are changes of dynamo activity and Joule heating.

Revisiting a possible relationship between solar activity and Earth rotation variability

NASA Astrophysics Data System (ADS)

Abarca del Rio, R.; Gambis, D.

2011-10-01

A variety of studies have searched to establish a possible relationship between the solar activity and earth variations (Danjon, 1958-1962; Challinor, 1971; Currie, 1980, Gambis, 1990). We are revisiting previous studies (Bourget et al, 1992, Abarca del Rio et al, 2003, Marris et al, 2004) concerning the possible relationship between solar activity variability and length of day (LOD) variations at decadal time scales. Assuming that changes in AAM for the entire atmosphere are accompanied by equal, but opposite, changes in the angular momentum of the earth it is possible to infer changes in LOD from global AAM time series, through the relation : delta (LOD) (ms) = 1.68 10^29 delta(AAM) (kgm2/s) (Rosen and Salstein, 1983), where δ(LOD) is given in milliseconds. Given the close relationship at seasonal to interannual time's scales between LOD and the Atmospheric Angular Momentum (AAM) (see Abarca del Rio et al., 2003) it is possible to infer from century long atmospheric simulations what may have been the variability in the associated LOD variability throughout the last century. In the absence of a homogeneous century long LOD time series, we take advantage of the recent atmospheric reanalyzes extending since 1871 (Compo, Whitaker and Sardeshmukh, 2006). The atmospheric data (winds) of these reanalyzes allow computing AAM up to the top of the atmosphere; though here only troposphere data (up to 100 hPa) was taken into account.

Temperature initiated passive cooling system

DOEpatents

Forsberg, C.W.

1994-11-01

A passive cooling system for cooling an enclosure only when the enclosure temperature exceeds a maximum standby temperature comprises a passive heat transfer loop containing heat transfer fluid having a particular thermodynamic critical point temperature just above the maximum standby temperature. An upper portion of the heat transfer loop is insulated to prevent two phase operation below the maximum standby temperature. 1 fig.

The Use of Daily Geodetic UT1 and LOD Data in the Optimal Estimation of UT1 and LOD With the JPL Kalman Earth Orientation Filter

NASA Technical Reports Server (NTRS)

Freedman, A. P.; Steppe, J. A.

1995-01-01

The Jet Propulsion Laboratory Kalman Earth Orientation Filter (KEOF) uses several of the Earth rotation data sets available to generate optimally interpolated UT1 and LOD series to support spacecraft navigation. This paper compares use of various data sets within KEOF.

Determining the 95% limit of detection for waterborne pathogen analyses from primary concentration to qPCR

USDA-ARS?s Scientific Manuscript database

The limit of detection (LOD) for qPCR-based analyses is not consistently defined or determined in studies on waterborne pathogens. Moreover, the LODs reported often reflect the qPCR assay rather than the entire sample process. Our objective was to develop a method to determine the 95% LOD (lowest co...

Identifying the role of initial wave parameters on tsunami focusing

NASA Astrophysics Data System (ADS)

Aydın, Baran

2018-04-01

Unexpected local tsunami amplification, which is referred to as tsunami focusing, is attributed to two different mechanisms: bathymetric features of the ocean bottom such as underwater ridges and dipolar shape of the initial wave itself. In this study, we characterize the latter; that is, we explore how amplitude and location of the focusing point vary with certain geometric parameters of the initial wave such as its steepness and crest length. Our results reveal two important features of tsunami focusing: for mild waves maximum wave amplitude increases significantly with transverse length of wave crest, while location of the focusing point is almost invariant. For steep waves, on the other hand, increasing crest length dislocates focusing point significantly, while it causes a rather small increase in wave maximum.

Melancholia in later life: late and early onset differences in presentation, course, and dementia risk.

PubMed

Sachs-Ericsson, Natalie; Moxley, Jerad H; Corsentino, Elizabeth; Rushing, Nicole Collins; Sheffler, Julia; Selby, Edward A; Gotlib, Ian; Steffens, David C

2014-09-01

Depression is a risk factor for cognitive decline and dementia. This risk may vary with age of onset and depression subtype. Late onset depression (LOD, 60 years and older) is associated with more cognitive decline, whereas early onset depression (EOD, before 60 years) is associated with more residual depressive symptoms. Potential differences may reflect divergent etiologies. These onset differences, however, have not been examined in the melancholic subtype of depression in older adults. Data were obtained from the Neurocognitive Outcomes of Depression in the Elderly study. Participants (N = 284, 73% EOD-melancholic (EOD-M) and 27% LOD-melancholic (LOD-M)) were followed up over 3 years. Factor analyses examined differences in baseline depressive symptoms. Hierarchical linear growth curve models examined changes in depressive symptoms (Montgomery-Asberg Depression Rating Scale) and cognition (mini mental state examination). An annual clinical review panel assigned diagnoses of dementia. The LOD-M participants had more vegetative symptoms at baseline. LOD-M exhibited greater cognitive decline but fewer residual depressive symptoms than EOD-M. Among participants who remained in the study for at least 1 year, in uncontrolled analyses, a greater percentage of LOD-M compared with EOD-M developed dementia (23.0% vs. 7.8%). Whereas in logistic analyses, controlling for baseline demographics, age at onset remained a predictor of dementia, the odds ratio suggested that the effect was relatively small. The EOD-M and LOD-M participants have a different presentation and course. LOD-M may represent a syndrome of neuropsychiatric deterioration with expression of both depressive symptoms and cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

Estimation of the Length of Day (LOD) from DORIS observations

NASA Astrophysics Data System (ADS)

Štěpánek, Petr; Hugentobler, Urs; Buday, Michal; Filler, Vratislav

2018-07-01

The paper is devoted to the estimation of the Length of the Day (LOD) from DORIS observations and summarizes the first successful experiment with LOD estimation at the level of geodetic precision. This result is confirmed by 9 years of DORIS data (2006.0-2015.0). The mean difference of the non smoothed LOD series with respect to the IERS C04 model reaches a value of tens μs and a standard deviation around 120 μs for the last years of the campaign 2012.0-2015.0. However, the mean difference with respect to the reference model varies over time, reaching negative values from -60 to -20 μs for the years 2006-2011 and positive values from 80 to 120 μs for the years 2012-2014. The time variable mean difference with respect to the changes in DORIS satellite constellation is discussed, as well as the possibility of the bias reduction applying the long-term averages of the cross-track harmonics or adjustment of the geopotential coefficient C20. Moreover, the possibility of LOD adjustment in the standard DORIS solution is discussed with focus on the station coordinates estimation. In addition, the power spectrum of the difference between estimated LOD and the reference model was performed, showing the domination of the annual signal. Also LOD estimated from single-satellite DORIS solutions was analyzed to identify satellite-specific issues. The paper includes a correlation analysis of the orbit parameters, Earth rotation parameters and the geopotential coefficient C20, based on covariance matrices from weekly solutions. High correlation around 0.96 was found for LOD and the sine amplitude of the cross-track harmonic empirical acceleration, which was also confirmed analytically.

Mapping of the serotonin 5-HT{sub 1D{beta}} autoreceptor gene on chromosome 6 and direct analysis for sequence variants

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

Lappalainen, J.; Dean, M.; Virkkunen, M.

1995-04-24

Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT{sub 1D{beta}} is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT{sub 1D{beta}} coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT{sub 1D{beta}} gene withmore » allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT{sub 1D{beta}} receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy. 34 refs., 3 figs., 1 tab.« less

Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

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

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North Americanmore » kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.« less

Forecasting irregular variations of UT1-UTC and LOD data caused by ENSO

NASA Astrophysics Data System (ADS)

Niedzielski, T.; Kosek, W.

2008-04-01

The research focuses on prediction of LOD and UT1-UTC time series up to one-year in the future with the particular emphasis on the prediction improvement during El Nĩ o or La Nĩ a n n events. The polynomial-harmonic least-squares model is applied to fit the deterministic function to LOD data. The stochastic residuals computed as the difference between LOD data and the polynomial- harmonic model reveal the extreme values driven by El Nĩ o or La Nĩ a. These peaks are modeled by the n n stochastic bivariate autoregressive prediction. This approach focuses on the auto- and cross-correlations between LOD and the axial component of the atmospheric angular momentum. This technique allows one to derive more accurate predictions than purely univariate forecasts, particularly during El Nĩ o/La n Nĩ a events. n

Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

PubMed

Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

2018-04-10

This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p < .001) after LOD with significant reduction in OV, AFC and vascular indices (VI, FI and VFI) of the right and left ovaries (p < .05). LOD significantly reduced ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

Fault feature analysis of cracked gear based on LOD and analytical-FE method

NASA Astrophysics Data System (ADS)

Wu, Jiateng; Yang, Yu; Yang, Xingkai; Cheng, Junsheng

2018-01-01

At present, there are two main ideas for gear fault diagnosis. One is the model-based gear dynamic analysis; the other is signal-based gear vibration diagnosis. In this paper, a method for fault feature analysis of gear crack is presented, which combines the advantages of dynamic modeling and signal processing. Firstly, a new time-frequency analysis method called local oscillatory-characteristic decomposition (LOD) is proposed, which has the attractive feature of extracting fault characteristic efficiently and accurately. Secondly, an analytical-finite element (analytical-FE) method which is called assist-stress intensity factor (assist-SIF) gear contact model, is put forward to calculate the time-varying mesh stiffness (TVMS) under different crack states. Based on the dynamic model of the gear system with 6 degrees of freedom, the dynamic simulation response was obtained for different tooth crack depths. For the dynamic model, the corresponding relation between the characteristic parameters and the degree of the tooth crack is established under a specific condition. On the basis of the methods mentioned above, a novel gear tooth root crack diagnosis method which combines the LOD with the analytical-FE is proposed. Furthermore, empirical mode decomposition (EMD) and ensemble empirical mode decomposition (EEMD) are contrasted with the LOD by gear crack fault vibration signals. The analysis results indicate that the proposed method performs effectively and feasibility for the tooth crack stiffness calculation and the gear tooth crack fault diagnosis.

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

Recombinational event between Norrie disease and DXS7 loci.

PubMed

Ngo, J T; Spence, M A; Cortessis, V; Sparkes, R S; Bateman, J B

1988-07-01

We have identified a family affected with X-linked recessive Norrie disease, in which a recombinational event occurred between the disease locus and the DXS7 locus identified by the probe L1.28. The addition of our family brings the total of published informative families to seven, with a maximum lod score of 7.58 at a recombination frequency of 0.038 +/- 0.036. This finding indicates that the L1.28 probe is useful but may not be completely reliable for prenatal diagnosis and that the gene for Norrie disease is not within the DNA sequence identified by the L1.28 probe.

Automatic Generation of Building Models with Levels of Detail 1-3

NASA Astrophysics Data System (ADS)

Nguatem, W.; Drauschke, M.; Mayer, H.

2016-06-01

We present a workflow for the automatic generation of building models with levels of detail (LOD) 1 to 3 according to the CityGML standard (Gröger et al., 2012). We start with orienting unsorted image sets employing (Mayer et al., 2012), we compute depth maps using semi-global matching (SGM) (Hirschmüller, 2008), and fuse these depth maps to reconstruct dense 3D point clouds (Kuhn et al., 2014). Based on planes segmented from these point clouds, we have developed a stochastic method for roof model selection (Nguatem et al., 2013) and window model selection (Nguatem et al., 2014). We demonstrate our workflow up to the export into CityGML.

Secular change of LOD caused by core evolution

NASA Astrophysics Data System (ADS)

Denis, C.; Rybicki, K. R.; Varga, P.

2003-04-01

Fossils and tidal deposits suggest that, on the average, the Earth's despinning rate had been five times less in the Proterozoic than in the Phanerozoic. This difference is probably due, for the major part, to the existence of a Proterozoic supercontinent. Nevertheless, core formation and core evolution should have compensated to some extent the effect of tidal friction, by diminishing the Earth's inertia moment. We have investigated quantitatively this contribution of the evolving core to the change of LOD. For the present epoch, we find that the solidification of the inner core causes a relative secular decrease of LOD of approximately 3 μs per century, whereas the macrodiffusion of iron oxides and sulfides from the D" into the outer core across the CMB (inasfar as Majewski's theory holds) leads to a relative secular decrease of LOD by about 15 μs per century. On the other hand, the theory of slow core formation developped by Runcorn in the early 1960s as a by-product of his theory of mantle-wide convection, leads to a relative secular decrease of LOD during most of the Proterozoic of about 0.25 ms per century. Although core formation is now widely assumed to have been a thermal run-away process that occurred shortly after the Earth itself had formed, Runcorn's theory of the growing core would nicely explain the observed palaeo-LOD curve. In any case, formation of the core implies, all in all, a relative decrease of LOD of typically 3 hours.

In Southern Africa, Brown Oculocutaneous Albinism (BOCA) Maps to the OCA2 Locus on Chromosome 15q: P-Gene Mutations Identified

PubMed Central

Manga, Prashiela; Kromberg, Jennifer G. R.; Turner, Angela; Jenkins, Trefor; Ramsay, Michele

2001-01-01

In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; θ=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype. PMID:11179026

Autosomal Dominant Nonsyndromic Cleft Lip and Palate: Significant Evidence of Linkage at 18q21.1

PubMed Central

Beiraghi, Soraya ; Nath, Swapan K. ; Gaines, Matthew ; Mandhyan, Desh D. ; Hutchings, David ; Ratnamala, Uppala ; McElreavey, Ken ; Bartoloni, Lucia ; Antonarakis, Gregory S. ; Antonarakis, Stylianos E. ; Radhakrishna, Uppala 

2007-01-01

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700–1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide–polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL=43.33 and P=.000061; nonparametric LOD=3.97 and P=.00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus “OFC11” (orofacial cleft 11). PMID:17564975

Mapping genetic variants for cranial vault shape in humans.

PubMed

Roosenboom, Jasmien; Lee, Myoung Keun; Hecht, Jacqueline T; Heike, Carrie L; Wehby, George L; Christensen, Kaare; Feingold, Eleanor; Marazita, Mary L; Maga, A Murat; Shaffer, John R; Weinberg, Seth M

2018-01-01

The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the genetic basis of normal vault shape in humans. We performed a genome-wide association study (GWAS) on three vault measures (maximum cranial width [MCW], maximum cranial length [MCL], and cephalic index [CI]) in a sample of 4419 healthy individuals of European ancestry. All measures were adjusted by sex, age, and body size, then tested for association with genetic variants spanning the genome. GWAS results for the two cohorts were combined via meta-analysis. Significant associations were observed at two loci: 15p11.2 (lead SNP rs2924767, p = 2.107 × 10-8) for MCW and 17q11.2 (lead SNP rs72841279, p = 5.29 × 10-9) for MCL. Additionally, 32 suggestive loci (p < 5x10-6) were observed. Several candidate genes were located in these loci, such as NLK, MEF2A, SOX9 and SOX11. Genome-wide linkage analysis of cranial vault shape in mice (N = 433) was performed to follow-up the associated candidate loci identified in the human GWAS. Two loci, 17q11.2 (c11.loc44 in mice) and 17q25.1 (c11.loc74 in mice), associated with cranial vault size in humans, were also linked with cranial vault size in mice (LOD scores: 3.37 and 3.79 respectively). These results provide further insight into genetic pathways and mechanisms underlying normal variation in human craniofacial morphology.

Mapping genetic variants for cranial vault shape in humans

PubMed Central

Lee, Myoung Keun; Hecht, Jacqueline T.; Heike, Carrie L.; Wehby, George L.; Christensen, Kaare; Feingold, Eleanor; Marazita, Mary L.; Weinberg, Seth M.

2018-01-01

The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the genetic basis of normal vault shape in humans. We performed a genome-wide association study (GWAS) on three vault measures (maximum cranial width [MCW], maximum cranial length [MCL], and cephalic index [CI]) in a sample of 4419 healthy individuals of European ancestry. All measures were adjusted by sex, age, and body size, then tested for association with genetic variants spanning the genome. GWAS results for the two cohorts were combined via meta-analysis. Significant associations were observed at two loci: 15p11.2 (lead SNP rs2924767, p = 2.107 × 10−8) for MCW and 17q11.2 (lead SNP rs72841279, p = 5.29 × 10−9) for MCL. Additionally, 32 suggestive loci (p < 5x10-6) were observed. Several candidate genes were located in these loci, such as NLK, MEF2A, SOX9 and SOX11. Genome-wide linkage analysis of cranial vault shape in mice (N = 433) was performed to follow-up the associated candidate loci identified in the human GWAS. Two loci, 17q11.2 (c11.loc44 in mice) and 17q25.1 (c11.loc74 in mice), associated with cranial vault size in humans, were also linked with cranial vault size in mice (LOD scores: 3.37 and 3.79 respectively). These results provide further insight into genetic pathways and mechanisms underlying normal variation in human craniofacial morphology. PMID:29698431

Surface mapping of spike potential fields: experienced EEGers vs. computerized analysis.

PubMed

Koszer, S; Moshé, S L; Legatt, A D; Shinnar, S; Goldensohn, E S

1996-03-01

An EEG epileptiform spike focus recorded with scalp electrodes is clinically localized by visual estimation of the point of maximal voltage and the distribution of its surrounding voltages. We compared such estimated voltage maps, drawn by experienced electroencephalographers (EEGers), with a computerized spline interpolation technique employed in the commercially available software package FOCUS. Twenty-two spikes were recorded from 15 patients during long-term continuous EEG monitoring. Maps of voltage distribution from the 28 electrodes surrounding the points of maximum change in slope (the spike maximum) were constructed by the EEGer. The same points of maximum spike and voltage distributions at the 29 electrodes were mapped by computerized spline interpolation and a comparison between the two methods was made. The findings indicate that the computerized spline mapping techniques employed in FOCUS construct voltage maps with similar maxima and distributions as the maps created by experienced EEGers. The dynamics of spike activity, including correlations, are better visualized using the computerized technique than by manual interpretation alone. Its use as a technique for spike localization is accurate and adds information of potential clinical value.

A novel locus for dilated cardiomyopathy maps to canine chromosome 8.

PubMed

Werner, Petra; Raducha, Michael G; Prociuk, Ulana; Sleeper, Meg M; Van Winkle, Thomas J; Henthorn, Paula S

2008-06-01

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

Comparative study of adaptive controller using MIT rules and Lyapunov method for MPPT standalone PV systems

NASA Astrophysics Data System (ADS)

Tariba, N.; Bouknadel, A.; Haddou, A.; Ikken, N.; Omari, Hafsa El; Omari, Hamid El

2017-01-01

The Photovoltaic Generator have a nonlinear characteristic function relating the intensity at the voltage I = f (U) and depend on the variation of solar irradiation and temperature, In addition, its point of operation depends directly on the load that it supplies. To fix this drawback, and to extract the maximum power available to the terminal of the generator, an adaptation stage is introduced between the generator and the load to couple the two elements as perfectly as possible. The adaptation stage is associated with a command called MPPT MPPT (Maximum Power Point Tracker) whose is used to force the PVG to operate at the MPP (Maximum Power Point) under variation of climatic conditions and load variation. This paper presents a comparative study between the adaptive controller for PV Systems using MIT rules and Lyapunov method to regulate the PV voltage. The Incremental Conductance (IC) algorithm is used to extract the maximum power from the PVG by calculating the voltage Vref, and the adaptive controller is used to regulate and track quickly the PV voltage. The two methods of the adaptive controller will be compared to prove their performance by using the PSIM tools and experimental test, and the mathematical model of step-up with PVG model will be presented.

Homozygosity mapping of a third Joubert syndrome locus to 6q23

PubMed Central

Lagier-Tourenne, C; Boltshauser, E; Breivik, N; Gribaa, M; Betard, C; Barbot, C; Koenig, M

2004-01-01

Background: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases. Methods: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci. Results: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q = 0 for the two families, respectively. Conclusions: Linkage between the disease and the D6S1620–D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction. PMID:15060101

Episodic Spin-up and Spin-down Torque on Earth

NASA Astrophysics Data System (ADS)

Slabinski, Victor J.; Mendonca, Antonio A.

2018-04-01

Variations in Earth rotation angle are traditionally expressed by the time difference (ΔT=TT-UT1) between Terrestrial Time (TT) as told by atomic clocks and Universal Time UT1, the time variable used by the Earth-rotation formula. A plot of ΔT versus TT over the past 160 years shows a continuous curve with approximate straight-line segments with different spans of order ~20 years. Removing the tidal and seasonal variations from the data gives these line segments which represent the “decadal variations” in Earth rotation.The slope of a straight-line segment is proportional to the departure of Earth rotation rate from a reference value at the time. The change in slope over the relatively short time between segments indicates an episodic spin-up or spin-down in Earth rotation. The daily combination of VLBI, SLR, and other modern data available since 1973 gives us accurate, daily values of ΔT and the corresponding LOD (Length Of Day) values during these episodes. These allow us to determine the rotational acceleration occurring then.The three largest spin-speed changes found during the VLBI era have the following characteristics:Episode _____________ Duration__ ΔLOD__LOD Rate1983 Dec 30-1984 Jan 28 ... 29 d ...-0.65 ms ..-8.3 ms/y ..........spin-up1989 Mar 15-1989 May 23 ...69 d ....0.68 .......+3.6 ..............spin-down1994 Jan 21-2001 Apr 01 ... 6.5 y ...-2.2 .........-0.36 ..extended spin-upFor the first two episodes listed, we find the acceleration grows from zero (or at least a relatively small value) to its extreme value in ~1 day, stays approximately constant at this value for 29 or 69 days, and then decays back to zero over ~1 day. The acceleration, while it occurs, gives an LOD rate much greater than the 0.02 ms/y rate from tidal friction.The third episode shows that occasionally a several-year-long episode occurs. The acceleration magnitude is smaller but can make a larger total change in LOD (and spin rate). Tidal friction requires >100 y to equal the LOD magnitude change from this episode.We do not know the cause or trigger for the episodes.

False Negative Rates of a Macrofoam-Swab Sampling Method with Low Surface Concentrations of Two Bacillus anthracis Surrogates via Real-Time PCR

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

Hutchison, Janine R.; Piepel, Gregory F.; Amidan, Brett G.

Surface sampling for Bacillus anthracis spores has traditionally relied on detection via bacterial cultivation methods. Although effective, this approach does not provide the level of organism specificity that can be gained through molecular techniques. False negative rates (FNR) and limits of detection (LOD) were determined for two B. anthracis surrogates with modified rapid viability-polymerase chain reaction (mRV-PCR) following macrofoam-swab sampling. This study was conducted in parallel with a previously reported study that analyzed spores using a plate-culture method. B. anthracis Sterne (BAS) or B. atrophaeus Nakamura (BG) spores were deposited onto four surface materials (glass, stainless steel, vinyl tile, andmore » plastic) at nine target concentrations (2 to 500 spores/coupon; 0.078 to 19.375 colony-forming units [CFU] per cm2). Mean FNR values for mRV-PCR analysis ranged from 0 to 0.917 for BAS and 0 to 0.875 for BG and increased as spore concentration decreased (over the concentrations investigated) for each surface material. FNRs based on mRV-PCR data were not statistically different for BAS and BG, but were significantly lower for glass than for vinyl tile. FNRs also tended to be lower for the mRV-PCR method compared to the culture method. The mRV-PCR LOD95 was lowest for glass (0.429 CFU/cm2 with BAS and 0.341 CFU/cm2 with BG) and highest for vinyl tile (0.919 CFU/cm2 with BAS and 0.917 CFU/cm2 with BG). These mRV-PCR LOD95 values were lower than the culture values (BAS: 0.678 to 1.023 CFU/cm2 and BG: 0.820 to 1.489 CFU/cm2). The FNR and LOD95 values reported in this work provide guidance for environmental sampling of Bacillus spores at low concentrations.« less

Flight trajectories with maximum tangential thrust in a central Newtonian field

NASA Astrophysics Data System (ADS)

Azizov, A. G.; Korshunova, N. A.

1983-07-01

The paper examines the two-dimensional problem of determining the optimal trajectories of a point moving with a limited per-second mass consumption in a central Newtonian field. It is shown that one of the cases in which the variational equations in the Meier formulation can be integrated in quadratures is motion with maximum tangential thrust. Trajectories corresponding to this motion are determined. By way of application, attention is given to the problem of determining the thrust which assures maximum kinetic energy for the point at the moment t = t1, corresponding to the mass consumption M0 - M1, where M0 and M1 are, respectively, the initial and final mass.

Estimating landscape carrying capacity through maximum clique analysis

USGS Publications Warehouse

Donovan, Therese; Warrington, Greg; Schwenk, W. Scott; Dinitz, Jeffrey H.

2012-01-01

Habitat suitability (HS) maps are widely used tools in wildlife science and establish a link between wildlife populations and landscape pattern. Although HS maps spatially depict the distribution of optimal resources for a species, they do not reveal the population size a landscape is capable of supporting--information that is often crucial for decision makers and managers. We used a new approach, "maximum clique analysis," to demonstrate how HS maps for territorial species can be used to estimate the carrying capacity, N(k), of a given landscape. We estimated the N(k) of Ovenbirds (Seiurus aurocapillus) and bobcats (Lynx rufus) in an 1153-km2 study area in Vermont, USA. These two species were selected to highlight different approaches in building an HS map as well as computational challenges that can arise in a maximum clique analysis. We derived 30-m2 HS maps for each species via occupancy modeling (Ovenbird) and by resource utilization modeling (bobcats). For each species, we then identified all pixel locations on the map (points) that had sufficient resources in the surrounding area to maintain a home range (termed a "pseudo-home range"). These locations were converted to a mathematical graph, where any two points were linked if two pseudo-home ranges could exist on the landscape without violating territory boundaries. We used the program Cliquer to find the maximum clique of each graph. The resulting estimates of N(k) = 236 Ovenbirds and N(k) = 42 female bobcats were sensitive to different assumptions and model inputs. Estimates of N(k) via alternative, ad hoc methods were 1.4 to > 30 times greater than the maximum clique estimate, suggesting that the alternative results may be upwardly biased. The maximum clique analysis was computationally intensive but could handle problems with < 1500 total pseudo-home ranges (points). Given present computational constraints, it is best suited for species that occur in clustered distributions (where the problem can be broken into several, smaller problems), or for species with large home ranges relative to grid scale where resampling the points to a coarser resolution can reduce the problem to manageable proportions.

