Cerebral atrophy in AIDS: a stereological study

DEFF Research Database (Denmark)

Oster, S; Christoffersen, P; Gundersen, H J

1993-01-01

Stereological estimates of mean volumes, surface areas, and cortical thicknesses were obtained on formalin-fixed brains from 19 men with AIDS and 19 controls. Volumes of neocortex, white matter, central brain nuclei, ventricles and archicortex were estimated using point counting and Cavalieri......'s unbiased principle for volume estimation. In AIDS, the mean volume of neocortex was reduced by 11%, and that of the central brain nuclei by 18%. Mean ventricular volume was increased by 55%. Mean neocortical thickness was reduced by 12%. The mean volume of white matter was reduced by 13%. The findings in 6...

DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Bichel, P; Jakobsen, A

1992-01-01

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained...... in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated...

Stereological estimation of nuclear volume in benign and atypical meningiomas

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1993-01-01

A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups....... The results demonstrate that atypical meningiomas can be distinguished from benign meningiomas by an objective stereological estimation of nuclear volume....

DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Bichel, P; Jakobsen, A

1992-01-01

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained...... in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated...... carcinoma of the uterine cervix....

Abdominal fat volume estimation by stereology on CT: a comparison with manual planimetry

Energy Technology Data Exchange (ETDEWEB)

Manios, G.E.; Mazonakis, M.; Damilakis, J. [University of Crete, Department of Medical Physics, Faculty of Medicine, Heraklion, Crete (Greece); Voulgaris, C.; Karantanas, A. [University of Crete, Department of Radiology, Faculty of Medicine, Heraklion, Crete (Greece)

2016-03-15

To deploy and evaluate a stereological point-counting technique on abdominal CT for the estimation of visceral (VAF) and subcutaneous abdominal fat (SAF) volumes. Stereological volume estimations based on point counting and systematic sampling were performed on images from 14 consecutive patients who had undergone abdominal CT. For the optimization of the method, five sampling intensities in combination with 100 and 200 points were tested. The optimum stereological measurements were compared with VAF and SAF volumes derived by the standard technique of manual planimetry on the same scans. Optimization analysis showed that the selection of 200 points along with the sampling intensity 1/8 provided efficient volume estimations in less than 4 min for VAF and SAF together. The optimized stereology showed strong correlation with planimetry (VAF: r = 0.98; SAF: r = 0.98). No statistical differences were found between the two methods (VAF: P = 0.81; SAF: P = 0.83). The 95 % limits of agreement were also acceptable (VAF: -16.5 %, 16.1 %; SAF: -10.8 %, 10.7 %) and the repeatability of stereology was good (VAF: CV = 4.5 %, SAF: CV = 3.2 %). Stereology may be successfully applied to CT images for the efficient estimation of abdominal fat volume and may constitute a good alternative to the conventional planimetric technique. (orig.)

Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy - A stereological study

DEFF Research Database (Denmark)

Salvesen, Lisette; Ullerup, Birgitte H; Sunay, Fatma B

2014-01-01

Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 age- and gender-matched control subjects with unbiased stereological methods. Compared to the control...

Current automated 3D cell detection methods are not a suitable replacement for manual stereologic cell counting

Directory of Open Access Journals (Sweden)

Christoph eSchmitz

2014-05-01

Full Text Available Stereologic cell counting has had a major impact on the field of neuroscience. A major bottleneck in stereologic cell counting is that the user must manually decide whether or not each cell is counted according to three-dimensional (3D stereologic counting rules by visual inspection within hundreds of microscopic fields-of-view per investigated brain or brain region. Reliance on visual inspection forces stereologic cell counting to be very labor-intensive and time-consuming, and is the main reason why biased, non-stereologic two-dimensional (2D cell counting approaches have remained in widespread use. We present an evaluation of the performance of modern automated cell detection and segmentation algorithms as a potential alternative to the manual approach in stereologic cell counting. The image data used in this study were 3D microscopic images of thick brain tissue sections prepared with a variety of commonly used nuclear and cytoplasmic stains. The evaluation compared the numbers and locations of cells identified unambiguously and counted exhaustively by an expert observer with those found by three automated 3D cell detection algorithms: nuclei segmentation from the FARSIGHT toolkit, nuclei segmentation by 3D multiple level set methods, and the 3D object counter plug-in for ImageJ. Of these methods, FARSIGHT performed best, with true-positive detection rates between 38–99% and false-positive rates from 3.6–82%. The results demonstrate that the current automated methods suffer from lower detection rates and higher false-positive rates than are acceptable for obtaining valid estimates of cell numbers. Thus, at present, stereologic cell counting with manual decision for object inclusion according to unbiased stereologic counting rules remains the only adequate method for unbiased cell quantification in histologic tissue sections.

Stereological estimation of nuclear mean volume in invasive meningiomas

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1996-01-01

A stereological estimation of nuclear mean volume in bone and brain invasive meningiomas was made. For comparison the nuclear mean volume of benign meningiomas was estimated. The aim was to investigate whether this method could discriminate between these groups. We found that the nuclear mean...... volume in the bone and brain invasive meningiomas was larger than in the benign tumors. The difference was significant and moreover it was seen that there was no overlap between the two groups. In the bone invasive meningiomas the nuclear mean volume appeared to be larger inside than outside the bone....... No significant difference in nuclear mean volume was found between brain and bone invasive meningiomas. The results demonstrate that invasive meningiomas differ from benign meningiomas by an objective stereological estimation of nuclear mean volume (p

UNBIASED ESTIMATORS OF SPECIFIC CONNECTIVITY

Directory of Open Access Journals (Sweden)

Jean-Paul Jernot

2011-05-01

Full Text Available This paper deals with the estimation of the specific connectivity of a stationary random set in IRd. It turns out that the "natural" estimator is only asymptotically unbiased. The example of a boolean model of hypercubes illustrates the amplitude of the bias produced when the measurement field is relatively small with respect to the range of the random set. For that reason unbiased estimators are desired. Such an estimator can be found in the literature in the case where the measurement field is a right parallelotope. In this paper, this estimator is extended to apply to measurement fields of various shapes, and to possess a smaller variance. Finally an example from quantitative metallography (specific connectivity of a population of sintered bronze particles is given.

Stereological estimation of nuclear volume and other quantitative histopathological parameters in the prognostic evaluation of supraglottic laryngeal squamous cell carcinoma

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Bennedbaek, O; Pilgaard, J

1989-01-01

The aim of this study was to investigate various approaches to the grading of malignancy in pre-treatment biopsies from patients with supraglottic laryngeal squamous cell carcinoma. The prospects of objective malignancy grading based on stereological estimation of the volume-weighted mean nuclear...... volume, nuclear Vv, and nuclear volume fraction, Vv(nuc/tis), along with morphometrical 2-dimensional estimation of nuclear density index, NI, and mitotic activity index, MI, were investigated and compared with the current morphological, multifactorial grading system. The reproducibility among two...... observers of the latter was poor in the material which consisted of 35 biopsy specimens. Unbiased estimates of nuclear Vv were on the average 385 microns3 (CV = 0.44), with more than 90% of the associated variance attributable to differences in nuclear Vv among individual lesions. Nuclear Vv was positively...

Digital stereology in neuropathology

DEFF Research Database (Denmark)

Kristiansen, Sarah Line Brøgger; Nyengaard, Jens Randel

2012-01-01

will therefore present the relevant stereological estimators for obtaining reliable quantitative structural data from brains and peripheral nerves when using digital light microscopy. It is discussed how to obtain brain and nerve fibre samples to fulfil the requirements for the estimators. A presentation......-dimensional structural knowledge. Accordingly, stereology is a science based on statistical sampling principles and geometric measures. The application of stereology to neuropathological studies allows the researcher to efficiently obtain a precise estimate of various structural quantities. This neuropathological review...

Stereological estimation of nuclear volume and other quantitative histopathological parameters in the prognostic evaluation of supraglottic laryngeal squamous cell carcinoma

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Bennedbaek, O; Pilgaard, J

1989-01-01

The aim of this study was to investigate various approaches to the grading of malignancy in pre-treatment biopsies from patients with supraglottic laryngeal squamous cell carcinoma. The prospects of objective malignancy grading based on stereological estimation of the volume-weighted mean nuclear...... observers of the latter was poor in the material which consisted of 35 biopsy specimens. Unbiased estimates of nuclear Vv were on the average 385 microns3 (CV = 0.44), with more than 90% of the associated variance attributable to differences in nuclear Vv among individual lesions. Nuclear Vv was positively....... None of the investigated categorical and quantitative parameters (cutoff points = means) reached the level of significance with respect to prognostic value. However, nuclear Vv showed the best information concerning survival (2p = 0.08), and this estimator offers optimal features for objective...

Unbiased Stereologic Estimation of the Spatial Distribution of Paget’s Disease in the Human Temporal Bone

DEFF Research Database (Denmark)

Bloch, Sune Land; Sørensen, Mads Sølvsten

2014-01-01

remodeling around the inner ear space and to compare it with that of otosclerosis in a contemporary context of temporal bone dynamics. MATERIALS AND METHODS: From the temporal bone collection of Massachusetts Eye and Ear Infirmary, 15 of 29 temporal bones with Paget's disease were selected to obtain...... an independent sample. All volume distributions were obtained along the normal axis of capsular bone remodeling activity by the use of vector-based stereology. RESULTS: Pagetic bone remodeling was distributed centrifugally around the inner ear space at the individual and the general level. This pattern...

The Optical Fractionator Technique to Estimate Cell Numbers in a Rat Model of Electroconvulsive Therapy

DEFF Research Database (Denmark)

Olesen, Mikkel Vestergaard; Needham, Esther Kjær; Pakkenberg, Bente

2017-01-01

are too high to count manually, and stereology is now the technique of choice whenever estimates of three-dimensional quantities need to be extracted from measurements on two-dimensional sections. All stereological methods are in principle unbiased; however, they rely on proper knowledge about...

DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Bichel, P; Jakobsen, A

1992-01-01

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained...... in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated...... of nuclear vv were only of marginal prognostic significance (2P = 0.07). However, Cox multivariate regression analysis showed independent prognostic value of patient age and nuclear vv along with clinical stage and DI. All other investigated variables were rejected from the model. A prognostic index...

Nondestructive, stereological estimation of canopy surface area

DEFF Research Database (Denmark)

Wulfsohn, Dvora-Laio; Sciortino, Marco; Aaslyng, Jesper M.

2010-01-01

We describe a stereological procedure to estimate the total leaf surface area of a plant canopy in vivo, and address the problem of how to predict the variance of the corresponding estimator. The procedure involves three nested systematic uniform random sampling stages: (i) selection of plants from...... a canopy using the smooth fractionator, (ii) sampling of leaves from the selected plants using the fractionator, and (iii) area estimation of the sampled leaves using point counting. We apply this procedure to estimate the total area of a chrysanthemum (Chrysanthemum morifolium L.) canopy and evaluate both...... the time required and the precision of the estimator. Furthermore, we compare the precision of point counting for three different grid intensities with that of several standard leaf area measurement techniques. Results showed that the precision of the plant leaf area estimator based on point counting...

Stereological estimates of nuclear volume in normal germ cells and carcinoma in situ of the human testis

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Müller, J

1990-01-01

Carcinoma in situ of the testis may appear many years prior to the development of an invasive tumour. Using point-sampled intercepts, base-line data concerning unbiased stereological estimates of the volume-weighted mean nuclear volume (nuclear vV) were obtained in 50 retrospective serial...... testicular biopsies from 10 patients with carcinoma in situ. All but two patients eventually developed an invasive growth. Testicular biopsies from 10 normal adult individuals and five prepubertal boys were included as controls. Nuclear vV in testicular carcinoma in situ was significantly larger than...... that of morphologically normal spermatogonia (2P = 1.0 x 10(-19)), with only minor overlap. Normal spermatogonia from controls had, on average, smaller nuclear vV than morphologically normal spermatogonia in biopsies with ipsi- or contra-lateral carcinoma in situ (2P = 5.2 x 10(-3)). No difference in nuclear vV was found...

PROBES, POPULATIONS, SAMPLES, MEASUREMENTS AND RELATIONS IN STEREOLOGY

Directory of Open Access Journals (Sweden)

Robert T Dehoff

2011-05-01

Full Text Available This summary paper provides an overview of the content of stereology. The typical problem at hand centers around some three dimensional object that has an internal structure that determines its function, performance, or response. To understand and quantify the geometry of that structure it is necessary to probe it with geometric entities: points, lines, planes volumes, etc. Meaningful results are obtained only if the set of probes chosen for use in the assessment is drawn uniformly from the population of such probes for the structure as a whole. This requires an understanding of the population of each kind of probe. Interaction of the probes with the structure produce geometric events which are the focus of stereological measurements. In almost all applications the measurement that is made is a simple count of the number of these events. Rigorous application of these requirements for sample design produce unbiased estimates of geometric properties of features in the structure no matter how complex are the features or what their arrangement in space. It is this assumption-free characteristic of the methodology that makes it a powerful tool for characterizing the internal structure of three dimensional objects.

Stereological estimation of nuclear volume in benign and atypical meningiomas

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1993-01-01

A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups...

Stereological analysis of spatial structures

DEFF Research Database (Denmark)

Hansen, Linda Vadgård

The thesis deals with stereological analysis of spatial structures. One area of focus has been to improve the precision of well-known stereological estimators by including information that is available via automatic image analysis. Furthermore, the thesis presents a stochastic model for star......-shaped three-dimensional objects using the radial function. It appears that the model is highly fleksiblel in the sense that it can be used to describe an object with arbitrary irregular surface. Results on the distribution of well-known local stereological volume estimators are provided....

Using biased image analysis for improving unbiased stereological number estimation - a pilot simulation study of the smooth fractionator

DEFF Research Database (Denmark)

Gardi, Jonathan Eyal; Nyengaard, Jens Randel; Gundersen, Hans Jørgen Gottlieb

2006-01-01

uniformly random sampling design and the ordinary simple random sampling design. The smooth protocol is performed using biased information from crude (but fully automatic) image analysis of the fields of view. The different design paradigms are compared using simulation in three different cell distributions......The smooth fractionator was introduced in 2002. The combination of a smoothing protocol with a computer-aided stereology tool provides better precision and a lighter workload. This study uses simulation to compare fractionator sampling based on the smooth design, the commonly used systematic...

Building unbiased estimators from non-Gaussian likelihoods with application to shear estimation

International Nuclear Information System (INIS)

Madhavacheril, Mathew S.; Sehgal, Neelima; McDonald, Patrick; Slosar, Anže

2015-01-01

We develop a general framework for generating estimators of a given quantity which are unbiased to a given order in the difference between the true value of the underlying quantity and the fiducial position in theory space around which we expand the likelihood. We apply this formalism to rederive the optimal quadratic estimator and show how the replacement of the second derivative matrix with the Fisher matrix is a generic way of creating an unbiased estimator (assuming choice of the fiducial model is independent of data). Next we apply the approach to estimation of shear lensing, closely following the work of Bernstein and Armstrong (2014). Our first order estimator reduces to their estimator in the limit of zero shear, but it also naturally allows for the case of non-constant shear and the easy calculation of correlation functions or power spectra using standard methods. Both our first-order estimator and Bernstein and Armstrong's estimator exhibit a bias which is quadratic in true shear. Our third-order estimator is, at least in the realm of the toy problem of Bernstein and Armstrong, unbiased to 0.1% in relative shear errors Δg/g for shears up to |g|=0.2

A note on stereological estimation of the volume-weighted second moment of particle volume

DEFF Research Database (Denmark)

Jensen, E B; Sørensen, Flemming Brandt

1991-01-01

It is shown that for a variety of biological particle shapes, the volume-weighted second moment of particle volume can be estimated stereologically using only the areas of particle transects, which can be estimated manually by point-counting....

Ridge regression estimator: combining unbiased and ordinary ridge regression methods of estimation

Directory of Open Access Journals (Sweden)

Sharad Damodar Gore

2009-10-01

Full Text Available Statistical literature has several methods for coping with multicollinearity. This paper introduces a new shrinkage estimator, called modified unbiased ridge (MUR. This estimator is obtained from unbiased ridge regression (URR in the same way that ordinary ridge regression (ORR is obtained from ordinary least squares (OLS. Properties of MUR are derived. Results on its matrix mean squared error (MMSE are obtained. MUR is compared with ORR and URR in terms of MMSE. These results are illustrated with an example based on data generated by Hoerl and Kennard (1975.

Stereological quantification of mast cells in human synovium

DEFF Research Database (Denmark)

Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T

1999-01-01

Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

STEREOLOGICAL ESTIMATION OF ITO CELLS FROM RAT LIVER USING THE OPTICAL FRACTIONATOR - A PRELIMINARY REPORT

Directory of Open Access Journals (Sweden)

Ricardo Marcos

2011-05-01

Full Text Available In the last two decades, much light has been shed on hepatic fibrosis, and the activation / proliferation of Ito cells (IC emerged to play a central role. Therefore, it is essential to have solid quantitative data in nonpathological statuses; yet, this data is scarce and confined to "number per area" or semiquantitative information. Moreover, the supposed heterogeneous distribution of IC in the hepatic lobule was never analysed with design-based (unbiased stereology. In the present study, the total number (N of IC in rat liver was estimated for the first time, by combining immunocytochemistry with the optical fractionator. Quantification was extended to the hepatocytes, to disclose the IC index, an often-used ratio in hepatology. Systematic uniform random liver sections were obtained from male Wistar rats (n = 3, and immunostained against glial fibrillary acidic protein (GFAP, a known specific marker for hepatic IC. For the first time, these were marked against GFAP in thick (30 μm paraffin sections. The estimated N of IC was 224E06; with a coefficient of error of 0.04 or 0.06, depending on the particular equation used (based on the so-called "quadratic approximation". The IC index was 91 IC/1000 hepatocytes. Concerning the lobular heterogeneity, it was proved the liver harbours a larger total number of periportal IC and hepatocytes.

Systematic versus random sampling in stereological studies.

Science.gov (United States)

West, Mark J

2012-12-01

The sampling that takes place at all levels of an experimental design must be random if the estimate is to be unbiased in a statistical sense. There are two fundamental ways by which one can make a random sample of the sections and positions to be probed on the sections. Using a card-sampling analogy, one can pick any card at all out of a deck of cards. This is referred to as independent random sampling because the sampling of any one card is made without reference to the position of the other cards. The other approach to obtaining a random sample would be to pick a card within a set number of cards and others at equal intervals within the deck. Systematic sampling along one axis of many biological structures is more efficient than random sampling, because most biological structures are not randomly organized. This article discusses the merits of systematic versus random sampling in stereological studies.

Unbiased estimation of the eyeball volume using the Cavalieri principle on computed tomography images.

Science.gov (United States)

Acer, Niyazi; Sahin, Bunyamin; Ucar, Tolga; Usanmaz, Mustafa

2009-01-01

The size of the eyeball has been the subject of a few studies. None of them used stereological methods to estimate the volume. In the current study, we estimated the volume of eyeball in normal men and women using the stereological methods. Eyeball volume (EV) was estimated using the Cavalieri principle as a combination of point-counting and planimetry techniques. We used computed tomography scans taken from 36 participants (15 men and 21 women) to estimate the EV. The mean (SD) EV values obtained by planimetry method were 7.49 (0.79) and 7.06 (0.85) cm in men and women, respectively. By using point-counting method, the mean (SD) values were 7.48 (0.85) and 7.21 (0.84) cm in men and women, respectively. There was no statistically significant difference between the findings from the 2 methods (P > 0.05). A weak correlation was found between the axial length of eyeball and the EV estimated by point counting and planimetry (P eyeball.