Novel versatile smart phone based Microplate readers for on-site diagnoses.

PubMed

Fu, Qiangqiang; Wu, Ze; Li, Xiuqing; Yao, Cuize; Yu, Shiting; Xiao, Wei; Tang, Yong

2016-07-15

Microplate readers are important diagnostic instruments, used intensively for various readout test kits (biochemical analysis kits and ELISA kits). However, due to their expensive and non-portability, commercial microplate readers are unavailable for home testing, community and rural hospitals, especially in developing countries. In this study, to provide a field-portable, cost-effective and versatile diagnostic tool, we reported a novel smart phone based microplate reader. The basic principle of this devise relies on a smart phone's optical sensor that measures transmitted light intensities of liquid samples. To prove the validity of these devises, developed smart phone based microplate readers were applied to readout results of various analytical targets. These targets included analanine aminotransferase (ALT; limit of detection (LOD) was 17.54 U/L), alkaline phosphatase (AKP; LOD was 15.56 U/L), creatinine (LOD was 1.35μM), bovine serum albumin (BSA; LOD was 0.0041mg/mL), prostate specific antigen (PSA; LOD was 0.76pg/mL), and ractopamine (Rac; LOD was 0.31ng/mL). The developed smart phone based microplate readers are versatile, portable, and inexpensive; they are unique because of their ability to perform under circumstances where resources and expertize are limited. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic modeling for rigid rotor bearing systems with a localized defect considering additional deformations at the sharp edges

NASA Astrophysics Data System (ADS)

Liu, Jing; Shao, Yimin

2017-06-01

Rotor bearing systems (RBSs) play a very valuable role for wind turbine gearboxes, aero-engines, high speed spindles, and other rotational machinery. An in-depth understanding of vibrations of the RBSs is very useful for condition monitoring and diagnosis applications of these machines. A new twelve-degree-of-freedom dynamic model for rigid RBSs with a localized defect (LOD) is proposed. This model can formulate the housing support stiffness, interfacial frictional moments including load dependent and load independent components, time-varying displacement excitation caused by a LOD, additional deformations at the sharp edges of the LOD, and lubricating oil film. The time-varying displacement model is determined by a half-sine function. A new method for calculating the additional deformations at the sharp edges of the LOD is analytical derived based on an elastic quarter-space method presented in the literature. The proposed dynamic model is utilized to analyze the influences of the housing support stiffness and LOD sizes on the vibration characteristics of the rigid RBS, which cannot be predicted by the previous dynamic models in the literature. The results show that the presented method can give a new dynamic modeling method for vibration formulation for a rigid RBS with and without the LOD on the races.

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study

PubMed Central

2010-01-01

Background Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. Methods Setting: Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. Results The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p = 0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p = 0.047). Conclusions CC, but not LOD, increases the complication rate in pregnant patients who received metformin. PMID:20465786

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study.

PubMed

Ott, Johannes; Kurz, Christine; Nouri, Kazem; Wirth, Stefan; Vytiska-Binstorfer, Elisabeth; Huber, Johannes C; Mayerhofer, Klaus

2010-05-13

Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p=0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p=0.047). CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

PubMed

Yang, Qiong; Tofler, Geoffrey H; Cupples, L Adrienne; Larson, Martin G; Feng, DaLi; Lindpaintner, Klaus; Levy, Daniel; D'Agostino, Ralph B; O'Donnell, Christopher J

2003-04-15

Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

40 CFR 1065.710 - Gasoline.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: Initial boiling point °C 24-35 2 24-36 10% point °C 49-57 37-48 ASTM D86-07a. 50% point °C 93-110 82-101... m3/m3 Maximum, 0.10 Maximum, 0.175 ASTM D1319-03. Aromatics Maximum, 0.35 Maximum, 0.304 Saturates.../liter Maximum, 0.0013 Maximum, 0.005 ASTM D3231-07. Total sulfur mg/kg Maximum, 80 Maximum, 80 ASTM...

Improving a maximum horizontal gradient algorithm to determine geological body boundaries and fault systems based on gravity data

NASA Astrophysics Data System (ADS)

Van Kha, Tran; Van Vuong, Hoang; Thanh, Do Duc; Hung, Duong Quoc; Anh, Le Duc

2018-05-01

The maximum horizontal gradient method was first proposed by Blakely and Simpson (1986) for determining the boundaries between geological bodies with different densities. The method involves the comparison of a center point with its eight nearest neighbors in four directions within each 3 × 3 calculation grid. The horizontal location and magnitude of the maximum values are found by interpolating a second-order polynomial through the trio of points provided that the magnitude of the middle point is greater than its two nearest neighbors in one direction. In theoretical models of multiple sources, however, the above condition does not allow the maximum horizontal locations to be fully located, and it could be difficult to correlate the edges of complicated sources. In this paper, the authors propose an additional condition to identify more maximum horizontal locations within the calculation grid. This additional condition will improve the method algorithm for interpreting the boundaries of magnetic and/or gravity sources. The improved algorithm was tested on gravity models and applied to gravity data for the Phu Khanh basin on the continental shelf of the East Vietnam Sea. The results show that the additional locations of the maximum horizontal gradient could be helpful for connecting the edges of complicated source bodies.

MSClique: Multiple Structure Discovery through the Maximum Weighted Clique Problem.

PubMed

Sanroma, Gerard; Penate-Sanchez, Adrian; Alquézar, René; Serratosa, Francesc; Moreno-Noguer, Francesc; Andrade-Cetto, Juan; González Ballester, Miguel Ángel

2016-01-01

We present a novel approach for feature correspondence and multiple structure discovery in computer vision. In contrast to existing methods, we exploit the fact that point-sets on the same structure usually lie close to each other, thus forming clusters in the image. Given a pair of input images, we initially extract points of interest and extract hierarchical representations by agglomerative clustering. We use the maximum weighted clique problem to find the set of corresponding clusters with maximum number of inliers representing the multiple structures at the correct scales. Our method is parameter-free and only needs two sets of points along with their tentative correspondences, thus being extremely easy to use. We demonstrate the effectiveness of our method in multiple-structure fitting experiments in both publicly available and in-house datasets. As shown in the experiments, our approach finds a higher number of structures containing fewer outliers compared to state-of-the-art methods.

A comparative study of artificial intelligent-based maximum power point tracking for photovoltaic systems

NASA Astrophysics Data System (ADS)

Hussain Mutlag, Ammar; Mohamed, Azah; Shareef, Hussain

2016-03-01

Maximum power point tracking (MPPT) is normally required to improve the performance of photovoltaic (PV) systems. This paper presents artificial intelligent-based maximum power point tracking (AI-MPPT) by considering three artificial intelligent techniques, namely, artificial neural network (ANN), adaptive neuro fuzzy inference system with seven triangular fuzzy sets (7-tri), and adaptive neuro fuzzy inference system with seven gbell fuzzy sets. The AI-MPPT is designed for the 25 SolarTIFSTF-120P6 PV panels, with the capacity of 3 kW peak. A complete PV system is modelled using 300,000 data samples and simulated in the MATLAB/SIMULINK. The AI-MPPT has been tested under real environmental conditions for two days from 8 am to 18 pm. The results showed that the ANN based MPPT gives the most accurate performance and then followed by the 7-tri-based MPPT.

Detection of enteropathogens associated with travelers’ diarrhea using a multiplex Luminex-based assay performed on stool samples smeared on Whatman FTA Elute cards

PubMed Central

Lalani, Tahaniyat; Tisdale, Michele D; Maguire, Jason D; Wongsrichanalai, Chansuda; Riddle, Mark S; Tribble, David R

2015-01-01

We evaluated the limits of detection (LoD) for an 11-plex PCR-Luminex assay performed on Whatman FTA Elute cards smeared with stool containing pathogens associated with travelers’ diarrhea. LoDs ranged between 102-105 CFU, PFU or cysts/g for most pathogens except Cryptosporidium. Campylobacter and norovirus LoD increased with prolonged storage of cards. PMID:26072151

Estimation and test for linkage between markers: a comparison of lod score and χ (2) test in a linkage study of maritime pine (Pinus pinaster Ait.).

PubMed

Gerber, S; Rodolphe, F

1994-06-01

The first step in the construction of a linkage map involves the estimation and test for linkage between all possible pairs of markers. The lod score method is used in many linkage studies for the latter purpose. In contrast with classical statistical tests, this method does not rely on the choice of a first-type error level. We thus provide a comparison between the lod score and a χ (2) test on linkage data from a gymnosperm, the maritime pine. The lod score appears to be a very conservative test with the usual thresholds. Its severity depends on the type of data used.

Major strengths and weaknesses of the lod score method.

PubMed

Ott, J

2001-01-01

Strengths and weaknesses of the lod score method for human genetic linkage analysis are discussed. The main weakness is its requirement for the specification of a detailed inheritance model for the trait. Various strengths are identified. For example, the lod score (likelihood) method has optimality properties when the trait to be studied is known to follow a Mendelian mode of inheritance. The ELOD is a useful measure for information content of the data. The lod score method can emulate various "nonparametric" methods, and this emulation is equivalent to the nonparametric methods. Finally, the possibility of building errors into the analysis will prove to be essential for the large amount of linkage and disequilibrium data expected in the near future.

Detection of lead in brass by laser-induced breakdown spectroscopy combined with laser-induced fluorescence

NASA Astrophysics Data System (ADS)

Goueguel, Christian; Laville, Stéphane; Loudyi, Hakim; Chaker, Mohamed; Sabsabi, Mohamad; Vidal, François

2008-06-01

Laser-Induced Breakdown Spectroscopy (LIBS) technique combined with Laser-Induced Fluorescence (LIF) is known to be a high sensitivity and high selectivity analytical technique. Although sub-ppm limits of detection (LoD) have already been demonstrated, there is still a constant and urgent need to reach lower LoDs. Here, we report results obtained for the detection of lead trace in brass samples. The plasma was produced by a Q-switched Nd:YAG laser at 1064 nm and then re-excited by a nanosecond optical parametric oscillator (OPO) laser tuned at 283.31 nm. Emission from Pb atoms was then observed at 405.78 nm. The experiments were performed in air at atmospheric pressure. We found out that the optimal conditions were obtained for an ablation fluence of 2-3 J/cm2 and inter-pulse delay of 8-10 μs. Also, excitation energy of about 200 μJ was required to maximize the Pb(I) 405.78 nm emission. Using the LIBS-LIFS technique, the LoD was estimated to be about 180 ppb over 100 laser shots, which corresponds to an improvement of about two orders of magnitude with that obtained using conventional LIBS.

A comparison of LOD and UT1-UTC forecasts by different combined prediction techniques

NASA Astrophysics Data System (ADS)

Kosek, W.; Kalarus, M.; Johnson, T. J.; Wooden, W. H.; McCarthy, D. D.; Popiński, W.

Stochastic prediction techniques including autocovariance, autoregressive, autoregressive moving average, and neural networks were applied to the UT1-UTC and Length of Day (LOD) International Earth Rotation and Reference Systems Servive (IERS) EOPC04 time series to evaluate the capabilities of each method. All known effects such as leap seconds and solid Earth zonal tides were first removed from the observed values of UT1-UTC and LOD. Two combination procedures were applied to predict the resulting LODR time series: 1) the combination of the least-squares (LS) extrapolation with a stochastic predition method, and 2) the combination of the discrete wavelet transform (DWT) filtering and a stochastic prediction method. The results of the combination of the LS extrapolation with different stochastic prediction techniques were compared with the results of the UT1-UTC prediction method currently used by the IERS Rapid Service/Prediction Centre (RS/PC). It was found that the prediction accuracy depends on the starting prediction epochs, and for the combined forecast methods, the mean prediction errors for 1 to about 70 days in the future are of the same order as those of the method used by the IERS RS/PC.

Improved geophysical excitation of length-of-day constrained by Earth orientation parameters and satellite gravimetry products

NASA Astrophysics Data System (ADS)

Yu, Nan; Li, Jiancheng; Ray, Jim; Chen, Wei

2018-05-01

At time scales shorter than about two years, non-tidal LOD variations are mainly excited by angular momentum exchanges between the atmospheric, oceanic, and continental hydrological fluid envelopes and the underlying solid Earth. But, neither agreement among different geophysical models for the fluid dynamics nor consistency with geodetic observations of LOD has reached satisfactory levels. This is mainly ascribed to significant discrepancies and uncertainties in the theories and assumptions adopted by different modeling groups, in their numerical methods, and in the accuracy and coverage of global input data fields. Based on careful comparisons with more accurate geodetic measurements and satellite gravimetry products (from satellite laser ranging, SLR), observed length-of day (LOD) and C20 geopotential time series can provide strong constraints to evaluate or form combined geophysical models. In this study, wavelet decomposition is used to extract several narrow-band components to compare in addition to considering the total signals. We then make refinements to the least difference combination (LDC) method proposed by Chen et al. (2013b) to form multi-model geophysical excitations. Two combination variants, called the weighted mean combination (WMC2 and WMC4), are also evaluated. All the multi-model methods attempt to extract the best-modeled frequency components from each geophysical model by relying on geodetic excitation and the C20 series as references. The comparative performances of the three combinations LDC, WMC2 and WMC4 and the original single models are determined. We find that (1) the Estimating the Circulation and Climate of the Ocean (ECCO) and Max-Planck-Institute for Meteorology Ocean Model (MPIOM) give a more reliable view of the ocean redistributions than the Ocean Model for Circulation and Tides (OMCT) used by European Centre for Medium-Range Weather Forecasts (ECMWF), especially for the annual component; (2) C20 series from SLR can provide a rigorous constraint for the total matter excitation of the geophysical fluids, especially for broadband parts; (3) the Sea-Level Angular Momentum functions (SLAM) term, correcting for sea level effects (global mass balance) put forward by the Earth System Modelling group at GFZ German Research Centre for Geosciences (ESMGFZ), can significantly improve the Hydrospheric Effective Angular Momentum functions (HAM) matter terms; (4) the LDC/WMC combinations are much better than the original individual geophysical model excitations, reducing the magnitude of unexplained LOD excitations to roughly the 10 μs level; (5) the level of residual LOD variations after removing models or model combinations is remarkably invariant with respect to LOD periods between ˜2 months and ˜3 years, being 12 to 14 μs for the best original models and 7 to 12 μs for our combinations; (6) while differences between the IERS 14C04 and the JPL SPACE2015 geodetic LOD time series are not negligible, errors in both series are still not large compared to the geophysical models (for periods >2 months) so the impact on excitation studies is minimal except at semi-annual periods and usually 14C04 compares better with excitation models. The improved geophysical models are recommended to replace the original ones as they present overwhelming advantages.

40 CFR 1039.515 - What are the test procedures related to not-to-exceed standards?

Code of Federal Regulations, 2010 CFR

2010-07-01

...; however, use the power value corresponding to the engine operation at 30% of maximum torque at the B speed... 50% torque/power points) and below the line formed by connecting the two points in paragraphs (b)(2)(ii) and (iii) of this section (the 50% and 70% torque/power points). The 30%, 50%, and 70% torque...

Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22.

PubMed

Scott, William K; Hauser, Elizabeth R; Schmechel, Donald E; Welsh-Bohmer, Kathleen A; Small, Gary W; Roses, Allen D; Saunders, Ann M; Gilbert, John R; Vance, Jeffery M; Haines, Jonathan L; Pericak-Vance, Margaret A

2003-11-01

Alzheimer disease (AD) is a complex disorder characterized by a wide range, within and between families, of ages at onset of symptoms. Consideration of age at onset as a covariate in genetic-linkage studies may reduce genetic heterogeneity and increase statistical power. Ordered-subsets analysis includes continuous covariates in linkage analysis by rank ordering families by a covariate and summing LOD scores to find a subset giving a significantly increased LOD score relative to the overall sample. We have analyzed data from 336 markers in 437 multiplex (>/=2 sampled individuals with AD) families included in a recent genomic screen for AD loci. To identify genetic heterogeneity by age at onset, families were ordered by increasing and decreasing mean and minimum ages at onset. Chromosomewide significance of increases in the LOD score in subsets relative to the overall sample was assessed by permutation. A statistically significant increase in the nonparametric multipoint LOD score was observed on chromosome 2q34, with a peak LOD score of 3.2 at D2S2944 (P=.008) in 31 families with a minimum age at onset between 50 and 60 years. The LOD score in the chromosome 9p region previously linked to AD increased to 4.6 at D9S741 (P=.01) in 334 families with minimum age at onset between 60 and 75 years. LOD scores were also significantly increased on chromosome 15q22: a peak LOD score of 2.8 (P=.0004) was detected at D15S1507 (60 cM) in 38 families with minimum age at onset >/=79 years, and a peak LOD score of 3.1 (P=.0006) was obtained at D15S153 (62 cM) in 43 families with mean age at onset >80 years. Thirty-one families were contained in both 15q22 subsets, indicating that these results are likely detecting the same locus. There is little overlap in these subsets, underscoring the utility of age at onset as a marker of genetic heterogeneity. These results indicate that linkage to chromosome 9p is strongest in late-onset AD and that regions on chromosome 2q34 and 15q22 are linked to early-onset AD and very-late-onset AD, respectively.

El Nino, La Nina and VLBI Measured LOD

NASA Technical Reports Server (NTRS)

Clark, Thomas A.; Gipson, J. M.; Ma, C.

1998-01-01

VLBI is one of the most important techniques for measuring Earth orientation parameters (EOP), and is unique in its ability to make high accuracy measurements of UT1, and its time derivative, which is related to changes in the length of day, conventionally called LOD. These measurements of EOP give constraints on geophysical models of the solid-Earth, atmosphere and oceans. Changes in EOP are due either to external torques from gravitational forces, or to the exchange of angular momentum between the Earth, atmosphere and oceans. The effect of the external torques is strictly harmonic and nature, and is therefore easy to remove. We analyze an LOD time series derived from VLBI measurements with the goal of comparing this to predictions from AAM, and various ENSO indices. Previous work by ourselves and other investigators demonstrated a high degree of coherence between atmospheric angular momentum (AAM) and EOP. We continue to see this. As the angular momentum of the atmosphere increases, the rate of rotation of the Earth decreases, and vice versa. The signature of the ENSO is particularly strong. At the peak of the 1982-83 El Nino increased LOD by almost 1 ms. This was subsequently followed by a reduction in LOD of 0.75 ms. At its peak, in February of 1998, the 1997-98 El Nino increased LOD by 0.8 msec. As predicted at the 1998 Spring AGU, this has been followed by an abrupt decrease in LOD which is currently -0.4 ms. At this time (August, 1998) the current ENSO continues to develop in new and unexpected ways. We plan to update our analysis with all data available prior to the Fall AGU.

Validation of the LOD score compared with APACHE II score in prediction of the hospital outcome in critically ill patients.

PubMed

Khwannimit, Bodin

2008-01-01

The Logistic Organ Dysfunction score (LOD) is an organ dysfunction score that can predict hospital mortality. The aim of this study was to validate the performance of the LOD score compared with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in a mixed intensive care unit (ICU) at a tertiary referral university hospital in Thailand. The data were collected prospectively on consecutive ICU admissions over a 24 month period from July1, 2004 until June 30, 2006. Discrimination was evaluated by the area under the receiver operating characteristic curve (AUROC). The calibration was assessed by the Hosmer-Lemeshow goodness-of-fit H statistic. The overall fit of the model was evaluated by the Brier's score. Overall, 1,429 patients were enrolled during the study period. The mortality in the ICU was 20.9% and in the hospital was 27.9%. The median ICU and hospital lengths of stay were 3 and 18 days, respectively, for all patients. Both models showed excellent discrimination. The AUROC for the LOD and APACHE II were 0.860 [95% confidence interval (CI) = 0.838-0.882] and 0.898 (95% Cl = 0.879-0.917), respectively. The LOD score had perfect calibration with the Hosmer-Lemeshow goodness-of-fit H chi-2 = 10 (p = 0.44). However, the APACHE II had poor calibration with the Hosmer-Lemeshow goodness-of-fit H chi-2 = 75.69 (p < 0.001). Brier's score showed the overall fit for both models were 0.123 (95%Cl = 0.107-0.141) and 0.114 (0.098-0.132) for the LOD and APACHE II, respectively. Thus, the LOD score was found to be accurate for predicting hospital mortality for general critically ill patients in Thailand.

A genomic scan for age at onset of Alzheimer's disease in 437 families from the NIMH Genetic Initiative.

PubMed

Dickson, M Ryan; Li, Jian; Wiener, Howard W; Perry, Rodney T; Blacker, Deborah; Bassett, Susan S; Go, Rodney C P

2008-09-05

We performed linkage analysis for age at onset (AAO) in the total Alzheimer's disease (AD) NIMH sample (N = 437 families). Families were subset as late-onset (320 families, AAO > or = 65) and early/mixed (117 families, at least 1 member with 50 < AAO < 65). Treating AAO as a censored trait, we obtained the gender and APOE adjusted residuals in a parametric survival model and analyzed the residuals as the quantitative trait (QT) in variance-component linkage analysis. For comparison, AAO-age at exam (AAE) was analyzed as the QT adjusting for affection status, gender, and APOE. Heritabilities for residual and AAO-AAE outcomes were 66.3% and 74.0%, respectively for the total sample, 56.0% and 57.0% in the late-onset sample, and 33.0% for both models in the early/mixed sample. The residual model yielded the largest peaks on chromosome 1 with LOD = 2.0 at 190 cM in the total set, LOD = 1.7 at 116 cM on chromosome 3 in the early/mixed subset, and LOD = 1.4 at 71 and 86 cM, respectively, on chromosome 6 in the late-onset subset. For the AAO-AAE outcome model the largest peaks were identified on chromosome 1 at 137 cM (LOD = 2.8) and chromosome 6 at 69 cM (LOD = 2.3) and 86 cM (LOD = 2.2) all in the late-onset subset. Additional peaks with LOD > or = 1 were identified on chromosomes 1, 2, 3, 6, 8, 9, 10, and 12 for the total sample and each subset. Results replicate previous findings, but identify additional suggestive peaks indicating the genetics of AAO in AD is complex with many chromosomal regions potentially containing modifying genes. 2008 Wiley-Liss, Inc.

Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks.

PubMed

Liu, Rui; Yue, Yingying; Hou, Zhenghua; Yuan, Yonggui; Wang, Qiao

2018-08-01

Abnormal functional connectivity (FC) in the default mode network (DMN) plays an important role in late-onset depression (LOD) patients. In this study, the risk predictors of LOD based on anterior and posterior DMN are explored. A total of 27 LOD patients and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging and cognitive assessments. Firstly, FCs within DMN sub-networks were determined by placing seeds in the ventral medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Secondly, multivariable logistic regression was used to identify risk factors for LOD patients. Finally, correlation analysis was performed to investigate the relationship between risk factors and the cognitive value. Multivariable logistic regression showed that the FCs between the vmPFC and right middle temporal gyrus (MTG) (vmPFC-MTG_R), FCs between the vmPFC and left precuneus (PCu), and FCs between the PCC and left PCu (PCC-PCu_L) were the risk factors for LOD. Furthermore, FCs of the vmPFC-MTG_R and PCC-PCu_L correlated with processing speed (R = 0.35, P = 0.002; R = 0.32, P = 0.009), and FCs of the vmPFC-MTG_R correlated with semantic memory (R = 0.41, P = 0.001). The study was a cross-sectional study. The results may be potentially biased because of a small sample. In this study, we confirmed that LOD patients mainly present cognitive deficits in processing speed and semantic memory. Moreover, our findings further suggested that FCs within DMN sub-networks associated with cognitions were risk factors, which may be used for the prediction of LOD. Copyright © 2018 Elsevier B.V. All rights reserved.

Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

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

Thomas, P.M.; Cote, G.J.; Hallman, D.M.

1995-02-01

Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [{theta} = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to bemore » assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release. 37 refs., 2 figs., 4 tabs.« less

Refinement of the NHS locus on chromosome Xp22.13 and analysis of five candidate genes.

PubMed

Toutain, Annick; Dessay, Benoît; Ronce, Nathalie; Ferrante, Maria-Immacolata; Tranchemontagne, Julie; Newbury-Ecob, Ruth; Wallgren-Pettersson, Carina; Burn, John; Kaplan, Josseline; Rossi, Annick; Russo, Silvia; Walpole, Ian; Hartsfield, James K; Oyen, Nina; Nemeth, Andrea; Bitoun, Pierre; Trump, Dorothy; Moraine, Claude; Franco, Brunella

2002-09-01

Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, dental abnormalities, dysmorphic features, and mental retardation in some cases. Previous studies have mapped the disease gene to a 2 cM interval on Xp22.2 between DXS43 and DXS999. We report additional linkage data resulting from the analysis of eleven independent NHS families. A maximum lod score of 9.94 (theta=0.00) was obtained at the RS1 locus and a recombination with locus DXS1195 on the telomeric side was observed in two families, thus refining the location of the gene to an interval of around 1 Mb on Xp22.13. Direct sequencing or SSCP analysis of the coding exons of five genes (SCML1, SCML2, STK9, RS1 and PPEF1), considered as candidate genes on the basis of their location in the critical interval, failed to detect any mutation in 12 unrelated NHS patients, thus making it highly unlikely that these genes are implicated in NHS.

Effective synthesis of magnetic porous molecularly imprinted polymers for efficient and selective extraction of cinnamic acid from apple juices.

PubMed

Shi, Shuyun; Fan, Dengxin; Xiang, Haiyan; Li, Huan

2017-12-15

An effective strategy was proposed to prepare novel magnetic porous molecularly imprinted polymers (MPMIPs) for highly selective extraction of cinnamic acid (CMA) from complex matrices. Characterization and various parameters affecting adsorption and desorption behaviors were investigated. Results revealed adsorption behavior between CMA and MPMIPs followed Freundlich equation adsorption isotherm with a maximum adsorption capacity at 4.35mg/g and pseudo-second-order reaction kinetics with equilibrium time at 60min. Subsequently, MPMIPs were successfully used to selectively extract CMA from apple juice with a relatively satisfactory recovery (92.7-101.4%). Coupling with high-performance liquid chromatography and ultraviolet detection (HPLC-UV), the limit of detection (LOD) for CMA was 0.006µg/mL, and the linear range (0.02-10μg/mL) was wide with correlation coefficient at 0.9995. Finally, the contents of CMA in two kinds of apple juices were determined as 0.132 and 0.120μg/mL. Results indicated the superiority of MPMIPs in the selective extraction field. Copyright © 2017 Elsevier Ltd. All rights reserved.

The slick hair coat locus maps to chromosome 20 in Senepol-derived cattle.

PubMed

Mariasegaram, M; Chase, C C; Chaparro, J X; Olson, T A; Brenneman, R A; Niedz, R P

2007-02-01

The ability to maintain normal temperatures during heat stress is an important attribute for cattle in the subtropics and tropics. Previous studies have shown that Senepol cattle and their crosses with Holstein, Charolais and Angus animals are as heat tolerant as Brahman cattle. This has been attributed to the slick hair coat of Senepol cattle, which is thought to be controlled by a single dominant gene. In this study, a genome scan using a DNA-pooling strategy indicated that the slick locus is most likely on bovine chromosome 20 (BTA20). Interval mapping confirmed the BTA20 assignment and refined the location of the locus. In total, 14 microsatellite markers were individually genotyped in two pedigrees consisting of slick and normal-haired cattle (n = 36), representing both dairy and beef breeds. The maximum LOD score was 9.4 for a 4.4-cM support interval between markers DIK2416 and BM4107. By using additional microsatellite markers in this region, and genotyping in six more pedigrees (n = 86), the slick locus was further localized to the DIK4835 - DIK2930 interval.

Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families

PubMed Central

Khan, Shahid Y.; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2015-01-01

Purpose This study was conducted to localize and identify causal mutations associated with autosomal recessive retinitis pigmentosa (RP) in consanguineous familial cases of Pakistani origin. Methods Ophthalmic examinations that included funduscopy and electroretinography (ERG) were performed to confirm the affectation status. Blood samples were collected from all participating individuals, and genomic DNA was extracted. A genome-wide scan was performed, and two-point logarithm of odds (LOD) scores were calculated. Sanger sequencing was performed to identify the causative variants. Subsequently, we performed whole exome sequencing to rule out the possibility of a second causal variant within the linkage interval. Sequence conservation was performed with alignment analyses of PDE6A orthologs, and in silico splicing analysis was completed with Human Splicing Finder version 2.4.1. Results A large multigenerational consanguineous family diagnosed with early-onset RP was ascertained. An ophthalmic clinical examination consisting of fundus photography and electroretinography confirmed the diagnosis of RP. A genome-wide scan was performed, and suggestive two-point LOD scores were observed with markers on chromosome 5q. Haplotype analyses identified the region; however, the region did not segregate with the disease phenotype in the family. Subsequently, we performed a second genome-wide scan that excluded the entire genome except the chromosome 5q region harboring PDE6A. Next-generation whole exome sequencing identified a splice acceptor site mutation in intron 16: c.2028–1G>A, which was completely conserved in PDE6A orthologs and was absent in ethnically matched 350 control chromosomes, the 1000 Genomes database, and the NHLBI Exome Sequencing Project. Subsequently, we investigated our entire cohort of RP familial cases and identified a second family who harbored a splice acceptor site mutation in intron 10: c.1408–2A>G. In silico analysis suggested that these mutations will result in the elimination of wild-type splice acceptor sites that would result in either skipping of the respective exon or the creation of a new cryptic splice acceptor site; both possibilities would result in retinal photoreceptor cells that lack PDE6A wild-type protein. Conclusions we report two splice acceptor site variations in PDE6A in consanguineous Pakistani families who manifested cardinal symptoms of RP. Taken together with our previously published work, our data suggest that mutations in PDE6A account for about 2% of the total genetic load of RP in our cohort and possibly in the Pakistani population as well. PMID:26321862

Perchlorate Exposure Through Water and Milk in Istanbul.

PubMed

Can, Ozge; Blount, Ben; Valentin-Blasini, Liza; Erdemgil, Yigit; Uzunoglu, Deniz; Aksoy, Murat; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim; Ozpinar, Aysel

2016-09-01

Perchlorate is a chemical pollutant that inhibits iodide uptake and may possibly impair thyroid function. Our previous study found widespread perchlorate exposure in non-pregnant, non-lactating, healthy women residing in Istanbul. The aim of this study is to assess the relative amounts of perchlorate exposure attributable to consumption of municipal water, bottled water and boxed milk available in Istanbul. Only trace levels of perchlorate were found in treated municipal water (58 % detectable, mean = 0.13 µg/L, maximum = 0.75 µg/L) and bottled water (7.4 % detectable, mean = 

Identification of candidate regions for a novel Usher syndrome type II locus.

PubMed

Ben Rebeh, Imen; Benzina, Zeineb; Dhouib, Houria; Hadjamor, Imen; Amyere, Mustapha; Ayadi, Leila; Turki, Khalil; Hammami, Bouthaina; Kmiha, Noureddine; Kammoun, Hassen; Hakim, Bochra; Charfedine, Ilhem; Vikkula, Miikka; Ghorbel, Abdelmonem; Ayadi, Hammadi; Masmoudi, Saber

2008-09-19

Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin. Affected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes. Haplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q. Our data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q.

The Prediction of Length-of-day Variations Based on Gaussian Processes

NASA Astrophysics Data System (ADS)

Lei, Y.; Zhao, D. N.; Gao, Y. P.; Cai, H. B.

2015-01-01

Due to the complicated time-varying characteristics of the length-of-day (LOD) variations, the accuracies of traditional strategies for the prediction of the LOD variations such as the least squares extrapolation model, the time-series analysis model, and so on, have not met the requirements for real-time and high-precision applications. In this paper, a new machine learning algorithm --- the Gaussian process (GP) model is employed to forecast the LOD variations. Its prediction precisions are analyzed and compared with those of the back propagation neural networks (BPNN), general regression neural networks (GRNN) models, and the Earth Orientation Parameters Prediction Comparison Campaign (EOP PCC). The results demonstrate that the application of the GP model to the prediction of the LOD variations is efficient and feasible.

Hierarchical automated clustering of cloud point set by ellipsoidal skeleton: application to organ geometric modeling from CT-scan images

NASA Astrophysics Data System (ADS)

Banegas, Frederic; Michelucci, Dominique; Roelens, Marc; Jaeger, Marc

1999-05-01

We present a robust method for automatically constructing an ellipsoidal skeleton (e-skeleton) from a set of 3D points taken from NMR or TDM images. To ensure steadiness and accuracy, all points of the objects are taken into account, including the inner ones, which is different from the existing techniques. This skeleton will be essentially useful for object characterization, for comparisons between various measurements and as a basis for deformable models. It also provides good initial guess for surface reconstruction algorithms. On output of the entire process, we obtain an analytical description of the chosen entity, semantically zoomable (local features only or reconstructed surfaces), with any level of detail (LOD) by discretization step control in voxel or polygon format. This capability allows us to handle objects at interactive frame rates once the e-skeleton is computed. Each e-skeleton is stored as a multiscale CSG implicit tree.

Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1

PubMed Central

Hedera, P; Toriello, H; Petty, E

2002-01-01

Methods: Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype. Results: Affected subjects had significant craniofacial abnormalities without any significant acral changes and thus had a phenotype consistent with a MFD variant. Distinctive features included hypoplasia of the zygomatic complex, micrognathia with malocclusion, auricular abnormalities with conductive hearing loss, and ptosis. Significantly negative two point lod scores were obtained for markers spanning the TCOF1 locus, excluding the possibility that the disease in our kindred is allelic with TCS. High resolution karyotype was normal. Conclusions: We report a kindred with a novel type of MFD that is not linked to the TCOF1 locus and is also clinically distinct from other types of AD MFD. Identification of additional families will facilitate identification of the gene causing this type of AD MFD and further characterisation of the clinical phenotype. PMID:12114479

Detection of enteropathogens associated with travelers' diarrhea using a multiplex Luminex-based assay performed on stool samples smeared on Whatman FTA Elute cards.

PubMed

Lalani, Tahaniyat; Tisdale, Michele D; Maguire, Jason D; Wongsrichanalai, Chansuda; Riddle, Mark S; Tribble, David R

2015-09-01

We evaluated the limits of detection (LoD) for an 11-plex PCR-Luminex assay performed on Whatman(™) FTA Elute cards smeared with stool containing pathogens associated with travelers' diarrhea. LoDs ranged from 10(2) to 10(5)CFU, PFU, or cysts/g for most pathogens except Cryptosporidium. Campylobacter and norovirus LoDs increased with prolonged storage of cards. Copyright © 2015 Elsevier Inc. All rights reserved.

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

Entity-based Stochastic Analysis of Search Results for Query Expansion and Results Re-Ranking

DTIC Science & Technology

2015-11-20

pages) and struc- tured data (e.g. Linked Open Data ( LOD ) [8]) coexist in var- ious forms. An important observation is that entity names (like names of...the top-L (e.g. L = 1, 000) results are retrieved. Then, Named Entity Recognition (NER) is applied in these results for identifying LOD entities. In...the next (optional) step, more semantic information about the identified entities is retrieved from the LOD (like properties and related entities). A

Concentrations of buparvaquone in milk and tissue of dairy cows.

PubMed

McDougall, S; Hillerton, J E; Pegram, D

2016-11-01

To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk. Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5 mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018 mg/kg for muscle and 0.00023 mg/L for milk. Concentrations of buparvaquone in milk and tissues were log10-transformed for analysis using multivariate models. In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3). Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows. Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.

Evaluation of aflatoxins and Aspergillus sp. contamination in raw peanuts and peanut-based products along the supply chain in Malaysia.

PubMed

Norlia, Mahror; Nor-Khaizura, M A R; Selamat, Jinap; Abu Bakar, Fatimah; Radu, Son; Chin, Cheow Keat

2018-06-18

The peanut supply chain in Malaysia is dominated by three main stakeholders (importers, manufacturers, retailers). The present study, aimed to determine the levels and critical points of aflatoxins and fungal contamination in peanuts along the supply chain. Specifically, two types of raw peanuts and six types of peanut-based products were collected (N = 178). Samples were analysed for aflatoxins by using High Performance Liquid Chromatography. Results revealed that the aflatoxins contamination was significantly higher (P≤0.05) in raw peanuts and peanut-based products from the retailers. However, there was no significant different (P≥0.05) in fungal contamination for both types of peanuts except for the total fungal count in raw peanuts from the retailers. Furthermore, raw peanut kernels from the retailers were the most contaminated ones ranged from

Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

PubMed Central

Massett, Michael P.; Avila, Joshua J.; Kim, Seung Kyum

2015-01-01

Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training. PMID:26710100

Interband cascade laser-based ppbv-level mid-infrared methane detection using two digital lock-in amplifier schemes

NASA Astrophysics Data System (ADS)

Song, Fang; Zheng, Chuantao; Yu, Di; Zhou, Yanwen; Yan, Wanhong; Ye, Weilin; Zhang, Yu; Wang, Yiding; Tittel, Frank K.

2018-03-01

A parts-per-billion in volume (ppbv) level mid-infrared methane (CH4) sensor system was demonstrated using second-harmonic wavelength modulation spectroscopy (2 f-WMS). A 3291 nm interband cascade laser (ICL) and a multi-pass gas cell (MPGC) with a 16 m optical path length were adopted in the reported sensor system. Two digital lock-in amplifier (DLIA) schemes, a digital signal processor (DSP)-based DLIA and a LabVIEW-based DLIA, were used for harmonic signal extraction. A limit of detection (LoD) of 13.07 ppbv with an averaging time of 2 s was achieved using the DSP-based DLIA and a LoD of 5.84 ppbv was obtained using the LabVIEW-based DLIA with the same averaging time. A rise time of 0→2 parts-per-million in volume (ppmv) and fall time of 2→0 ppmv were observed. Outdoor atmospheric CH4 concentration measurements were carried out to evaluate the sensor performance using the two DLIA schemes.

The Influence of Internal and External Torques on Titan's Length-of-day Variations

NASA Astrophysics Data System (ADS)

van Hoolst, T.; Karatekin, O.; Rambaux, N.

2008-12-01

Cassini radar observations show that Titan's spin is slightly faster than synchronous spin. Angular momentum exchange between Titan and its atmosphere is the most likely cause of the observed non-synchronous rotation. We study the effect of Saturn's gravitational torque and torques between Titan's internal layers on the length-of-day (LOD) variations driven by the atmosphere. Those torques depend on the equatorial flattening of Titan resulting from static tides raised by Saturn. We calculate Titan's flattening under the assumption of hydrostatic equilibrium and show that the gravitational forcing by Saturn, due to misalignment of the long axis of Titan with the line joining the mass centers of Titan and Saturn, reduces the LOD variations with respect to those for a spherical Titan by an order of magnitude. Internal gravitational and pressure coupling between the ice shell and the interior beneath a putative ocean tends to diminish any differential rotation between shell and interior and reduces further the LOD variations by a few times. For the current estimate of the atmospheric torque, we obtain LOD variations of a hydrostatic Titan that are more than 50 times smaller than the observations indicate when a subsurface ocean exists and more than 100 times smaller when Titan has no ocean. Moreover, Saturn's torque causes the rotation to be slower than synchronous in contrast to the Cassini observations. Those large differences with the observations suggest that non-hydrostatic effects in Titan are important. In particular, we show that the amplitude and phase of the calculated rotation variations would be similar to the observed values if non-hydrostatic effects strongly reduce the equatorial flattening of the ice shell above an internal ocean. Alternatively, the calculated LOD variations could be increased if the atmospheric torque is larger than predicted or if fast viscous relaxation of the ice shell could reduce the gravitational coupling, but it remains to be studied if a two order of magnitude increase is possible and if these effects can explain the phase difference of the predicted rotation variations.

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states.

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states. PMID:23393608

From cellular lysis to microarray detection, an integrated thermoplastic elastomer (TPE) point of care Lab on a Disc.

PubMed

Roy, Emmanuel; Stewart, Gale; Mounier, Maxence; Malic, Lidija; Peytavi, Régis; Clime, Liviu; Madou, Marc; Bossinot, Maurice; Bergeron, Michel G; Veres, Teodor

2015-01-21

We present an all-thermoplastic integrated sample-to-answer centrifugal microfluidic Lab-on-Disc system (LoD) for nucleic acid analysis. The proposed CD system and engineered platform were employed for analysis of Bacillus atrophaeus subsp. globigii spores. The complete assay comprised cellular lysis, polymerase chain reaction (PCR) amplification, amplicon digestion, and microarray hybridization on a plastic support. The fluidic robustness and operating efficiency of the assay were ensured through analytical optimization of microfluidic tools enabling beneficial implementation of capillary valves and accurate control of all flow timing procedures. The assay reliability was further improved through the development of two novel microfluidic strategies for reagents mixing and flow delay on the CD platform. In order to bridge the gap between the proof-of-concept LoD and production prototype demonstration, low-cost thermoplastic elastomer (TPE) was selected as the material for CD fabrication and assembly, allowing the use of both, high quality hot-embossing and injection molding processes. Additionally, the low-temperature and pressure-free assembly and bonding properties of TPE material offer a pertinent solution for simple and efficient loading and storage of reagents and other on-board components. This feature was demonstrated through integration and conditioning of microbeads, magnetic discs, dried DNA buffer reagents and spotted DNA array inserts. Furthermore, all microfluidic functions and plastic parts were designed according to the current injection mold-making knowledge for industrialization purposes. Therefore, the current work highlights a seamless strategy that promotes a feasible path for the transfer from prototype toward realistic industrialization. This work aims to establish the full potential for TPE-based centrifugal system as a mainstream microfluidic diagnostic platform for clinical diagnosis, water and food safety, and other molecular diagnostic applications.

Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families.

PubMed

Barral, Sandra; Vardarajan, Badri N; Reyes-Dumeyer, Dolly; Faber, Kelley M; Bird, Thomas D; Tsuang, Debby; Bennett, David A; Rosenberg, Roger; Boeve, Bradley F; Graff-Radford, Neill R; Goate, Alison M; Farlow, Martin; Lantigua, Rafael; Medrano, Martin Z; Wang, Xinbing; Kamboh, M Ilyas; Barmada, Mahmud Muhiedine; Schaid, Daniel J; Foroud, Tatiana M; Weamer, Elise A; Ottman, Ruth; Sweet, Robert A; Mayeux, Richard

2015-11-01

Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt] ​logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 × 10(-7)). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 × 10(-5)). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 × 10(-5)) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pseudoautosomal Linkage of Hodgkin Disease

PubMed Central

Horwitz, Marshall; Wiernik2, Peter H.

1999-01-01

Summary Heritable factors appear to account for much of the risk for Hodgkin disease (HD). There is evidence for an HLA-linked gene, but other predisposing loci remain unaccounted for. The observation of a family coinheriting both HD and Leri-Weill dyschondrosteosis (LWD) suggests that a gene conferring risk for HD resides adjacent to the LWD locus. The gene responsible for LWD, SHOX, localizes to the short-arm pseudoautosomal region (PAR) of the X and Y chromosomes. A unique segregation pattern for PAR-linked genes has been predicted—that affected sibs will tend to be same sex. An excess of sex-concordant affected sib pairs with HD has been noted but has been attributed to an environmental etiology. These two observations—sex concordance in sib pairs with HD and cosegregation of HD and LWD—impelled a test of the hypothesis that there is a PAR-localized gene for HD. By first scoring recombinations dissociating sex from phenotype in individuals from pedigrees with LWD, we determined a male maximum recombination frequency (θmax) of .405. This places SHOX near the short-arm telomeres of the sex chromosome and supports the prediction that PAR recombination is obligatory for spermatogenesis. By inferring recombinations between HD and sexual phenotype in sib pairs, we predict, for the postulated HD gene, a male θmax as high as .254, which places it in proximity to SHOX. Morton's nonparametric affected-sib-pair “β” model was used in the evaluation of linkage between HD and phenotypic sex and gave a LOD score of 2.41. Using this approach, we reevaluated evidence for HLA linkage in HD in haplotyped sib pairs and found a LOD score of 2.00. The resulting β values indicate that the putative PAR- and HLA-linked loci account for 29% and 40%, respectively, of the heritability of HD in an American population. PMID:10521308

Strategy for Sensitive and Specific Detection of Yersinia pestis in Skeletons of the Black Death Pandemic

PubMed Central

Seifert, Lisa; Harbeck, Michaela; Thomas, Astrid; Hoke, Nadja; Zöller, Lothar; Wiechmann, Ingrid; Grupe, Gisela; Scholz, Holger C.; Riehm, Julia M.

2013-01-01

Yersinia pestis has been identified as the causative agent of the Black Death pandemic in the 14th century. However, retrospective diagnostics in human skeletons after more than 600 years are critical. We describe a strategy following a modern diagnostic algorithm and working under strict ancient DNA regime for the identification of medieval human plague victims. An initial screening and DNA quantification assay detected the Y. pestis specific pla gene of the high copy number plasmid pPCP1. Results were confirmed by conventional PCR and sequence analysis targeting both Y. pestis specific virulence plasmids pPCP1 and pMT1. All assays were meticulously validated according to human clinical diagnostics requirements (ISO 15189) regarding efficiency, sensitivity, specificity, and limit of detection (LOD). Assay specificity was 100% tested on 41 clinically relevant bacteria and 29 Y. pseudotuberculosis strains as well as for DNA of 22 Y. pestis strains and 30 previously confirmed clinical human plague samples. The optimized LOD was down to 4 gene copies. 29 individuals from three different multiple inhumations were initially assessed as possible victims of the Black Death pandemic. 7 samples (24%) were positive in the pPCP1 specific screening assay. Confirmation through second target pMT1 specific PCR was successful for 4 of the positive individuals (14%). A maximum of 700 and 560 copies per µl aDNA were quantified in two of the samples. Those were positive in all assays including all repetitions, and are candidates for future continuative investigations such as whole genome sequencing. We discuss that all precautions taken here for the work with aDNA are sufficient to prevent external sample contamination and fulfill the criteria of authenticity. With regard to retrospective diagnostics of a human pathogen and the uniqueness of ancient material we strongly recommend using a careful strategy and validated assays as presented in our study. PMID:24069445

Strategy for sensitive and specific detection of Yersinia pestis in skeletons of the black death pandemic.

PubMed

Seifert, Lisa; Harbeck, Michaela; Thomas, Astrid; Hoke, Nadja; Zöller, Lothar; Wiechmann, Ingrid; Grupe, Gisela; Scholz, Holger C; Riehm, Julia M

2013-01-01

Yersinia pestis has been identified as the causative agent of the Black Death pandemic in the 14(th) century. However, retrospective diagnostics in human skeletons after more than 600 years are critical. We describe a strategy following a modern diagnostic algorithm and working under strict ancient DNA regime for the identification of medieval human plague victims. An initial screening and DNA quantification assay detected the Y. pestis specific pla gene of the high copy number plasmid pPCP1. Results were confirmed by conventional PCR and sequence analysis targeting both Y. pestis specific virulence plasmids pPCP1 and pMT1. All assays were meticulously validated according to human clinical diagnostics requirements (ISO 15189) regarding efficiency, sensitivity, specificity, and limit of detection (LOD). Assay specificity was 100% tested on 41 clinically relevant bacteria and 29 Y. pseudotuberculosis strains as well as for DNA of 22 Y. pestis strains and 30 previously confirmed clinical human plague samples. The optimized LOD was down to 4 gene copies. 29 individuals from three different multiple inhumations were initially assessed as possible victims of the Black Death pandemic. 7 samples (24%) were positive in the pPCP1 specific screening assay. Confirmation through second target pMT1 specific PCR was successful for 4 of the positive individuals (14%). A maximum of 700 and 560 copies per µl aDNA were quantified in two of the samples. Those were positive in all assays including all repetitions, and are candidates for future continuative investigations such as whole genome sequencing. We discuss that all precautions taken here for the work with aDNA are sufficient to prevent external sample contamination and fulfill the criteria of authenticity. With regard to retrospective diagnostics of a human pathogen and the uniqueness of ancient material we strongly recommend using a careful strategy and validated assays as presented in our study.

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

Campbell, Keri R.; Judge, Elizabeth J.; Barefield, James E.

We show the analysis of light water reactor simulated used nuclear fuel using laser-induced breakdown spectroscopy (LIBS) is explored using a simplified version of the main oxide phase. The main oxide phase consists of the actinides, lanthanides, and zirconium. The purpose of this study is to develop a rapid, quantitative technique for measuring zirconium in a uranium dioxide matrix without the need to dissolve the material. A second set of materials including cerium oxide is also analyzed to determine precision and limit of detection (LOD) using LIBS in a complex matrix. Two types of samples are used in this study:more » binary and ternary oxide pellets. The ternary oxide, (U,Zr,Ce)O 2 pellets used in this study are a simplified version the main oxide phase of used nuclear fuel. The binary oxides, (U,Ce)O 2 and (U,Zr)O 2 are also examined to determine spectral emission lines for Ce and Zr, potential spectral interferences with uranium and baseline LOD values for Ce and Zr in a UO 2 matrix. In the spectral range of 200 to 800 nm, 33 cerium lines and 25 zirconium lines were identified and shown to have linear correlation values (R 2) > 0.97 for both the binary and ternary oxides. The cerium LOD in the (U,Ce)O 2 matrix ranged from 0.34 to 1.08 wt% and 0.94 to 1.22 wt% in (U,Ce,Zr)O 2 for 33 of Ce emission lines. The zirconium limit of detection in the (U,Zr)O 2 matrix ranged from 0.84 to 1.15 wt% and 0.99 to 1.10 wt% in (U,Ce,Zr)O 2 for 25 Zr lines. Finally, the effect of multiple elements in the plasma and the impact on the LOD is discussed.« less

Effect of genomic drift of influenza PCR tests.

PubMed

Stellrecht, Kathleen A; Nattanmai, Seela M; Butt, Jumshan; Maceira, Vincente P; Espino, Alvin A; Castro, Allan J; Landes, Allen; Dresser, Nicolas; Butt, Shafiq A

2017-08-01

Nucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014-2015 season were associated with significant genetic drift; however, the effect on testing was unknown. We compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas ® Influenza A/B test (cIAB), and Xpert ® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu. Of the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu's and cIAB's LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt's highest LOD was with the Swiss strain. Strain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of the effect of three-dimensional mantle density heterogeneity on earth rotation in tidal frequencies.