A new unbiased stochastic derivative estimator for discontinuous sample performances with structural parameters

NARCIS (Netherlands)

Peng, Yijie; Fu, Michael C.; Hu, Jian Qiang; Heidergott, Bernd

In this paper, we propose a new unbiased stochastic derivative estimator in a framework that can handle discontinuous sample performances with structural parameters. This work extends the three most popular unbiased stochastic derivative estimators: (1) infinitesimal perturbation analysis (IPA), (2)

A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research.

Science.gov (United States)

Mühlfeld, Christian; Nyengaard, Jens Randel; Mayhew, Terry M

2010-01-01

The aim of stereological methods in biomedical research is to obtain quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections. With immunogold labeling, stereology can even be used for the quantitative analysis of the distribution of molecules within tissues and cells. Nowadays, a large number of design-based stereological methods offer an efficient quantitative approach to intriguing questions in cardiac research, such as "Is there a significant loss of cardiomyocytes during progression from ventricular hypertrophy to heart failure?" or "Does a specific treatment reduce the degree of fibrosis in the heart?" Nevertheless, the use of stereological methods in cardiac research is rare. The present review article demonstrates how some of the potential pitfalls in quantitative microscopy may be avoided. To this end, we outline the concepts of design-based stereology and illustrate their practical applications to a wide range of biological questions in cardiac research. We hope that the present article will stimulate researchers in cardiac research to incorporate design-based stereology into their study designs, thus promoting an unbiased quantitative 3D microscopy.

Classification of tubulo-papillary renal cortical tumours using estimates of nuclear volume

DEFF Research Database (Denmark)

Brooks, B; Sørensen, Flemming Brandt; Olsen, S

1993-01-01

The classification of renal cortical tumours is problematic, with no clear division of benign from malignant tumours. Unbiased stereological estimates of volume-weighted nuclear volume (nuclear vv) were obtained by point sampling of nuclear intercepts in a retrospective study of 36 variably sized...

Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus

DEFF Research Database (Denmark)

Hosseini-Sharifabad, Mohammad; Nyengaard, Jens Randel

2007-01-01

Tools recently developed in stereology were employed for unbiased estimation of the neuronal number and volume in three major subdivisions of rat hippocampus (dentate granular, CA1 and CA3 pyramidal layers). The optical fractionator is used extensively in quantitative studies of the hippocampus; ...

A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

Science.gov (United States)

Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

2015-01-01

Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

Stereology, an unbiased methodological approach to study plant anatomy and cytology: Past, present and future

Czech Academy of Sciences Publication Activity Database

Kubínová, Lucie; Radochová, Barbora; Lhotáková, Z.; Kubínová, Z.; Albrechtová, J.

2017-01-01

Roč. 36, č. 3 (2017), s. 187-205 ISSN 1580-3139 R&D Projects: GA MŠk(CZ) LM2015062 Institutional support: RVO:67985823 Keywords : chloroplast * confocal microscopy * leaf anatomy * mesophyll * stereological methods * systematic uniform random sampling Subject RIV: FS - Medical Facilities ; Equipment OBOR OECD: Medical laboratory technology (including laboratory samples analysis Impact factor: 1.135, year: 2016

Application of stereological methods to estimate post-mortem brain surface area using 3T MRI

DEFF Research Database (Denmark)

Furlong, Carolyn; García-Fiñana, Marta; Puddephat, Michael

2013-01-01

The Cavalieri and Vertical Sections methods of design based stereology were applied in combination with 3 tesla (i.e. 3T) Magnetic Resonance Imaging (MRI) to estimate cortical and subcortical volume, area of the pial surface, area of the grey-white matter boundary, and thickness of the cerebral...

Unbiased estimators for spatial distribution functions of classical fluids

Science.gov (United States)

Adib, Artur B.; Jarzynski, Christopher

2005-01-01

We use a statistical-mechanical identity closely related to the familiar virial theorem, to derive unbiased estimators for spatial distribution functions of classical fluids. In particular, we obtain estimators for both the fluid density ρ(r) in the vicinity of a fixed solute and the pair correlation g(r) of a homogeneous classical fluid. We illustrate the utility of our estimators with numerical examples, which reveal advantages over traditional histogram-based methods of computing such distributions.

Estimates of nuclear volume in plaque and tumor-stage mycosis fungoides. A new prognostic indicator

DEFF Research Database (Denmark)

Brooks, B; Sørensen, Flemming Brandt; Thestrup-Pedersen, K

1994-01-01

It is well documented that mycosis fungoides (MF), a cutaneous T-cell lymphoma, has a variable clinical course. Unbiased stereological estimates of three-dimensional volume-weighted mean nuclear size (nucl vV) of mycosis cells were obtained in a retrospective study of 18 patients with a total of ...

Morphometric changes in the spinal cord during prenatal life: a stereological study in sheep.

Science.gov (United States)

Sadeghinezhad, Javad; Zadsar, Narges; Hasanzadeh, Beal

2018-03-01

This study describes the volumetric changes in the spinal cord during prenatal life in sheep using quantitative stereological methods. Twenty healthy sheep fetuses were included in the present study, divided into four groups representing 9-11, 12-14, 15-17, and 18-20 weeks of gestation. In each group, the spinal cord was dissected out and sampled according to the unbiased systematic random sampling method then used for stereological estimations. The total volume of spinal cord, volume of gray matter (GM), volume of white matter (WM), ratio of GM volume to WM volume, and volume of central canal (CC) were estimated in the whole spinal cord and its various regions using Cavalieri's principle. The total volume of the spinal cord increased 8 times from week 9 to week 20. The cervical region showed the greatest (9.7 times) and the sacral region the least (6.3 times) volumetric change. The CC volume of the whole spinal cord increased 5.8 times from week 9 to week 20. The cervical region developed faster (8.2 times) and the thoracic region slower (4.4 times) than the total spinal cord. During development, the volume ratio of GM to WM decreased from lower toward upper regions. The greatest volume changes occurred mostly in weeks 9-11 and 12-14. The cervical region showed the greatest volume changes in comparison with other regions of the spinal cord.

Efficient stereological approaches for the volumetry of a normal or enlarged spleen from MDCT images

Energy Technology Data Exchange (ETDEWEB)

Mazonakis, Michalis; Stratakis, John; Damilakis, John [University of Crete, Department of Medical Physics, Faculty of Medicine, P.O. Box 2208, Iraklion, Crete (Greece)

2015-06-01

To introduce efficient stereological approaches for estimating the volume of a normal or enlarged spleen from MDCT. All study participants underwent an abdominal MDCT. The first group included 20 consecutive patients with splenomegaly and the second group consisted of 20 subjects with a normal spleen. Splenic volume estimations were performed using the stereological point counting method. Stereological assessments were optimized using the systematic slice sampling procedure. Planimetric measurements based on manual tracing of splenic boundaries on each slice were taken as reference values. Stereological analysis using five to eight systematically sampled slices provided enlarged splenic volume estimations with a mean precision of 4.9 ± 1.0 % in a mean time of 2.3 ± 0.4 min. A similar measurement duration and error was observed for normal splenic volume assessment using four to seven systematically selected slices. These stereological approaches slightly but insignificantly overestimated the volume of a normal and enlarged spleen compared to planimetry (P > 0.05) with a mean difference of -1.3 ± 4.3 % and -2.7 ± 5.2 %, respectively. The two methods were highly correlated (r ≥ 0.96). The variability of repeated stereological estimations was below 3.8 %. The proposed stereological approaches enable the rapid, reproducible, and accurate splenic volume estimation from MDCT data in patients with or without splenomegaly. (orig.)

Newsletter '76 in stereology

International Nuclear Information System (INIS)

Ondracek, G.

1976-08-01

The present newsletter on stereology deals with a brief outlook about stereological problems to be solved in the future, compares definitions in pattern recognition and stereology and exposes the main notions of mathematical morphology used in quantitative metallography. This includes the description of the main stereological equations relating the parameters describing the dimensional features to the parameters measured in plane sections as well as a special type of equation for practical uses by which the average fiber length in composite materials can be determined. In this context the methods of particle shape descriptions have been summarized and reviewed and an example is given, how particle size and shape distributions can be measured statistically by automatic feature analysis of morphometric sections. - The introduction of stereological microstructural parameters into microstructure - property equations opens the way to calculate the materials properties by a stereological microstructure analysis and extends the possibilities of the common microstructural quality control. This is demonstrated for WC-Co hard metals. (orig./GSC) [de

Statistics as Unbiased Estimators: Exploring the Teaching of Standard Deviation

Science.gov (United States)

Wasserman, Nicholas H.; Casey, Stephanie; Champion, Joe; Huey, Maryann

2017-01-01

This manuscript presents findings from a study about the knowledge for and planned teaching of standard deviation. We investigate how understanding variance as an unbiased (inferential) estimator--not just a descriptive statistic for the variation (spread) in data--is related to teachers' instruction regarding standard deviation, particularly…

Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods

Science.gov (United States)

Mao, Xiao W.; Archambeau, John O.; Kubinova, Lucie; Boyle, Soames; Petersen, Georgia; Grove, Roger; Nelson, G. A. (Principal Investigator)

2003-01-01

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (Ppopulations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

THE APPLICATION OF STEREOLOGY METHOD FOR ESTIMATING THE NUMBER OF 3D BaTiO3 – CERAMIC GRAINS CONTACT SURFACES

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Vojislav V Mitić

2011-05-01

Full Text Available Methods of stereological study are of great importance for structural research of electronic ceramic materials including BaTiO3-ceramic materials. The broad application of ceramics, based on barium-titanate, in advanced electronics nowadays demands a constant research of its structure, that through the correlation structureproperties, a fundamental in the basic materials properties prognosis triad (technology-structure-properties, leads to further prognosis and properties design of these ceramics. Microstructure properties of BaTiO3- ceramic material, expressed in grains' boundary contact, are of basic importance for electric properties of this material, particularly the capacity. In this paper, a significant step towards establishing control under capacitive properties of BaTiO3-ceramics is being done by estimating the number of grains contact surfaces. Defining an efficient stereology method for estimating the number of BaTiO3-ceramic grains contact surfaces, we have started from a mathematical model of mutual grains distribution in the prescribed volume of BaTiO3-ceramic sample. Since the real microstructure morphology of BaTiO3-ceramics is in some way disordered, spherical shaped grains, using computer-modelling methods, are approximated by polyhedra with a great number of small convex polygons. By dividing the volume of BaTiO3-ceramic sample with the definite number of parallel planes, according to a given pace, into the intersection plane a certain number of grains contact surfaces are identified. According to quantitative estimation of 2D stereological parameters the modelled 3D internal microstructure is obtained. Experiments were made by using the scanning electronic microscopy (SEM method with the ceramic samples prepared under pressing pressures up to 150 MPa and sintering temperature up to 1370°C while the obtained microphotographs were used as a base of confirming the validity of presented stereology method. This paper, by applying

An Example of an Improvable Rao-Blackwell Improvement, Inefficient Maximum Likelihood Estimator, and Unbiased Generalized Bayes Estimator.

Science.gov (United States)

Galili, Tal; Meilijson, Isaac

2016-01-02

The Rao-Blackwell theorem offers a procedure for converting a crude unbiased estimator of a parameter θ into a "better" one, in fact unique and optimal if the improvement is based on a minimal sufficient statistic that is complete. In contrast, behind every minimal sufficient statistic that is not complete, there is an improvable Rao-Blackwell improvement. This is illustrated via a simple example based on the uniform distribution, in which a rather natural Rao-Blackwell improvement is uniformly improvable. Furthermore, in this example the maximum likelihood estimator is inefficient, and an unbiased generalized Bayes estimator performs exceptionally well. Counterexamples of this sort can be useful didactic tools for explaining the true nature of a methodology and possible consequences when some of the assumptions are violated. [Received December 2014. Revised September 2015.].

STEREOLOGICAL ANALYSIS OF SHAPE

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Asger Hobolth

2011-05-01

Full Text Available This paper concerns the problem of making stereological inference about the shape variability in a population of spatial particles. Under rotational invariance the shape variability can be estimated from central planar sections through the particles. A simple, but flexible, parametric model for rotation invariant spatial particles is suggested. It is shown how the parameters of the model can be estimated from observations on central sections. The corresponding model for planar particles is also discussed in some detail.

Unbiased multi-fidelity estimate of failure probability of a free plane jet

Science.gov (United States)

Marques, Alexandre; Kramer, Boris; Willcox, Karen; Peherstorfer, Benjamin

2017-11-01

Estimating failure probability related to fluid flows is a challenge because it requires a large number of evaluations of expensive models. We address this challenge by leveraging multiple low fidelity models of the flow dynamics to create an optimal unbiased estimator. In particular, we investigate the effects of uncertain inlet conditions in the width of a free plane jet. We classify a condition as failure when the corresponding jet width is below a small threshold, such that failure is a rare event (failure probability is smaller than 0.001). We estimate failure probability by combining the frameworks of multi-fidelity importance sampling and optimal fusion of estimators. Multi-fidelity importance sampling uses a low fidelity model to explore the parameter space and create a biasing distribution. An unbiased estimate is then computed with a relatively small number of evaluations of the high fidelity model. In the presence of multiple low fidelity models, this framework offers multiple competing estimators. Optimal fusion combines all competing estimators into a single estimator with minimal variance. We show that this combined framework can significantly reduce the cost of estimating failure probabilities, and thus can have a large impact in fluid flow applications. This work was funded by DARPA.

Application of Singh et al., unbiased estimator in a dual to ratio-cum ...

African Journals Online (AJOL)

This paper applied an unbiased estimator in a dual to ratio–cum-product estimator in sample surveys to double sampling design. Its efficiency over the conventional biased double sampling design estimator was determined based on the conditions attached to its supremacy. Three different data sets were used to testify to ...

An asymptotically unbiased minimum density power divergence estimator for the Pareto-tail index

DEFF Research Database (Denmark)

Dierckx, Goedele; Goegebeur, Yuri; Guillou, Armelle

2013-01-01

We introduce a robust and asymptotically unbiased estimator for the tail index of Pareto-type distributions. The estimator is obtained by fitting the extended Pareto distribution to the relative excesses over a high threshold with the minimum density power divergence criterion. Consistency...

A novel approach to non-biased systematic random sampling: a stereologic estimate of Purkinje cells in the human cerebellum.

Science.gov (United States)

Agashiwala, Rajiv M; Louis, Elan D; Hof, Patrick R; Perl, Daniel P

2008-10-21

Non-biased systematic sampling using the principles of stereology provides accurate quantitative estimates of objects within neuroanatomic structures. However, the basic principles of stereology are not optimally suited for counting objects that selectively exist within a limited but complex and convoluted portion of the sample, such as occurs when counting cerebellar Purkinje cells. In an effort to quantify Purkinje cells in association with certain neurodegenerative disorders, we developed a new method for stereologic sampling of the cerebellar cortex, involving calculating the volume of the cerebellar tissues, identifying and isolating the Purkinje cell layer and using this information to extrapolate non-biased systematic sampling data to estimate the total number of Purkinje cells in the tissues. Using this approach, we counted Purkinje cells in the right cerebella of four human male control specimens, aged 41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells, respectively. The precision of the method is seen when comparing the density of the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3, respectively. Prior literature documents Purkinje cell counts ranging from 14.8 to 30.5 million cells. These data demonstrate the accuracy of our approach. Our novel approach, which offers an improvement over previous methodologies, is of value for quantitative work of this nature. This approach could be applied to morphometric studies of other similarly complex tissues as well.

Newsletter '77 in stereology

International Nuclear Information System (INIS)

Ondracek, G.

1977-12-01

There are three groups of contributions forming the present Newsletter in Stereology which are such of theoretical type, stereological activities in bio-sciences and quatitative image analysis in materials science. The report is introduced by two papers treating theoretical problems as the definition of particle size based on the total curvature and the definition of pattern recognition categories. It than follows a summarizing description and comparison of alternative techniques used to measure and conclude stereological parameters in bio-sciences. The discussion includes the sample preparation, semi- and complete automatic measuring procedures as well as the computation of primary data. The biological part ends by considering the use of those quantitative microscopical methods to investigate and classify foreign compounds inside the human liver stereologically. The materials science part reports about tests made on steel specimens to evaluate the accuracy of automatic microstructural analyses and about the use of image 'erosion' and 'dilatation' to measure microstructural parameters automatically. The last subject is part of a serie on morphology in quantitative metallography started in the previous Newsletter '76. The last paper on materials sciences considers the use of stereology and microstructural analysis in respect to a quality control, choosing WC-Co hardmetals as an example, where stereologically defined microstructural parameters do not serve only to describe microstructures quantitatively but also provide a usefull tool to determine properties indirectly. (orig.) [de

Stereological quantification of tumor volume, mean nuclear volume and total number of melanoma cells correlated with morbidity and mortality

DEFF Research Database (Denmark)

Bønnelykke-Behrndtz, Marie Louise; Sørensen, Flemming Brandt; Damsgaard, Tine Engberg

2008-01-01

potential indicators of prognosis. Sixty patients who underwent surgery at the Department of Plastic Surgery, Aarhus University Hospital, from 1991 to 1994 were included in the study. Total tumor volume was estimated by the Cavalieri technique, total number of tumor cells by the optical dissector principle...... showed a significant impact on both disease-free survival (p=0.001) and mortality (p=0.009). In conclusion, tumor volume and total number of cancer cells were highly reproducible but did not add additional, independent prognostic information regarding the study population.......Stereological quantification of tumor volume, total number of tumor cells and mean nuclear volume provides unbiased data, regardless of the three-dimensional shape of the melanocytic lesion. The aim of the present study was to investigate whether these variables are reproducible and may represent...

The efficiency of systematic sampling in stereology-reconsidered

DEFF Research Database (Denmark)

Gundersen, Hans Jørgen Gottlieb; Jensen, Eva B. Vedel; Kieu, K

1999-01-01

In the present paper, we summarize and further develop recent research in the estimation of the variance of stereological estimators based on systematic sampling. In particular, it is emphasized that the relevant estimation procedure depends on the sampling density. The validity of the variance...... estimation is examined in a collection of data sets, obtained by systematic sampling. Practical recommendations are also provided in a separate section....

Design-based stereological estimation of the total number of cardiac myocytes in histological sections

DEFF Research Database (Denmark)

Brüel, Annemarie; Nyengaard, Jens Randel

2005-01-01

in LM sections using design-based stereology. MATERIALS AND METHODS: From formalin-fixed left rat ventricles (LV) isotropic uniformly random sections were cut. The total number of myocyte nuclei per LV was estimated using the optical disector. Two-microm-thick serial paraffin sections were stained......BACKGROUND: Counting the total number of cardiac myocytes has not previously been possible in ordinary histological sections using light microscopy (LM) due to difficulties in defining the myocyte borders properly. AIM: To describe a method by which the total number of cardiac myocytes is estimated...... with antibodies against cadherin and type IV collagen to visualise the intercalated discs and the myocyte membranes, respectively. Using the physical disector in "local vertical windows" of the serial sections, the average number of nuclei per myocyte was estimated.RESULTS: The total number of myocyte nuclei...

Stereological estimation of nuclear volume in benign and malignant melanocytic lesions of the skin. Inter- and intraobserver variability of malignancy grading

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Ottosen, P D

1991-01-01

The volume-weighted, mean nuclear volume (nuclear vv) may be estimated without any assumptions regarding nuclear shape using modern stereological techniques. As a part of an investigation concerning the prospects of nuclear vv for classification and malignancy grading of cutaneous melanocytic tum...

Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex

DEFF Research Database (Denmark)

Walløe, Solveig; Pakkenberg, Bente; Fabricius, Katrine

2014-01-01

estimates and were often very time-consuming. Within the last 20-30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected...