PubMed

Liu, Lanbo; Chao, Benjamin F; Sun, Wenke; Kuang, Weijia

2016-11-01

In this paper we report the assessment of the effect of the three-dimensional (3D) density heterogeneity in the mantle on Earth Orientation Parameters (EOP) (i.e., the polar motion, or PM, and the length of day, or LOD) in the tidal frequencies. The 3D mantle density model is estimated based upon a global S-wave velocity tomography model (S16U6L8) and the mineralogical knowledge derived from laboratory experiment. The lateral density variation is referenced against the Preliminary Reference Earth Model (PREM). Using this approach the effects of the heterogeneous mantle density variation in all three tidal frequencies (zonal long periods, tesseral diurnal, and sectorial semidiurnal) are estimated in both PM and LOD. When compared with mass or density perturbations originated on the earth's surface such as the oceanic and barometric changes, the heterogeneous mantle only contributes less than 10% of the total variation in PM and LOD in tidal frequencies. Nevertheless, including the 3D variation of the density in the mantle into account explained a substantial portion of the discrepancy between the observed signals in PM and LOD extracted from the lump-sum values based on continuous space geodetic measurement campaigns (e.g., CONT94) and the computed contribution from ocean tides as predicted by tide models derived from satellite altimetry observations (e.g., TOPEX/Poseidon). In other word, the difference of the two, at all tidal frequencies (long-periods, diurnals, and semi-diurnals) contains contributions of the lateral density heterogeneity of the mantle. Study of the effect of mantle density heterogeneity effect on torque-free earth rotation may provide useful constraints to construct the Reference Earth Model (REM), which is the next major objective in global geophysics research beyond PREM.

QTL analysis of dietary obesity in C57BL/6byj X 129P3/J F2 mice: diet- and sex-dependent effects.

PubMed

Lin, Cailu; Theodorides, Maria L; McDaniel, Amanda H; Tordoff, Michael G; Zhang, Qinmin; Li, Xia; Bosak, Natalia; Bachmanov, Alexander A; Reed, Danielle R

2013-01-01

Obesity is a heritable trait caused by complex interactions between genes and environment, including diet. Gene-by-diet interactions are difficult to study in humans because the human diet is hard to control. Here, we used mice to study dietary obesity genes, by four methods. First, we bred 213 F2 mice from strains that are susceptible [C57BL/6ByJ (B6)] or resistant [129P3/J (129)] to dietary obesity. Percent body fat was assessed after mice ate low-energy diet and again after the same mice ate high-energy diet for 8 weeks. Linkage analyses identified QTLs associated with dietary obesity. Three methods were used to filter candidate genes within the QTL regions: (a) association mapping was conducted using >40 strains; (b) differential gene expression and (c) comparison of genomic DNA sequence, using two strains closely related to the progenitor strains from Experiment 1. The QTL effects depended on whether the mice were male or female or which diet they were recently fed. After feeding a low-energy diet, percent body fat was linked to chr 7 (LOD=3.42). After feeding a high-energy diet, percent body fat was linked to chr 9 (Obq5; LOD=3.88), chr 12 (Obq34; LOD=3.88), and chr 17 (LOD=4.56). The Chr 7 and 12 QTLs were sex dependent and all QTL were diet-dependent. The combination of filtering methods highlighted seven candidate genes within the QTL locus boundaries: Crx, Dmpk, Ahr, Mrpl28, Glo1, Tubb5, and Mut. However, these filtering methods have limitations so gene identification will require alternative strategies, such as the construction of congenics with very small donor regions.

Force-displacement differences in the lower extremities of young healthy adults between drop jumps and drop landings.

PubMed

Hackney, James M; Clay, Rachel L; James, Meredith

2016-10-01

We measured ground reaction force and lower extremity shortening in ten healthy, young adults in order to compare five trials of drop jumps to drop landings. Our dependent variable was the percentage of displacement (shortening) between the markers on the ASIS and second metatarsal heads on each LE, relative to the maximum shortening (100% displacement) for that trial at the point of greatest ground reaction force. We defined this as "percent displacement at maximum force" (%dFmax). The sample mean %dFmax was 0.73%±0.14% for the drop jumps, and 0.47%±0.09% for the drop landings. The mean within-subject difference score was 0.26%±0.20%. Two-tailed paired t test comparing %dFmax between the drop jump and drop landing yielded P=0.002. For all participants in this study, the %dFmax was greater in drop jumps than in drop landings. This indicates that in drop jumps, the point of maximum force and of maximum shortening was nearly simultaneous, compared to drop landings, where the point of maximum shortening followed that of maximum force by a greater proportion. This difference in force to displacement behavior is explained by linear spring behavior in drop jumps, and linear damping behavior in drop landings. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of geological materials containing uranium using laser-induced breakdown spectroscopy (LIBS)

NASA Astrophysics Data System (ADS)

Barefield, James E.; Judge, Elizabeth J.; Campbell, Keri R.; Colgan, James P.; Kilcrease, David P.; Johns, Heather M.; Wiens, Roger C.; McInroy, Rhonda E.; Martinez, Ronald K.; Clegg, Samuel M.

2016-06-01

Laser induced breakdown spectroscopy (LIBS) is a rapid atomic emission spectroscopy technique that can be configured for a variety of applications including space, forensics, and industry. LIBS can also be configured for stand-off distances or in-situ, under vacuum, high pressure, atmospheric or different gas environments, and with different resolving-power spectrometers. The detection of uranium in a complex geological matrix under different measurement schemes is explored in this paper. Although many investigations have been completed in an attempt to detect and quantify uranium in different matrices at in-situ and standoff distances, this work detects and quantifies uranium in a complex matrix under Martian and ambient air conditions. Investigation of uranium detection using a low resolving-power LIBS system at stand-off distances (1.6 m) is also reported. The results are compared to an in-situ LIBS system with medium resolving power and under ambient air conditions. Uranium has many thousands of emission lines in the 200-800 nm spectral region. In the presence of other matrix elements and at lower concentrations, the limit of detection of uranium is significantly reduced. The two measurement methods (low and high resolving-power spectrometers) are compared for limit of detection (LOD). Of the twenty-one potential diagnostic uranium emission lines, seven (409, 424, 434, 435, 436, 591, and 682 nm) have been used to determine the LOD for pitchblende in a dunite matrix using the ChemCam test bed LIBS system. The LOD values determined for uranium transitions in air are 409.013 nm (24,700 ppm), 424.167 nm (23,780 ppm), 434.169 nm (24,390 ppm), 435.574 nm (35,880 ppm), 436.205 nm (19,340 ppm), 591.539 nm (47,310 ppm), and 682.692 nm (18,580 ppm). The corresponding LOD values determined for uranium transitions in 7 Torr CO2 are 424.167 nm (25,760 ppm), 434.169 nm (40,800 ppm), 436.205 nm (32,050 ppm), 591.539 nm (15,340 ppm), and 682.692 nm (29,080 ppm). The LOD values determine for uranium emission lines using the medium resolving power (10,000 λ/Δλ) LIBS system for the dunite matrix in air are 409.013 nm (6120 ppm), 424.167 nm (5356 ppm), 434.169 nm (5693 ppm), 435.574 nm (6329 ppm), 436.205 nm (2142 ppm), and 682.692 nm (10,741 ppm). The corresponding LOD values determined for uranium transitions in a SiO2 matrix are 409.013 nm (272 ppm), 424.167 nm (268 ppm), 434.169 nm (402 ppm), 435.574 nm (1067 ppm), 436.205 nm (482 ppm), and 682.692 nm (720 ppm). The impact of spectral resolution, atmospheric conditions, matrix elements, and measurement distances on LOD is discussed. The measurements will assist one in selecting the proper system components based upon the application and the required analytical performance.

Determination of acrylamide and acrylic acid by isocratic liquid chromatography with pulsed electrochemical detection.

PubMed

Casella, Innocenzo G; Pierri, Marianna; Contursi, Michela

2006-02-24

The electrochemical behaviour of the polycrystalline platinum electrode towards the oxidation/reduction of short-chain unsaturated aliphatic molecules such as acrylamide and acrylic acid was investigated in acidic solutions. Analytes were separated by reverse phase liquid chromatographic and quantified using a pulsed amperometric detection. A new two-step waveform, is introduced for detection of acrylamide and acrylic acid. Detection limits (LOD) of 20 nM (1. 4 microg/kg) and 45 nM (3.2 microg/kg) were determined in water solutions containing acrylamide and acrylic acid, respectively. Compared to the classical three-step waveform, the proposed two-step waveform shows favourable analytical performance in terms of LOD, linear range, precision and improved long-term reproducibility. The proposed analytical method combined with clean-up procedure accomplished by Carrez clearing reagent and subsequent extraction with a strong cation exchanger cartridges (SPE), was successfully used for the quantification of low concentrations of acrylamide in foodstuffs such as coffee and potato fries.

A quantitative trait locus mixture model that avoids spurious LOD score peaks.

PubMed Central

Feenstra, Bjarke; Skovgaard, Ib M

2004-01-01

In standard interval mapping of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. At any given location in the genome, the evidence of a putative QTL is measured by the likelihood ratio of the mixture model compared to a single normal distribution (the LOD score). This approach can occasionally produce spurious LOD score peaks in regions of low genotype information (e.g., widely spaced markers), especially if the phenotype distribution deviates markedly from a normal distribution. Such peaks are not indicative of a QTL effect; rather, they are caused by the fact that a mixture of normals always produces a better fit than a single normal distribution. In this study, a mixture model for QTL mapping that avoids the problems of such spurious LOD score peaks is presented. PMID:15238544

A quantitative trait locus mixture model that avoids spurious LOD score peaks.

PubMed

Feenstra, Bjarke; Skovgaard, Ib M

2004-06-01

In standard interval mapping of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. At any given location in the genome, the evidence of a putative QTL is measured by the likelihood ratio of the mixture model compared to a single normal distribution (the LOD score). This approach can occasionally produce spurious LOD score peaks in regions of low genotype information (e.g., widely spaced markers), especially if the phenotype distribution deviates markedly from a normal distribution. Such peaks are not indicative of a QTL effect; rather, they are caused by the fact that a mixture of normals always produces a better fit than a single normal distribution. In this study, a mixture model for QTL mapping that avoids the problems of such spurious LOD score peaks is presented.

The Little Ice Age was 1.0-1.5 °C cooler than current warm period according to LOD and NAO

NASA Astrophysics Data System (ADS)

Mazzarella, Adriano; Scafetta, Nicola

2018-02-01

We study the yearly values of the length of day (LOD, 1623-2016) and its link to the zonal index (ZI, 1873-2003), the Northern Atlantic oscillation index (NAO, 1659-2000) and the global sea surface temperature (SST, 1850-2016). LOD is herein assumed to be mostly the result of the overall circulations occurring within the ocean-atmospheric system. We find that LOD is negatively correlated with the global SST and with both the integral function of ZI and NAO, which are labeled as IZI and INAO. A first result is that LOD must be driven by a climatic change induced by an external (e.g. solar/astronomical) forcing since internal variability alone would have likely induced a positive correlation among the same variables because of the conservation of the Earth's angular momentum. A second result is that the high correlation among the variables implies that the LOD and INAO records can be adopted as global proxies to reconstruct past climate change. Tentative global SST reconstructions since the seventeenth century suggest that around 1700, that is during the coolest period of the Little Ice Age (LIA), SST could have been about 1.0-1.5 °C cooler than the 1950-1980 period. This estimated LIA cooling is greater than what some multiproxy global climate reconstructions suggested, but it is in good agreement with other more recent climate reconstructions including those based on borehole temperature data.

Modeling and visualizing borehole information on virtual globes using KML

NASA Astrophysics Data System (ADS)

Zhu, Liang-feng; Wang, Xi-feng; Zhang, Bing

2014-01-01

Advances in virtual globes and Keyhole Markup Language (KML) are providing the Earth scientists with the universal platforms to manage, visualize, integrate and disseminate geospatial information. In order to use KML to represent and disseminate subsurface geological information on virtual globes, we present an automatic method for modeling and visualizing a large volume of borehole information. Based on a standard form of borehole database, the method first creates a variety of borehole models with different levels of detail (LODs), including point placemarks representing drilling locations, scatter dots representing contacts and tube models representing strata. Subsequently, the level-of-detail based (LOD-based) multi-scale representation is constructed to enhance the efficiency of visualizing large numbers of boreholes. Finally, the modeling result can be loaded into a virtual globe application for 3D visualization. An implementation program, termed Borehole2KML, is developed to automatically convert borehole data into KML documents. A case study of using Borehole2KML to create borehole models in Shanghai shows that the modeling method is applicable to visualize, integrate and disseminate borehole information on the Internet. The method we have developed has potential use in societal service of geological information.

Status and Prospects for Combined GPS LOD and VLBI UT1 Measurements

NASA Astrophysics Data System (ADS)

Senior, K.; Kouba, J.; Ray, J.

2010-01-01

A Kalman filter was developed to combine VLBI estimates of UT1-TAI with biased length of day (LOD) estimates from GPS. The VLBI results are the analyses of the NASA Goddard Space Flight Center group from 24-hr multi-station observing sessions several times per week and the nearly daily 1-hr single-baseline sessions. Daily GPS LOD estimates from the International GNSS Service (IGS) are combined with the VLBI UT1-TAI by modeling the natural excitation of LOD as the integral of a white noise process (i.e., as a random walk) and the UT1 variations as the integration of LOD, similar to the method described by Morabito et al. (1988). To account for GPS technique errors, which express themselves mostly as temporally correlated biases in the LOD measurements, a Gauss-Markov model has been added to assimilate the IGS data, together with a fortnightly sinusoidal term to capture errors in the IGS treatments of tidal effects. Evaluated against independent atmospheric and oceanic axial angular momentum (AAM + OAM) excitations and compared to other UT1/LOD combinations, ours performs best overall in terms of lowest RMS residual and highest correlation with (AAM + OAM) over sliding intervals down to 3 d. The IERS 05C04 and Bulletin A combinations show strong high-frequency smoothing and other problems. Until modified, the JPL SPACE series suffered in the high frequencies from not including any GPS-based LODs. We find, surprisingly, that further improvements are possible in the Kalman filter combination by selective rejection of some VLBI data. The best combined results are obtained by excluding all the 1-hr single-baseline UT1 data as well as those 24-hr UT1 measurements with formal errors greater than 5 μs (about 18% of the multi-baseline sessions). A rescaling of the VLBI formal errors, rather than rejection, was not an effective strategy. These results suggest that the UT1 errors of the 1-hr and weaker 24-hr VLBI sessions are non-Gaussian and more heterogeneous than expected, possibly due to the diversity of observing geometries used, other neglected systematic effects, or to the much shorter observational averaging interval of the single-baseline sessions. UT1 prediction services could benefit from better handling of VLBI inputs together with proper assimilation of IGS LOD products, including using the Ultra-rapid series that is updated four times daily with 15 hr delay.

A nucleic acid strand displacement system for the multiplexed detection of tuberculosis-specific mRNA using quantum dots

NASA Astrophysics Data System (ADS)

Gliddon, H. D.; Howes, P. D.; Kaforou, M.; Levin, M.; Stevens, M. M.

2016-05-01

The development of rapid, robust and high performance point-of-care diagnostics relies on the advancement and combination of various areas of research. We have developed an assay for the detection of multiple mRNA molecules that combines DNA nanotechnology with fluorescent nanomaterials. The core switching mechanism is toehold-mediated strand displacement. We have used fluorescent quantum dots (QDs) as signal transducers in this assay, as they bring many benefits including bright fluorescence and multiplexing abilities. The resulting assay is capable of multiplexed detection of long RNA targets against a high concentration of background non-target RNA, with high sensitivity and specificity and limits of detection in the nanomolar range using only a standard laboratory plate reader. We demonstrate the utility of our QD-based system for the detection of two genes selected from a microarray-derived tuberculosis-specific gene expression signature. Levels of up- and downregulated gene transcripts comprising this signature can be combined to give a disease risk score, making the signature more amenable for use as a diagnostic marker. Our QD-based approach to detect these transcripts could pave the way for novel diagnostic assays for tuberculosis.The development of rapid, robust and high performance point-of-care diagnostics relies on the advancement and combination of various areas of research. We have developed an assay for the detection of multiple mRNA molecules that combines DNA nanotechnology with fluorescent nanomaterials. The core switching mechanism is toehold-mediated strand displacement. We have used fluorescent quantum dots (QDs) as signal transducers in this assay, as they bring many benefits including bright fluorescence and multiplexing abilities. The resulting assay is capable of multiplexed detection of long RNA targets against a high concentration of background non-target RNA, with high sensitivity and specificity and limits of detection in the nanomolar range using only a standard laboratory plate reader. We demonstrate the utility of our QD-based system for the detection of two genes selected from a microarray-derived tuberculosis-specific gene expression signature. Levels of up- and downregulated gene transcripts comprising this signature can be combined to give a disease risk score, making the signature more amenable for use as a diagnostic marker. Our QD-based approach to detect these transcripts could pave the way for novel diagnostic assays for tuberculosis. Electronic supplementary information (ESI) available: Base pair mismatch tuning of CProbes. Binding capacity of the QDs. Theoretical limit of detection (LOD) for the monoplex systems. Kinetics of strand displacement. Kinetics of QProbe-CProbe binding. LOD and saturation point calculations. See DOI: 10.1039/c6nr00484a

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot–Marie–Tooth disease

PubMed Central

Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G.; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

2013-01-01

Charcot–Marie–Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

PubMed Central

Cross, Robert W.; Boisen, Matthew L.; Millett, Molly M.; Nelson, Diana S.; Oottamasathien, Darin; Hartnett, Jessica N.; Jones, Abigal B.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A.; Fusco, Marnie L.; Abelson, Dafna M.; Oda, Shunichiro; Brown, Bethany L.; Pham, Ha; Rowland, Megan M.; Agans, Krystle N.; Geisbert, Joan B.; Heinrich, Megan L.; Kulakosky, Peter C.; Shaffer, Jeffrey G.; Schieffelin, John S.; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M.; Wilson, Russell B.; Saphire, Erica Ollmann; Pitts, Kelly R.; Khan, Sheik Humarr; Grant, Donald S.; Geisbert, Thomas W.; Branco, Luis M.; Garry, Robert F.

2016-01-01

Background. Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013–2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. Methods. Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. Results. The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription–polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 105–9.0 × 108 genomes/mL. Conclusions. The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. PMID:27587634

The correlation function for density perturbations in an expanding universe. I - Linear theory

NASA Technical Reports Server (NTRS)

Mcclelland, J.; Silk, J.

1977-01-01

The evolution of the two-point correlation function for adiabatic density perturbations in the early universe is studied. Analytical solutions are obtained for the evolution of linearized spherically symmetric adiabatic density perturbations and the two-point correlation function for these perturbations in the radiation-dominated portion of the early universe. The results are then extended to the regime after decoupling. It is found that: (1) adiabatic spherically symmetric perturbations comparable in scale with the maximum Jeans length would survive the radiation-dominated regime; (2) irregular fluctuations are smoothed out up to the scale of the maximum Jeans length in the radiation era, but regular fluctuations might survive on smaller scales; (3) in general, the only surviving structures for irregularly shaped adiabatic density perturbations of arbitrary but finite scale in the radiation regime are the size of or larger than the maximum Jeans length in that regime; (4) infinite plane waves with a wavelength smaller than the maximum Jeans length but larger than the critical dissipative damping scale could survive the radiation regime; and (5) black holes would also survive the radiation regime and might accrete sufficient mass after decoupling to nucleate the formation of galaxies.

Highly sensitive screening method for nitroaromatic, nitramine and nitrate ester explosives by high performance liquid chromatography-atmospheric pressure ionization-mass spectrometry (HPLC-API-MS) in forensic applications.

PubMed

Xu, Xiaoma; van de Craats, Anick M; de Bruyn, Peter C A M

2004-11-01

A highly sensitive screening method based on high performance liquid chromatography atmospheric pressure ionization mass spectrometry (HPLC-API-MS) has been developed for the analysis of 21 nitroaromatic, nitramine and nitrate ester explosives, which include the explosives most commonly encountered in forensic science. Two atmospheric pressure ionization (API) methods, atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), and various experimental conditions have been applied to allow for the detection of all 21 explosive compounds. The limit of detection (LOD) in the full-scan mode has been found to be 0.012-1.2 ng on column for the screening of most explosives investigated. For nitrobenzene, an LOD of 10 ng was found with the APCI method in the negative mode. Although the detection of nitrobenzene, 2-, 3-, and 4-nitrotoluene is hindered by the difficult ionization of these compounds, we have found that by forming an adduct with glycine, LOD values in the range of 3-16 ng on column can be achieved. Compared with previous screening methods with thermospray ionization, the API method has distinct advantages, including simplicity and stability of the method applied, an extended screening range and a low detection limit for the explosives studied.

Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

PubMed

Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

2010-04-05

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

Analysis of group B streptococcal isolates from infants and pregnant women in Portugal revealing two lineages with enhanced invasiveness.

PubMed

Martins, E R; Pessanha, M A; Ramirez, M; Melo-Cristino, J

2007-10-01

The populations of group B streptococcus (GBS) associated with vaginal carriage in pregnant women and invasive neonatal infections in Portugal were compared. GBS isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE) profiling, and multilocus sequence typing (MLST). Serotypes III and V accounted for 44% of all colonization isolates (n = 269), whereas serotypes III and Ia amounted to 69% of all invasive isolates (n = 64). Whereas serotype Ia was associated with early-onset disease (EOD), serotype III was associated with late-onset disease (LOD). Characterization by PFGE and MLST identified very diverse populations in carriage and invasive disease. Serotype Ia was represented mainly by a single PFGE cluster defined by sequence type 23 (ST23) and the infrequent ST24. In contrast, serotype III was found in a large number of PFGE clusters and STs, but a single PFGE cluster defined by ST17 was found to be associated with invasive disease. Although serotype III was associated only with LOD, ST17 showed an enhanced capacity to cause both EOD and LOD. Our data reinforce the evidence for enhanced invasiveness of ST17 and identify a lineage expressing serotype Ia capsule and represented by ST23 and ST24 as having enhanced potential to cause EOD.

Quantitative trait loci for abdominal fat and BMI in Hispanic-Americans and African-Americans: the IRAS Family study.

PubMed

Norris, J M; Langefeld, C D; Scherzinger, A L; Rich, S S; Bookman, E; Beck, S R; Saad, M F; Haffner, S M; Bergman, R N; Bowden, D W; Wagenknecht, L E

2005-01-01

To conduct linkage analysis for body mass index (BMI, kg/m2), waist-to-hip ratio (WHR), visceral adipose tissue mass (VAT, cm2) and subcutaneous adipose tissue mass (SAT, cm2) using a whole genome scan. Cross-sectional family study. African-American families from Los Angeles (AA, n=21 extended pedigrees) and Hispanic-American families (HA) from San Antonio, TX (HA-SA, n=33 extended pedigrees) and San Luis Valley, CO (HA-SLV, n=12 extended pedigrees), totaling 1049 individuals in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. VAT and SAT were measured using a computed tomography scan obtained at the fourth and fifth lumbar vertebrae. All phenotypes were adjusted for age, gender, and study center. VAT, SAT, and WHR were analyzed both unadjusted and adjusted for BMI. Significant linkage to BMI was found at D3S2387 (LOD=3.67) in African-Americans, and at D17S1290 in Hispanic-Americans (LOD=2.76). BMI-adjusted WHR was linked to 12q13-21 (D12S297 (LOD=2.67) and D12S1052 (LOD=2.60)) in Hispanic-Americans. The peak LOD score for BMI-adjusted VAT was found at D11S2006 (2.36) in Hispanic families from San Antonio. BMI-adjusted SAT was linked to D5S820 in Hispanic families (LOD=2.64). Evidence supporting linkage of WHR at D11S2006, VAT at D17S1290, and SAT at D1S1609, D3S2387, and D6S1056 was dependent on BMI, such that the LOD scores became nonsignificant after adjustment of these phenotypes for BMI. Our findings both replicate previous linkage regions and suggest novel regions in the genome that may harbor quantitative trait locis contributing to variation in measures of adiposity.

Bose gases near resonance: Renormalized interactions in a condensate

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

Zhou, Fei, E-mail: feizhou@phas.ubc.ca; Mashayekhi, Mohammad S.

2013-01-15

Bose gases at large scattering lengths or beyond the usual dilute limit for a long time have been one of the most challenging problems in many-body physics. In this article, we investigate the fundamental properties of a near-resonance Bose gas and illustrate that three-dimensional Bose gases become nearly fermionized near resonance when the chemical potential as a function of scattering lengths reaches a maximum and the atomic condensates lose metastability. The instability and accompanying maximum are shown to be a precursor of the sign change of g{sub 2}, the renormalized two-body interaction between condensed atoms. g{sub 2} changes from effectivelymore » repulsive to attractive when approaching resonance from the molecular side, even though the scattering length is still positive. This occurs when dimers, under the influence of condensates, emerge at zero energy in the atomic gases at a finite positive scattering length. We carry out our studies of Bose gases via applying a self-consistent renormalization group equation which is further subject to a boundary condition. We also comment on the relation between the approach here and the diagrammatic calculation in an early article [D. Borzov, M.S. Mashayekhi, S. Zhang, J.-L. Song, F. Zhou, Phys. Rev. A 85 (2012) 023620]. - Highlights: Black-Right-Pointing-Pointer A Bose gas becomes nearly fermionized when its chemical potential approaches a maximum near resonance. Black-Right-Pointing-Pointer At the maximum, an onset instability sets in at a positive scattering length. Black-Right-Pointing-Pointer Condensates strongly influence the renormalization flow of few-body running coupling constants. Black-Right-Pointing-Pointer The effective two-body interaction constant changes its sign at a positive scattering length.« less

Automated centrifugal-microfluidic platform for DNA purification using laser burst valve and coriolis effect.

PubMed

Choi, Min-Seong; Yoo, Jae-Chern

2015-04-01

We report a fully automated DNA purification platform with a micropored membrane in the channel utilizing centrifugal microfluidics on a lab-on-a-disc (LOD). The microfluidic flow in the LOD, into which the reagents are injected for DNA purification, is controlled by a single motor and laser burst valve. The sample and reagents pass successively through the micropored membrane in the channel when each laser burst valve is opened. The Coriolis effect is used by rotating the LOD bi-directionally to increase the purity of the DNA, thereby preventing the mixing of the waste and elution solutions. The total process from the lysed sample injection into the LOD to obtaining the purified DNA was finished within 7 min with only one manual step. The experimental result for Salmonella shows that the proposed microfluidic platform is comparable to the existing devices in terms of the purity and yield of DNA.

Enhanced LOD Concepts for Virtual 3d City Models

NASA Astrophysics Data System (ADS)

Benner, J.; Geiger, A.; Gröger, G.; Häfele, K.-H.; Löwner, M.-O.

2013-09-01

Virtual 3D city models contain digital three dimensional representations of city objects like buildings, streets or technical infrastructure. Because size and complexity of these models continuously grow, a Level of Detail (LoD) concept effectively supporting the partitioning of a complete model into alternative models of different complexity and providing metadata, addressing informational content, complexity and quality of each alternative model is indispensable. After a short overview on various LoD concepts, this paper discusses the existing LoD concept of the CityGML standard for 3D city models and identifies a number of deficits. Based on this analysis, an alternative concept is developed and illustrated with several examples. It differentiates between first, a Geometric Level of Detail (GLoD) and a Semantic Level of Detail (SLoD), and second between the interior building and its exterior shell. Finally, a possible implementation of the new concept is demonstrated by means of an UML model.

Desiderata for an authoritative Representation of MeSH in RDF.

PubMed

Winnenburg, Rainer; Bodenreider, Olivier

2014-01-01

The Semantic Web provides a framework for the integration of resources on the web, which facilitates information integration and interoperability. RDF is the main representation format for Linked Open Data (LOD). However, datasets are not always made available in RDF by their producers and the Semantic Web community has had to convert some of these datasets to RDF in order for these datasets to participate in the LOD cloud. As a result, the LOD cloud sometimes contains outdated, partial and even inaccurate RDF datasets. We review the LOD landscape for one of these resources, MeSH, and analyze the characteristics of six existing representations in order to identify desirable features for an authoritative version, for which we create a prototype. We illustrate the suitability of this prototype on three common use cases. NLM intends to release an authoritative representation of MeSH in RDF (beta version) in the Fall of 2014.

Desiderata for an authoritative Representation of MeSH in RDF

PubMed Central

Winnenburg, Rainer; Bodenreider, Olivier

2014-01-01

The Semantic Web provides a framework for the integration of resources on the web, which facilitates information integration and interoperability. RDF is the main representation format for Linked Open Data (LOD). However, datasets are not always made available in RDF by their producers and the Semantic Web community has had to convert some of these datasets to RDF in order for these datasets to participate in the LOD cloud. As a result, the LOD cloud sometimes contains outdated, partial and even inaccurate RDF datasets. We review the LOD landscape for one of these resources, MeSH, and analyze the characteristics of six existing representations in order to identify desirable features for an authoritative version, for which we create a prototype. We illustrate the suitability of this prototype on three common use cases. NLM intends to release an authoritative representation of MeSH in RDF (beta version) in the Fall of 2014. PMID:25954433

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia

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

Okoro, C.; Bell, R.; Sham, P.

DeLisi et al. have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant, recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2more » method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees. 29 refs., 1 tab.« less

Single-molecule detection of proteins with antigen-antibody interaction using resistive-pulse sensing of submicron latex particles

NASA Astrophysics Data System (ADS)

Takakura, T.; Yanagi, I.; Goto, Y.; Ishige, Y.; Kohara, Y.

2016-03-01

We developed a resistive-pulse sensor with a solid-state pore and measured the latex agglutination of submicron particles induced by antigen-antibody interaction for single-molecule detection of proteins. We fabricated the pore based on numerical simulation to clearly distinguish between monomer and dimer latex particles. By measuring single dimers agglutinated in the single-molecule regime, we detected single human alpha-fetoprotein molecules. Adjusting the initial particle concentration improves the limit of detection (LOD) to 95 fmol/l. We established a theoretical model of the LOD by combining the reaction kinetics and the counting statistics to explain the effect of initial particle concentration on the LOD. The theoretical model shows how to improve the LOD quantitatively. The single-molecule detection studied here indicates the feasibility of implementing a highly sensitive immunoassay by a simple measurement method using resistive-pulse sensing.

Viewer-centered and body-centered frames of reference in direct visuomotor transformations.

PubMed

Carrozzo, M; McIntyre, J; Zago, M; Lacquaniti, F

1999-11-01

It has been hypothesized that the end-point position of reaching may be specified in an egocentric frame of reference. In most previous studies, however, reaching was toward a memorized target, rather than an actual target. Thus, the role played by sensorimotor transformation could not be disassociated from the role played by storage in short-term memory. In the present study the direct process of sensorimotor transformation was investigated in reaching toward continuously visible targets that need not be stored in memory. A virtual reality system was used to present visual targets in different three-dimensional (3D) locations in two different tasks, one with visual feedback of the hand and arm position (Seen Hand) and the other without such feedback (Unseen Hand). In the Seen Hand task, the axes of maximum variability and of maximum contraction converge toward the mid-point between the eyes. In the Unseen Hand task only the maximum contraction correlates with the sight-line and the axes of maximum variability are not viewer-centered but rotate anti-clockwise around the body and the effector arm during the move from the right to the left workspace. The bulk of findings from these and previous experiments support the hypothesis of a two-stage process, with a gradual transformation from viewer-centered to body-centered and arm-centered coordinates. Retinal, extra-retinal and arm-related signals appear to be progressively combined in superior and inferior parietal areas, giving rise to egocentric representations of the end-point position of reaching.

A gene (ETM) for essential tremor maps to chromosome 2p22-p25.

PubMed

Higgins, J J; Pho, L T; Nee, L E

1997-11-01

We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited "pure" essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22-p25 establish linkage to this region with a maximum LOD score (Zmax) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15-cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system.

Development of microwave assisted spectrophotometric method for the determination of glucose

NASA Astrophysics Data System (ADS)

Ali, Asif; Hussain, Zahid; Arain, Muhammad Balal; Shah, Nasrullah; Khan, Khalid Mohammad; Gulab, Hussain; Zada, Amir

2016-01-01

A spectrophotometric method was developed based on the microwave assisted synthesis of Maillard product. Various conditions of the reaction were optimized by varying the relative concentration of the reagents, operating temperature and volume of solutions used in the reaction in the microwave synthesizer. The absorbance of the microwave synthesized Maillard product was measured in the range of 360-740 nm using UV-Visible spectrophotometer. Based on the maximum absorbance, 370 nm was selected as the optimum wave length for further studies. The LOD and LOQ of glucose was found 3.08 μg mL- 1 and 9.33 μg mL- 1 with standard deviation of ± 0.05. The developed method was also applicable to urine sample.

Kohn anomalies in momentum dependence of magnetic susceptibility of some three-dimensional systems

NASA Astrophysics Data System (ADS)

Stepanenko, A. A.; Volkova, D. O.; Igoshev, P. A.; Katanin, A. A.

2017-11-01

We study a question of the presence of Kohn points, yielding at low temperatures nonanalytic momentum dependence of magnetic susceptibility near its maximum, in electronic spectra of some threedimensional systems. In particular, we consider a one-band model on face-centered cubic lattice with hopping between the nearest and next-nearest neighbors, which models some aspects of the dispersion of ZrZn2, and the two-band model on body-centered cubic lattice, modeling the dispersion of chromium. For the former model, it is shown that Kohn points yielding maxima of susceptibility exist in a certain (sufficiently wide) region of electronic concentrations; the dependence of the wave vectors, corresponding to the maxima, on the chemical potential is investigated. For the two-band model, we show the existence of the lines of Kohn points, yielding maximum susceptibility, whose position agrees with the results of band structure calculations and experimental data on the wave vector of antiferromagnetism of chromium.

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families.

PubMed

Bouzigon, Emmanuelle; Dizier, Marie-Hélène; Krähenbühl, Christine; Lemainque, Arnaud; Annesi-Maesano, Isabella; Betard, Christine; Bousquet, Jean; Charpin, Denis; Gormand, Frédéric; Guilloud-Bataille, Michel; Just, Jocelyne; Le Moual, Nicole; Maccario, Jean; Matran, Régis; Neukirch, Françoise; Oryszczyn, Marie-Pierre; Paty, Evelyne; Pin, Isabelle; Rosenberg-Bourgin, Myriam; Vervloet, Daniel; Kauffmann, Francine; Lathrop, Mark; Demenais, Florence

2004-12-15

A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P

Detection limits of quantitative and digital PCR assays and their influence in presence-absence surveys of environmental DNA

USGS Publications Warehouse

Hunter, Margaret; Dorazio, Robert M.; Butterfield, John S.; Meigs-Friend, Gaia; Nico, Leo; Ferrante, Jason A.

2017-01-01

A set of universal guidelines is needed to determine the limit of detection (LOD) in PCR-based analyses of low concentration DNA. In particular, environmental DNA (eDNA) studies require sensitive and reliable methods to detect rare and cryptic species through shed genetic material in environmental samples. Current strategies for assessing detection limits of eDNA are either too stringent or subjective, possibly resulting in biased estimates of species’ presence. Here, a conservative LOD analysis grounded in analytical chemistry is proposed to correct for overestimated DNA concentrations predominantly caused by the concentration plateau, a nonlinear relationship between expected and measured DNA concentrations. We have used statistical criteria to establish formal mathematical models for both quantitative and droplet digital PCR. To assess the method, a new Grass Carp (Ctenopharyngodon idella) TaqMan assay was developed and tested on both PCR platforms using eDNA in water samples. The LOD adjustment reduced Grass Carp occupancy and detection estimates while increasing uncertainty – indicating that caution needs to be applied to eDNA data without LOD correction. Compared to quantitative PCR, digital PCR had higher occurrence estimates due to increased sensitivity and dilution of inhibitors at low concentrations. Without accurate LOD correction, species occurrence and detection probabilities based on eDNA estimates are prone to a source of bias that cannot be reduced by an increase in sample size or PCR replicates. Other applications also could benefit from a standardized LOD such as GMO food analysis, and forensic and clinical diagnostics.

Publishing NASA Metadata as Linked Open Data for Semantic Mashups

NASA Astrophysics Data System (ADS)

Wilson, Brian; Manipon, Gerald; Hua, Hook

2014-05-01

Data providers are now publishing more metadata in more interoperable forms, e.g. Atom or RSS 'casts', as Linked Open Data (LOD), or as ISO Metadata records. A major effort on the part of the NASA's Earth Science Data and Information System (ESDIS) project is the aggregation of metadata that enables greater data interoperability among scientific data sets regardless of source or application. Both the Earth Observing System (EOS) ClearingHOuse (ECHO) and the Global Change Master Directory (GCMD) repositories contain metadata records for NASA (and other) datasets and provided services. These records contain typical fields for each dataset (or software service) such as the source, creation date, cognizant institution, related access URL's, and domain and variable keywords to enable discovery. Under a NASA ACCESS grant, we demonstrated how to publish the ECHO and GCMD dataset and services metadata as LOD in the RDF format. Both sets of metadata are now queryable at SPARQL endpoints and available for integration into "semantic mashups" in the browser. It is straightforward to reformat sets of XML metadata, including ISO, into simple RDF and then later refine and improve the RDF predicates by reusing known namespaces such as Dublin core, georss, etc. All scientific metadata should be part of the LOD world. In addition, we developed an "instant" drill-down and browse interface that provides faceted navigation so that the user can discover and explore the 25,000 datasets and 3000 services. The available facets and the free-text search box appear in the left panel, and the instantly updated results for the dataset search appear in the right panel. The user can constrain the value of a metadata facet simply by clicking on a word (or phrase) in the "word cloud" of values for each facet. The display section for each dataset includes the important metadata fields, a full description of the dataset, potentially some related URL's, and a "search" button that points to an OpenSearch GUI that is pre-configured to search for granules within the dataset. We will present our experiences with converting NASA metadata into LOD, discuss the challenges, illustrate some of the enabled mashups, and demonstrate the latest version of the "instant browse" interface for navigating multiple metadata collections.

A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees.

PubMed

Curtis, David; Knight, Jo; Sham, Pak C

2005-09-01

Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods.

A Novel Locus For Dilated Cardiomyopathy Maps to Canine Chromosome 8

PubMed Central

Werner, Petra; Raducha, Michael G.; Prociuk, Ulana; Sleeper, Meg M.; Henthorn, Paula S.

2008-01-01

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint LOD scores of 10.8 and 14, respectively. The locus maps to a 3.9 Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure. PMID:18442891

Developing Multidimensional Likert Scales Using Item Factor Analysis: The Case of Four-Point Items

ERIC Educational Resources Information Center

Asún, Rodrigo A.; Rdz-Navarro, Karina; Alvarado, Jesús M.

2016-01-01

This study compares the performance of two approaches in analysing four-point Likert rating scales with a factorial model: the classical factor analysis (FA) and the item factor analysis (IFA). For FA, maximum likelihood and weighted least squares estimations using Pearson correlation matrices among items are compared. For IFA, diagonally weighted…

Computational simulations of vocal fold vibration: Bernoulli versus Navier-Stokes.

PubMed

Decker, Gifford Z; Thomson, Scott L

2007-05-01

The use of the mechanical energy (ME) equation for fluid flow, an extension of the Bernoulli equation, to predict the aerodynamic loading on a two-dimensional finite element vocal fold model is examined. Three steady, one-dimensional ME flow models, incorporating different methods of flow separation point prediction, were compared. For two models, determination of the flow separation point was based on fixed ratios of the glottal area at separation to the minimum glottal area; for the third model, the separation point determination was based on fluid mechanics boundary layer theory. Results of flow rate, separation point, and intraglottal pressure distribution were compared with those of an unsteady, two-dimensional, finite element Navier-Stokes model. Cases were considered with a rigid glottal profile as well as with a vibrating vocal fold. For small glottal widths, the three ME flow models yielded good predictions of flow rate and intraglottal pressure distribution, but poor predictions of separation location. For larger orifice widths, the ME models were poor predictors of flow rate and intraglottal pressure, but they satisfactorily predicted separation location. For the vibrating vocal fold case, all models resulted in similar predictions of mean intraglottal pressure, maximum orifice area, and vibration frequency, but vastly different predictions of separation location and maximum flow rate.

RadShield: semiautomated shielding design using a floor plan driven graphical user interface

PubMed Central

Wu, Dee H.; Yang, Kai; Rutel, Isaac B.

2016-01-01

The purpose of this study was to introduce and describe the development of RadShield, a Java‐based graphical user interface (GUI), which provides a base design that uniquely performs thorough, spatially distributed calculations at many points and reports the maximum air‐kerma rate and barrier thickness for each barrier pursuant to NCRP Report 147 methodology. Semiautomated shielding design calculations are validated by two approaches: a geometry‐based approach and a manual approach. A series of geometry‐based equations were derived giving the maximum air‐kerma rate magnitude and location through a first derivative root finding approach. The second approach consisted of comparing RadShield results with those found by manual shielding design by an American Board of Radiology (ABR)‐certified medical physicist for two clinical room situations: two adjacent catheterization labs, and a radiographic and fluoroscopic (R&F) exam room. RadShield's efficacy in finding the maximum air‐kerma rate was compared against the geometry‐based approach and the overall shielding recommendations by RadShield were compared against the medical physicist's shielding results. Percentage errors between the geometry‐based approach and RadShield's approach in finding the magnitude and location of the maximum air‐kerma rate was within 0.00124% and 14 mm. RadShield's barrier thickness calculations were found to be within 0.156 mm lead (Pb) and 0.150 mm lead (Pb) for the adjacent catheterization labs and R&F room examples, respectively. However, within the R&F room example, differences in locating the most sensitive calculation point on the floor plan for one of the barriers was not considered in the medical physicist's calculation and was revealed by the RadShield calculations. RadShield is shown to accurately find the maximum values of air‐kerma rate and barrier thickness using NCRP Report 147 methodology. Visual inspection alone of the 2D X‐ray exam distribution by a medical physicist may not be sufficient to accurately select the point of maximum air‐kerma rate or barrier thickness. PACS number(s): 87.55.N, 87.52.‐g, 87.59.Bh, 87.57.‐s PMID:27685128

RadShield: semiautomated shielding design using a floor plan driven graphical user interface.

PubMed

DeLorenzo, Matthew C; Wu, Dee H; Yang, Kai; Rutel, Isaac B

2016-09-08

The purpose of this study was to introduce and describe the development of RadShield, a Java-based graphical user interface (GUI), which provides a base design that uniquely performs thorough, spatially distributed calculations at many points and reports the maximum air-kerma rate and barrier thickness for each barrier pursuant to NCRP Report 147 methodology. Semiautomated shielding design calculations are validated by two approaches: a geometry-based approach and a manual approach. A series of geometry-based equations were derived giv-ing the maximum air-kerma rate magnitude and location through a first derivative root finding approach. The second approach consisted of comparing RadShield results with those found by manual shielding design by an American Board of Radiology (ABR)-certified medical physicist for two clinical room situations: two adjacent catheterization labs, and a radiographic and fluoroscopic (R&F) exam room. RadShield's efficacy in finding the maximum air-kerma rate was compared against the geometry-based approach and the overall shielding recommendations by RadShield were compared against the medical physicist's shielding results. Percentage errors between the geometry-based approach and RadShield's approach in finding the magnitude and location of the maximum air-kerma rate was within 0.00124% and 14 mm. RadShield's barrier thickness calculations were found to be within 0.156 mm lead (Pb) and 0.150 mm lead (Pb) for the adjacent catheteriza-tion labs and R&F room examples, respectively. However, within the R&F room example, differences in locating the most sensitive calculation point on the floor plan for one of the barriers was not considered in the medical physicist's calculation and was revealed by the RadShield calculations. RadShield is shown to accurately find the maximum values of air-kerma rate and barrier thickness using NCRP Report 147 methodology. Visual inspection alone of the 2D X-ray exam distribution by a medical physicist may not be sufficient to accurately select the point of maximum air-kerma rate or barrier thickness. © 2016 The Authors.

Object recognition and localization from 3D point clouds by maximum-likelihood estimation

NASA Astrophysics Data System (ADS)

Dantanarayana, Harshana G.; Huntley, Jonathan M.

2017-08-01

We present an algorithm based on maximum-likelihood analysis for the automated recognition of objects, and estimation of their pose, from 3D point clouds. Surfaces segmented from depth images are used as the features, unlike `interest point'-based algorithms which normally discard such data. Compared to the 6D Hough transform, it has negligible memory requirements, and is computationally efficient compared to iterative closest point algorithms. The same method is applicable to both the initial recognition/pose estimation problem as well as subsequent pose refinement through appropriate choice of the dispersion of the probability density functions. This single unified approach therefore avoids the usual requirement for different algorithms for these two tasks. In addition to the theoretical description, a simple 2 degrees of freedom (d.f.) example is given, followed by a full 6 d.f. analysis of 3D point cloud data from a cluttered scene acquired by a projected fringe-based scanner, which demonstrated an RMS alignment error as low as 0.3 mm.

Linkage analysis in nuclear families. 2: Relationship between affected sib-pair tests and lod score analysis.

PubMed

Knapp, M; Seuchter, S A; Baur, M P

1994-01-01

It is believed that the main advantage of affected sib-pair tests is that their application requires no information about the underlying genetic mechanism of the disease. However, here it is proved that the mean test, which can be considered the most prominent of the affected sib-pair tests, is equivalent to lod score analysis for an assumed recessive mode of inheritance, irrespective of the true mode of the disease. Further relationships of certain sib-pair tests and lod score analysis under specific assumed genetic modes are investigated.

A genome-wide linkage scan for quantitative trait loci underlying obesity related phenotypes in 434 Caucasian families.

PubMed

Zhao, Lan-Juan; Xiao, Peng; Liu, Yong-Jun; Xiong, Dong-Hai; Shen, Hui; Recker, Robert R; Deng, Hong-Wen

2007-03-01

To identify quantitative trait loci (QTLs) that contribute to obesity, we performed a large-scale whole genome linkage scan (WGS) involving 4,102 individuals from 434 Caucasian families. The most pronounced linkage evidence was found at the genomic region 20p11-12 for fat mass (LOD = 3.31) and percentage fat mass (PFM) (LOD = 2.92). We also identified several regions showing suggestive linkage signals (threshold LOD = 1.9) for obesity phenotypes, including 5q35, 8q13, 10p12, and 17q11.

Exploring the Processes of Generating LOD (0-2) Citygml Models in Greater Municipality of Istanbul

NASA Astrophysics Data System (ADS)

Buyuksalih, I.; Isikdag, U.; Zlatanova, S.

2013-08-01

3D models of cities, visualised and exploded in 3D virtual environments have been available for several years. Currently a large number of impressive realistic 3D models have been regularly presented at scientific, professional and commercial events. One of the most promising developments is OGC standard CityGML. CityGML is object-oriented model that support 3D geometry and thematic semantics, attributes and relationships, and offers advanced options for realistic visualization. One of the very attractive characteristics of the model is the support of 5 levels of detail (LOD), starting from 2.5D less accurate model (LOD0) and ending with very detail indoor model (LOD4). Different local government offices and municipalities have different needs when utilizing the CityGML models, and the process of model generation depends on local and domain specific needs. Although the processes (i.e. the tasks and activities) for generating the models differs depending on its utilization purpose, there are also some common tasks (i.e. common denominator processes) in the model generation of City GML models. This paper focuses on defining the common tasks in generation of LOD (0-2) City GML models and representing them in a formal way with process modeling diagrams.

Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters.

PubMed

Riedel, Timothy E; Zimmer-Faust, Amity G; Thulsiraj, Vanessa; Madi, Tania; Hanley, Kaitlyn T; Ebentier, Darcy L; Byappanahalli, Muruleedhara; Layton, Blythe; Raith, Meredith; Boehm, Alexandria B; Griffith, John F; Holden, Patricia A; Shanks, Orin C; Weisberg, Stephen B; Jay, Jennifer A

2014-04-01

Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters

USGS Publications Warehouse

Riedel, Timothy E.; Zimmer-Faust, Amity G.; Thulsiraj, Vanessa; Madi, Tania; Hanley, Kaitlyn T.; Ebentier, Darcy L.; Byappanahalli, Muruleedhara N.; Layton, Blythe; Raith, Meredith; Boehm, Alexandria B.; Griffith, John F.; Holden, Patricia A.; Shanks, Orin C.; Weisberg, Stephen B.; Jay, Jennifer A.

2014-01-01

Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample.

Fuel freeze-point investigations. Final report, September 1982-March 1984

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

Desmarais, L.A.; Tolle, F.F.

1984-07-01

The objective of this program was to conduct a detailed assessment of the low-temperature environment to which USAF aircraft are exposed for the purpose of defining a maximum acceptable fuel freeze-point and also to define any operational changes required with the use of a high freeze-point fuel. A previous study of B-52, C-141, and KC-135 operational missions indicated that the -58 C freeze point specification was too conservative. Based on recommendations resulting from the previous program, several improvements in the method of analysis were made, such as: expansion of the atmospheric temperature data base, the addition of ground temperature analysis,more » the addition of fuel-freezing analysis to the one-dimensional fuel-temperature computer program, and the examination of heat transfer in external fuel tanks, such as pylon or tip tanks. The B-52, C-141, and KC-135 mission were analyzed again, along with the operational missions of two tactical airplanes, the A-10 and F-15; -50C was determined to be the maximum allowable freeze point for a general-purpose USAF aviation turbine fuel. Higher freeze points can be tolerated if the probability of operational interference is acceptably low or if operational changes can be made. Study of atmospheric temperatures encountered for the missions of the five-study aircraft indicates that a maximum freeze point of -48 C would not likely create any operational difficulties in Northern Europe.« less

Two Quantitative Trait Loci Influence Whipworm (Trichuris trichiura) Infection in a Nepalese Population

PubMed Central

Williams-Blangero, Sarah; VandeBerg, John L.; Subedi, Janardan; Jha, Bharat; Dyer, T.D.; Blangero, John

2014-01-01

Background Whipworm (Trichuris trichiura) is a soil-transmitted helminth which infects over a billion people. It is a serious public health problem in many developing countries and can result in deficits in growth and cognitive development. In a follow-up study of a significant heritability for whipworm infection, we conducted the first genome scan for susceptibility to this important parasitic disease. Methods We assessed whipworm eggs per gram of feces in 1253 members of the Jirel population of eastern Nepal. All sampled individuals belonged to a single pedigree containing over 26,000 relative pairs that are informative for genetic analysis. Results Linkage analysis of genome scan data generated for the pedigree provided unambiguous evidence for two quantitative trait loci influencing susceptibility to whipworm infection, one located on chromosome 9 (LOD = 3.35, genome-wide p = 0.0138) and the other located on chromosome 18 (LOD = 3.29, genome-wide p = 0.0159). There was also suggestive evidence for two loci located on chromosomes 12 and 13 influencing whipworm infection. Conclusion The results of this first genome scan for susceptibility to whipworm infection may ultimately lead to the identification of novel targets for vaccine and drug development efforts. PMID:18462166

Roles of Copper and a Conserved Aspartic Acid in the Autocatalytic Hydroxylation of a Specific Tryptophan Residue during Cysteine Tryptophylquinone Biogenesis.