EARLY HISTORY OF GEOMETRIC PROBABILITY AND STEREOLOGY

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Magdalena Hykšová

2012-03-01

Full Text Available The paper provides an account of the history of geometric probability and stereology from the time of Newton to the early 20th century. It depicts the development of two parallel ways: on one hand, the theory of geometric probability was formed with minor attention paid to other applications than those concerning spatial chance games. On the other hand, practical rules of the estimation of area or volume fraction and other characteristics, easily deducible from geometric probability theory, were proposed without the knowledge of this branch. A special attention is paid to the paper of J.-É. Barbier published in 1860, which contained the fundamental stereological formulas, but remained almost unnoticed both by mathematicians and practicians.

Assessment of left ventricular function and mass by MR imaging: a stereological study based on the systematic slice sampling procedure.

Science.gov (United States)

Mazonakis, Michalis; Sahin, Bunyamin; Pagonidis, Konstantin; Damilakis, John

2011-06-01

The aim of this study was to combine the stereological technique with magnetic resonance (MR) imaging data for the volumetric and functional analysis of the left ventricle (LV). Cardiac MR examinations were performed in 13 consecutive subjects with known or suspected coronary artery disease. The end-diastolic volume (EDV), end-systolic volume, ejection fraction (EF), and mass were estimated by stereology using the entire slice set depicting LV and systematic sampling intensities of 1/2 and 1/3 that provided samples with every second and third slice, respectively. The repeatability of stereology was evaluated. Stereological assessments were compared with the reference values derived by manually tracing the endocardial and epicardial contours on MR images. Stereological EDV and EF estimations obtained by the 1/3 systematic sampling scheme were significantly different from those by manual delineation (P sampling intensity of 1/2 (P > .05). For these stereological approaches, a high correlation (r(2) = 0.80-0.93) and clinically acceptable limits of agreement were found with the reference method. Stereological estimations obtained by both sample sizes presented comparable coefficient of variation values of 2.9-5.8%. The mean time for stereological measurements on the entire slice set was 3.4 ± 0.6 minutes and it was reduced to 2.5 ± 0.5 minutes with the 1/2 systematic sampling scheme. Stereological analysis on systematic samples of MR slices generated by the 1/2 sampling intensity provided efficient and quick assessment of LV volumes, function, and mass. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Automatic sampling for unbiased and efficient stereological estimation using the proportionator in biological studies

DEFF Research Database (Denmark)

Gardi, Jonathan Eyal; Nyengaard, Jens Randel; Gundersen, Hans Jørgen Gottlieb

2008-01-01

Quantification of tissue properties is improved using the general proportionator sampling and estimation procedure: automatic image analysis and non-uniform sampling with probability proportional to size (PPS). The complete region of interest is partitioned into fields of view, and every field...... of view is given a weight (the size) proportional to the total amount of requested image analysis features in it. The fields of view sampled with known probabilities proportional to individual weight are the only ones seen by the observer who provides the correct count. Even though the image analysis...... cerebellum, total number of orexin positive neurons in transgenic mice brain, and estimating the absolute area and the areal fraction of β islet cells in dog pancreas.  The proportionator was at least eight times more efficient (precision and time combined) than traditional computer controlled sampling....

Critical point relascope sampling for unbiased volume estimation of downed coarse woody debris

Science.gov (United States)

Jeffrey H. Gove; Michael S. Williams; Mark J. Ducey; Mark J. Ducey

2005-01-01

Critical point relascope sampling is developed and shown to be design-unbiased for the estimation of log volume when used with point relascope sampling for downed coarse woody debris. The method is closely related to critical height sampling for standing trees when trees are first sampled with a wedge prism. Three alternative protocols for determining the critical...

Improving efficiency in stereology

DEFF Research Database (Denmark)

Keller, Kresten Krarup; Andersen, Ina Trolle; Andersen, Johnnie Bremholm

2013-01-01

of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned......, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We...... conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology....

[Simulation and data analysis of stereological modeling based on virtual slices].

Science.gov (United States)

Wang, Hao; Shen, Hong; Bai, Xiao-yan

2008-05-01

To establish a computer-assisted stereological model for simulating the process of slice section and evaluate the relationship between section surface and estimated three-dimensional structure. The model was designed by mathematic method as a win32 software based on the MFC using Microsoft visual studio as IDE for simulating the infinite process of sections and analysis of the data derived from the model. The linearity of the fitting of the model was evaluated by comparison with the traditional formula. The win32 software based on this algorithm allowed random sectioning of the particles distributed randomly in an ideal virtual cube. The stereological parameters showed very high throughput (>94.5% and 92%) in homogeneity and independence tests. The data of density, shape and size of the section were tested to conform to normal distribution. The output of the model and that from the image analysis system showed statistical correlation and consistency. The algorithm we described can be used for evaluating the stereologic parameters of the structure of tissue slices.

Estimating unbiased economies of scale of HIV prevention projects: a case study of Avahan.

Science.gov (United States)

Lépine, Aurélia; Vassall, Anna; Chandrashekar, Sudha; Blanc, Elodie; Le Nestour, Alexis

2015-04-01

Governments and donors are investing considerable resources on HIV prevention in order to scale up these services rapidly. Given the current economic climate, providers of HIV prevention services increasingly need to demonstrate that these investments offer good 'value for money'. One of the primary routes to achieve efficiency is to take advantage of economies of scale (a reduction in the average cost of a health service as provision scales-up), yet empirical evidence on economies of scale is scarce. Methodologically, the estimation of economies of scale is hampered by several statistical issues preventing causal inference and thus making the estimation of economies of scale complex. In order to estimate unbiased economies of scale when scaling up HIV prevention services, we apply our analysis to one of the few HIV prevention programmes globally delivered at a large scale: the Indian Avahan initiative. We costed the project by collecting data from the 138 Avahan NGOs and the supporting partners in the first four years of its scale-up, between 2004 and 2007. We develop a parsimonious empirical model and apply a system Generalized Method of Moments (GMM) and fixed-effects Instrumental Variable (IV) estimators to estimate unbiased economies of scale. At the programme level, we find that, after controlling for the endogeneity of scale, the scale-up of Avahan has generated high economies of scale. Our findings suggest that average cost reductions per person reached are achievable when scaling-up HIV prevention in low and middle income countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of the Physical Disector Principle for Quantification of Dopaminergic Neuronal Loss in a Rat 6-Hydroxydopamine Nigral Lesion Model of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Katrine Fabricius

2017-12-01

Full Text Available Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson's disease and in animal models of nigrostriatal degeneration. Therefore, we applied an established automated physical disector principle in a fractionator design for efficient stereological quantitative analysis of tyrosine hydroxylase (TH-positive dopamine neurons in the substantia nigra pars compacta of hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA lesions. We obtained reliable estimates of dopamine neuron numbers, and established the relationship between behavioral asymmetry and dopamine neuron loss on the lesioned side. In conclusion, the automated physical disector principle provided a useful and efficient tool for unbiased estimation of TH-positive neurons in rat midbrain, and should prove valuable for investigating neuroprotective strategies in 6-OHDA model of parkinsonism, while generalizing to other immunohistochemically-defined cell populations.

An unbiased estimator of the variance of simple random sampling using mixed random-systematic sampling

OpenAIRE

Padilla, Alberto

2009-01-01

Systematic sampling is a commonly used technique due to its simplicity and ease of implementation. The drawback of this simplicity is that it is not possible to estimate the design variance without bias. There are several ways to circumvent this problem. One method is to suppose that the variable of interest has a random order in the population, so the sample variance of simple random sampling without replacement is used. By means of a mixed random - systematic sample, an unbiased estimator o...

Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer.

Science.gov (United States)

Eriksen, Ann C; Andersen, Johnnie B; Kristensson, Martin; dePont Christensen, René; Hansen, Torben F; Kjær-Frifeldt, Sanne; Sørensen, Flemming B

2017-08-29

Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphocytes (TILs) may be rewarding, but the lack of a standardized analytic technique is a major concern. Manual stereological counting is considered the gold standard, but digital pathology with image analysis is preferred due to time efficiency. The purpose of this study was to compare manual stereological estimates of TILs with automatic counts obtained by image analysis, and at the same time investigate the heterogeneity of TILs. From 43 patients treated for stage II CC in 2002 three paraffin embedded, tumor containing tissue blocks were selected one of them representing the deepest invasive tumor front. Serial sections from each of the 129 blocks were immunohistochemically stained for CD3 and CD8, and the slides were scanned. Stereological estimates of the numerical density and area fraction of TILs were obtained using the computer-assisted newCAST stereology system. For the image analysis approach an app-based algorithm was developed using Visiopharm Integrator System software. For both methods the tumor areas of interest (invasive front and central area) were manually delineated by the observer. Based on all sections, the Spearman's correlation coefficients for density estimates varied from 0.9457 to 0.9638 (p heterogeneity, intra-class correlation coefficients (ICC) for CD3+ TILs varied from 0.615 to 0.746 in the central area, and from 0.686 to 0.746 in the invasive area. ICC for CD8+ TILs varied from 0.724 to 0.775 in the central area, and from 0.746 to 0.765 in the invasive area. Exact objective and time efficient estimates of numerical densities and area fractions of CD3+ and CD8+ TILs in stage II colon cancer can be obtained by image analysis and are highly correlated to the corresponding estimates obtained by the gold standard based on stereology

Unbiased minimum variance estimator of a matrix exponential function. Application to Boltzmann/Bateman coupled equations solving

International Nuclear Information System (INIS)

Dumonteil, E.; Diop, C. M.

2009-01-01

This paper derives an unbiased minimum variance estimator (UMVE) of a matrix exponential function of a normal wean. The result is then used to propose a reference scheme to solve Boltzmann/Bateman coupled equations, thanks to Monte Carlo transport codes. The last section will present numerical results on a simple example. (authors)

Stereological estimation of surface area and barrier thickness of fish gills in vertical sections.

Science.gov (United States)

Da Costa, Oscar T F; Pedretti, Ana Carolina E; Schmitz, Anke; Perry, Steven F; Fernandes, Marisa N

2007-01-01

Previous morphometric methods for estimation of the volume of components, surface area and thickness of the diffusion barrier in fish gills have taken advantage of the highly ordered structure of these organs for sampling and surface area estimations, whereas the thickness of the diffusion barrier has been measured orthogonally on perpendicularly sectioned material at subjectively selected sites. Although intuitively logical, these procedures do not have a demonstrated mathematical basis, do not involve random sampling and measurement techniques, and are not applicable to the gills of all fish. The present stereological methods apply the principles of surface area estimation in vertical uniform random sections to the gills of the Brazilian teleost Arapaima gigas. The tissue was taken from the entire gill apparatus of the right-hand or left-hand side (selected at random) of the fish by systematic random sampling and embedded in glycol methacrylate for light microscopy. Arches from the other side were embedded in Epoxy resin. Reference volume was estimated by the Cavalieri method in the same vertical sections that were used for surface density and volume density measurements. The harmonic mean barrier thickness of the water-blood diffusion barrier was calculated from measurements taken along randomly selected orientation lines that were sine-weighted relative to the vertical axis. The values thus obtained for the anatomical diffusion factor (surface area divided by barrier thickness) compare favourably with those obtained for other sluggish fish using existing methods.

Practical Stereology Applications for the Pathologist.

Science.gov (United States)

Brown, Danielle L

2017-05-01

Qualitative histopathology is the gold standard for routine examination of morphological tissue changes in the regulatory or academic environment. The human eye is exceptional for pattern recognition but often cannot detect small changes in quantity. In cases where detection of subtle quantitative changes is critical, more sensitive methods are required. Two-dimensional histomorphometry can provide additional quantitative information and is quite useful in many cases. However, the provided data may not be referent to the entire tissue and, as such, it makes several assumptions, which are sources of bias. In contrast, stereology is design based rather than assumption based and uses stringent sampling methods to obtain accurate and precise 3-dimensional information using geometrical and statistical principles. Recent advances in technology have made stereology more approachable and practical for the pathologist in both regulatory and academic environments. This review introduces pathologists to the basic principles of stereology and walks the reader through some real-world examples for the application of these principles in the workplace.

Introduction into integral geometry and stereology

DEFF Research Database (Denmark)

Kiderlen, Markus

Statistics and Random Fields and is a self-containing introduction into integral geometry and its applications in stereology. The most important integral geometric tools for stereological applications are kinematic formulas and results of Blaschke-Petkantschin type. Therefore, Crofton's formula......This text is the extended version of two talks held at the Summer Academy Stochastic Geometry, Spatial Statistics and Random Fields in the Soellerhaus, Germany, in September 2009. It forms (with slight modifications) a chapter of the Springer lecture notes Lectures on Stochastic Geometry, Spatial...

Estimating Unbiased Land Cover Change Areas In The Colombian Amazon Using Landsat Time Series And Statistical Inference Methods

Science.gov (United States)

Arevalo, P. A.; Olofsson, P.; Woodcock, C. E.

2017-12-01

Unbiased estimation of the areas of conversion between land categories ("activity data") and their uncertainty is crucial for providing more robust calculations of carbon emissions to the atmosphere, as well as their removals. This is particularly important for the REDD+ mechanism of UNFCCC where an economic compensation is tied to the magnitude and direction of such fluxes. Dense time series of Landsat data and statistical protocols are becoming an integral part of forest monitoring efforts, but there are relatively few studies in the tropics focused on using these methods to advance operational MRV systems (Monitoring, Reporting and Verification). We present the results of a prototype methodology for continuous monitoring and unbiased estimation of activity data that is compliant with the IPCC Approach 3 for representation of land. We used a break detection algorithm (Continuous Change Detection and Classification, CCDC) to fit pixel-level temporal segments to time series of Landsat data in the Colombian Amazon. The segments were classified using a Random Forest classifier to obtain annual maps of land categories between 2001 and 2016. Using these maps, a biannual stratified sampling approach was implemented and unbiased stratified estimators constructed to calculate area estimates with confidence intervals for each of the stable and change classes. Our results provide evidence of a decrease in primary forest as a result of conversion to pastures, as well as increase in secondary forest as pastures are abandoned and the forest allowed to regenerate. Estimating areas of other land transitions proved challenging because of their very small mapped areas compared to stable classes like forest, which corresponds to almost 90% of the study area. Implications on remote sensing data processing, sample allocation and uncertainty reduction are also discussed.

Blood capillary length estimation from three-dimensional microscopic data by image analysis and stereology.

Science.gov (United States)

Kubínová, Lucie; Mao, Xiao Wen; Janáček, Jiří

2013-08-01

Studies of the capillary bed characterized by its length or length density are relevant in many biomedical studies. A reliable assessment of capillary length from two-dimensional (2D), thin histological sections is a rather difficult task as it requires physical cutting of such sections in randomized directions. This is often technically demanding, inefficient, or outright impossible. However, if 3D image data of the microscopic structure under investigation are available, methods of length estimation that do not require randomized physical cutting of sections may be applied. Two different rat brain regions were optically sliced by confocal microscopy and resulting 3D images processed by three types of capillary length estimation methods: (1) stereological methods based on a computer generation of isotropic uniform random virtual test probes in 3D, either in the form of spatial grids of virtual "slicer" planes or spherical probes; (2) automatic method employing a digital version of the Crofton relations using the Euler characteristic of planar sections of the binary image; and (3) interactive "tracer" method for length measurement based on a manual delineation in 3D of the axes of capillary segments. The presented methods were compared in terms of their practical applicability, efficiency, and precision.

Note on an Identity Between Two Unbiased Variance Estimators for the Grand Mean in a Simple Random Effects Model.

Science.gov (United States)

Levin, Bruce; Leu, Cheng-Shiun

2013-01-01

We demonstrate the algebraic equivalence of two unbiased variance estimators for the sample grand mean in a random sample of subjects from an infinite population where subjects provide repeated observations following a homoscedastic random effects model.

Practical application of stereological methods in experimental kidney animal models.

Science.gov (United States)

Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Multifractals embedded in short time series: An unbiased estimation of probability moment

Science.gov (United States)

Qiu, Lu; Yang, Tianguang; Yin, Yanhua; Gu, Changgui; Yang, Huijie

2016-12-01

An exact estimation of probability moments is the base for several essential concepts, such as the multifractals, the Tsallis entropy, and the transfer entropy. By means of approximation theory we propose a new method called factorial-moment-based estimation of probability moments. Theoretical prediction and computational results show that it can provide us an unbiased estimation of the probability moments of continuous order. Calculations on probability redistribution model verify that it can extract exactly multifractal behaviors from several hundred recordings. Its powerfulness in monitoring evolution of scaling behaviors is exemplified by two empirical cases, i.e., the gait time series for fast, normal, and slow trials of a healthy volunteer, and the closing price series for Shanghai stock market. By using short time series with several hundred lengths, a comparison with the well-established tools displays significant advantages of its performance over the other methods. The factorial-moment-based estimation can evaluate correctly the scaling behaviors in a scale range about three generations wider than the multifractal detrended fluctuation analysis and the basic estimation. The estimation of partition function given by the wavelet transform modulus maxima has unacceptable fluctuations. Besides the scaling invariance focused in the present paper, the proposed factorial moment of continuous order can find its various uses, such as finding nonextensive behaviors of a complex system and reconstructing the causality relationship network between elements of a complex system.

Blood Capillary Length Estimation from Three-Dimensional Microscopic Data by Image Analysis and Stereology

Czech Academy of Sciences Publication Activity Database

Kubínová, Lucie; Mao, X. W.; Janáček, Jiří

2013-01-01

Roč. 19, č. 4 (2013), s. 898-906 ISSN 1431-9276 R&D Projects: GA MŠk(CZ) ME09010; GA MŠk(CZ) LH13028; GA ČR(CZ) GAP108/11/0794 Institutional research plan: CEZ:AV0Z5011922 Institutional support: RVO:67985823 Keywords : capillaries * confocal microscopy * image analysis * length * rat brain * stereology Subject RIV: EA - Cell Biology Impact factor: 1.757, year: 2013

Unbiased estimation of human body composition by the Cavalieri method using magnetic resonance imaging

International Nuclear Information System (INIS)

Roberts, N.; Reid, N.M.K.; Brodie, D.A.; Bourne, M.; Edwards, R.H.T.; Cruz-Orive, L.M.

1993-01-01

The classical methods for estimating the volume of human body compartments in vivo (e.g. skin-fold thickness for fat, radioisotope counting for different compartments, etc.) are generally indirect and rely on essentially empirical relationships - hence they are biased to unknown degrees. The advent of modern non-invasive scanning techniques, such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) is now widening the scope of volume quantification, especially in combination with stereological methods. Apart from its superior soft tissue contrast, MRI enjoys the distinct advantage of not using ionizing radiations. By a proper landmarking and control of the scanner couch, an adult male volunteer was scanned exhaustively into parallel systematic MR ''sections''. Four compartments were defined, namely bone, muscle, organs and fat (which included the skin), and their corresponding volumes were easily and efficiently estimated by the Cavalieri method: the total section area of a compartment times the section interval estimates the volume of the compartment without bias. Formulae and nomograms are given to predict the errors and to optimize the design. To estimate an individual's muscle volume with a 5% coefficient of error, 10 sections and less than 10 min point counting (to estimate the relevant section areas) are required. Bone and fat require about twice as much work. To estimate the mean muscle volume of a population with the same error contribution, from a random sample of six subjects, the workload per subject can be divided by √ 6, namely 4 min per subject. For a given number of sections planimetry would be as accurate but far more time consuming than point counting. (author)

Hippocampal MR volumetry

Science.gov (United States)

Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.