PubMed

Williamson, Heather R; Sehanobish, Esha; Shiller, Alan M; Sanchez-Amat, Antonio; Davidson, Victor L

2017-02-21

The first posttranslational modification step in the biosynthesis of the tryptophan-derived quinone cofactors is the autocatalytic hydroxylation of a specific Trp residue at position C-7 on the indole side chain. Subsequent modifications are catalyzed by modifying enzymes, but the mechanism by which this first step occurs is unknown. LodA possesses a cysteine tryptophylquinone (CTQ) cofactor. Metal analysis as well as spectroscopic and kinetic studies of the mature and precursor forms of a D512A LodA variant provides evidence that copper is required for the initial hydroxylation of the precursor protein and that if alternative metals are bound, the modification does not occur and the precursor is unstable. It is shown that the mature native LodA also contains loosely bound copper, which affects the visible absorbance spectrum and quenches the fluorescence spectrum that is attributed to the mature CTQ cofactor. When copper is removed, the fluorescence appears, and when it is added back to the protein, the fluorescence is quenched, indicating that copper reversibly binds in the proximity of CTQ. Removal of copper does not diminish the enzymatic activity of LodA. This distinguishes LodA from enzymes with protein-derived tyrosylquinone cofactors in which copper is present near the cofactor and is absolutely required for activity. Mechanisms are proposed for the role of copper in the hydroxylation of the unactivated Trp side chain. These results demonstrate that the reason that the highly conserved Asp512 is critical for LodA, and possibly all tryptophylquinone enzymes, is not because it is required for catalysis but because it is necessary for CTQ biosynthesis, more specifically to facilitate the initial copper-dependent hydroxylation of a specific Trp residue.

Determination of lithium and transition metals in Li1 Ni1/3 Co1/3 Mn1/3 O2 (NCM) cathode material for lithium-ion batteries by capillary electrophoresis.

PubMed

Vortmann-Westhoven, Britta; Lürenbaum, Constantin; Winter, Martin; Nowak, Sascha

2017-02-01

In this work, we present a novel electrophoretic method that was developed for the determination of lithium and transition metals in LiNi 1/3 Co 1/3 Mn 1/3 O 2 cathode material after microwave digestion. The cations in the digested LiNi 1/3 Co 1/3 Mn 1/3 O 2 material were separated by CE and the element content was determined by UV/Vis detection. To characterize the precision of the measurements, the RSDs and concentrations were calculated and compared to those obtained with ICP-optical emission spectrometry (ICP-OES). Furthermore, a certified reference material (BCR 176R-fly ash) was investigated for all techniques. For active material components, the LOD and LOQ were determined. The LODs and LOQs for the metals determined by CE were as follows: lithium (LOD/LOQ): 17.41/62.70 μg/L, cobalt (LOD/LOQ): 348.4/1283 μg/L, manganese (LOD/LOQ): 540.2/2095 μg/L, and nickel (LOD/LOQ): 838.0/2982 μg/L. Recovery rates for lithium were in the range of 95-103%. It could be proven that with the new technique, the results for the determination of the lithium content of active material were comparable with those obtained by ICP-OES and ion chromatography. Furthermore, the recovery rates of the transition metals were determined to be between 96 and 110% by CE and ICP-OES. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection limits of quantitative and digital PCR assays and their influence in presence-absence surveys of environmental DNA.

PubMed

Hunter, Margaret E; Dorazio, Robert M; Butterfield, John S S; Meigs-Friend, Gaia; Nico, Leo G; Ferrante, Jason A

2017-03-01

A set of universal guidelines is needed to determine the limit of detection (LOD) in PCR-based analyses of low-concentration DNA. In particular, environmental DNA (eDNA) studies require sensitive and reliable methods to detect rare and cryptic species through shed genetic material in environmental samples. Current strategies for assessing detection limits of eDNA are either too stringent or subjective, possibly resulting in biased estimates of species' presence. Here, a conservative LOD analysis grounded in analytical chemistry is proposed to correct for overestimated DNA concentrations predominantly caused by the concentration plateau, a nonlinear relationship between expected and measured DNA concentrations. We have used statistical criteria to establish formal mathematical models for both quantitative and droplet digital PCR. To assess the method, a new Grass Carp (Ctenopharyngodon idella) TaqMan assay was developed and tested on both PCR platforms using eDNA in water samples. The LOD adjustment reduced Grass Carp occupancy and detection estimates while increasing uncertainty-indicating that caution needs to be applied to eDNA data without LOD correction. Compared to quantitative PCR, digital PCR had higher occurrence estimates due to increased sensitivity and dilution of inhibitors at low concentrations. Without accurate LOD correction, species occurrence and detection probabilities based on eDNA estimates are prone to a source of bias that cannot be reduced by an increase in sample size or PCR replicates. Other applications also could benefit from a standardized LOD such as GMO food analysis and forensic and clinical diagnostics. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Influence of the surface magnetic field of a cylindrical permanent magnet on the maximum levitation force in high-Tc superconductors

NASA Astrophysics Data System (ADS)

Zhao, Xian-Feng; Liu, Yuan

2006-06-01

In this paper we present the dependence of the maximum levitation force (FzMax) of a high-Tc superconductor on the surface magnetic field (Bs) of a cylindrical permanent magnet, based on the Bean critical state model and Ampère's law. A transition point of Bs is found at which the relation between FzMax and Bs changes: while the surface magnetic field is less than the transition point the dependence is subjected to a nonlinear function, otherwise it is a linear one. The two different relations are estimated to correspond to partial penetration of the shielding currents in the interior of the superconductor below the transition point and complete penetration above it, respectively. Furthermore, the influence of the geometrical properties of superconductors on the transition point of Bs is discussed, which shows a quadratic polynomial function between the transition points and the radii and the thickness of superconductors. Some optimum contours of the transition point of Bs are presented in order to achieve large levitation forces.

The effect of gravitational and pressure torques on Titan's length-of-day variations

NASA Astrophysics Data System (ADS)

Van Hoolst, T.; Rambaux, N.; Karatekin, Ö.; Baland, R.-M.

2009-03-01

Cassini radar observations show that Titan's spin is slightly faster than synchronous spin. Angular momentum exchange between Titan's surface and the atmosphere over seasonal time scales corresponding to Saturn's orbital period of 29.5 year is the most likely cause of the observed non-synchronous rotation. We study the effect of Saturn's gravitational torque and torques between internal layers on the length-of-day (LOD) variations driven by the atmosphere. Because static tides deform Titan into an ellipsoid with the long axis approximately in the direction to Saturn, non-zero gravitational and pressure torques exist that can change the rotation rate of Titan. For the torque calculation, we estimate the flattening of Titan and its interior layers under the assumption of hydrostatic equilibrium. The gravitational forcing by Saturn, due to misalignment of the long axis of Titan with the line joining the mass centers of Titan and Saturn, reduces the LOD variations with respect to those for a spherical Titan by an order of magnitude. Internal gravitational and pressure coupling between the ice shell and the interior beneath a putative ocean tends to reduce any differential rotation between shell and interior and reduces further the LOD variations by a few times. For the current estimate of the atmospheric torque, we obtain LOD variations of a hydrostatic Titan that are more than 100 times smaller than the observations indicate when Titan has no ocean as well as when a subsurface ocean exists. Moreover, Saturn's torque causes the rotation to be slower than synchronous in contrast to the Cassini observations. The calculated LOD variations could be increased if the atmospheric torque is larger than predicted and or if fast viscous relaxation of the ice shell could reduce the gravitational coupling, but it remains to be studied if a two order of magnitude increase is possible and if these effects can explain the phase difference of the predicted rotation variations. Alternatively, the large differences with the observations may suggest that non-hydrostatic effects in Titan are important. In particular, we show that the amplitude and phase of the calculated rotation variations are similar to the observed values if non-hydrostatic effects could strongly reduce the equatorial flattening of the ice shell above an internal ocean.

Low-cost mercury (II) ion sensor by biosynthesized gold nanoparticles (AuNPs)

NASA Astrophysics Data System (ADS)

Guerrero, Jet G.; Candano, Gabrielle Jackie; Mendoza, Aileen Nicole; Paderanga, Marciella; Cardino, Krenz John; Locsin, Alessandro; Bibon, Cherilou

2017-11-01

Biosynthesis of gold nanoparticles has attracted the curiosity of scientists over the past few decades. Nanoparticles have been proven to exhibit enhanced properties and offer a variety of applications in different fields of study. Utilizing nanoparticles instead of bulky equipment and noxious chemicals has become more convenient; reagents needed for synthesis have been proven to be benign (mostly aqueous solutions) and are cost-effective. In this study, gold nanoparticles were biosynthesized using guyabano (Annonamuricata) peel samples as the source of reducing agents. The optimum concentration ratio of gold chloride to guyabano extract was determined to be 1:7. Characterization studies were accomplished using UV Vis Spectroscopy, Fourier Transform Electron Microscopy (FTIR) and Scanning Electron Microscopy (SEM). Spectroscopic maximum absorbance was found to be at 532 nm thereby confirming the presence of gold nanoparticles. Hydroxyl (O-H stretching), carbonyl (C=O stretching), and amide (N-H stretching) functional groups shown in the FTIR spectra are present on possible reducing agents such as phenols, alkaloids, and saponins found in the plant extract. SEM images revealed spherical shaped nanoparticles with mean diameter of 23.18 nm. It was observed that the bio-synthesized AuNPs were selective to mercury ions through uniform color change from wine red to yellow. A novel smartphone-based mercury (II) ions assay was developed using the gold nanoparticles. A calibration curve correlated the analytical response (Red intensity) to the concentrations of Hg 2+ ions. Around 94% of the variations in the intensity is accounted for by the variations in the concentration of mercury (II) ions suggesting a good linear relationship between the two variables. A relative standard deviation (RSD) of less than 1% was achieved at all individual points. The metal sensor displayed a sensitivity of 0.039 R.I./ppm with an LOD of 93.79 ppm. Thus, the bio-fabricated gold nanoparticles can be utilized as a possible sensor for mercury (II) ions in solution.

A novel 'splice site' HCN4 Gene mutation, c.1737+1 G>T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability.

PubMed

Hategan, Lidia; Csányi, Beáta; Ördög, Balázs; Kákonyi, Kornél; Tringer, Annamária; Kiss, Orsolya; Orosz, Andrea; Sághy, László; Nagy, István; Hegedűs, Zoltán; Rudas, László; Széll, Márta; Varró, András; Forster, Tamás; Sepp, Róbert

2017-08-15

The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate<60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings. The identified novel 'splice site' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting the number and sizes of IBD regions among family members and evaluating the family size requirement for linkage studies.

PubMed

Yang, Wanling; Wang, Zhanyong; Wang, Lusheng; Sham, Pak-Chung; Huang, Peng; Lau, Yu Lung

2008-12-01

With genotyping of high-density single nucleotide polymorphisms (SNPs) replacing that of microsatellite markers in linkage studies, it becomes possible to accurately determine the genomic regions shared identity by descent (IBD) by family members. In addition to evaluating the likelihood of linkage for a region with the underlining disease (the LOD score approach), an appropriate question to ask is what would be the expected number and sizes of IBD regions among the affecteds, as there could be more than one region reaching the maximum achievable LOD score for a given family. Here, we introduce a computer program to allow the prediction of the total number of IBD regions among family members and their sizes. Reversely, it can be used to predict the portion of the genome that can be excluded from consideration according to the family size and user-defined inheritance mode and penetrance. Such information has implications on the feasibility of conducting linkage analysis on a given family of certain size and structure or on a few small families when interfamily homogeneity can be assumed. It can also help determine the most relevant members to be genotyped for such a study. Simulation results showed that the IBD regions containing true mutations are usually larger than regions IBD due to random chance. We have made use of this feature in our program to allow evaluation of the identified IBD regions based on Bayesian probability calculation and simulation results.

Comparison of field portable measurements of ultrafine TiO2: X-ray fluorescence, laser-induced breakdown spectroscopy, and Fourier-transform infrared spectroscopy.

PubMed

LeBouf, Ryan F; Miller, Arthur L; Stipe, Christopher; Brown, Jonathan; Murphy, Nate; Stefaniak, Aleksandr B

2013-06-01

Laboratory measurements of ultrafine titanium dioxide (TiO2) particulate matter loaded on filters were made using three field portable methods (X-ray fluorescence (XRF), laser-induced breakdown spectroscopy (LIBS), and Fourier-transform infrared (FTIR) spectroscopy) to assess their potential for determining end-of-shift exposure. Ultrafine TiO2 particles were aerosolized and collected onto 37 mm polycarbonate track-etched (PCTE) filters in the range of 3 to 578 μg titanium (Ti). Limit of detection (LOD), limit of quantification (LOQ), and calibration fit were determined for each measurement method. The LOD's were 11.8, 0.032, and 108 μg Ti per filter, for XRF, LIBS, and FTIR, respectively and the LOQ's were 39.2, 0.11, and 361 μg Ti per filter, respectively. The XRF calibration curve was linear over the widest dynamic range, up to the maximum loading tested (578 μg Ti per filter). LIBS was more sensitive but, due to the sample preparation method, the highest loaded filter measurable was 252 μg Ti per filter. XRF and LIBS had good predictability measured by regressing the predicted mass to the gravimetric mass on the filter. XRF and LIBS produced overestimations of 4% and 2%, respectively, with coefficients of determination (R(2)) of 0.995 and 0.998. FTIR measurements were less dependable due to interference from the PCTE filter media and overestimated mass by 2% with an R(2) of 0.831.

Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

PubMed

Sankila, E M; Pakarinen, L; Kääriäinen, H; Aittomäki, K; Karjalainen, S; Sistonen, P; de la Chapelle, A

1995-01-01

Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)

Weekly Online Quizzes to a Mathematics Course for Engineering Students

ERIC Educational Resources Information Center

Gaspar Martins, Sandra

2017-01-01

A set of weekly optional online quizzes was used with 104 students on a Multivariable Calculus course (MC), via the Moodle online system. These quizzes contributed a maximum of two extra points, and this was awarded if the student scored more than 9 points (out of 20) on the exam. All the students got the same questions and could resubmit the…

Aspects Of 40- to 50-Day Oscillations In LOD And AAM

NASA Technical Reports Server (NTRS)

Dickey, Jean O.; Marcus, Steven L.; Ghil, Michael

1992-01-01

Report presents study of fluctuations in rotation of Earth, focusing on irregular intraseasonal oscillations in length of day (LOD) and atmospheric angular momentum (AAM) with periods varying from 40 to 50 days. Study draws upon and extends results of prior research.

An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator.

PubMed

Yoo, Yong Kyoung; Yoon, Dae Sung; Kim, Gangeun; Kim, Jinsik; Han, Sung Il; Lee, Junwoo; Chae, Myung-Sic; Lee, Sang-Myung; Lee, Kyu Hyoung; Hwang, Kyo Seon; Lee, Jeong Hoon

2017-10-30

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.

The amyloid precursor protein locus and very-late-onset Alzheimer disease.

PubMed

Olson, J M; Goddard, K A; Dudek, D M

2001-10-01

Although mutations in the amyloid-beta precursor protein (APP) gene are known to confer high risk of Alzheimer disease (AD) to a small percentage of families in which it has early onset, convincing evidence of a major role for the APP locus in late-onset AD has not been forthcoming. In this report, we have used a covariate-based affected-sib-pair linkage method to analyze the chromosome 21 clinical and genetic data obtained on affected sibships by the National Institute of Mental Health Alzheimer Disease Genetics Initiative. The baseline model (without covariates) gave a LOD score of 0.02, which increases to 1.43 when covariates representing the additive effects of E2 and E4 are added. Larger increases in LOD scores were found when age at last examination/death (LOD score 5.54; P=.000002) or age at onset plus disease duration (LOD score 5.63; P=.000006) were included in the linkage model. We conclude that the APP locus may predispose to AD in the very elderly.

Backward deletion to minimize prediction errors in models from factorial experiments with zero to six center points

NASA Technical Reports Server (NTRS)

Holms, A. G.

1980-01-01

Population model coefficients were chosen to simulate a saturated 2 to the 4th fixed-effects experiment having an unfavorable distribution of relative values. Using random number studies, deletion strategies were compared that were based on the F-distribution, on an order statistics distribution of Cochran's, and on a combination of the two. The strategies were compared under the criterion of minimizing the maximum prediction error, wherever it occurred, among the two-level factorial points. The strategies were evaluated for each of the conditions of 0, 1, 2, 3, 4, 5, or 6 center points. Three classes of strategies were identified as being appropriate, depending on the extent of the experimenter's prior knowledge. In almost every case the best strategy was found to be unique according to the number of center points. Among the three classes of strategies, a security regret class of strategy was demonstrated as being widely useful in that over a range of coefficients of variation from 4 to 65%, the maximum predictive error was never increased by more than 12% over what it would have been if the best strategy had been used for the particular coefficient of variation. The relative efficiency of the experiment, when using the security regret strategy, was examined as a function of the number of center points, and was found to be best when the design used one center point.

Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI.

PubMed

Shen, Zonglin; Jiang, Linling; Yang, Shuran; Ye, Jing; Dai, Nan; Liu, Xiaoyan; Li, Na; Lu, Jin; Liu, Fang; Lu, Yi; Sun, Xuejin; Cheng, Yuqi; Xu, Xiufeng

2017-01-01

Previous work exhibited different brain grey matter volume (GMV) changes between patients with early adult onset depression (EOD, age 18-29) and later adult onset depression (LOD, age 30-44) by using 30-year-old as the cut-off age. To identify whether regional homogeneity (ReHo) changes are also different between EOD and LOD by using same cut-off age, we used resting-state functional magnetic resonance imaging (fMRI) to detect the abnormal ReHo between patients with EOD and LOD in the present study. Resting-state fMRI scans of 58 patients with EOD, 62 patients with LOD, 60 young healthy controls (HC), and 52 old HC were obtained. The ReHo approach was used to analyze the images. The ANOVA analysis revealed that the ReHo values in the frontoparietal, occipital, and cerebellar regions were significantly different among the four groups. Relative to patients with LOD, patients with EOD displayed significantly increased ReHo in the left precuneus, and decreased ReHo in the right fusiform. The ReHo values in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups. Compared to young HC, patients with EOD showed significantly increased ReHo in the right frontoparietal regions and the right calcarine. Furthermore, the increased ReHo in the right frontoparietal regions, right insula and left hippocampus, and decreased ReHo in the left inferior occipital gyrus, right middle occipital gyrus, left calcarine, and left supplementary motor area were observed in patients with LOD when compared to old HC. The ReHo of brain areas that were related to mood regulation was changed in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different ReHo abnormalities relative to each age-matched comparison group, suggesting that depressed adult patients with different age-onset might have different pathological mechanism.

Determination of legacy and novel brominated flame retardants in dust from end of life office equipment and furniture from Pretoria, South Africa.

PubMed

Nkabinde, Sylvia N; Okonkwo, Jonathan O; Olukunle, Olubiyi I; Daso, Adegbenro P

2018-05-01

Indoor dust is known to be a source of human exposure to brominated flame retardants (BFRs) and these consists of the legacy polybrominated diphenyl ethers (PBDEs), total hexabromocyclododecane (T-HBCDD) and the "Novel or alternate" Brominated flame retardants (NBFRs). In this study, x-ray fluorescence (XRF) analyser was employed to measure elemental bromine contents in office furniture and electronics as the first indication of the possible presence of BFRs. To investigate the possible BFRs present, a total of 21 dust samples were collected from surfaces of electronic equipment and office furniture and were analysed using gas chromatography-mass spectrometry (GC-MS). The concentrations of ∑ 7 BDE- congeners ranged from 50 to 3346ngng -1 . Of the ∑ 7 BDE congeners analysed, BDE-209, -183 and -99 were the most dominant congeners. The concentrations observed ranged from

Interannual variations in length-of-day (LOD) as a tool to assess climate variability and climate change

NASA Astrophysics Data System (ADS)

Lehmann, E.

2016-12-01

On interannual time scales the atmosphere affects significantly fluctuations in the geodetic quantity of length-of-day (LOD). This effect is directly proportional to perturbations in the relative angular momentum of the atmosphere (AAM) computed from zonal winds. During El Niño events tropospheric westerlies increase due to elevated sea surface temperatures (SST) in the Pacific inducing peak anomalies in relative AAM and correspondingly, in LOD. However, El Niño events affect LOD variations differently strong and the causes of this varying effect are yet not clear. Here, we investigate the LOD-El Niño relationship in the 20th and 21st century (1982-2100) whether the quantity of LOD can be used as a geophysical tool to assess variability and change in a future climate. In our analysis we applied a windowed discrete Fourier transform on all de-seasonalized data to remove climatic signals outside of the El Niño frequency band. LOD (data: IERS) was related in space and time to relative AAM and SSTs (data: ERA-40 reanalysis, IPCC ECHAM05-OM1 20C, A1B). Results from mapped Pearson correlation coefficients and time frequency behavior analysis identified a teleconnection pattern that we term the EN≥65%-index. The EN≥65%-index prescribes a significant change in variation in length-of-day of +65% and more related to (1) SST anomalies of >2° in the Pacific Niño region (160°E-80°W, 5°S-5°N), (2) corresponding stratospheric warming anomalies of the quasi-biennial oscillation (QBO), and (3) strong westerly winds in the lower equatorial stratosphere. In our analysis we show that the coupled atmosphere-ocean conditions prescribed in the EN≥65%-index apply to the extreme El Niño events of 19982/83 and 1997/98, and to 75% of all El Niño events in the last third of the 21st century. At that period of time the EN≥65%-index describes a projected altered base state of the equatorial Pacific that shows almost continuous El Niño conditions under climate warming.

The influence of bias magnetization of nanoparticles on GMR sensor signal and sensitivity for the ultra-low concentration detection

NASA Astrophysics Data System (ADS)

Zhang, Yang; Xu, Jie; Cao, Derang; Li, Qiang; Zhao, Guoxia; Sun, Nian X.; Li, Shandong

2018-05-01

In the broad research of the GMR bio-sensing technology, it is vital to explore appropriate magnetic labels and its influences on the detection signal. In this work, four kinds of ferrite particles of γ-Fe2O3, CoFe2O4, NiFe2O4 and NiZnFe2O4 were prepared through calcining the Dimethyl Formamide (DMF) solution of the transition metal nitrates [Fe(NO3)3 and X(NO3)2, X = Co, Ni, Zn] to study the effect of magnetic properties on detection signals using a DC in-plane measuring method. It was revealed that for four particles, the output voltage differences |ΔV| between with and without magnetic particles exhibit log-linear functions of the particles concentrations x in the range from 0.1 to 10 ng/mL. A very low limitation of detection (LOD) of 0.1 ng/mL for all the samples was obtained, which is two orders smaller than that in the previous work. Moreover, the change of output voltage difference at the LOD (|ΔVlim|) is proportional to the magnetization at bias field (bias magnetization, Mbias), which indicates that larger Mbias leads to a lower LOD. This work provides a useful guidance in selecting or preparing magnetic labels to enhance the sensitivity of GMR biosensors.

Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco Family Study

PubMed Central

Ehlers, Cindy L.; Gizer, Ian R.; Vieten, Cassandra; Wilhelmsen, Kirk C.

2010-01-01

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of “craving” and “withdrawal” using a family study design. Participants were 2524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis, however, linkage analyses of cannabis “craving” and the cannabis withdrawal symptom of “nervous, tense, restless or irritable” revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes. PMID:19937978

Use of experimental design for optimisation of the cold plasma ICP-MS determination of lithium, aluminum and iron in soft drinks and alcoholic beverages.

PubMed

Bianchi, F; Careri, M; Maffini, M; Mangia, A; Mucchino, C

2003-01-01

A sensitive method for the simultaneous determination of (7)Li, (27)Al and (56)Fe by cold plasma ICP-MS was developed and validated. Experimental design was used to investigate the effects of torch position, torch power, lens 2 voltage, and coolant flow. Regression models and desirability functions were applied to find the experimental conditions providing the highest global sensitivity in a multi-elemental analysis. Validation was performed in terms of limits of detection (LOD), limits of quantitation (LOQ), linearity and precision. LODs were 1.4 and 159 ng L(-1) for (7)Li and (56)Fe, respectively; the highest LOD found being that for (27)Al (425 ng L(-1)). Linear ranges of 5 orders of magnitude for Li and 3 orders for Fe were statistically verified for each compound. Precision was evaluated by testing two concentration levels, and good results in terms of both intra-day repeatability and intermediate precision were obtained. RSD values lower than 4.8% at the lowest concentration level were calculated for intra-day repeatability. Commercially available soft drinks and alcoholic beverages contained in different packaging materials (TetraPack, polyethylene terephthalate (PET), commercial cans and glass) were analysed, and all the analytes were detected and quantitated. Copyright 2002 John Wiley & Sons, Ltd.

Construction of an integrated genetic map for Capsicum baccatum L.