1994-09-01

Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR

Unbiased free energy estimates in fast nonequilibrium transformations using Gaussian mixtures

International Nuclear Information System (INIS)

Procacci, Piero

2015-01-01

In this paper, we present an improved method for obtaining unbiased estimates of the free energy difference between two thermodynamic states using the work distribution measured in nonequilibrium driven experiments connecting these states. The method is based on the assumption that any observed work distribution is given by a mixture of Gaussian distributions, whose normal components are identical in either direction of the nonequilibrium process, with weights regulated by the Crooks theorem. Using the prototypical example for the driven unfolding/folding of deca-alanine, we show that the predicted behavior of the forward and reverse work distributions, assuming a combination of only two Gaussian components with Crooks derived weights, explains surprisingly well the striking asymmetry in the observed distributions at fast pulling speeds. The proposed methodology opens the way for a perfectly parallel implementation of Jarzynski-based free energy calculations in complex systems

Stereology as a tool to assess reproduction strategy and fecundity of teleost fishes

DEFF Research Database (Denmark)

Bucholtz, Rikke Hagstrøm

methods to assess fecundity and reproductive strategies. The strength of the stereological method being that, in combination with conventional histological analysis, quantification of all oocyte categories is possible, as well as registration of qualitative characteristics relating to spawning history...... of oocyte dynamics in fish and were successfully implemented in herring ovaries for quantification of both oocyte numbers and sizes as well as total volume fraction of atretic oocytes, introducing a negligible error to the total variance of estimates. The histological nature of the stereological methods...... facilitated a ready validation of maturity data, distinguishing first time spawners from repeat spawners, as well as a ready recognition of ongoing oocyte recruitment in early maturity stages, early stage atresia, POFs and residual eggs. Analyzing a sample of females all collected during a short time frame...

STEREOLOGY FROM ONE OF ALL THE POSSIBLE ANGLES

Directory of Open Access Journals (Sweden)

Leszek Wojnar

2011-05-01

Full Text Available Relation between image analysis and stereology is discussed in terms of different fields of applications, especially materials science, biology and medicine. Some long-term tendencies observed as well as possible future trends are discussed. The need of a wider use of image analysis techniques including ma1hematical morphology in any field of science is demons1rated. Simultaneously, the significance of stereological background in automatic quantification of1he investigated structures is confirmed.

Total regional and global number of synapses in the human brain neocortex

NARCIS (Netherlands)

Tang, Y.; Nyengaard, J.R.; Groot, D.M.G. de; Jorgen, H.; Gundersen, G.

2001-01-01

An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region

Brain Volume Estimation Enhancement by Morphological Image Processing Tools

Directory of Open Access Journals (Sweden)

Zeinali R.

2017-12-01

Full Text Available Background: Volume estimation of brain is important for many neurological applications. It is necessary in measuring brain growth and changes in brain in normal/ abnormal patients. Thus, accurate brain volume measurement is very important. Magnetic resonance imaging (MRI is the method of choice for volume quantification due to excellent levels of image resolution and between-tissue contrast. Stereology method is a good method for estimating volume but it requires to segment enough MRI slices and have a good resolution. In this study, it is desired to enhance stereology method for volume estimation of brain using less MRI slices with less resolution. Methods: In this study, a program for calculating volume using stereology method has been introduced. After morphologic method, dilation was applied and the stereology method enhanced. For the evaluation of this method, we used T1-wighted MR images from digital phantom in BrainWeb which had ground truth. Results: The volume of 20 normal brain extracted from BrainWeb, was calculated. The volumes of white matter, gray matter and cerebrospinal fluid with given dimension were estimated correctly. Volume calculation from Stereology method in different cases was made. In three cases, Root Mean Square Error (RMSE was measured. Case I with T=5, d=5, Case II with T=10, D=10 and Case III with T=20, d=20 (T=slice thickness, d=resolution as stereology parameters. By comparing these results of two methods, it is obvious that RMSE values for our proposed method are smaller than Stereology method. Conclusion: Using morphological operation, dilation allows to enhance the estimation volume method, Stereology. In the case with less MRI slices and less test points, this method works much better compared to Stereology method.

Quantifying high dimensional entanglement with two mutually unbiased bases

Directory of Open Access Journals (Sweden)

Paul Erker

2017-07-01

Full Text Available We derive a framework for quantifying entanglement in multipartite and high dimensional systems using only correlations in two unbiased bases. We furthermore develop such bounds in cases where the second basis is not characterized beyond being unbiased, thus enabling entanglement quantification with minimal assumptions. Furthermore, we show that it is feasible to experimentally implement our method with readily available equipment and even conservative estimates of physical parameters.

ON THE VOLUME FROM PLANAR SECTIONS THROUGH A CURVE

Directory of Open Access Journals (Sweden)

Ximo Gual-Arnau

2011-05-01

Full Text Available We derive a formula to obtain the volume of a compact domain from planar sections through a curve. From this formula we propose a stereological estimator for the volume which generalizes some known unbiased estimators which use a systematic sampling scheme. Moreover we formulate a Cavalieri's principle for compact domains is spaces of constant curvature λ.

Unbiased estimators of coincidence and correlation in non-analogous Monte Carlo particle transport

International Nuclear Information System (INIS)

Szieberth, M.; Kloosterman, J.L.

2014-01-01

Highlights: • The history splitting method was developed for non-Boltzmann Monte Carlo estimators. • The method allows variance reduction for pulse-height and higher moment estimators. • It works in highly multiplicative problems but Russian roulette has to be replaced. • Estimation of higher moments allows the simulation of neutron noise measurements. • Biased sampling of fission helps the effective simulation of neutron noise methods. - Abstract: The conventional non-analogous Monte Carlo methods are optimized to preserve the mean value of the distributions. Therefore, they are not suited to non-Boltzmann problems such as the estimation of coincidences or correlations. This paper presents a general method called history splitting for the non-analogous estimation of such quantities. The basic principle of the method is that a non-analogous particle history can be interpreted as a collection of analogous histories with different weights according to the probability of their realization. Calculations with a simple Monte Carlo program for a pulse-height-type estimator prove that the method is feasible and provides unbiased estimation. Different variance reduction techniques have been tried with the method and Russian roulette turned out to be ineffective in high multiplicity systems. An alternative history control method is applied instead. Simulation results of an auto-correlation (Rossi-α) measurement show that even the reconstruction of the higher moments is possible with the history splitting method, which makes the simulation of neutron noise measurements feasible

Classification of tubulo-papillary renal cortical tumours using estimates of nuclear volume

DEFF Research Database (Denmark)

Brooks, B; Sørensen, Flemming Brandt; Olsen, S

1993-01-01

The classification of renal cortical tumours is problematic, with no clear division of benign from malignant tumours. Unbiased stereological estimates of volume-weighted nuclear volume (nuclear vv) were obtained by point sampling of nuclear intercepts in a retrospective study of 36 variably sized...... = 241 microns 3) and 15 tumours classified as renal cell carcinomas with diameters > 3 cm, or aggressive histological pattern (average nuclear vv = 229 microns 3) (2p = 0.68). In this subtype of renal cortical tumours, estimates of nuclear vv do not support the historical convention of using a 3 cm...... tumour diameter as the dividing line between adenomas and carcinomas, but support the theory of a single group of tumours. As most of the truly incidental renal cortical tumours are less than 1 cm in diameter, this limit could be considered. Such small benign cortical nodules have never been reported...

Quantitative relationships in delphinid neocortex

DEFF Research Database (Denmark)

Mortensen, Heidi S.; Pakkenberg, Bente; Dam, Maria

2014-01-01

total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species...

Stereological analysis of nuclear volume in recurrent meningiomas

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1994-01-01

A stereological estimation of nuclear volume in recurrent and non-recurrent meningiomas was made. The aim was to investigate whether this method could discriminate between these two groups. We found that the mean nuclear volumes in recurrent meningiomas were all larger at debut than in any...... of the control tumors. The mean nuclear volume of the individual recurrent tumors appeared to change with time, showing a tendency to diminish. A relationship between large nuclear volume at presentation and number of or time interval between recurrences was not found. We conclude that measurement of mean...... nuclear volume in meningiomas might help identify a group at risk of recurrence....

A handheld support system to facilitate stereological measurements and mapping of branching structures

DEFF Research Database (Denmark)

Gardi, J.E.; Wulfsohn, Dvora-Laiô; Nyengaard, J.R.

2007-01-01

specifications, software and Graphical User Interface (GUI) development, functionality and application of the handheld system using four examples: (1) sampling monkey lung bronchioles for estimation of diameter and wall thickness (2) sampling rat kidney for estimating number of arteries and arterioles......‘BranchSampler' is a system for computer-assisted manual stereology written for handheld devices running Windows CE. The system has been designed specifically to streamline data collection and optimize sampling of tree-like branching structures, with particular aims of reducing user errors, saving...

Stereological estimate of the total number of neurons in spinal segment D9 of the red-eared turtle

DEFF Research Database (Denmark)

Walløe, Solveig; Nissen, Ulla Vig; Berg, Rune W

2011-01-01

The red-eared turtle is an important animal model for investigating the neural activity in the spinal circuit that generates motor behavior. However, basic anatomical features, including the number of neurons in the spinal segments involved, are unknown. In the present study, we estimate the total...... number of neurons in segment D9 of the spinal cord in the red-eared turtle (Trachemys scripta elegans) using stereological cell counting methods. In transverse spinal cord sections stained with modified Giemsa, motoneurons (MNs), interneurons (INs), and non-neuronal cells were distinguished according...... to location and morphology. Each cell type was then counted separately using an optical disector with the cell nucleus as counting item. The number of cells in segment D9 was as follows (mean ± SE): MNs, 2049 ± 74; INs, 16,135 ± 316; non-neuronal cells, 47,504 ± 478 (n = 6). These results provide the first...

Unbiased estimation of the liver volume by the Cavalieri principle using magnetic resonance images

International Nuclear Information System (INIS)

Sahin, Buenyamin; Emirzeoglu, Mehmet; Uzun, Ahmet; Incesu, Luetfi; Bek, Yueksel; Bilgic, Sait; Kaplan, Sueleyman

2003-01-01

Objective: It is often useful to know the exact volume of the liver, such as in monitoring the effects of a disease, treatment, dieting regime, training program or surgical application. Some non-invasive methodologies have been previously described which estimate the volume of the liver. However, these preliminary techniques need special software or skilled performers and they are not ideal for daily use in clinical practice. Here, we describe a simple, accurate and practical technique for estimating liver volume without changing the routine magnetic resonance imaging scanning procedure. Materials and methods: In this study, five normal livers, obtained from cadavers, were scanned by 0.5 T MR machine, in horizontal and sagittal planes. The consecutive sections, in 10 mm thickness, were used to estimate the whole volume of the liver by means of the Cavalieri principle. The volume estimations were done by three different performers to evaluate the reproducibility. Results: There are no statistical differences between the performers and real liver volumes (P>0.05). There is also high correlation between the estimates of performers and the real liver volume (r=0.993). Conclusion: We conclude that the combination of MR imaging with the Cavalieri principle is a non-invasive, direct and unbiased technique that can be safely applied to estimate liver volume with a very moderate workload per individual

Stereological, functional and molecular studies of development and disease : a collection of published works 1981 to 2013

OpenAIRE

Bertram, John F.

2016-01-01

The unifying theme throughout this Doctorate of Science thesis is the development, refinement and utilisation of stereological techniques to study tissue structures in development, and in adult health and disease. Stereology is the discipline based on geometric probability theory that enables us to quantify structures in three-dimensional space. Stereological techniques are often applied in material science as well as biomedical science. When applied to histology and pathology, stereology can...

Assessing the Effects of Fibrosis on Lung Function by Light Microscopy-Coupled Stereology

DEFF Research Database (Denmark)

Pilecki, Bartosz; Sørensen, Grith Lykke

2017-01-01

Pulmonary diseases such as fibrosis are characterized by structural abnormalities that lead to impairment of proper lung function. Stereological analysis of serial tissue sections allows detection and quantitation of subtle changes in lung architecture. Here, we describe a stereology-based method...

Quantitative analysis of the renal aging in rats. Stereological study

OpenAIRE

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins Filho, Eduardo Lopes; Fraga, Rogério de

2016-01-01

ABSTRACT PURPOSE: To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. METHODS: Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glo...

STEREOLOGICAL ANALYSIS OF THE COCHLEAR NUCLEI OF MONKEY (MACACA FASCICULARIS AFTER DEAFFERENTATION

Directory of Open Access Journals (Sweden)

Ana M Insausti

2011-05-01

Full Text Available The cochlear nuclei (CN in the brainstem receive the input signals from the inner ear through the cochlear nerve, and transmit these signals to higher auditory centres. A variety of lesions of the cochlear nerve cause deafness. As reported in the literature, artificial removal of auditive input, or 'deafferentation', induces structural alterations in the CN. The purpose of this study was to estimate a number of relevant stereological parameters of the CN in control and deafferented Macaca fascicularis monkeys.

Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors. Practical technique and use in prognostic evaluation

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Braendgaard, H; Chistiansen, A O

1991-01-01

The use of morphometry and modern stereology in malignancy grading of brain tumors is only poorly investigated. The aim of this study was to present these quantitative methods. A retrospective feasibility study of 46 patients with supratentorial brain tumors was carried out to demonstrate...... the practical technique. The continuous variables were correlated with the subjective, qualitative WHO classification of brain tumors, and the prognostic value of the parameters was assessed. Well differentiated astrocytomas (n = 14) had smaller estimates of the volume-weighted mean nuclear volume and mean...... nuclear profile area, than those of anaplastic astrocytomas (n = 13) (2p = 3.1.10(-3) and 2p = 4.8.10(-3), respectively). No differences were seen between the latter type of tumor and glioblastomas (n = 19). The nuclear index was of the same magnitude in all three tumor types, whereas the mitotic index...

Variance estimation for generalized Cavalieri estimators

OpenAIRE

Johanna Ziegel; Eva B. Vedel Jensen; Karl-Anton Dorph-Petersen

2011-01-01

The precision of stereological estimators based on systematic sampling is of great practical importance. This paper presents methods of data-based variance estimation for generalized Cavalieri estimators where errors in sampling positions may occur. Variance estimators are derived under perturbed systematic sampling, systematic sampling with cumulative errors and systematic sampling with random dropouts. Copyright 2011, Oxford University Press.

Thick methacrylate sections devoid of lost caps simplify stereological quantifications based on the optical fractionator design

DEFF Research Database (Denmark)

Andersen, Stine Hasselholt; Lykkesfeldt, Jens; Larsen, Jytte Overgaard

2015-01-01

Abstract In neuroscience, the optical fractionator technique is frequently used for unbiased cell number estimations. Although unbiased in theory, the practical application of the technique is often biased by the necessity of introducing a guard zone at one side of the disector to counter lost caps...

PLASTICITY OF SKELETAL MUSCLE STUDIED BY STEREOLOGY

Directory of Open Access Journals (Sweden)

Ida Eržen

2011-05-01

Full Text Available The present contribution provides an overview of stereological methods applied in the skeletal muscle research at the Institute of Anatomy of the Medical Faculty in Ljubljana. Interested in skeletal muscle plasticity we studied three different topics: (i expression of myosin heavy chain isoforms in slow and fast muscles under experimental conditions, (ii frequency of satellite cells in young and old human and rat muscles and (iii capillary supply of rat fast and slow muscles. We analysed the expression of myosin heavy chain isoforms within slow rat soleus and fast extensor digitorum longus muscles after (i homotopic and heterotopic transplantation of both muscles, (ii low frequency electrical stimulation of the fast muscle and (iii transposition of the fast nerve to the slow muscle. The models applied were able to turn the fast muscle into a completely slow muscle, but not vice versa. One of the indicators for the regenerative potential of skeletal muscles is its satellite cell pool. The estimated parameters, number of satellite cells per unit fibre length, corrected to the reference sarcomere length (Nsc/Lfib and number of satellite cells per number of nuclei (myonuclei and satellite cell nuclei (Nsc/Nnucl indicated that the frequency of M-cadherin stained satellite cells declines in healthy old human and rat muscles compared to young muscles. To access differences in capillary densities among slow and fast muscles and slow and fast muscle fibres, we have introduced Slicer and Fakir methods, and tested them on predominantly slow and fast rat muscles. Discussing three different topics that require different approach, the present paper reflects the three decades of the development of stereological methods: 2D analysis by simple point counting in the 70's, the disector in the 80's and virtual spatial probes in the 90's. In all methods the interactive computer assisted approach was utilised.

The Dimensions of the Orbital Cavity Based on High-Resolution Computed Tomography of Human Cadavers

DEFF Research Database (Denmark)

Felding, Ulrik Ascanius; Bloch, Sune Land; Buchwald, Christian von

2016-01-01

for surface area. To authors' knowledge, this study is the first to have measured the entire surface area of the orbital cavity.The volume and surface area of the orbital cavity were estimated in computed tomography scans of 11 human cadavers using unbiased stereological sampling techniques. The mean (± SD......) total volume and total surface area of the orbital cavities was 24.27 ± 3.88 cm and 32.47 ± 2.96 cm, respectively. There was no significant difference in volume (P = 0.315) or surface area (P = 0.566) between the 2 orbital cavities.The stereological technique proved to be a robust and unbiased method...... that may be used as a gold standard for comparison with automated computer software. Future imaging studies in blow-out fracture patients may be based on individual and relative calculation involving both herniated volume and fractured surface area in relation to the total volume and surface area...

Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years

Energy Technology Data Exchange (ETDEWEB)

Mayer, Kristina N. [University Children' s Hospital of Zurich, Center for MR Research, Zurich (Switzerland); University Children' s Hospital, Pediatric Cardiology, Zurich (Switzerland); Latal, Beatrice [University Children' s Hospital, Child Development Center, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland); Knirsch, Walter [University Children' s Hospital, Pediatric Cardiology, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland); Scheer, Ianina [University Children' s Hospital, Department for Diagnostic Neuroradiology, Zurich (Switzerland); Rhein, Michael von [University Children' s Hospital, Child Development Center, Zurich (Switzerland); Reich, Bettina; Bauer, Juergen; Gummel, Kerstin [Justus-Liebig University, Pediatric Heart Center, University Hospital Giessen, Giessen (Germany); Roberts, Neil [University of Edinburgh, Clinical Research and Imaging Centre (CRIC), The Queens Medical Research Institute (QMRI), Edinburgh (United Kingdom); O' Gorman Tuura, Ruth [University Children' s Hospital of Zurich, Center for MR Research, Zurich (Switzerland); University Children' s Hospital, Children' s Research Center, Zurich (Switzerland)

2016-09-15

The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9-42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities. (orig.)

Comparison of automated brain volumetry methods with stereology in children aged 2 to 3 years

International Nuclear Information System (INIS)

Mayer, Kristina N.; Latal, Beatrice; Knirsch, Walter; Scheer, Ianina; Rhein, Michael von; Reich, Bettina; Bauer, Juergen; Gummel, Kerstin; Roberts, Neil; O'Gorman Tuura, Ruth

2016-01-01

The accurate and precise measurement of brain volumes in young children is important for early identification of children with reduced brain volumes and an increased risk for neurodevelopmental impairment. Brain volumes can be measured from cerebral MRI (cMRI), but most neuroimaging tools used for cerebral segmentation and volumetry were developed for use in adults and have not been validated in infants or young children. Here, we investigate the feasibility and accuracy of three automated software methods (i.e., SPM, FSL, and FreeSurfer) for brain volumetry in young children and compare the measures with corresponding volumes obtained using the Cavalieri method of modern design stereology. Cerebral MRI data were collected from 21 children with a complex congenital heart disease (CHD) before Fontan procedure, at a median age of 27 months (range 20.9-42.4 months). Data were segmented with SPM, FSL, and FreeSurfer, and total intracranial volume (ICV) and total brain volume (TBV) were compared with corresponding measures obtained using the Cavalieri method. Agreement between the estimated brain volumes (ICV and TBV) relative to the gold standard stereological volumes was strongest for FreeSurfer (p < 0.001) and moderate for SPM segment (ICV p = 0.05; TBV p = 0.006). No significant association was evident between ICV and TBV obtained using SPM NewSegment and FSL FAST and the corresponding stereological volumes. FreeSurfer provides an accurate method for measuring brain volumes in young children, even in the presence of structural brain abnormalities. (orig.)