PubMed

Moulin, M M; Rodrigues, R; Ramos, H C C; Bento, C S; Sudré, C P; Gonçalves, L S A; Viana, A P

2015-06-18

Capsicum baccatum L. is one of the five Capsicum domesticated species and has multiple uses in the food, pharmaceutical and cosmetic industries. This species is also a valuable source of genes for chili pepper breeding, especially genes for disease resistance and fruit quality. However, knowledge of the genetic structure of C. baccatum is limited. A reference map for C. baccatum (2n = 2x = 24) based on 42 microsatellite, 85 inter-simple sequence repeat, and 56 random amplified polymorphic DNA markers was constructed using an F2 population consisting of 203 individuals. The map was generated using the JoinMap software (version 4.0) and the linkage groups were formed and ordered using a LOD score of 3.0 and maximum of 40% recombination. The genetic map consisted of 12 major and four minor linkage groups covering a total genome distance of 2547.5 cM with an average distance of 14.25 cM between markers. Of the 152 pairs of microsatellite markers available for Capsicum annuum, 62 were successfully transferred to C. baccatum, generating polymorphism. Forty-two of these markers were mapped, allowing the introduction of C. baccatum in synteny studies with other species of the genus Capsicum.

A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3.

PubMed

Hassan, Muhammad Jawad; Santos, Regie Lyn P; Rafiq, Muhammad Arshad; Chahrour, Maria H; Pham, Thanh L; Wajid, Muhammad; Hijab, Nadine; Wambangco, Michael; Lee, Kwanghyuk; Ansar, Muhammad; Yan, Kai; Ahmad, Wasim; Leal, Suzanne M

2006-01-01

Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for approximately 75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants.

A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3

PubMed Central

Hassan, Muhammad Jawad; Santos, Regie Lyn P.; Rafiq, Muhammad Arshad; Chahrour, Maria H.; Pham, Thanh L.; Wajid, Muhammad; Hijab, Nadine; Wambangco, Michael; Lee, Kwanghyuk; Ansar, Muhammad; Yan, Kai; Ahmad, Wasim; Leal, Suzanne M.

2010-01-01

Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants. PMID:16261342

Localization of Usher syndrome type II to chromosome 1q.

PubMed

Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J

1990-06-01

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.

A maximum power point tracking algorithm for buoy-rope-drum wave energy converters

NASA Astrophysics Data System (ADS)

Wang, J. Q.; Zhang, X. C.; Zhou, Y.; Cui, Z. C.; Zhu, L. S.

2016-08-01

The maximum power point tracking control is the key link to improve the energy conversion efficiency of wave energy converters (WEC). This paper presents a novel variable step size Perturb and Observe maximum power point tracking algorithm with a power classification standard for control of a buoy-rope-drum WEC. The algorithm and simulation model of the buoy-rope-drum WEC are presented in details, as well as simulation experiment results. The results show that the algorithm tracks the maximum power point of the WEC fast and accurately.

Utilizing Maximum Power Point Trackers in Parallel to Maximize the Power Output of a Solar (Photovoltaic) Array

DTIC Science & Technology

2012-12-01

photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase... photovoltaic (PV) system to use a maximum power point tracker ( MPPT ) to increase the power output of the solar array. Currently, most military... MPPT ) is an optimizing circuit that is used in conjunction with photovoltaic (PV) arrays to achieve the maximum delivery of power from the array

Secular changes of LOD associated with a growth of the inner core

NASA Astrophysics Data System (ADS)

Denis, C.; Rybicki, K. R.; Varga, P.

2006-05-01

From recent estimates of the age of the inner core based on the theory of thermal evolution of the core, we estimate that nowadays the growth of the inner core may perhaps contribute to the observed overall secular increase of LOD caused mainly by tidal friction (i.e., 1.72 ms per century) by a relative decrease of 2 to 7 μs per century. Another, albeit much less plausible, hypothesis is that crystallization of the inner core does not produce any change of LOD, but makes the inner core rotate differentially with respect to the outer core and mantle.

Determination of Oversulphated Chondroitin Sulphate and Dermatan Sulphate in unfractionated heparin by (1)H-NMR - Collaborative study for quantification and analytical determination of LoD.

PubMed

McEwen, I; Mulloy, B; Hellwig, E; Kozerski, L; Beyer, T; Holzgrabe, U; Wanko, R; Spieser, J-M; Rodomonte, A

2008-12-01

Oversulphated Chondroitin Sulphate (OSCS) and Dermatan Sulphate (DS) in unfractionated heparins can be identified by nuclear magnetic resonance spectrometry (NMR). The limit of detection (LoD) of OSCS is 0.1% relative to the heparin content. This LoD is obtained at a signal-to-noise ratio (S/N) of 2000:1 of the heparin methyl signal. Quantification is best obtained by comparing peak heights of the OSCS and heparin methyl signals. Reproducibility of less than 10% relative standard deviation (RSD) has been obtained. The accuracy of quantification was good.

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors.

PubMed

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus.

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors

PubMed Central

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus. PMID:18466597

Highly sensitive C-reactive protein (CRP) assay using metal-enhanced fluorescence (MEF)

NASA Astrophysics Data System (ADS)

Zhang, Yi; Keegan, Gemma L.; Stranik, Ondrej; Brennan-Fournet, Margaret E.; McDonagh, Colette

2015-07-01

Fluorescence has been extensively employed in the area of diagnostic immunoassays. A significant enhancement of fluorescence can be achieved when noble metal nanoparticles are placed in close proximity to fluorophores. This effect, referred to as metal-enhanced fluorescence (MEF), has the potential to produce immunoassays with a high sensitivity and a low limit of detection (LOD). In this study, we investigate the fluorescence enhancement effect of two different nanoparticle systems, large spherical silver nanoparticles (AgNPs) and gold edge-coated triangular silver nanoplates, and both systems were evaluated for MEF. The extinction properties and electric field enhancement of both systems were modeled, and the optimum system, spherical AgNPs, was used in a sandwich immunoassay for human C-reactive protein with a red fluorescent dye label. A significant enhancement in the fluorescence was observed, which corresponded to an LOD improvement of 19-fold compared to a control assay without AgNPs.

Weighted combination of LOD values oa splitted into frequency windows

NASA Astrophysics Data System (ADS)

Fernandez, L. I.; Gambis, D.; Arias, E. F.

In this analysis a one-day combined time series of LOD(length-of-day) estimates is presented. We use individual data series derived by 7 GPS and 3 SLR analysis centers, which routinely contribute to the IERS database over a recent 27-month period (Jul 1996 - Oct 1998). The result is compared to the multi-technique combined series C04 produced by the Central Bureau of the IERS that is commonly used as a reference for the study of the phenomena of Earth rotation variations. The Frequency Windows Combined Series procedure brings out a time series, which is close to C04 but shows an amplitude difference that might explain the evident periodic behavior present in the differences of these two combined series. This method could be useful to generate a new time series to be used as a reference in the high frequency variations of the Earth rotation studies.

Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin.

PubMed

Mecklenburg, M; Lindbladh, C; Li, H; Mosbach, K; Danielsson, B

1993-08-01

A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay-based biosensors. The implications of these results upon on-line analysis are discussed.

An aptamer-based paper microfluidic device for the colorimetric determination of cocaine.

PubMed

Wang, Ling; Musile, Giacomo; McCord, Bruce R

2018-02-01

A method utilizing paper microfluidics coupled with gold nanoparticles and two anticocaine aptamers has been developed to detect seized cocaine samples. The ready-to-use format involves the use of a paper strip that produces a color change resulting from the salt-induced aggregation of gold nanoparticles producing a visible color change indicating the presence of the drug. This format is specific for the detection of cocaine. The visual LOD for the method was 2.5 μg and the camera based LOD was 2.36 μg. The operation of the device is easy and rapid, and does not require extensive training or instrumentation. All of the materials utilized in the device are safe and environmental friendly. This device should prove a useful tool for the screening of forensic samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitive Detection of Francisella tularensis Directly from Whole Blood by Use of the GeneXpert System.

PubMed

Banada, Padmapriya P; Deshpande, Srinidhi; Chakravorty, Soumitesh; Russo, Riccardo; Occi, James; Meister, Gabriel; Jones, Kelly J; Gelhaus, Carl H; Valderas, Michelle W; Jones, Martin; Connell, Nancy; Alland, David

2017-01-01

Francisella tularensis is a potential bioterrorism agent that is highly infectious at very low doses. Diagnosis of tularemia by blood culture and nucleic acid-based diagnostic tests is insufficiently sensitive. Here, we demonstrate a highly sensitive F. tularensis assay that incorporates sample processing and detection into a single cartridge suitable for point-of-care detection. The assay limit of detection (LOD) and dynamic range were determined in a filter-based cartridge run on the GeneXpert system. F. tularensis DNA in buffer or CFU of F. tularensis was spiked into human or macaque blood. To simulate detection in human disease, the assay was tested on blood drawn from macaques infected with F. tularensis Schu S4 at daily intervals. Assay detection was compared to that with a conventional quantitative PCR (qPCR) assay and blood culture. The assay LOD was 0.1 genome equivalents (GE) per reaction and 10 CFU/ml F. tularensis in both human and macaque blood. In infected macaques, the assay detected F. tularensis on days 1 to 4 postinfection in 21%, 17%, 60%, and 83% of macaques, respectively, compared to conventional qPCR positivity rates of 0%, 0%, 30%, and 100% and CFU detection of blood culture at 0%, 0%, 0%, and 10% positive, respectively. Assay specificity was 100%. The new cartridge-based assay can rapidly detect F. tularensis in bloodstream infections directly in whole blood at the early stages of infection with a sensitivity that is superior to that of other methods. The simplicity of the automated testing procedures may make this test suitable for rapid point-of-care detection. Copyright © 2016 American Society for Microbiology.

A simple 96 well microfluidic chip combined with visual and densitometry detection for resource-poor point of care testing

PubMed Central

Yang, Minghui; Sun, Steven; Kostov, Yordan

2010-01-01

There is a well-recognized need for low cost biodetection technologies for resource-poor settings with minimal medical infrastructure. Lab-on-a-chip (LOC) technology has the ability to perform biological assays in such settings. The aim of this work is to develop a low cost, high-throughput detection system for the analysis of 96 samples simultaneously outside the laboratory setting. To achieve this aim, several biosensing elements were combined: a syringe operated ELISA lab-on-a-chip (ELISA-LOC) which integrates fluid delivery system into a miniature 96-well plate; a simplified non-enzymatic reporter and detection approach using a gold nanoparticle-antibody conjugate as a secondary antibody and silver enhancement of the visual signal; and Carbon nanotubes (CNT) to increase primary antibody immobilization and improve assay sensitivity. Combined, these elements obviate the need for an ELISA washer, electrical power for operation and a sophisticated detector. We demonstrate the use of the device for detection of Staphylococcal enterotoxin B, a major foodborne toxin using three modes of detection, visual detection, CCD camera and document scanner. With visual detection or using a document scanner to measure the signal, the limit of detection (LOD) was 0.5ng/ml. In addition to visual detection, for precise quantitation of signal using densitometry and a CCD camera, the LOD was 0.1ng/ml for the CCD analysis and 0.5 ng/ml for the document scanner. The observed sensitivity is in the same range as laboratory-based ELISA testing. The point of care device can analyze 96 samples simultaneously, permitting high throughput diagnostics in the field and in resource poor areas without ready access to laboratory facilities or electricity. PMID:21503269

Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection.

PubMed

Cross, Robert W; Boisen, Matthew L; Millett, Molly M; Nelson, Diana S; Oottamasathien, Darin; Hartnett, Jessica N; Jones, Abigal B; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A; Fusco, Marnie L; Abelson, Dafna M; Oda, Shunichiro; Brown, Bethany L; Pham, Ha; Rowland, Megan M; Agans, Krystle N; Geisbert, Joan B; Heinrich, Megan L; Kulakosky, Peter C; Shaffer, Jeffrey G; Schieffelin, John S; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M; Wilson, Russell B; Saphire, Erica Ollmann; Pitts, Kelly R; Khan, Sheik Humarr; Grant, Donald S; Geisbert, Thomas W; Branco, Luis M; Garry, Robert F

2016-10-15

Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 10 5 -9.0 × 10 8 genomes/mL. The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Simultaneous determination of C1-C4 carboxylic acids and aldehydes using 2,4-dinitrophenylhydrazine-impregnated silica gel and high-performance liquid chromatography.

PubMed

Uchiyama, Shigehisa; Matsushima, Erika; Aoyagi, Shohei; Ando, Masanori

2004-10-01

A new method for the simultaneous determination of aliphatic carboxylic acids and aldehydes in air is described. In this work, carboxylic acids were allowed to react with 2,4-dinitrophenylhydrazine (DNPH) to form the corresponding carboxylic 2,4-dinitrophenylhydrazides. These derivatives have excellent thermal stability, with melting points higher than those of the corresponding hydrazones by 32-50 degrees C. C1-C4 carboxylic acid 2,4-dinitrophenylhydrazides exhibited maximum absorption wavelengths of 331-334 nm and molar absorption coefficients of 1.4 x 10(4) L/mol/cm. They were completely separated by high-performance liquid chromatography (HPLC) with an RP-Amide C16 column. Cartridges packed with DNPH-coated silica particles (DNPH cartridge) were used for sampling formic acid and aldehydes. Formic acid was physically adsorbed on the silica particles as the first step of the sampling mechanism. Gradual reaction with DNPH followed. Formic acid reacted very slowly with DNPH at room temperature (20 degrees C), but reacted completely at 80 degrees C over 4 h. In field measurements, the sample air was drawn through a DNPH cartridge. After sampling, the cartridges were heated at 80 degrees C for 5 h and extracted with acetonitrile for HPLC analysis. Under these optimized conditions, the LOD is 0.4 ug/m(3) for an air sample collected for 24 h at 100 mL/min (144 L).

Computational study for optimization of a plasmon FET as a molecular biosensor

NASA Astrophysics Data System (ADS)

Ciappesoni, Mark; Cho, Seongman; Tian, Jieyuan; Kim, Sung Jin

2018-02-01

Surface Plasmon Resonance (SPR) is currently being widely studied as it exhibits sensitive optical properties to changes in in the refractive index of the surrounding medium. As novel devices using SPR have been developing rapidly there is a necessity to develop models and simulation environments that will allow for continued development and optimization of these devices. A biological sensing device of interest is the Plasmon FET which has been proven experimentally to have a limit of detection (LOD) of 20pg/ml while being immune to the absorption of the medium. The Plasmon FET is a metal-semiconductor-metal detector which employ functionalized gold nanostructures on a semi-conducting layer. This direct approach has the advantages of not requiring readout optics reducing size and allowing for point-of -care measurements. Using Lumerical FDTD and Device numerical solvers, we can report an advanced simulation environment illustrating several key sensor specifications including LOD, resolution, sensitivity, and dynamic range, for a variety of biological markers providing a comprehensive analysis of a Direct Plasmon-to-Electric conversion device designed to function with colored mediums (eg.whole blood). This model allows for the simulation and optimization of a plasmonic sensor that already o ers advantages in size, operability, and multiplexing-capability, with real time monitoring.

The Extended Core Coax: A novel nanoarchitecture for lab-on-a-chip electrochemical diagnostics

NASA Astrophysics Data System (ADS)

Valera, Amy E.; D'Imperio, Luke; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

We report a novel nanoarchitecture, the Extended Core Coax (ECC) that has applicability for the detection of biomarkers in lab-on-a-chip diagnostic devices. ECC is capable of providing accessible, highly sensitive, and specific disease diagnosis at point-of-care. The architecture represents a vertically oriented nanocoax comprised of a gold inner metal core that extends 200nm above a chrome outer metal shield, separated by a dielectric annulus. Each ECC chip contains 7 discrete sensing arrays, 0.49 mm2 in size, containing 35,000 nanoscale coaxes wired in parallel. Previous non-extended nanocoaxial architectures have demonstrated a limit of detection (LOD) of 2 ng/mL of cholera toxin using an off-chip setup. This sensitivity compares favorably to the standard optical ELISA used in clinical settings. The ECC matches this LOD, and additionally offers the benefit of specific and reliable biofunctionalization on the extended gold core. Thus, the ECC is an attractive candidate for development as a full lab-on-a-chip biosensor for detection of infectious disease biomarkers, such as cholera toxin, through tethering of biomarker recognition proteins, such as antibodies, directly on the device. Support from the National Institutes of Health (National Cancer Institute award No. CA137681 and National Institute of Allergy and Infectious Diseases award No. AI100216).

The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates.

PubMed

Tazi, Asmaa; Disson, Olivier; Bellais, Samuel; Bouaboud, Abdelouhab; Dmytruk, Nicolas; Dramsi, Shaynoor; Mistou, Michel-Yves; Khun, Huot; Mechler, Charlotte; Tardieux, Isabelle; Trieu-Cuot, Patrick; Lecuit, Marc; Poyart, Claire

2010-10-25

Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17-specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood-brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies.

Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

PubMed Central

Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

2007-01-01

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

Improving maximum power point tracking of partially shaded photovoltaic system by using IPSO-BELBIC

NASA Astrophysics Data System (ADS)

Al-Alim El-Garhy, M. Abd; Mubarak, R. I.; El-Bably, M.

2017-08-01

Solar photovoltaic (PV) arrays in remote applications are often related to the rapid changes in the partial shading pattern. Rapid changes of the partial shading pattern make the tracking of maximum power point (MPP) of the global peak through the local ones too difficult. An essential need to make a fast and efficient algorithm to detect the peaks values which always vary as the sun irradiance changes. This paper presents two algorithms based on the improved particle swarm optimization technique one of them with PID controller (IPSO-PID), and the other one with Brain Emotional Learning Based Intelligent Controller (IPSO-BELBIC). These techniques improve the maximum power point (MPP) tracking capabilities for photovoltaic (PV) system under partial shading circumstances. The main aim of these improved algorithms is to accelerate the velocity of IPSO to reach to (MPP) and increase its efficiency. These algorithms also improve the tracking time under complex irradiance conditions. Based on these conditions, the tracking time of these presented techniques improves to 2 msec, with an efficiency of 100%.

Lab-on-a-Disc Platform for Automated Chemical Cell Lysis.

PubMed

Seo, Moo-Jung; Yoo, Jae-Chern

2018-02-26

Chemical cell lysis is an interesting topic in the research to Lab-on-a-Disc (LOD) platforms on account of its perfect compatibility with the centrifugal spin column format. However, standard procedures followed in chemical cell lysis require sophisticated non-contact temperature control as well as the use of pressure resistant valves. These requirements pose a significant challenge thereby making the automation of chemical cell lysis on an LOD extremely difficult to achieve. In this study, an LOD capable of performing fully automated chemical cell lysis is proposed, where a combination of chemical and thermal methods has been used. It comprises a sample inlet, phase change material sheet (PCMS)-based temperature sensor, heating chamber, and pressure resistant valves. The PCMS melts and solidifies at a certain temperature and thus is capable of indicating whether the heating chamber has reached a specific temperature. Compared to conventional cell lysis systems, the proposed system offers advantages of reduced manual labor and a compact structure that can be readily integrated onto an LOD. Experiments using Salmonella typhimurium strains were conducted to confirm the performance of the proposed cell lysis system. The experimental results demonstrate that the proposed system has great potential in realizing chemical cell lysis on an LOD whilst achieving higher throughput in terms of purity and yield of DNA thereby providing a good alternative to conventional cell lysis systems.

Performance limitations of label-free sensors in molecular diagnosis using complex samples

NASA Astrophysics Data System (ADS)

Varma, Manoj

2016-03-01

Label-free biosensors promised a paradigm involving direct detection of biomarkers from complex samples such as serum without requiring multistep sample processing typical of labelled methods such as ELISA or immunofluorescence assays. Label-free sensors have witnessed decades of development with a veritable zoo of techniques available today exploiting a multitude of physical effects. It is appropriate now to critically assess whether label-free technologies have succeeded in delivering their promise with respect to diagnostic applications, particularly, ambitious goals such as early cancer detection using serum biomarkers, which require low limits of detection (LoD). Comparison of nearly 120 limits of detection (LoD) values reported by labelled and label-free sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Data from experiments where labelled and label-free assays were performed simultaneously using the same assay parameters also confirm that the LoD achieved by labelled techniques is 2 to 3 orders of magnitude better than that by label-free techniques. Furthermore, label-free techniques required significant signal amplification, for e.g. using nanoparticle conjugated secondary antibodies, to achieve LoDs comparable to labelled methods substantially deviating from the original "direct detection" paradigm. This finding has important implications on the practical limits of applying label-free detection methods for molecular diagnosis.

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

PubMed

De Frène, Veerle; Gerris, Jan; Weyers, Steven; Dhont, Marc; Vansteelandt, Stijn; Annemans, Lieven; De Sutter, Petra

2015-01-01

Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients. © 2015 S. Karger AG, Basel.

Comparison of false-negative rates and limits of detection following macrofoam-swab sampling of Bacillus anthracis surrogates via Rapid Viability PCR and plate culture.

PubMed

Hutchison, J R; Piepel, G F; Amidan, B G; Hess, B M; Sydor, M A; Deatherage Kaiser, B L

2018-05-01

We evaluated the effects of Bacillus anthracis surrogates, low surface concentrations, surface materials and assay methods on false-negative rate (FNR) and limit of detection (LOD 95 ) for recovering Bacillus spores using a macrofoam-swab sampling procedure. Bacillus anthracis Sterne or Bacillus atrophaeus Nakamura spores were deposited over a range of low target concentrations (2-500 per coupon) onto glass, stainless steel, vinyl tile and plastic. Samples were assayed using a modified Rapid Viability-PCR (mRV-PCR) method and the traditional plate culture method to obtain FNR and LOD 95 results. Mean FNRs tended to be lower for mRV-PCR compared to culturing, and increased as spore concentration decreased for all surface materials. Surface material, but not B. anthracis surrogate, influenced FNRs with the mRV-PCR method. The mRV-PCR LOD 95 was lowest for glass and highest for vinyl tile. LOD 95 values overall were lower for mRV-PCR than for the culture method. This study adds to the limited data on FNR and LOD 95 for mRV-PCR and culturing methods with low concentrations of B. anthracis sampled from various surface materials by the CDC macrofoam-swab method. These are key inputs for planning characterization and clearance studies for low contamination levels of B. anthracis. © 2018 The Society for Applied Microbiology.

Long-Term Occurrence of Deoxynivalenol in Feed and Feed Raw Materials with a Special Focus on South Korea.

PubMed

Park, Juhee; Chang, Hansub; Kim, Dongho; Chung, Soohyun; Lee, Chan

2018-03-16

The Fusarium fungi produce toxic substances called mycotoxins, which can cause disease and harmful effects in grains, livestock, and humans. Deoxynivalenol (DON), also known as vomitoxin, is one of the Fusarium mycotoxins that is known to cause vomiting in livestock. This study shows the occurrence of deoxynivalenol in feedstuffs (compound feed and feed ingredients) between 2009 and 2016 in South Korea. A total of 653 domestic samples were collected at five time points, including 494 compound feed samples and 159 feed ingredient samples. DON contamination levels were analyzed using high-performance liquid chromatography (HPLC) with pretreatment using an immunoaffinity column (IAC). The limit of detection (LOD) and the limit of quantification (LOQ) were estimated at 1-10 µg/kg and 3-35 µg/kg, respectively. Two compound feeds (two gestating sow feed samples) out of 160 pig feed samples exceeded the European Commission (EC) guidance value, while no feed ingredient samples exceeded the EC or South Korean guidance values. There were statistically significant differences in the mean contamination levels of compound feed and feed ingredients that indicated a decreasing trend over time.

Long-Term Occurrence of Deoxynivalenol in Feed and Feed Raw Materials with a Special Focus on South Korea

PubMed Central

Park, Juhee; Chang, Hansub; Kim, Dongho; Chung, Soohyun

2018-01-01

The Fusarium fungi produce toxic substances called mycotoxins, which can cause disease and harmful effects in grains, livestock, and humans. Deoxynivalenol (DON), also known as vomitoxin, is one of the Fusarium mycotoxins that is known to cause vomiting in livestock. This study shows the occurrence of deoxynivalenol in feedstuffs (compound feed and feed ingredients) between 2009 and 2016 in South Korea. A total of 653 domestic samples were collected at five time points, including 494 compound feed samples and 159 feed ingredient samples. DON contamination levels were analyzed using high-performance liquid chromatography (HPLC) with pretreatment using an immunoaffinity column (IAC). The limit of detection (LOD) and the limit of quantification (LOQ) were estimated at 1–10 µg/kg and 3–35 µg/kg, respectively. Two compound feeds (two gestating sow feed samples) out of 160 pig feed samples exceeded the European Commission (EC) guidance value, while no feed ingredient samples exceeded the EC or South Korean guidance values. There were statistically significant differences in the mean contamination levels of compound feed and feed ingredients that indicated a decreasing trend over time. PMID:29547546

Occupational exposure assessment of magnetic fields generated by induction heating equipment-the role of spatial averaging.