Entanglement in mutually unbiased bases

Energy Technology Data Exchange (ETDEWEB)

Wiesniak, M; Zeilinger, A [Vienna Center for Quantum Science and Technology (VCQ), Faculty of Physics, University of Vienna, Boltzmanngasse 5, 1090 Vienna (Austria); Paterek, T, E-mail: tomasz.paterek@nus.edu.sg [Centre for Quantum Technologies, National University of Singapore, 3 Science Drive 2, 117543 Singapore (Singapore)

2011-05-15

One of the essential features of quantum mechanics is that most pairs of observables cannot be measured simultaneously. This phenomenon manifests itself most strongly when observables are related to mutually unbiased bases. In this paper, we shed some light on the connection between mutually unbiased bases and another essential feature of quantum mechanics, quantum entanglement. It is shown that a complete set of mutually unbiased bases of a bipartite system contains a fixed amount of entanglement, independent of the choice of the set. This has implications for entanglement distribution among the states of a complete set. In prime-squared dimensions we present an explicit experiment-friendly construction of a complete set with a particularly simple entanglement distribution. Finally, we describe the basic properties of mutually unbiased bases composed of product states only. The constructions are illustrated with explicit examples in low dimensions. We believe that the properties of entanglement in mutually unbiased bases may be one of the ingredients to be taken into account to settle the question of the existence of complete sets. We also expect that they will be relevant to applications of bases in the experimental realization of quantum protocols in higher-dimensional Hilbert spaces.

Stereology of human myometrium in pregnancy: influence of maternal body mass index and age.

LENUS (Irish Health Repository)

Sweeney, Eva M

2013-04-01

Knowledge of the stereology of human myometrium in pregnancy is limited. Uterine contractile performance may be altered in association with maternal obesity and advanced maternal age. The aim of this study was to investigate the stereology of human myometrium in pregnancy, and to evaluate a potential influence of maternal body mass index (BMI) and age.

Prediction of prognosis in patients with epidural hematoma by a new stereological method

International Nuclear Information System (INIS)

Kalkan, E.; Cander, B.; Gul, M.; Girisgin, S.; Karabagli, H.; Sahin, B.

2007-01-01

Epidural hematoma (EH) is a serious clinical event observed in 2% of head trauma patients. Studies regarding the effects of epidural hematoma volume (EHV) on prognosis are not sufficient. In this study, we applied the volume fraction approach of the stereological method to estimate the hematoma to brain volume fraction (HBVF), and investigated the relation between the HBVF and prognosis. Fifty-nine EH patients (46 male and 13 female subjects, with average age of 21 years) admitted to the emergency clinic were included. The HBVF was estimated on the printed films of cranial computed tomography scans. For this purpose, common point counting grids were superimposed over the scan frames. According to the clinical results, patients were divided into three groups as complete recovery (43), disability (8) and exitus (8). The HBVF was compared with the clinical results. HBVF was determined as 4.6% in the patients with recovery, 8.1% in disability, and 7.6% in exitus patients. The HBVF values were lowest in recovery patients, and the difference between the recovery and the other two groups was statistically significant (p=0.007). However, there was no statistically significant difference in HBVF between disability and exitus patients (p>0.05). In conclusion, the HBVF can be an important tool to determine prognosis, and it can be measured using the volume fraction approach of stereological methods as developed in the present study. (author)

Histological versus stereological methods applied at spermatogonia during normal human development

DEFF Research Database (Denmark)

Cortes, D

1990-01-01

The number of spermatogonia per tubular transverse section (S/T), and the percentage of seminiferous tubulus containing spermatogonia (the fertility index (FI] were measured in 40 pairs of normal autopsy testes aged 28 weeks of gestation-40 years. S/T and FI showed similar changes during the whole...... period, and were minimal between 1 and 4 years. The number of spermatogonia per testis (S/testis) and the number of spermatogonia per cm3 testis tissue (S/cm3) were estimated by stereological methods in the same testes. S/T and FI respectively were significantly correlated both to S/testis and S/cm3. So...

Empirical Bayes Estimation of Semi-parametric Hierarchical Mixture Models for Unbiased Characterization of Polygenic Disease Architectures

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Jo Nishino

2018-04-01

Full Text Available Genome-wide association studies (GWAS suggest that the genetic architecture of complex diseases consists of unexpectedly numerous variants with small effect sizes. However, the polygenic architectures of many diseases have not been well characterized due to lack of simple and fast methods for unbiased estimation of the underlying proportion of disease-associated variants and their effect-size distribution. Applying empirical Bayes estimation of semi-parametric hierarchical mixture models to GWAS summary statistics, we confirmed that schizophrenia was extremely polygenic [~40% of independent genome-wide SNPs are risk variants, most within odds ratio (OR = 1.03], whereas rheumatoid arthritis was less polygenic (~4 to 8% risk variants, significant portion reaching OR = 1.05 to 1.1. For rheumatoid arthritis, stratified estimations revealed that expression quantitative loci in blood explained large genetic variance, and low- and high-frequency derived alleles were prone to be risk and protective, respectively, suggesting a predominance of deleterious-risk and advantageous-protective mutations. Despite genetic correlation, effect-size distributions for schizophrenia and bipolar disorder differed across allele frequency. These analyses distinguished disease polygenic architectures and provided clues for etiological differences in complex diseases.

Stereology application in the investigation of physical and mechanical properties of porous materials

International Nuclear Information System (INIS)

Cytermann, Richard.

1979-04-01

The sintering of carbonyl nickel powders has been studied through stereology (quantitative microscopy) associated with different physical and mechanical measurements. This study demonstrated that a set of stereological parameters, such as porosity, grain size, mean pore volume ..., was necessary to characterize porous parts with the same porosity obtained through different ways. On the one hand, stereology permitted to elucidate powder shape and speed of pressure rising influence on the compacting process. On the other hand, the study of physical and mechanical properties related to their microstructure led to distinguish: properties such as elasticity modulus independant of compacting pressure, sintering temperature and powder shape. Their evolution has been characterized through contiguity coefficient; properties such as tensile strength dependant of sintering parameters. Their characterization required the simultaneous measurement of porosity mean pore volume, shape factor and grain size [fr

Quantitative analysis of the renal aging in rats. Stereological study.

Science.gov (United States)

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Light scattering in porous materials: Geometrical optics and stereological approach

International Nuclear Information System (INIS)

Malinka, Aleksey V.

2014-01-01

Porous material has been considered from the point of view of stereology (geometrical statistics), as a two-phase random mixture of solid material and air. Considered are the materials having the refractive index with the real part that differs notably from unit and the imaginary part much less than unit. Light scattering in such materials has been described using geometrical optics. These two – the geometrical optics laws and the stereological approach – allow one to obtain the inherent optical properties of such a porous material, which are basic in the radiative transfer theory: the photon survival probability, the scattering phase function, and the polarization properties (Mueller matrix). In this work these characteristics are expressed through the refractive index of the material and the random chord length distribution. The obtained results are compared with the traditional approach, modeling the porous material as a pack of particles of different shapes. - Highlights: • Porous material has been considered from the point of view of stereology. • Properties of a two-phase random mixture of solid material and air are considered. • Light scattering in such materials has been described using geometrical optics. • The inherent optical properties of such a porous material have been obtained

Stereological estimation of ovarian volume and number of follicles in low dose of Vitex agnus castus treated mice

OpenAIRE

HAMIDIAN, Gholamreza; YAHYAVI, Fariba

2014-01-01

Vitex agnus castus (VAC) has been proven to have a wide range of biological activities. It is commonly used in the treatment of menstrual disorders resulting from corpus luteum deficiency, including premenstrual symptoms and spasmodic dysmenorrheal, for certain menopausal conditions, and for insufficient lactation. The aim of this study was to investigate the effects of low dose of VAC essential oil on ovarian volume and oocyte number in mice by stereological technique. In this study 10 young...

Assessment of in vivo MR imaging compared to physical sections in vitro-A quantitative study of brain volumes using stereology

DEFF Research Database (Denmark)

Jelsing, Jacob; Rostrup, Egill; Markenroth, Karin

2005-01-01

The object of the present study was to compare stereological estimates of brain volumes obtained in vivo by magnetic resonance imaging (MRI) to corresponding volumes from physical sections in vitro. Brains of ten domestic pigs were imaged using a 3-T scanner. The volumes of different brain....... However, although intraobserver difference of MRI estimates was acceptable, the interobserver difference was not. A statistical highly significant difference of 11-41% was observed between observers for volume estimates of all compartments considered. The study demonstrates that quantitative MRI...

Confocal stereology and image analysis: methods for estimating geometrical characteristics of cells and tissues from three-dimensional confocal images

Czech Academy of Sciences Publication Activity Database

Kubínová, Lucie; Janáček, Jiří; Karen, Petr; Radochová, Barbora; Difato, Francesco; Krekule, Ivan

2004-01-01

Roč. 53, Suppl.1 (2004), s. S47-S55 ISSN 0862-8408 R&D Projects: GA ČR GA304/01/0257; GA ČR GA310/02/1470; GA AV ČR KJB6011309; GA AV ČR KJB5039302 Grant - others:SI - CZ(CZ) KONTAKT 001/2001 Institutional research plan: CEZ:AV0Z5011922 Keywords : confocal microscopy * image analysis * stereology Subject RIV: EA - Cell Biology Impact factor: 1.140, year: 2004

Decreased Volume of the Cerebral Ventricles on CT Images in Gilles de la Tourette’s Syndrome

Directory of Open Access Journals (Sweden)

Lisbeth Regeur

1999-01-01

Full Text Available The aim of the present study was to estimate the volume of the ventricular system comprising lateral plus third ventricles in patients with Gilles de la Tourette's syndrome on computed tomographic (CT scannings using unbiased stereological principles and to compare that volume with a control group. We found a significantly reduced ventricular volume in 24 patients with Gilles de la Tourette's syndrome (GTS compared with 28 controls.

Stereological Cell Morphometry In Right Atrium Myocardium Of Primates

Science.gov (United States)

Mandarim-De-Lacerda, Carlos A...; Hureau, Jacques

1986-07-01

The mechanism by which the cardiac impulse is propagated in normal hearts from its origin in the sinus node to the atrio-ventricular node has not been agreed on fully. We studied the "internodal posterior tract" through the crista terminalis by light microscopy and stereological morphometry. The hearts of 12 Papio cynocephalus were perfused , after sacrifice,with phosphate-buffered formol saline. The regions of the crista terminalis (CT), interatrial septum (IAS), atrioventricular bundle (AVB) and interventricular septum (IVS) were cut off and embedded in paraplast and sectioned (10 4m). The multipurpose test system M 42 was superimposed over the photomicrographs (1,890 points test, ESR = 2%) to the stereological computing. The quantitative results show that the cells from CT were more closely relationed with IAS cells than others cells (IVS and AVB cells). This results are not a morphological evidence to establish the specificity of the "internodal posterior tract". The cellular arrangement and anatomical variation in CT myocardium is very important.

Digital immunohistochemistry wizard: image analysis-assisted stereology tool to produce reference data set for calibration and quality control.

Science.gov (United States)

Plancoulaine, Benoît; Laurinaviciene, Aida; Meskauskas, Raimundas; Baltrusaityte, Indra; Besusparis, Justinas; Herlin, Paulette; Laurinavicius, Arvydas

2014-01-01

Digital image analysis (DIA) enables better reproducibility of immunohistochemistry (IHC) studies. Nevertheless, accuracy of the DIA methods needs to be ensured, demanding production of reference data sets. We have reported on methodology to calibrate DIA for Ki67 IHC in breast cancer tissue based on reference data obtained by stereology grid count. To produce the reference data more efficiently, we propose digital IHC wizard generating initial cell marks to be verified by experts. Digital images of proliferation marker Ki67 IHC from 158 patients (one tissue microarray spot per patient) with an invasive ductal carcinoma of the breast were used. Manual data (mD) were obtained by marking Ki67-positive and negative tumour cells, using a stereological method for 2D object enumeration. DIA was used as an initial step in stereology grid count to generate the digital data (dD) marks by Aperio Genie and Nuclear algorithms. The dD were collected into XML files from the DIA markup images and overlaid on the original spots along with the stereology grid. The expert correction of the dD marks resulted in corrected data (cD). The percentages of Ki67 positive tumour cells per spot in the mD, dD, and cD sets were compared by single linear regression analysis. Efficiency of cD production was estimated based on manual editing effort. The percentage of Ki67-positive tumor cells was in very good agreement in the mD, dD, and cD sets: regression of cD from dD (R2=0.92) reflects the impact of the expert editing the dD as well as accuracy of the DIA used; regression of the cD from the mD (R2=0.94) represents the consistency of the DIA-assisted ground truth (cD) with the manual procedure. Nevertheless, the accuracy of detection of individual tumour cells was much lower: in average, 18 and 219 marks per spot were edited due to the Genie and Nuclear algorithm errors, respectively. The DIA-assisted cD production in our experiment saved approximately 2/3 of manual marking. Digital IHC wizard

First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.

Science.gov (United States)

Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied

2016-11-01

Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (pcartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.

A simple and efficient alternative to implementing systematic random sampling in stereological designs without a motorized microscope stage.

Science.gov (United States)

Melvin, Neal R; Poda, Daniel; Sutherland, Robert J

2007-10-01

When properly applied, stereology is a very robust and efficient method to quantify a variety of parameters from biological material. A common sampling strategy in stereology is systematic random sampling, which involves choosing a random sampling [corrected] start point outside the structure of interest, and sampling relevant objects at [corrected] sites that are placed at pre-determined, equidistant intervals. This has proven to be a very efficient sampling strategy, and is used widely in stereological designs. At the microscopic level, this is most often achieved through the use of a motorized stage that facilitates the systematic random stepping across the structure of interest. Here, we report a simple, precise and cost-effective software-based alternative to accomplishing systematic random sampling under the microscope. We believe that this approach will facilitate the use of stereological designs that employ systematic random sampling in laboratories that lack the resources to acquire costly, fully automated systems.

Stereological brain volume changes in post-weaned socially isolated rats

DEFF Research Database (Denmark)

Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

2010-01-01

Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... have evaluated the neuroanatomical changes in this animal model in comparison to changes seen in schizophrenia. In this study, we applied stereological volume estimates to evaluate the total brain, the ventricular system, and the pyramidal and granular cell layers of the hippocampus in male and female...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

UTILIZATION OF STEREOLOGY FOR QUANTITATIVE ANALYSIS OF PLASTIC DEFORMATION OF FORMING PIECES

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Maroš Martinkovič

2012-01-01

Full Text Available Mechanical working leads to final properties of forming pieces, which are affected by conditions of production technology. Utilization of stereology leads to the detail analysis of three-dimensional plastic deformed material structure by different forming technologies, e.g. forging, extruding, upsetting, metal spinning, drawing etc. The microstructure of cold drawing wires was analyzed. Grain boundaries orientation was measured on the parallel section of wire with a different degree of deformation and direct axis plastic deformation was evaluated in bulk formed part. The strain of probes on their sections was obtained using stereology by measurement of degree of grain boundary orientation which was converted to deformation using model of conversion of grain boundary orientation degree to deformation.

Mutually unbiased bases and semi-definite programming

Energy Technology Data Exchange (ETDEWEB)

Brierley, Stephen; Weigert, Stefan, E-mail: steve.brierley@ulb.ac.be, E-mail: stefan.weigert@york.ac.uk

2010-11-01

A complex Hilbert space of dimension six supports at least three but not more than seven mutually unbiased bases. Two computer-aided analytical methods to tighten these bounds are reviewed, based on a discretization of parameter space and on Groebner bases. A third algorithmic approach is presented: the non-existence of more than three mutually unbiased bases in composite dimensions can be decided by a global optimization method known as semidefinite programming. The method is used to confirm that the spectral matrix cannot be part of a complete set of seven mutually unbiased bases in dimension six.

Mutually unbiased bases and semi-definite programming

International Nuclear Information System (INIS)

Brierley, Stephen; Weigert, Stefan

2010-01-01

A complex Hilbert space of dimension six supports at least three but not more than seven mutually unbiased bases. Two computer-aided analytical methods to tighten these bounds are reviewed, based on a discretization of parameter space and on Groebner bases. A third algorithmic approach is presented: the non-existence of more than three mutually unbiased bases in composite dimensions can be decided by a global optimization method known as semidefinite programming. The method is used to confirm that the spectral matrix cannot be part of a complete set of seven mutually unbiased bases in dimension six.

Triangulation based inclusion probabilities: a design-unbiased sampling approach

OpenAIRE

Fehrmann, Lutz; Gregoire, Timothy; Kleinn, Christoph

2011-01-01

A probabilistic sampling approach for design-unbiased estimation of area-related quantitative characteristics of spatially dispersed population units is proposed. The developed field protocol includes a fixed number of 3 units per sampling location and is based on partial triangulations over their natural neighbors to derive the individual inclusion probabilities. The performance of the proposed design is tested in comparison to fixed area sample plots in a simulation with two forest stands. ...

Losing the rose tinted glasses: neural substrates of unbiased belief updating in depression

Directory of Open Access Journals (Sweden)

Neil eGarrett

2014-08-01

Full Text Available Recent evidence suggests that a state of good mental health is associated with biased processing of information that supports a positively skewed view of the future. Depression, on the other hand, is associated with unbiased processing of such information. Here, we use brain imaging in conjunction with a belief update task administered to clinically depressed patients and healthy controls to characterize brain activity that supports unbiased belief updating in clinically depressed individuals. Our results reveal that unbiased belief updating in depression is mediated by strong neural coding of estimation errors in response to both good news (in left inferior frontal gyrus and bilateral superior frontal gyrus and bad news (in right inferior parietal lobule and right inferior frontal gyrus regarding the future. In contrast, intact mental health was linked to a relatively attenuated neural coding of bad news about the future. These findings identify a neural substrate mediating the breakdown of biased updating in Major Depression Disorder, which may be essential for mental health.

Confocal stereology: an efficient tool for measurement of microscopic structures

Czech Academy of Sciences Publication Activity Database

Kubínová, Lucie; Janáček, Jiří

2015-01-01

Roč. 360, č. 1 (2015), s. 13-28 ISSN 0302-766X R&D Projects: GA MŠk(CZ) LH13028 Institutional support: RVO:67985823 Keywords : 3-D images * confocal microscopy * geometrical characteristics * spatial probes * stereology Subject RIV: EA - Cell Biology Impact factor: 2.948, year: 2015

Estimating Unbiased Treatment Effects in Education Using a Regression Discontinuity Design

Directory of Open Access Journals (Sweden)

William C. Smith

2014-08-01

Full Text Available The ability of regression discontinuity (RD designs to provide an unbiased treatment effect while overcoming the ethical concerns plagued by Random Control Trials (RCTs make it a valuable and useful approach in education evaluation. RD is the only explicitly recognized quasi-experimental approach identified by the Institute of Education Statistics to meet the prerequisites of a causal relationship. Unfortunately, the statistical complexity of the RD design has limited its application in education research. This article provides a less technical introduction to RD for education researchers and practitioners. Using visual analysis to aide conceptual understanding, the article walks readers through the essential steps of a Sharp RD design using hypothetical, but realistic, district intervention data and provides additional resources for further exploration.