PubMed

Kos, Bor; Valič, Blaž; Kotnik, Tadej; Gajšek, Peter

2012-10-07

Induction heating equipment is a source of strong and nonhomogeneous magnetic fields, which can exceed occupational reference levels. We investigated a case of an induction tempering tunnel furnace. Measurements of the emitted magnetic flux density (B) were performed during its operation and used to validate a numerical model of the furnace. This model was used to compute the values of B and the induced in situ electric field (E) for 15 different body positions relative to the source. For each body position, the computed B values were used to determine their maximum and average values, using six spatial averaging schemes (9-285 averaging points) and two averaging algorithms (arithmetic mean and quadratic mean). Maximum and average B values were compared to the ICNIRP reference level, and E values to the ICNIRP basic restriction. Our results show that in nonhomogeneous fields, the maximum B is an overly conservative predictor of overexposure, as it yields many false positives. The average B yielded fewer false positives, but as the number of averaging points increased, false negatives emerged. The most reliable averaging schemes were obtained for averaging over the torso with quadratic averaging, with no false negatives even for the maximum number of averaging points investigated.

Maximum power point tracking for photovoltaic applications by using two-level DC/DC boost converter

NASA Astrophysics Data System (ADS)

Moamaei, Parvin

Recently, photovoltaic (PV) generation is becoming increasingly popular in industrial applications. As a renewable and alternative source of energy they feature superior characteristics such as being clean and silent along with less maintenance problems compared to other sources of the energy. In PV generation, employing a Maximum Power Point Tracking (MPPT) method is essential to obtain the maximum available solar energy. Among several proposed MPPT techniques, the Perturbation and Observation (P&O;) and Model Predictive Control (MPC) methods are adopted in this work. The components of the MPPT control system which are P&O; and MPC algorithms, PV module and high gain DC-DC boost converter are simulated in MATLAB Simulink. They are evaluated theoretically under rapidly and slowly changing of solar irradiation and temperature and their performance is shown by the simulation results, finally a comprehensive comparison is presented.

Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American-Diabetes Heart Study

PubMed Central

Palmer, Nicholette D.; Divers, Jasmin; Lu, Lingyi; Register, Thomas C.; Carr, J. Jeffrey; Hicks, Pamela J.; Smith, S. Carrie; Xu, Jianzhao; Judd, Suzanne E.; Irvin, Marguerite R.; Gutierrez, Orlando M.; Bowden, Donald W.; Wagenknecht, Lynne E.; Langefeld, Carl D.; Freedman, Barry I.

2016-01-01

Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American-Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2 (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P=1.38×10−82) and novel (rs12741813 and rs10863774 with VDBP, P<6.43×10−5) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits. PMID:27032714

Meta-analysis of genome-wide scans for blood pressure in African American and Nigerian samples. The National Heart, Lung, and Blood Institute GeneLink Project.

PubMed

Rice, Treva; Cooper, Richard S; Wu, Xiaodong; Bouchard, Claude; Rankinen, Tuomo; Rao, D C; Jaquish, Cashell E; Fabsitz, Richard R; Province, Michael A

2006-03-01

In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage. In the current study using the National Heart, Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks). The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented approximately 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity. Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants.

Laser-induced breakdown spectroscopy of light water reactor simulated used nuclear fuel: Main oxide phase

DOE PAGES

Campbell, Keri R.; Judge, Elizabeth J.; Barefield, James E.; ...

2017-04-22

We show the analysis of light water reactor simulated used nuclear fuel using laser-induced breakdown spectroscopy (LIBS) is explored using a simplified version of the main oxide phase. The main oxide phase consists of the actinides, lanthanides, and zirconium. The purpose of this study is to develop a rapid, quantitative technique for measuring zirconium in a uranium dioxide matrix without the need to dissolve the material. A second set of materials including cerium oxide is also analyzed to determine precision and limit of detection (LOD) using LIBS in a complex matrix. Two types of samples are used in this study:more » binary and ternary oxide pellets. The ternary oxide, (U,Zr,Ce)O 2 pellets used in this study are a simplified version the main oxide phase of used nuclear fuel. The binary oxides, (U,Ce)O 2 and (U,Zr)O 2 are also examined to determine spectral emission lines for Ce and Zr, potential spectral interferences with uranium and baseline LOD values for Ce and Zr in a UO 2 matrix. In the spectral range of 200 to 800 nm, 33 cerium lines and 25 zirconium lines were identified and shown to have linear correlation values (R 2) > 0.97 for both the binary and ternary oxides. The cerium LOD in the (U,Ce)O 2 matrix ranged from 0.34 to 1.08 wt% and 0.94 to 1.22 wt% in (U,Ce,Zr)O 2 for 33 of Ce emission lines. The zirconium limit of detection in the (U,Zr)O 2 matrix ranged from 0.84 to 1.15 wt% and 0.99 to 1.10 wt% in (U,Ce,Zr)O 2 for 25 Zr lines. Finally, the effect of multiple elements in the plasma and the impact on the LOD is discussed.« less

Magnification of starting torques of dc motors by maximum power point trackers in photovoltaic systems

NASA Technical Reports Server (NTRS)

Appelbaum, J.; Singer, S.

1989-01-01

A calculation of the starting torque ratio of permanent magnet, series, and shunt-excited dc motors powered by solar cell arrays is presented for two cases, i.e., with and without a maximum-power-point tracker (MPPT). Defining motor torque magnification by the ratio of the motor torque with an MPPT to the motor torque without an MPPT, a magnification of 3 for the permanent magnet motor and a magnification of 7 for both the series and shunt motors are obtained. The study also shows that all motor types are less sensitive to solar insolation variation in systems including MPPTs as compared to systems without MPPTs.

The calculation of transport properties in quantum liquids using the maximum entropy numerical analytic continuation method: Application to liquid para-hydrogen

PubMed Central

Rabani, Eran; Reichman, David R.; Krilov, Goran; Berne, Bruce J.

2002-01-01

We present a method based on augmenting an exact relation between a frequency-dependent diffusion constant and the imaginary time velocity autocorrelation function, combined with the maximum entropy numerical analytic continuation approach to study transport properties in quantum liquids. The method is applied to the case of liquid para-hydrogen at two thermodynamic state points: a liquid near the triple point and a high-temperature liquid. Good agreement for the self-diffusion constant and for the real-time velocity autocorrelation function is obtained in comparison to experimental measurements and other theoretical predictions. Improvement of the methodology and future applications are discussed. PMID:11830656

Miniaturization of a homogeneous fluorescence immunoassay based on energy transfer using nanotiter plates as high-density sample carriers.

PubMed

Schobel, U; Coille, I; Brecht, A; Steinwand, G M; Gauglitz, G

2001-11-01

The miniaturization of a homogeneous competitive immunoassay to a final assay volume of 70 nL is described. As the sample carrier, disposable plastic nanotiter plates (NTP) with dimensions of 2 x 2 cm2 containing 25 x 25 wells, corresponding to approximately 15,000 wells on a traditional 96-well microtiter plate footprint, were used. Sample handling was accomplished by a piezoelectrically actuated micropipet. To reduce evaporation while pipetting the assays, the NTP was handled in a closed humid chamber and cooled to the point of condensation. To avoid washing steps, a homogeneous assay was developed that was based on energy-transfer (ET). As a model system, an antibody-based assay for the detection of the environmentally relevant compound, simazine, in drinking water was chosen. Antibodies were labeled with the long-wavelength-excitable sulfoindocyanine dye Cy5 (donor), and a tracer was synthesized by labeling BSA with a triazine derivative and the acceptor dye Cy5.5. At low analyte concentrations, the tracer was preferably bound to the antibody binding sites. As a result of the close proximity of Cy5.5 and Cy5, an efficient quenching of the Cy5 fluorescence occurred. Higher analyte concentrations led to a progressive binding of the analyte to the antibody binding sites. The increased Cy5 fluorescence was determined by using a scanning laser-induced fluorescence detector. The limit of detection (LOD), using an antibody concentration of 20 nM, was 0.32 microg/L, or 1.11 x 10(-16) mol of simazine. In comparison, the LOD of the 96-well microtiter-plate-based ET immunoassay (micro-ETIA) was 0.15 microg/L, or 1.87 x 10(-13) mol. The LOD of the optimized micro-ETIA at 1 nM IgG, was 0.01 microg/L.

Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay.

PubMed

Merrigan, Stephen D; Owen, William E; Straseski, Joely A

2015-01-01

Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods. Manufacturer-specified limits of blank (LoB), detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active-B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics, Dundee, Scotland, UK). Manufacturer's claims of LoB, LoD, LoQ, imprecision, interference, and linearity to the highest point tested (113.4 pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) = 6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced: (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r = 0.950 (n = 221). This assay performed acceptably for LoB, LoD, LoQ, imprecision, interference, linearity and method comparison to the predicate device (AxSYM). An additional comparison to a manual Active-B12 EIA method performed similarly, with minor exceptions. This study determined that the ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a high-throughput alternative for automated testing of this emerging marker of cobalamin deficiency.

Further linkage data on Norrie disease.

PubMed

Kivlin, J D; Sanborn, G E; Wright, E; Cannon, L; Carey, J

1987-03-01

We obtained a LOD score of +1.61 using DNA marker L1.28 in 5 generations of a family with Norrie disease, raising the total LOD score to +5.42. There have been no recombinations between the 2 loci in any family to date, making the marker useful for genetic counseling.

METHODS OF DEALING WITH VALUES BELOW THE LIMIT OF DETECTION USING SAS

EPA Science Inventory

Due to limitations of chemical analysis procedures, small values cannot be precisely measured. These values are said to be below the limit of detection (LOD). In statistical analyses, these values are often censored and substituted with a constant value, such as half the LOD,...

A hybrid framework for quantifying the influence of data in hydrological model calibration

NASA Astrophysics Data System (ADS)

Wright, David P.; Thyer, Mark; Westra, Seth; McInerney, David

2018-06-01

Influence diagnostics aim to identify a small number of influential data points that have a disproportionate impact on the model parameters and/or predictions. The key issues with current influence diagnostic techniques are that the regression-theory approaches do not provide hydrologically relevant influence metrics, while the case-deletion approaches are computationally expensive to calculate. The main objective of this study is to introduce a new two-stage hybrid framework that overcomes these challenges, by delivering hydrologically relevant influence metrics in a computationally efficient manner. Stage one uses computationally efficient regression-theory influence diagnostics to identify the most influential points based on Cook's distance. Stage two then uses case-deletion influence diagnostics to quantify the influence of points using hydrologically relevant metrics. To illustrate the application of the hybrid framework, we conducted three experiments on 11 hydro-climatologically diverse Australian catchments using the GR4J hydrological model. The first experiment investigated how many data points from stage one need to be retained in order to reliably identify those points that have the hightest influence on hydrologically relevant metrics. We found that a choice of 30-50 is suitable for hydrological applications similar to those explored in this study (30 points identified the most influential data 98% of the time and reduced the required recalibrations by 99% for a 10 year calibration period). The second experiment found little evidence of a change in the magnitude of influence with increasing calibration period length from 1, 2, 5 to 10 years. Even for 10 years the impact of influential points can still be high (>30% influence on maximum predicted flows). The third experiment compared the standard least squares (SLS) objective function with the weighted least squares (WLS) objective function on a 10 year calibration period. In two out of three flow metrics there was evidence that SLS, with the assumption of homoscedastic residual error, identified data points with higher influence (largest changes of 40%, 10%, and 44% for the maximum, mean, and low flows, respectively) than WLS, with the assumption of heteroscedastic residual errors (largest changes of 26%, 6%, and 6% for the maximum, mean, and low flows, respectively). The hybrid framework complements existing model diagnostic tools and can be applied to a wide range of hydrological modelling scenarios.

Non-trivial behavior of the low temperature maximum of dielectric constant and location of the end critical point in Na0.5Bi0.5TiO3-0.06BaTiO3 lead free relaxor ferroelectrics crystals detected by acoustic emission

NASA Astrophysics Data System (ADS)

Dul'kin, Evgeniy; Tiagunova, Jenia; Mojaev, Evgeny; Roth, Michael

2018-01-01

[001] lead free relaxor ferroelectrics crystals of Na0.5Bi0.5TiO3-0.06BaTiO3 were studied by means of dielectric and acoustic emission methods in the temperature range of 25-240 °C and under a dc bias electric field up to 0.4 kV/cm. A temperature maximum of the dielectric constant was found near 170 °C, as well as the acoustic emission bursts pointed out to both the depolarization temperature near 120 °C and the temperature, corresponding to the maximum of dielectric constant, near 170 °C. While the depolarization temperature increased linearly, the temperature of the dielectric constant maximum was shown to exhibit a V-shape behavior under an electric field: it initially decreases, reaches a sharp minimum at some small threshold electric field of 0.15 kV/cm, and then starts to increase similar to the Curie temperature of the normal ferroelectrics, as the field enhances. Acoustic emission bursts, accompanying the depolarization temperature, weakened with the enhancing field, whereas the ones accompanying the temperature of the dielectric constant maximum exhibited two maxima: near 0.1 kV/cm and near 0.3 kV/cm. The meaning of these two acoustic emission maxima is discussed.

Thousand-fold fluorescent signal amplification for mHealth diagnostics

PubMed Central

Balsam, Joshua; Rasooly, Reuven; Bruck, Hugh Alan; Rasooly, Avraham

2013-01-01

The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes a multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement. The capillary array enables a ~100X increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10 nM. Computational image stacking enables another ~10X increase in signal sensitivity, further reducing the LOD for webcam from 10 nM to 1 nM. To demonstrate the feasibility of the device for the detection of disease-related biomarkers, Adenovirus DNA labeled with SYBR Green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein. The combination of the two signal amplification approaches enables a ~1000X increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed. The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth’s clinical utility, especially for telemedicine and for resource-poor settings and global health applications. PMID:23928092

Thousand-fold fluorescent signal amplification for mHealth diagnostics.

PubMed

Balsam, Joshua; Rasooly, Reuven; Bruck, Hugh Alan; Rasooly, Avraham

2014-01-15

The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement. The capillary array enables a ~100× increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10nM. Computational image stacking enables another ~10× increase in signal sensitivity, further reducing the LOD for webcam from 10nM to 1 nM. To demonstrate the feasibility of the device for the detection of disease-related biomarkers, adenovirus DNA labeled with SYBR green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5 ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein. The combination of the two signal amplification approaches enables a ~1000× increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10 ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed. The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth's clinical utility, especially for telemedicine and for resource-poor settings and global health applications. Published by Elsevier B.V.

A direct comparison of decision rules for early discharge of suspected acute coronary syndromes in the era of high sensitivity troponin.

PubMed

Chew, Pei Gee; Frost, Fredrick; Mullen, Liam; Fisher, Michael; Zadeh, Heidar; Grainger, Ruth; Albouaini, Khaled; Dodd, James; Patel, Bilal; Velavan, Periaswamy; Kunadian, Babu; Rawat, Anju; Obafemi, Toba; Tong, Sarah; Jones, Julia; Khand, Aleem

2018-02-01

We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (<5 ng/l) combined with a presentation non-ischaemic electrocardiogram is superior to low-risk Global Registry of Acute Coronary Events (GRACE) (<75), Thrombolysis in Myocardial Infarction (TIMI) (≤1) and History, ECG, Age, Risk factors and Troponin (HEART) score (≤3) as an aid to early, safe discharge for suspected acute coronary syndrome. In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year. Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively. HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h), due to limited numbers, are excluded from these conclusions.

An approach for the regularization of a power flow solution around the maximum loading point

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

Kataoka, Y.

1992-08-01

In the conventional power flow solution, the boundary conditions are directly specified by active power and reactive power at each node, so that the singular point coincided with the maximum loading point. For this reason, the computations are often disturbed by ill-condition. This paper proposes a new method for getting the wide-range regularity by giving some modifications to the conventional power flow solution method, thereby eliminating the singular point or shifting it to the region with the voltage lower than that of the maximum loading point. Then, the continuous execution of V-P curves including maximum loading point is realized. Themore » efficiency and effectiveness of the method are tested in practical 598-nodes system in comparison with the conventional method.« less

A quantitative study on accumulation of age mass around stagnation points in nested flow systems

NASA Astrophysics Data System (ADS)

Jiang, Xiao-Wei; Wan, Li; Ge, Shemin; Cao, Guo-Liang; Hou, Guang-Cai; Hu, Fu-Sheng; Wang, Xu-Sheng; Li, Hailong; Liang, Si-Hai

2012-12-01

The stagnant zones in nested flow systems have been assumed to be critical to accumulation of transported matter, such as metallic ions and hydrocarbons in drainage basins. However, little quantitative research has been devoted to prove this assumption. In this paper, the transport of age mass is used as an example to demonstrate that transported matter could accumulate around stagnation points. The spatial distribution of model age is analyzed in a series of drainage basins of different depths. We found that groundwater age has a local or regional maximum value around each stagnation point, which proves the accumulation of age mass. In basins where local, intermediate and regional flow systems are all well developed, the regional maximum groundwater age occurs at the regional stagnation point below the basin valley. This can be attributed to the long travel distances of regional flow systems as well as stagnancy of the water. However, when local flow systems dominate, the maximum groundwater age in the basin can be located around the local stagnation points due to stagnancy, which are far away from the basin valley. A case study is presented to illustrate groundwater flow and age in the Ordos Plateau, northwestern China. The accumulation of age mass around stagnation points is confirmed by tracer age determined by 14C dating in two boreholes and simulated age near local stagnation points under different dispersivities. The results will help shed light on the relationship between groundwater flow and distributions of groundwater age, hydrochemistry, mineral resources, and hydrocarbons in drainage basins.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-04-01

To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.

77 FR 23690 - Applications for New Awards; Promise Neighborhoods Program-Planning Grant Competition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... (prohibiting discrimination on the basis of race, color, or national origin); Section 504 of the Rehabilitation... Department will review and award points only for a maximum of two of the competitive preference priorities... the two priorities it wishes the Department to consider for purposes of earning the competitive...

Estimation of the POD function and the LOD of a qualitative microbiological measurement method.

PubMed

Wilrich, Cordula; Wilrich, Peter-Theodor

2009-01-01

Qualitative microbiological measurement methods in which the measurement results are either 0 (microorganism not detected) or 1 (microorganism detected) are discussed. The performance of such a measurement method is described by its probability of detection as a function of the contamination (CFU/g or CFU/mL) of the test material, or by the LOD(p), i.e., the contamination that is detected (measurement result 1) with a specified probability p. A complementary log-log model was used to statistically estimate these performance characteristics. An intralaboratory experiment for the detection of Listeria monocytogenes in various food matrixes illustrates the method. The estimate of LOD50% is compared with the Spearman-Kaerber method.

Correlation between quantitative traits and correlation between corresponding LOD scores: detection of pleiotropic effects.

PubMed

Ulgen, Ayse; Han, Zhihua; Li, Wentian

2003-12-31

We address the question of whether statistical correlations among quantitative traits lead to correlation of linkage results of these traits. Five measured quantitative traits (total cholesterol, fasting glucose, HDL cholesterol, blood pressure, and triglycerides), and one derived quantitative trait (total cholesterol divided by the HDL cholesterol) are used for phenotype correlation studies. Four of them are used for linkage analysis. We show that although correlation among phenotypes partially reflects the correlation among linkage analysis results, the LOD-score correlations are on average low. The most significant peaks found by using different traits do not often overlap. Studying covariances at specific locations in LOD scores may provide clues for further bivariate linkage analyses.

Easy calculations of lod scores and genetic risks on small computers.

PubMed Central

Lathrop, G M; Lalouel, J M

1984-01-01

A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139

LOD score exclusion analyses for candidate QTLs using random population samples.

PubMed

Deng, Hong-Wen

2003-11-01

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans.

PubMed

Barkley, Ruth Ann; Brown, Andrew C; Hanis, Craig L; Kardia, Sharon L; Turner, Stephen T; Boerwinkle, Eric

2003-07-01

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52). No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

The occurrence and source identification of bisphenol compounds in wastewaters.

PubMed

Česen, Marjeta; Lenarčič, Kaja; Mislej, Vesna; Levstek, Meta; Kovačič, Ana; Cimrmančič, Bernardka; Uranjek, Nataša; Kosjek, Tina; Heath, David; Dolenc, Marija Sollner; Heath, Ester

2018-03-01

This study reports the occurrence of eight bisphenols (BPs): bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and bisphenol Z (BPZ) in wastewaters (WWs). Sample preparation involved pre-concentration with SPE cartridges (Oasis HLB), followed by derivatization using N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide with 1% tert-butyldimethylchlorosilane. Chemical analysis was based on gas chromatography-mass spectrometry. A validated method with limits of detection (LODs) at ngL -1 range was applied to WWs collected at five Slovene wastewater treatment plants (WWTPs) and WW inflows from industrial, commercial and residential sources entering the sewerage systems of two catchments (Domžale-Kamnik (DK) and Ljubljana (LJ)). The presence of all BPs was confirmed in three inflows in DK and two inflows in the LJ catchments. High cumulative concentrations of all BPs were determined in WW from food processing facilities (LJ: 3030ngL -1 and DK: 599ngL -1 ). A high detection frequency was observed in the WW from two textile cleaning companies (6 BPs for LJ and 8 BPs for DK). The analysis of WW from WWTPs revealed that only BPF (36.7ngL -1 ) and BPS (40.6ngL -1 ) were >LODs in the influents, whereas other BPs were detected also in the effluents. BPZ was found in the highest concentration (403ngL -1 at WWTP-DK). WW collected at this WWTP also contained the highest amount of BPE (238ngL -1 ). Although BPs removal could not be directly compared between the WWTPs, with the exception of BPAP and BPB in the case of two smaller WWTPs (6.39%-43.2%) bisphenols were in general highly removed (≥96.2%). Finally, levels of BPC>LOD are reported for first time (WWTP in the DK catchment: 1.01ngL -1 -11.8ngL -1 ; LJ inflow from food processing plant up to 2560ngL -1 ). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Collision avoidance for aircraft in abort landing

NASA Astrophysics Data System (ADS)

Mathwig, Jarret

We study the collision avoidance between two aircraft flying in the same vertical plane: a host aircraft on a glide path and an intruder aircraft on a horizontal trajectory below that of the host aircraft and heading in the opposite direction. Assuming that the intruder aircraft is uncooperative, the host aircraft executes an optimal abort landing maneuver: it applies maximum thrust setting and maximum angle of attack lifting the flight path over the original path, thereby increasing the timewise minimum distance between the two aircraft and, in this way, avoiding the potential collision. In the presence of weak constraints on the aircraft and/or the environment, the angle of attack must be brought to the maximum value and kept there until the maximin point is reached. On the other hand, in the presence of strong constraints on the aircraft and the environment, desaturation of the angle of attack might have to take place before the maximin point is reached. This thesis includes four parts. In the first part, after an introduction and review of the available literature, we reformulate and solve the one-subarc Chebyshev maximin problem as a two-subarc Bolza-Pontryagin problem in which the avoidance and the recovery maneuvers are treated simultaneously. In the second part, we develop a guidance scheme (gamma guidance) capable of approximating the optimal trajectory in real time. In the third part, we present the algorithms employed to solve the one-subarc and two-subarc problems. In the fourth part, we decompose the two-subarc Bolza-Pontryagin problem into two one-subarc problems: the avoidance problem and the recovery problem, to be solved in sequence; remarkably, for problems where the ratio of total maneuver time to avoidance time is sufficiently large (≥5), this simplified procedure predicts accurately the location of the maximin point as well as the maximin distance.

Microprocessor-controlled step-down maximum-power-point tracker for photovoltaic systems

NASA Astrophysics Data System (ADS)

Mazmuder, R. K.; Haidar, S.

1992-12-01

An efficient maximum power point tracker (MPPT) has been developed and can be used with a photovoltaic (PV) array and a load which requires lower voltage than the PV array voltage to be operated. The MPPT makes the PV array to operate at maximum power point (MPP) under all insolation and temperature, which ensures the maximum amount of available PV power to be delivered to the load. The performance of the MPPT has been studied under different insolation levels.

Rapid screening of drugs of abuse in human urine by high-performance liquid chromatography coupled with high resolution and high mass accuracy hybrid linear ion trap-Orbitrap mass spectrometry.

PubMed

Li, Xiaowen; Shen, Baohua; Jiang, Zheng; Huang, Yi; Zhuo, Xianyi

2013-08-09

A novel analytical toxicology method has been developed for the analysis of drugs of abuse in human urine by using a high resolution and high mass accuracy hybrid linear ion trap-Orbitrap mass spectrometer (LTQ-Orbitrap-MS). This method allows for the detection of different drugs of abuse, including amphetamines, cocaine, opiate alkaloids, cannabinoids, hallucinogens and their metabolites. After solid-phase extraction with Oasis HLB cartridges, spiked urine samples were analysed by HPLC/LTQ-Orbitrap-MS using an electrospray interface in positive ionisation mode, with resolving power of 30,000 full width at half maximum (FWHM). Gradient elution off of a Hypersil Gold PFP column (50mm×2.1mm) allowed to resolve 65 target compounds and 3 internal standards in a total chromatographic run time of 20min. Validation of this method consisted of confirmation of identity, selectivity, linearity, limit of detection (LOD), lowest limits of quantification (LLOQ), accuracy, precision, extraction recovery and matrix effect. The regression coefficients (r(2)) for the calibration curves (LLOQ - 100ng/mL) in the study were ≥0.99. The LODs for 65 validated compounds were better than 5ng/ml except for 4 compounds. The relative standard deviation (RSD), which was used to estimate repeatability at three concentrations, was always less than 15%. The recovery of extraction and matrix effects were above 50 and 70%, respectively. Mass accuracy was always better than 2ppm, corresponding to a maximum mass error of 0.8 millimass units (mmu). The accurate masses of characteristic fragments were obtained by collisional experiments for a more reliable identification of the analytes. Automated data analysis and reporting were performed using ToxID software with an exact mass database. This procedure was then successfully applied to analyse drugs of abuse in a real urine sample from subject who was assumed to be drug addict. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.