CONDITIONS FOR EXACT CAVALIERI ESTIMATION

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Mónica Tinajero-Bravo

2014-03-01

Full Text Available Exact Cavalieri estimation amounts to zero variance estimation of an integral with systematic observations along a sampling axis. A sufficient condition is given, both in the continuous and the discrete cases, for exact Cavalieri sampling. The conclusions suggest improvements on the current stereological application of fractionator-type sampling.

STEREOLOGICAL QUANTITATION OF LEYDIG AND SERTOLI CELLS IN THE TESTIS FROM YOUNG AND OLD MEN

Directory of Open Access Journals (Sweden)

Peter M Petersen

2011-05-01

Full Text Available One of the newer stereological methods, the optical fractionator, was applied to the study of the effects of ageing on the human testis. The estimated total number of Sertoli and Leydig cells per testis in men younger than 30 years were 430×106 (CV = SD/mean = 0.35 and 117×106 (CV = 0.53, respectively, while in men older than 50 years the estimated total Sertoli cell number was 266×106 (CV = 0.46 and the mean Leydig cell number 83×106 (CV = 0.53. The difference between the number of Sertoli cells in men younger than 30 years compared with men older than 50 years was close to statistical significance (p = 0.052 while no differences was found in total Leydig cell number (p = 0.22.

Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. II. Stereologic and histologic observations in cynomolgus monkeys

DEFF Research Database (Denmark)

Schou, Søren; Holmstrup, Palle; Skovgaard, Lene Theil

2003-01-01

autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment......autogenous bone graft; guided bone regeneration; histology; membrane; non-human primates; oral implants; osseointegration; pathalogy; peri-implantitis; stereology; treatment...

Stereological study of postnatal development in the mouse utricular macula

DEFF Research Database (Denmark)

Kirkegaard, Mette; Nyengaard, Jens Randel

2005-01-01

This study describes the morphometric changes taking place in the utricular macula of mice with ages in geometric progression from 1 to 512 days after birth. By using design-based stereological methods, the total volume and surface area of the sensory epithelium as well the total number of the ha...

Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex.

Directory of Open Access Journals (Sweden)

María García-Amado

Full Text Available Cell number alterations in the amygdaloid complex (AC might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL, corticomedial and central groups, 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3 and mean cell numbers (x10(6 were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.

Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex.

Science.gov (United States)

García-Amado, María; Prensa, Lucía

2012-01-01

Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.

Mutually unbiased bases

Indian Academy of Sciences (India)

Mutually unbiased bases play an important role in quantum cryptography [2] and in the optimal determination of the density operator of an ensemble [3,4]. A density operator ρ in N-dimensions depends on N2 1 real quantities. With the help of MUB's, any such density operator can be encoded, in an optimal way, in terms of ...

Markovian description of unbiased polymer translocation

International Nuclear Information System (INIS)

Mondaini, Felipe; Moriconi, L.

2012-01-01

We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

Markovian description of unbiased polymer translocation

Energy Technology Data Exchange (ETDEWEB)

Mondaini, Felipe [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil); Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, UnED Angra dos Reis, Angra dos Reis, 23953-030, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil)

2012-10-01

We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

Quantifying Golgi structure using EM: combining volume-SEM and stereology for higher throughput.

Science.gov (United States)

Ferguson, Sophie; Steyer, Anna M; Mayhew, Terry M; Schwab, Yannick; Lucocq, John Milton

2017-06-01

Investigating organelles such as the Golgi complex depends increasingly on high-throughput quantitative morphological analyses from multiple experimental or genetic conditions. Light microscopy (LM) has been an effective tool for screening but fails to reveal fine details of Golgi structures such as vesicles, tubules and cisternae. Electron microscopy (EM) has sufficient resolution but traditional transmission EM (TEM) methods are slow and inefficient. Newer volume scanning EM (volume-SEM) methods now have the potential to speed up 3D analysis by automated sectioning and imaging. However, they produce large arrays of sections and/or images, which require labour-intensive 3D reconstruction for quantitation on limited cell numbers. Here, we show that the information storage, digital waste and workload involved in using volume-SEM can be reduced substantially using sampling-based stereology. Using the Golgi as an example, we describe how Golgi populations can be sensed quantitatively using single random slices and how accurate quantitative structural data on Golgi organelles of individual cells can be obtained using only 5-10 sections/images taken from a volume-SEM series (thereby sensing population parameters and cell-cell variability). The approach will be useful in techniques such as correlative LM and EM (CLEM) where small samples of cells are treated and where there may be variable responses. For Golgi study, we outline a series of stereological estimators that are suited to these analyses and suggest workflows, which have the potential to enhance the speed and relevance of data acquisition in volume-SEM.

A comparison of porosity analysis using 2D stereology estimates and 3D serial sectioning for additively manufactured Ti 6Al 2Sn 4Zr 2Mo alloy

International Nuclear Information System (INIS)

Ganti, Satya R.; Velez, Michael A.; Geier, Brian A.; Hayes, Brian J.; Turner, Bryan J.; Jenkins, Elizabeth J.

2017-01-01

Porosity is a typical defect in additively manufactured (AM) parts. Such defects limit the properties and performance of AM parts, and therefore need to be characterized accurately. Current methods for characterization of defects and microstructure rely on classical stereological methods that extrapolate information from two dimensional images. The automation of serial sectioning provides an opportunity to precisely and accurately quantify porosity in three dimensions in materials. In this work, we analyzed the porosity of an additively manufactured Ti 6Al 2Sn 4Zr 2Mo sample using Robo-Met.3D "r"e"g"i"s"t"e"r"e"d, an automated serial sectioning system. Image processing for three dimensional reconstruction of the serial-sectioned two dimensional images was performed using open source image analysis software (Fiji/ImageJ, Dream.3D, Paraview). The results from this 3D serial sectioning analysis were then compared to classical 2D stereological methods (Saltykov stereological theory). We found that for this dataset, the classical 2D methods underestimated the porosity size and distributions of the larger pores; a critical attribute to fatigue behavior of the AM part. The results suggest that acquiring experimental data with equipment such as Robo-Met.3D "r"e"g"i"s"t"e"r"e"d to measure the number and size of particles such as pores in a volume irrespective of knowing their shape is a better choice.

Within-subject template estimation for unbiased longitudinal image analysis.

Science.gov (United States)

Reuter, Martin; Schmansky, Nicholas J; Rosas, H Diana; Fischl, Bruce

2012-07-16

Longitudinal image analysis has become increasingly important in clinical studies of normal aging and neurodegenerative disorders. Furthermore, there is a growing appreciation of the potential utility of longitudinally acquired structural images and reliable image processing to evaluate disease modifying therapies. Challenges have been related to the variability that is inherent in the available cross-sectional processing tools, to the introduction of bias in longitudinal processing and to potential over-regularization. In this paper we introduce a novel longitudinal image processing framework, based on unbiased, robust, within-subject template creation, for automatic surface reconstruction and segmentation of brain MRI of arbitrarily many time points. We demonstrate that it is essential to treat all input images exactly the same as removing only interpolation asymmetries is not sufficient to remove processing bias. We successfully reduce variability and avoid over-regularization by initializing the processing in each time point with common information from the subject template. The presented results show a significant increase in precision and discrimination power while preserving the ability to detect large anatomical deviations; as such they hold great potential in clinical applications, e.g. allowing for smaller sample sizes or shorter trials to establish disease specific biomarkers or to quantify drug effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of quantitative estimation of intracerebral hemorrhage and infarct volumes after thromboembolism in an embolic stroke model

DEFF Research Database (Denmark)

Eriksen, Nina; Rasmussen, Rune Skovgaard; Overgaard, Karsten

2014-01-01

. Group 1 was treated with saline, and group 2 was treated with 20 mg/kg recombinant tissue plasminogen activator to promote intracerebral hemorrhages. Stereology, semiautomated computer estimation, and manual erythrocyte counting were used to test the precision and efficiency of determining the size...... measurements, the stereological method was the most efficient and advantageous. CONCLUSIONS: We found that stereology was the superior method for quantification of hemorrhagic volume, especially for rodent petechial bleeding, which is otherwise difficult to measure. Our results suggest the possibility...

AUTOMATIC ESTIMATION OF SIZE PARAMETERS USING VERIFIED COMPUTERIZED STEREOANALYSIS

Directory of Open Access Journals (Sweden)

Peter R Mouton

2011-05-01

Full Text Available State-of-the-art computerized stereology systems combine high-resolution video microscopy and hardwaresoftware integration with stereological methods to assist users in quantifying multidimensional parameters of importance to biomedical research, including volume, surface area, length, number, their variation and spatial distribution. The requirement for constant interactions between a trained, non-expert user and the targeted features of interest currently limits the throughput efficiency of these systems. To address this issue we developed a novel approach for automatic stereological analysis of 2-D images, Verified Computerized Stereoanalysis (VCS. The VCS approach minimizes the need for user interactions with high contrast [high signal-to-noise ratio (S:N] biological objects of interest. Performance testing of the VCS approach confirmed dramatic increases in the efficiency of total object volume (size estimation, without a loss of accuracy or precision compared to conventional computerized stereology. The broad application of high efficiency VCS to high-contrast biological objects on tissue sections could reduce labor costs, enhance hypothesis testing, and accelerate the progress of biomedical research focused on improvements in health and the management of disease.

Unbiased Sampling and Meshing of Isosurfaces

KAUST Repository

Yan, Dongming

2014-05-07

In this paper, we present a new technique to generate unbiased samples on isosurfaces. An isosurface, F(x,y,z) = c , of a function, F , is implicitly defined by trilinear interpolation of background grid points. The key idea of our approach is that of treating the isosurface within a grid cell as a graph (height) function in one of the three coordinate axis directions, restricted to where the slope is not too high, and integrating / sampling from each of these three. We use this unbiased sampling algorithm for applications in Monte Carlo integration, Poisson-disk sampling, and isosurface meshing.

Unbiased Sampling and Meshing of Isosurfaces

KAUST Repository

Yan, Dongming; Wallner, Johannes; Wonka, Peter

2014-01-01

In this paper, we present a new technique to generate unbiased samples on isosurfaces. An isosurface, F(x,y,z) = c , of a function, F , is implicitly defined by trilinear interpolation of background grid points. The key idea of our approach is that of treating the isosurface within a grid cell as a graph (height) function in one of the three coordinate axis directions, restricted to where the slope is not too high, and integrating / sampling from each of these three. We use this unbiased sampling algorithm for applications in Monte Carlo integration, Poisson-disk sampling, and isosurface meshing.

Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

DEFF Research Database (Denmark)

Ellingsen, A R; Sørensen, F B; Larsen, Jytte Overgaard

2001-01-01

with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared......Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin...... with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically...

The total number of Leydig and Sertoli cells in the testes of men across various age groups - a stereological study

DEFF Research Database (Denmark)

Petersen, Peter M; Seierøe, Karina; Pakkenberg, Bente

2015-01-01

is particularly sensitive to methodological problems. Therefore, using the optical fractionator technique and a sampling design specifically optimized for human testes, we estimated the total number of Sertoli and Leydig cells in the testes from 26 post mortem male subjects ranging in age from 16 to 80 years...... of Sertoli cells with age; no such decline was found for Leydig cells. Quantitative stereological analysis of post mortem tissue may help understand the influence of age or disease on the number of human testicular cells....

Personalized recommendation based on unbiased consistence

Science.gov (United States)

Zhu, Xuzhen; Tian, Hui; Zhang, Ping; Hu, Zheng; Zhou, Tao

2015-08-01

Recently, in physical dynamics, mass-diffusion-based recommendation algorithms on bipartite network provide an efficient solution by automatically pushing possible relevant items to users according to their past preferences. However, traditional mass-diffusion-based algorithms just focus on unidirectional mass diffusion from objects having been collected to those which should be recommended, resulting in a biased causal similarity estimation and not-so-good performance. In this letter, we argue that in many cases, a user's interests are stable, and thus bidirectional mass diffusion abilities, no matter originated from objects having been collected or from those which should be recommended, should be consistently powerful, showing unbiased consistence. We further propose a consistence-based mass diffusion algorithm via bidirectional diffusion against biased causality, outperforming the state-of-the-art recommendation algorithms in disparate real data sets, including Netflix, MovieLens, Amazon and Rate Your Music.

Practicable methods for histological section thickness measurement in quantitative stereological analyses.

Science.gov (United States)

Matenaers, Cyrill; Popper, Bastian; Rieger, Alexandra; Wanke, Rüdiger; Blutke, Andreas

2018-01-01

of SR to efficiently provide accurate section thickness measurements as a prerequisite for reliable estimates of dependent quantitative stereological parameters.

Surface tensor estimation from linear sections

DEFF Research Database (Denmark)

Kousholt, Astrid; Kiderlen, Markus; Hug, Daniel

From Crofton's formula for Minkowski tensors we derive stereological estimators of translation invariant surface tensors of convex bodies in the n-dimensional Euclidean space. The estimators are based on one-dimensional linear sections. In a design based setting we suggest three types of estimators....... These are based on isotropic uniform random lines, vertical sections, and non-isotropic random lines, respectively. Further, we derive estimators of the specific surface tensors associated with a stationary process of convex particles in the model based setting....

Surface tensor estimation from linear sections

DEFF Research Database (Denmark)

Kousholt, Astrid; Kiderlen, Markus; Hug, Daniel

2015-01-01

From Crofton’s formula for Minkowski tensors we derive stereological estimators of translation invariant surface tensors of convex bodies in the n-dimensional Euclidean space. The estimators are based on one-dimensional linear sections. In a design based setting we suggest three types of estimators....... These are based on isotropic uniform random lines, vertical sections, and non-isotropic random lines, respectively. Further, we derive estimators of the specific surface tensors associated with a stationary process of convex particles in the model based setting....

Quantum process reconstruction based on mutually unbiased basis

International Nuclear Information System (INIS)

Fernandez-Perez, A.; Saavedra, C.; Klimov, A. B.

2011-01-01

We study a quantum process reconstruction based on the use of mutually unbiased projectors (MUB projectors) as input states for a D-dimensional quantum system, with D being a power of a prime number. This approach connects the results of quantum-state tomography using mutually unbiased bases with the coefficients of a quantum process, expanded in terms of MUB projectors. We also study the performance of the reconstruction scheme against random errors when measuring probabilities at the MUB projectors.

Estimation of the simple correlation coefficient.

Science.gov (United States)

Shieh, Gwowen

2010-11-01

This article investigates some unfamiliar properties of the Pearson product-moment correlation coefficient for the estimation of simple correlation coefficient. Although Pearson's r is biased, except for limited situations, and the minimum variance unbiased estimator has been proposed in the literature, researchers routinely employ the sample correlation coefficient in their practical applications, because of its simplicity and popularity. In order to support such practice, this study examines the mean squared errors of r and several prominent formulas. The results reveal specific situations in which the sample correlation coefficient performs better than the unbiased and nearly unbiased estimators, facilitating recommendation of r as an effect size index for the strength of linear association between two variables. In addition, related issues of estimating the squared simple correlation coefficient are also considered.

The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

Science.gov (United States)

Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

2014-12-01

To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

DEFF Research Database (Denmark)

Ladekarl, M; Sørensen, Flemming Brandt

1993-01-01

This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI......) with those obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ...

Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

DEFF Research Database (Denmark)

Ladekarl, M; Sørensen, Flemming Brandt

1993-01-01

This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI...... obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ lesions...

Communication among neurons.

Science.gov (United States)

Marner, Lisbeth

2012-04-01

The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

Evaluation of FITC-induced atopic dermatitis-like disease in NC/Nga mice and BALB/c mice using computer-assisted stereological toolbox, a computer-aided morphometric system

DEFF Research Database (Denmark)

Hvid, Malene; Jensen, Helene Kofoed; Deleuran, Bent

2009-01-01

Stereological Toolbox as a stereological method, the mice were sensitized to FITC and the histological efficiency of disease induction with regard to inflammation and CD4+ and CD8+ lymphocytes, in addition to mast cells, was evaluated. The method was validated by comparison to a conventional semiquantitative...

The influence of SO4 and NO3 to the acidity (pH) of rainwater using minimum variance quadratic unbiased estimation (MIVQUE) and maximum likelihood methods

Science.gov (United States)

Dilla, Shintia Ulfa; Andriyana, Yudhie; Sudartianto

2017-03-01

Acid rain causes many bad effects in life. It is formed by two strong acids, sulfuric acid (H2SO4) and nitric acid (HNO3), where sulfuric acid is derived from SO2 and nitric acid from NOx {x=1,2}. The purpose of the research is to find out the influence of So4 and NO3 levels contained in the rain to the acidity (pH) of rainwater. The data are incomplete panel data with two-way error component model. The panel data is a collection of some of the observations that observed from time to time. It is said incomplete if each individual has a different amount of observation. The model used in this research is in the form of random effects model (REM). Minimum variance quadratic unbiased estimation (MIVQUE) is used to estimate the variance error components, while maximum likelihood estimation is used to estimate the parameters. As a result, we obtain the following model: Ŷ* = 0.41276446 - 0.00107302X1 + 0.00215470X2.

Unbiased diffusion of Brownian particles on disordered correlated potentials

International Nuclear Information System (INIS)

Salgado-Garcia, Raúl; Maldonado, Cesar

2015-01-01

In this work we study the diffusion of non-interacting overdamped particles, moving on unbiased disordered correlated potentials, subjected to Gaussian white noise. We obtain an exact expression for the diffusion coefficient which allows us to prove that the unbiased diffusion of overdamped particles on a random polymer does not depend on the correlations of the disordered potentials. This universal behavior of the unbiased diffusivity is a direct consequence of the validity of the Einstein relation and the decay of correlations of the random polymer. We test the independence on correlations of the diffusion coefficient for correlated polymers produced by two different stochastic processes, a one-step Markov chain and the expansion-modification system. Within the accuracy of our simulations, we found that the numerically obtained diffusion coefficient for these systems agree with the analytically calculated ones, confirming our predictions. (paper)

Unbiased contaminant removal for 3D galaxy power spectrum measurements

Science.gov (United States)

Kalus, B.; Percival, W. J.; Bacon, D. J.; Samushia, L.

2016-11-01

We assess and develop techniques to remove contaminants when calculating the 3D galaxy power spectrum. We separate the process into three separate stages: (I) removing the contaminant signal, (II) estimating the uncontaminated cosmological power spectrum and (III) debiasing the resulting estimates. For (I), we show that removing the best-fitting contaminant (mode subtraction) and setting the contaminated components of the covariance to be infinite (mode deprojection) are mathematically equivalent. For (II), performing a quadratic maximum likelihood (QML) estimate after mode deprojection gives an optimal unbiased solution, although it requires the manipulation of large N_mode^2 matrices (Nmode being the total number of modes), which is unfeasible for recent 3D galaxy surveys. Measuring a binned average of the modes for (II) as proposed by Feldman, Kaiser & Peacock (FKP) is faster and simpler, but is sub-optimal and gives rise to a biased solution. We present a method to debias the resulting FKP measurements that does not require any large matrix calculations. We argue that the sub-optimality of the FKP estimator compared with the QML estimator, caused by contaminants, is less severe than that commonly ignored due to the survey window.

An Unbiased Unscented Transform Based Kalman Filter for 3D Radar

Institute of Scientific and Technical Information of China (English)

WANGGuohong; XIUJianjuan; HEYou

2004-01-01

As a derivative-free alternative to the Extended Kalman filter (EKF) in the framework of state estimation, the Unscented Kalman filter (UKF) has potential applications in nonlinear filtering. By noting the fact that the unscented transform is generally biased when converting the radar measurements from spherical coordinates into Cartesian coordinates, a new filtering algorithm for 3D radar, called Unbiased unscented Kalman filter (UUKF), is proposed. The new algorithm is validated by Monte Carlo simulation runs. Simulation results show that the UUKF is more effective than the UKF, EKF and the Converted measurement Kalman filter (CMKF).

No correlation between ultrasound placental grading at 31-34 weeks of gestation and a surrogate estimate of organ function at term obtained by stereological analysis.

Science.gov (United States)

Yin, T T; Loughna, P; Ong, S S; Padfield, J; Mayhew, T M

2009-08-01

We test the experimental hypothesis that early changes in the ultrasound appearance of the placenta reflect poor or reduced placental function. The sonographic (Grannum) grade of placental maturity was compared to placental function as expressed by the morphometric oxygen diffusive conductance of the villous membrane. Ultrasonography was used to assess the Grannum grade of 32 placentas at 31-34 weeks of gestation. Indications for the scans included a history of previous fetal abnormalities, previous fetal growth problems or suspicion of IUGR. Placentas were classified from grade 0 (most immature) to grade III (most mature). We did not exclude smokers or complicated pregnancies as we aimed to correlate the early appearance of mature placentas with placental function. After delivery, microscopical fields on formalin-fixed, trichrome-stained histological sections of each placenta were obtained by multistage systematic uniform random sampling. Using design-based stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal surface of villous trophoblast to adluminal surface of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, were derived secondarily as were estimates of the mean diameters and total lengths of villi and fetal capillaries. Group comparisons were drawn using analysis of variance. We found no significant differences in placental volume or composition or in the dimensions or diffusive conductances of the villous membrane. Subsequent exclusion of smokers did not alter these main findings. Grannum grades at 31-34 weeks of gestation appear not to provide reliable predictors of the functional capacity of the term placenta as expressed by the surrogate measure, morphometric diffusive conductance.

Stereologic estimation of nucleolar volume in ocular melanoma

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Gamel, J W; McCurdy, J

1993-01-01

The aim of this study was to investigate the relationships between one-, two-, and three-dimensional histomorphometric estimators of nucleolar size in ordinary histologic sections of uveal melanomas from 144 patients. In addition, the prognostic value of the various size parameters was studied. T...

Unbiased tensor-based morphometry: improved robustness and sample size estimates for Alzheimer's disease clinical trials.

Science.gov (United States)

Hua, Xue; Hibar, Derrek P; Ching, Christopher R K; Boyle, Christina P; Rajagopalan, Priya; Gutman, Boris A; Leow, Alex D; Toga, Arthur W; Jack, Clifford R; Harvey, Danielle; Weiner, Michael W; Thompson, Paul M

2013-02-01

Various neuroimaging measures are being evaluated for tracking Alzheimer's disease (AD) progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated. Here we analyzed the full MRI dataset from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) and assessed several sources of bias that can arise when tracking brain changes with structural brain imaging methods, as part of a pipeline for tensor-based morphometry (TBM). In all healthy subjects who completed MRI scanning at screening, 6, 12, and 24months, brain atrophy was essentially linear with no detectable bias in longitudinal measures. In power analyses for clinical trials based on these change measures, only 39AD patients and 95 mild cognitive impairment (MCI) subjects were needed for a 24-month trial to detect a 25% reduction in the average rate of change using a two-sided test (α=0.05, power=80%). Further sample size reductions were achieved by stratifying the data into Apolipoprotein E (ApoE) ε4 carriers versus non-carriers. We show how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI. Copyright © 2012 Elsevier Inc. All rights reserved.

Some new, simple and efficient stereological methods and their use in pathological research and diagnosis

DEFF Research Database (Denmark)

Gundersen, H J; Bendtsen, T F; Korbo, L

1988-01-01

Stereology is a set of simple and efficient methods for quantitation of three-dimensional microscopic structures which is specifically tuned to provide reliable data from sections. Within the last few years, a number of new methods has been developed which are of special interest to pathologists...... are invariably simple and easy....

ON ESTIMATION AND HYPOTHESIS TESTING OF THE GRAIN SIZE DISTRIBUTION BY THE SALTYKOV METHOD

Directory of Open Access Journals (Sweden)

Yuri Gulbin

2011-05-01

Full Text Available The paper considers the problem of validity of unfolding the grain size distribution with the back-substitution method. Due to the ill-conditioned nature of unfolding matrices, it is necessary to evaluate the accuracy and precision of parameter estimation and to verify the possibility of expected grain size distribution testing on the basis of intersection size histogram data. In order to review these questions, the computer modeling was used to compare size distributions obtained stereologically with those possessed by three-dimensional model aggregates of grains with a specified shape and random size. Results of simulations are reported and ways of improving the conventional stereological techniques are suggested. It is shown that new improvements in estimating and testing procedures enable grain size distributions to be unfolded more efficiently.

Using the Optical Fractionator to Estimate Total Cell Numbers in the Normal and Abnormal Developing Human Forebrain

DEFF Research Database (Denmark)

Larsen, Karen B

2017-01-01

abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples...

No postnatal doubling of number of neurons in human Broca's areas (Brodmann areas 44 and 45)? A stereological study.

Science.gov (United States)

Uylings, H B M; Malofeeva, L I; Bogolepova, I N; Jacobsen, A M; Amunts, K; Zilles, K

2005-01-01

In this study we explored whether a postnatal doubling of the total number of neurons occurs in the human Brodmann areas 44 and 45 (Broca's area). We describe the most recent error prediction formulae and their application for the modern stereological estimators for volume and number of neurons. We estimated the number of neurons in 3D optical disector probes systematically random sampled throughout the entire Brodmann areas (BA) 44 and 45 in developing and young adult cases. In the relatively small number of male and female cases studied no substantial postnatal increase in total number of neurons occurred in areas 44 and 45; the volume of these areas reached adult values around 7 years. In addition, we did find indications that a shift from a right-over-left to a left-over-right asymmetry may occur in the volume of BA 45 during postnatal development. No major asymmetry in total number of neurons in BA 44 and 45 was detected.

The optical rotator

DEFF Research Database (Denmark)

Tandrup, T; Gundersen, Hans Jørgen Gottlieb; Jensen, Eva B. Vedel

1997-01-01

further discuss the methods derived from this principle and present two new local volume estimators. The optical rotator benefits from information obtained in all three dimensions in thick sections but avoids over-/ underprojection problems at the extremes of the cell. Using computer-assisted microscopes......The optical rotator is an unbiased, local stereological principle for estimation of cell volume and cell surface area in thick, transparent slabs, The underlying principle was first described in 1993 by Kieu Jensen (T. Microsc. 170, 45-51) who also derived an estimator of length, In this study we...... the extra measurements demand minimal extra effort and make this estimator even more efficient when it comes to estimation of individual cell size than many of the previous local estimators, We demonstrate the principle of the optical rotator in an example (the cells in the dorsal root ganglion of the rat...

Three-dimensional stereology as a tool for evaluating bladder outlet obstruction

DEFF Research Database (Denmark)

Wijk, J. Van der; Wijk, J. Van der; Horn, T.

2008-01-01

-cup biopsy, taken during cystoscopy, was stereologically evaluated to determine the smooth muscle cell volume and the fractions of collagen and smooth muscle using light and electron microscopy. Results. The collagen fraction was higher in patients than in controls (probably because the patients were older...... tract symptoms (LUTS) suggestive of BOO and five controls (mean age 48.6 years; range 43-53 years) without LUTS were studied. All participants underwent a full examination, including determination of the International Prostate Symptom Score, laboratory analysis and a urodynamic evaluation. A cold...

Introducing Stereology as a Tool to Assess the Severity of Psoriasis

DEFF Research Database (Denmark)

Kamp, Søren; Stenderup, Karin; Rosada, Cecilia

2008-01-01

to histological specimens in order to obtain three-dimensional properties from two-dimensional tissue samples. The psoriasis xenograft model used in this trial is accepted as a leading animal model for psoriasis. Psoriatic skin from psoriatic patients was grafted onto severe combined immunodeficient (SCID) mice......  The purpose of this study was to introduce stereology as a novel tool in assessing the severity of psoriasis. Psoriasis is a well described chronic inflammatory skin disease affecting approximately 2% of the Caucasian population.   The severity of psoriasis has been assessed by a multitude...

Mutually Unbiased Maximally Entangled Bases for the Bipartite System Cd⊗ C^{dk}

Science.gov (United States)

Nan, Hua; Tao, Yuan-Hong; Wang, Tian-Jiao; Zhang, Jun

2016-10-01

The construction of maximally entangled bases for the bipartite system Cd⊗ Cd is discussed firstly, and some mutually unbiased bases with maximally entangled bases are given, where 2≤ d≤5. Moreover, we study a systematic way of constructing mutually unbiased maximally entangled bases for the bipartite system Cd⊗ C^{dk}.

Higher-dimensional orbital-angular-momentum-based quantum key distribution with mutually unbiased bases

CSIR Research Space (South Africa)

Mafu, M

2013-09-01

Full Text Available We present an experimental study of higher-dimensional quantum key distribution protocols based on mutually unbiased bases, implemented by means of photons carrying orbital angular momentum. We perform (d + 1) mutually unbiased measurements in a...

Local digital algorithms for estimating the mean integrated curvature of r-regular sets

DEFF Research Database (Denmark)

Svane, Anne Marie

, no asymptotically unbiased estimator of this type exists in dimension greater than or equal to three, while for stationary isotropic lattices, asymptotically unbiased estimators are plenty. Both results follow from a general formula that we state and prove, describing the asymptotic behavior of hit...

Unbiased group-wise image registration: applications in brain fiber tract atlas construction and functional connectivity analysis.

Science.gov (United States)

Geng, Xiujuan; Gu, Hong; Shin, Wanyong; Ross, Thomas J; Yang, Yihong

2011-10-01

We propose an unbiased implicit-reference group-wise (IRG) image registration method and demonstrate its applications in the construction of a brain white matter fiber tract atlas and the analysis of resting-state functional MRI (fMRI) connectivity. Most image registration techniques pair-wise align images to a selected reference image and group analyses are performed in the reference space, which may produce bias. The proposed method jointly estimates transformations, with an elastic deformation model, registering all images to an implicit reference corresponding to the group average. The unbiased registration is applied to build a fiber tract atlas by registering a group of diffusion tensor images. Compared to reference-based registration, the IRG registration improves the fiber track overlap within the group. After applying the method in the fMRI connectivity analysis, results suggest a general improvement in functional connectivity maps at a group level in terms of larger cluster size and higher average t-scores.

Estimation of expected value for lognormal and gamma distributions

International Nuclear Information System (INIS)

White, G.C.

1978-01-01

Concentrations of environmental pollutants tend to follow positively skewed frequency distributions. Two such density functions are the gamma and lognormal. Minimum variance unbiased estimators of the expected value for both densities are available. The small sample statistical properties of each of these estimators were compared for its own distribution, as well as the other distribution to check the robustness of the estimator. Results indicated that the arithmetic mean provides an unbiased estimator when the underlying density function of the sample is either lognormal or gamma, and that the achieved coverage of the confidence interval is greater than 75 percent for coefficients of variation less than two. Further Monte Carlo simulations were conducted to study the robustness of the above estimators by simulating a lognormal or gamma distribution with the expected value of a particular observation selected from a uniform distribution before the lognormal or gamma observation is generated. Again, the arithmetic mean provides an unbiased estimate of expected value, and the coverage of the confidence interval is greater than 75 percent for coefficients of variation less than two

Unbiased tensor-based morphometry: Improved robustness and sample size estimates for Alzheimer’s disease clinical trials

Science.gov (United States)

Hua, Xue; Hibar, Derrek P.; Ching, Christopher R.K.; Boyle, Christina P.; Rajagopalan, Priya; Gutman, Boris A.; Leow, Alex D.; Toga, Arthur W.; Jack, Clifford R.; Harvey, Danielle; Weiner, Michael W.; Thompson, Paul M.

2013-01-01

Various neuroimaging measures are being evaluated for tracking Alzheimer’s disease (AD) progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated. Here we analyzed the full MRI dataset from the first phase of Alzheimer’s Disease Neuroimaging Initiative (ADNI-1) from the first phase of Alzheimer’s Disease Neuroimaging Initiative (ADNI-1) and assessed several sources of bias that can arise when tracking brain changes with structural brain imaging methods, as part of a pipeline for tensor-based morphometry (TBM). In all healthy subjects who completed MRI scanning at screening, 6, 12, and 24 months, brain atrophy was essentially linear with no detectable bias in longitudinal measures. In power analyses for clinical trials based on these change measures, only 39 AD patients and 95 mild cognitive impairment (MCI) subjects were needed for a 24-month trial to detect a 25% reduction in the average rate of change using a two-sided test (α=0.05, power=80%). Further sample size reductions were achieved by stratifying the data into Apolipoprotein E (ApoE) ε4 carriers versus non-carriers. We show how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI. PMID:23153970

Technical note: A stereological analysis of the cross-sectional variability of the femoral osteon population

DEFF Research Database (Denmark)

Villa, Chiara; Lynnerup, Niels

2010-01-01

Unbiased selection of regions of interest (ROIs) and unbiased definition of histological structures are needed to improve the repeatability of microscopic methods for age at death determination and to reduce operator subjectivity. We present results obtained by selecting ROIs according to stereol...

On semiautomatic estimation of surface area

DEFF Research Database (Denmark)

Dvorak, J.; Jensen, Eva B. Vedel

2013-01-01

and the surfactor. For ellipsoidal particles, it is shown that the flower estimator is equal to the pivotal estimator based on support function measurements along four perpendicular rays. This result makes the pivotal estimator a powerful approximation to the flower estimator. In a simulation study of prolate....... If the segmentation is correct the estimate is computed automatically, otherwise the expert performs the necessary measurements manually. In case of convex particles we suggest to base the semiautomatic estimation on the so-called flower estimator, a new local stereological estimator of particle surface area....... For convex particles, the estimator is equal to four times the area of the support set (flower set) of the particle transect. We study the statistical properties of the flower estimator and compare its performance to that of two discretizations of the flower estimator, namely the pivotal estimator...

ON THE PRECISION OF THE NUCLEATOR

Directory of Open Access Journals (Sweden)

Javier González-Villa

2017-06-01

Full Text Available The nucleator is a design unbiased method of local stereology for estimating the volume of a bounded object. The only information required lies in the intersection of the object with an isotropic random ray emanating from a fixed point (called the pivotal point associated with the object. For instance, the volume of a neuron can be estimated from a random ray emanating from its nucleolus. The nucleator is extensively used in biosciences because it is efficient and easy to apply. The estimator variance can be reduced by increasing the number of rays. In an earlier paper a systematic sampling design was proposed, and theoretical variance predictors were derived, for the corresponding volume estimator. Being the only variance predictors hitherto available for the nucleator, our basic goal was to check their statistical performance by means of Monte Carlo resampling on computer reconstructions of real objects. As a plus, the empirical distribution of the volume estimator revealed statistical properties of practical relevance.

A sampling scheme intended for tandem measurements of sodium transport and microvillous surface area in the coprodaeal epithelium of hens on high- and low-salt diets.

Science.gov (United States)

Mayhew, T M; Dantzer, V; Elbrønd, V S; Skadhauge, E

1990-12-01

A tissue sampling protocol for combined morphometric and physiological studies on the mucosa of the avian coprodaeum is presented. The morphometric goal is to estimate the surface area due to microvilli at the epithelial cell apex and the proposed scheme is illustrated using material from three White Plymouth Rock hens. The scheme is designed to satisfy sampling requirements for the unbiased estimation of surface areas by vertical sectioning coupled with cycloid test lines and it incorporates a number of useful internal checks. It relies on multi-level sampling with four levels of stereological estimation. At Level I, macroscopic estimates of coprodaeal volume are obtained. Light microscopy is employed at Level II to calculate epithelial volume density. Levels III and IV require low and high power electron microscopy to estimate the surface density of the epithelial apical border and the amplification factor due to microvilli. Worked examples of the calculation steps are provided.

Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

Science.gov (United States)

Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

2004-12-01

As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

Science.gov (United States)

Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

2011-01-01

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

Effect of praziquantel administration on hepatic stereology of mice infected with Schistosoma mansoni and fed a low-protein diet

Directory of Open Access Journals (Sweden)

L.A. Barros

2009-09-01

Full Text Available A study was undertaken to investigate the effect of administering praziquantel (PZQ, focusing on the liver stereological findings of malnourished mice infected with Schistosoma mansoni. Thirty female Swiss Webster mice (age: 21 days; weight: 8-14 g were fed either a low-protein diet (8% or standard chow (22% protein for 15 days. Five mice in each group were infected with 50 cercariae each of the BH strain (Brazil. PZQ therapy (80 mg/kg body weight, per day was started on the 50th day of infection and consisted of daily administration for 5 days. Volume density (hepatocytes, sinusoids and hepatic fibrosis was determined by stereology using a light microscope. Body weight gain and total serum albumin levels were always lower in undernourished mice. Our stereological study demonstrated that treatment increased both volume density of hepatocytes in mice fed standard chow (47.56%, treated group and 12.06%, control and low-protein chow (30.98%, treated group and 21.44%, control, and hepatic sinusoids [standard chow (12.52%, treated group and 9.06%, control, low-protein chow (14.42%, treated group and 8.46%, control], while hepatic fibrosis was reduced [standard chow (39.92%, treated group and 78.88%, control and low-protein chow (54.60%, treated group and 70.10%, control]. On the other hand, mice fed low-protein chow decreased density volume of hepatocytes and hepatic fibrosis. In conclusion, our findings indicate that treatment with PZQ ameliorates hepatic schistosomiasis pathology even in mice fed a low-protein diet.

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas

DEFF Research Database (Denmark)

Bundgaard, T; Sørensen, Flemming Brandt; Gaihede, M

1992-01-01

BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, ...

Probability Theory Plus Noise: Descriptive Estimation and Inferential Judgment.

Science.gov (United States)

Costello, Fintan; Watts, Paul

2018-01-01

We describe a computational model of two central aspects of people's probabilistic reasoning: descriptive probability estimation and inferential probability judgment. This model assumes that people's reasoning follows standard frequentist probability theory, but it is subject to random noise. This random noise has a regressive effect in descriptive probability estimation, moving probability estimates away from normative probabilities and toward the center of the probability scale. This random noise has an anti-regressive effect in inferential judgement, however. These regressive and anti-regressive effects explain various reliable and systematic biases seen in people's descriptive probability estimation and inferential probability judgment. This model predicts that these contrary effects will tend to cancel out in tasks that involve both descriptive estimation and inferential judgement, leading to unbiased responses in those tasks. We test this model by applying it to one such task, described by Gallistel et al. ). Participants' median responses in this task were unbiased, agreeing with normative probability theory over the full range of responses. Our model captures the pattern of unbiased responses in this task, while simultaneously explaining systematic biases away from normatively correct probabilities seen in other tasks. Copyright © 2018 Cognitive Science Society, Inc.

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

Science.gov (United States)

Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Microstructure characterization via stereological relations — A shortcut for beginners

Energy Technology Data Exchange (ETDEWEB)

Pabst, Willi, E-mail: pabstw@vscht.cz; Gregorová, Eva; Uhlířová, Tereza

2015-07-15

Stereological relations that can be routinely applied for the quantitative characterization of microstructures of heterogeneous single- and two-phase materials via global microstructural descriptors are reviewed. It is shown that in the case of dense, single-phase polycrystalline materials (e.g., transparent yttrium aluminum garnet ceramics) two quantities have to be determined, the interface density (or, equivalently, the mean chord length of the grains) and the mean curvature integral density (or, equivalently, the Jeffries grain size), while for two-phase materials (e.g., highly porous, cellular alumina ceramics), one additional quantity, the volume fraction (porosity), is required. The Delesse–Rosiwal law is recalled and size measures are discussed. It is shown that the Jeffries grain size is based on the triple junction line length density, while the mean chord length of grains is based on the interface density (grain boundary area density). In contrast to widespread belief, however, these two size measures are not alternative, but independent (and thus complementary), measures of grain size. Concomitant with this fact, a clear distinction between linear and planar grain size numbers is proposed. Finally, based on our concept of phase-specific quantities, it is shown that under certain conditions it is possible to define a Jeffries size also for two-phase materials and that the ratio of the mean chord length and the Jeffries size has to be considered as an invariant number for a certain type of microstructure, i.e., a characteristic value that is independent of the absolute size of the microstructural features (e.g., grains, inclusions or pores). - Highlights: • Stereology-based image analysis is reviewed, including error considerations. • Recipes are provided for measuring global metric microstructural descriptors. • Size measures are based on interface density and mean curvature integral density. • Phase-specific quantities and a generalized

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

Science.gov (United States)

2009-10-01

Williams, J. H., A. Whiten, T. Suddendorf, and D. I. Perrett (2001). Imitation, mirror neurons and autism . Neurosci. Biobehav. Rev. 25:287–295. AQ11...subjects with unbiased stereological methods revealed that autism is associated with profound global desynchronization of neuronal growth within the...structural and functional deterioration. 15. SUBJECT TERMS Autism , Developmental Delay of Neuronal Growth, Desynchronization of Brain Development 16

Minimum variance linear unbiased estimators of loss and inventory

International Nuclear Information System (INIS)

Stewart, K.B.

1977-01-01

The article illustrates a number of approaches for estimating the material balance inventory and a constant loss amount from the accountability data from a sequence of accountability periods. The approaches all lead to linear estimates that have minimum variance. Techniques are shown whereby ordinary least squares, weighted least squares and generalized least squares computer programs can be used. Two approaches are recursive in nature and lend themselves to small specialized computer programs. Another approach is developed that is easy to program; could be used with a desk calculator and can be used in a recursive way from accountability period to accountability period. Some previous results are also reviewed that are very similar in approach to the present ones and vary only in the way net throughput measurements are statistically modeled. 5 refs

Statistically and Computationally Efficient Estimating Equations for Large Spatial Datasets

KAUST Repository

Sun, Ying; Stein, Michael L.

2014-01-01

For Gaussian process models, likelihood based methods are often difficult to use with large irregularly spaced spatial datasets, because exact calculations of the likelihood for n observations require O(n3) operations and O(n2) memory. Various approximation methods have been developed to address the computational difficulties. In this paper, we propose new unbiased estimating equations based on score equation approximations that are both computationally and statistically efficient. We replace the inverse covariance matrix that appears in the score equations by a sparse matrix to approximate the quadratic forms, then set the resulting quadratic forms equal to their expected values to obtain unbiased estimating equations. The sparse matrix is constructed by a sparse inverse Cholesky approach to approximate the inverse covariance matrix. The statistical efficiency of the resulting unbiased estimating equations are evaluated both in theory and by numerical studies. Our methods are applied to nearly 90,000 satellite-based measurements of water vapor levels over a region in the Southeast Pacific Ocean.

Statistically and Computationally Efficient Estimating Equations for Large Spatial Datasets

KAUST Repository

Sun, Ying

2014-11-07

For Gaussian process models, likelihood based methods are often difficult to use with large irregularly spaced spatial datasets, because exact calculations of the likelihood for n observations require O(n3) operations and O(n2) memory. Various approximation methods have been developed to address the computational difficulties. In this paper, we propose new unbiased estimating equations based on score equation approximations that are both computationally and statistically efficient. We replace the inverse covariance matrix that appears in the score equations by a sparse matrix to approximate the quadratic forms, then set the resulting quadratic forms equal to their expected values to obtain unbiased estimating equations. The sparse matrix is constructed by a sparse inverse Cholesky approach to approximate the inverse covariance matrix. The statistical efficiency of the resulting unbiased estimating equations are evaluated both in theory and by numerical studies. Our methods are applied to nearly 90,000 satellite-based measurements of water vapor levels over a region in the Southeast Pacific Ocean.

Effect of Sodium Cyclamate on the Rat Fetal Exocrine Pancreas: a Karyometric and Stereological Study

OpenAIRE

MARTINS, Alex Tadeu; SANTOS, Fabiano de Sant`Ana dos; SCANNAVINO, Fabio Luiz Ferreira; PIRES, Juliana Rico; ZUZA, Elizangela Partata; PADOVANI JUNIOR, Joao Armando; AZOUBEL, Reinaldo; MATEO, Miguel Angel Sala Di; LOPES, Ruberval Armando

2010-01-01

The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. The objective of this study was to evaluate karyometric and stereological alterations in the rat fetal pancreas resulting from the intraperitoneal administration of sodium cyclamate. The exocrine pancreas of ten fetuses of rats were evaluated, five treated and five controls chosen at random, i...

About mutually unbiased bases in even and odd prime power dimensions

Science.gov (United States)

Durt, Thomas

2005-06-01

Mutually unbiased bases generalize the X, Y and Z qubit bases. They possess numerous applications in quantum information science. It is well known that in prime power dimensions N = pm (with p prime and m a positive integer), there exists a maximal set of N + 1 mutually unbiased bases. In the present paper, we derive an explicit expression for those bases, in terms of the (operations of the) associated finite field (Galois division ring) of N elements. This expression is shown to be equivalent to the expressions previously obtained by Ivanovic (1981 J. Phys. A: Math. Gen. 14 3241) in odd prime dimensions, and Wootters and Fields (1989 Ann. Phys. 191 363) in odd prime power dimensions. In even prime power dimensions, we derive a new explicit expression for the mutually unbiased bases. The new ingredients of our approach are, basically, the following: we provide a simple expression of the generalized Pauli group in terms of the additive characters of the field, and we derive an exact groupal composition law between the elements of the commuting subsets of the generalized Pauli group, renormalized by a well-chosen phase-factor.

About mutually unbiased bases in even and odd prime power dimensions

International Nuclear Information System (INIS)

Durt, Thomas

2005-01-01

Mutually unbiased bases generalize the X, Y and Z qubit bases. They possess numerous applications in quantum information science. It is well known that in prime power dimensions N = p m (with p prime and m a positive integer), there exists a maximal set of N + 1 mutually unbiased bases. In the present paper, we derive an explicit expression for those bases, in terms of the (operations of the) associated finite field (Galois division ring) of N elements. This expression is shown to be equivalent to the expressions previously obtained by Ivanovic (1981 J. Phys. A: Math. Gen. 14 3241) in odd prime dimensions, and Wootters and Fields (1989 Ann. Phys. 191 363) in odd prime power dimensions. In even prime power dimensions, we derive a new explicit expression for the mutually unbiased bases. The new ingredients of our approach are, basically, the following: we provide a simple expression of the generalized Pauli group in terms of the additive characters of the field, and we derive an exact groupal composition law between the elements of the commuting subsets of the generalized Pauli group, renormalized by a well-chosen phase-factor

Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

Science.gov (United States)

Kielar, Catherine; Sawiak, Stephen J; Navarro Negredo, Paloma; Tse, Desmond H Y; Morton, A Jennifer

2012-01-01

Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/-)) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/-) mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/-) mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/-) and Cplx1(+/+) mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/-) mice when compared to Cplx1(+/+) animals. Our study is the first to describe pathological changes in Cplx1(-/-) mouse brain. We suggest that the ataxia in Cplx1(-/-) mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/-) mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.

Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

Directory of Open Access Journals (Sweden)

Catherine Kielar

Full Text Available Complexins (Cplxs are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/- have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/- mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/- mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/- and Cplx1(+/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/- mice when compared to Cplx1(+/+ animals. Our study is the first to describe pathological changes in Cplx1(-/- mouse brain. We suggest that the ataxia in Cplx1(-/- mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/- mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.

Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus in comparison with human (Homo sapiens: quantitative and functional implications.

Directory of Open Access Journals (Sweden)

Brian Chin Wing Kot

Full Text Available The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5 µm(3 and 7.02×10(5 µm(3 respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

Estimation After a Group Sequential Trial.

Science.gov (United States)

Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Kenward, Michael G; Tsiatis, Anastasios A; Davidian, Marie; Verbeke, Geert

2015-10-01

Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al (2012) and Milanzi et al (2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, N = n or N = 2 n . In this paper, we consider the more practically useful setting of sample sizes in a the finite set { n 1 , n 2 , …, n L }. It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why

Stereological observations of platelet-reinforced mullite- and zirconia-matrix composites

International Nuclear Information System (INIS)

Cherian, I.K.; Kriven, W.M.; Lehigh, M.D.; Nettleship, I.

1996-01-01

Recently, the effect of solid inclusions on the sintering of ceramic powders has been explained in terms of a back-stress that opposes densification. Several analyses have been proposed to describe this problem. However, little quantitative information exists concerning the effect of reinforcement on microstructural evolution. This study compares the microstructural development of zirconia and mullite matrices in the presence of alumina platelets. The effect of platelet loading on density is similar for both composites. Quantitative stereological examinations reveal that the average grain size and pore size are finer for the zirconia-matrix composite. The platelet loading does not have any noticeable effect on the average grain size of the matrix in either composite. However, the average pore size increases as the volume fraction of platelets increases for both materials. Contiguity measurements have detected some aggregation of platelets in the zirconia-matrix composite

Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study.

Science.gov (United States)

Khoshvakhti, Habib; Yurt, K Kübra; Altunkaynak, B Zuhal; Türkmen, Aysın P; Elibol, Ebru; Aydın, Işınsu; Kıvrak, Elfide G; Önger, M Emin; Kaplan, Süleyman

2015-01-01

In this study, we aimed to investigate the effect of diclofenac sodium (DS) and melatonin (MEL) on kidney of the prenatally administered rats. Pregnant rats were divided into the control, physiological saline, DS, and DS + MEL groups. All injections were given beginning from the 5th day after mating to the 15th day of the pregnancy. Physical dissector and Cavalieri principle were used to estimate the numerical density and total number of glomeruli and the volumetric parameters of kidney, respectively. Our stereological results indicated that DS application during the pregnancy lead to decrease in the mean volume, numerical density, and total number of the glomeruli (p  0.05). Light microscopic investigation showed congestion in blood vessels and shrinkage of the Bowman's space in the DS group. Moreover, there was degeneration in nephrons including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys of the DS-treated group. However, usage of the MEL with the DS caused preventing of these pathological alterations in the kidney. We suggested that DS might lead to adverse effects in the kidneys of the rats that are prenatally subjected to this drug. Fortunately, these adverse effects can be prevented by the melatonin supplementation.

The Herschel/HIFI unbiased spectral survey of the solar-mass protostar IRAS16293

Science.gov (United States)

Bottinelli, S.; Caux, E.; Cecarelli, C.; Kahane, C.

2012-03-01

Unbiased spectral surveys are powerful tools to study the chemistry and the physics of star forming regions, because they can provide a complete census of the molecular content and the observed lines probe the physical structure of the source. While unbiased surveys at the millimeter and sub-millimeter wavelengths observable from ground-based telescopes have previously been performed towards several high-mass protostars, very little data exist on low-mass protostars, with only one such ground-based survey carried out towards this kind of object. However, since low-mass protostars are believed to resemble our own Sun's progenitor, the information provided by spectral surveys is crucial in order to uncover the birth mechanisms of low-mass stars and hence of our Sun. To help fill up this gap in our understanding, we carried out an almost complete spectral survey towards the solar-type protostar IRAS16293-2422 with the HIFI instrument onboard Herschel. The observations covered a range of about 700 GHz, in which a few hundreds lines were detected with more than 3σ confidence interval certainty and identified. All the detected lines which were free from obvious blending effects were fitted with Gaussians to estimate their basic kinematic properties. Contrarily to what is observed in the millimeter range, no lines from complex organic molecules have been observed. In this work, we characterize the different components of IRAS16293-2422 (a known binary at least) by analyzing the numerous emission and absorption lines identified.

THE CAVALIERI ESTIMATOR WITH UNEQUAL SECTION SPACING REVISITED

Directory of Open Access Journals (Sweden)

Markus Kiderlen

2017-06-01

Full Text Available The Cavalieri method allows to estimate the volume of a compact object from area measurements in equidistant parallel planar sections. However, the spacing and thickness of sections can be quite irregular in applications. Recent publications have thus focused on the effect of random variability in section spacing, showing that the classical Cavalieri estimator is still unbiased when the stack of parallel planes is stationary, but that the existing variance approximations must be adjusted. The present paper considers the special situation, where the distances between consecutive section planes can be measured and thus where Cavalieri’s estimator can be replaced by a quadrature rule with randomized sampling points. We show that, under mild conditions, the trapezoid rule and Simpson’s rule lead to unbiased volume estimators and give simulation results that indicate that a considerable variance reduction compared to the generalized Cavalieri estimator can be achieved.

Stereological comparison of oocyte recruitment and batch fecundity estimates from paraffin and resin sections using spawning albacore (Thunnus alalunga) ovaries as a case study

Science.gov (United States)

Saber, Sámar; Macías, David; Ortiz de Urbina, Josetxu; Kjesbu, Olav Sigurd

2015-01-01

Traditional histological protocols in marine fish reproductive laboratories using paraffin as the embedding medium are now increasingly being replaced with protocols using resin instead. These procedures entail different degrees of tissue shrinkage complicating direct comparisons of measurement results across laboratories or articles. In this work we selected ovaries of spawning Mediterranean albacore (Thunnus alalunga) as the subject of our study to address the issue of structural changes, by contrasting values on oocyte recruitment and final batch fecundity given from the same tissue samples in both paraffin and resin. A modern stereological method, the oocyte packing density (OPD) theory, was used supported by initial studies on ovarian tissue sampling and measurement design. Examples of differences in the volume fraction of oocyte stages, free space and connective tissue were found between the embedding media. Mean oocyte diameters were smaller in paraffin than in resin with differences ranging between 0.5% in primary growth and 24.3% in hydration (HYD) stage oocytes. Fresh oocyte measurements showed that oocytes shrank as a consequence of the embedding process, reaching the maximal degree of shrinkage for oocytes in the HYD stage (45.8% in paraffin and 26.5% in resin). In order to assess the effect of oocyte shrinkage on the OPD result, and thereby on relative batch fecundity (Fr), oocyte diameters corrected and uncorrected for shrinkage, were used for estimations. Statistical significant differences were found (P based on either oocytes in the germinal vesicle migration stage or HYD stage. As a valuable adjunct, the present use of the OPD theory made it possible to document that the oocyte recruitment of spawning ovaries of Mediterranean albacore followed the typical pattern of an asynchronous oocyte development and indeterminate fecundity.

Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

Science.gov (United States)

Karlsen, Anna Schou; Pakkenberg, Bente

2011-11-01

The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

Stereological Methods for Estimation of Total Number of Particles in ...

African Journals Online (AJOL)

In certain organs, like the brain, it is important to count the number of neurons associated with a particular function or region. The count gives an estimate of the electronic units available for a specific task or are endowed with a quantum of electrical energy. Similar studies can be extended in organs like the kidney, glands ...

Poisson sampling - The adjusted and unadjusted estimator revisited

Science.gov (United States)

Michael S. Williams; Hans T. Schreuder; Gerardo H. Terrazas

1998-01-01

The prevailing assumption, that for Poisson sampling the adjusted estimator "Y-hat a" is always substantially more efficient than the unadjusted estimator "Y-hat u" , is shown to be incorrect. Some well known theoretical results are applicable since "Y-hat a" is a ratio-of-means estimator and "Y-hat u" a simple unbiased estimator...

Unbiased reduced density matrices and electronic properties from full configuration interaction quantum Monte Carlo

International Nuclear Information System (INIS)

Overy, Catherine; Blunt, N. S.; Shepherd, James J.; Booth, George H.; Cleland, Deidre; Alavi, Ali

2014-01-01

Properties that are necessarily formulated within pure (symmetric) expectation values are difficult to calculate for projector quantum Monte Carlo approaches, but are critical in order to compute many of the important observable properties of electronic systems. Here, we investigate an approach for the sampling of unbiased reduced density matrices within the full configuration interaction quantum Monte Carlo dynamic, which requires only small computational overheads. This is achieved via an independent replica population of walkers in the dynamic, sampled alongside the original population. The resulting reduced density matrices are free from systematic error (beyond those present via constraints on the dynamic itself) and can be used to compute a variety of expectation values and properties, with rapid convergence to an exact limit. A quasi-variational energy estimate derived from these density matrices is proposed as an accurate alternative to the projected estimator for multiconfigurational wavefunctions, while its variational property could potentially lend itself to accurate extrapolation approaches in larger systems

Unbiased methods for removing systematics from galaxy clustering measurements

Science.gov (United States)

Elsner, Franz; Leistedt, Boris; Peiris, Hiranya V.

2016-02-01

Measuring the angular clustering of galaxies as a function of redshift is a powerful method for extracting information from the three-dimensional galaxy distribution. The precision of such measurements will dramatically increase with ongoing and future wide-field galaxy surveys. However, these are also increasingly sensitive to observational and astrophysical contaminants. Here, we study the statistical properties of three methods proposed for controlling such systematics - template subtraction, basic mode projection, and extended mode projection - all of which make use of externally supplied template maps, designed to characterize and capture the spatial variations of potential systematic effects. Based on a detailed mathematical analysis, and in agreement with simulations, we find that the template subtraction method in its original formulation returns biased estimates of the galaxy angular clustering. We derive closed-form expressions that should be used to correct results for this shortcoming. Turning to the basic mode projection algorithm, we prove it to be free of any bias, whereas we conclude that results computed with extended mode projection are biased. Within a simplified setup, we derive analytical expressions for the bias and discuss the options for correcting it in more realistic configurations. Common to all three methods is an increased estimator variance induced by the cleaning process, albeit at different levels. These results enable unbiased high-precision clustering measurements in the presence of spatially varying systematics, an essential step towards realizing the full potential of current and planned galaxy surveys.

Nonlinear unbiased minimum-variance filter for Mars entry autonomous navigation under large uncertainties and unknown measurement bias.

Science.gov (United States)

Xiao, Mengli; Zhang, Yongbo; Fu, Huimin; Wang, Zhihua

2018-05-01

High-precision navigation algorithm is essential for the future Mars pinpoint landing mission. The unknown inputs caused by large uncertainties of atmospheric density and aerodynamic coefficients as well as unknown measurement biases may cause large estimation errors of conventional Kalman filters. This paper proposes a derivative-free version of nonlinear unbiased minimum variance filter for Mars entry navigation. This filter has been designed to solve this problem by estimating the state and unknown measurement biases simultaneously with derivative-free character, leading to a high-precision algorithm for the Mars entry navigation. IMU/radio beacons integrated navigation is introduced in the simulation, and the result shows that with or without radio blackout, our proposed filter could achieve an accurate state estimation, much better than the conventional unscented Kalman filter, showing the ability of high-precision Mars entry navigation algorithm. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

High levels of absorption in orientation-unbiased, radio-selected 3CR Active Galaxies

Science.gov (United States)

Wilkes, Belinda J.; Haas, Martin; Barthel, Peter; Leipski, Christian; Kuraszkiewicz, Joanna; Worrall, Diana; Birkinshaw, Mark; Willner, Steven P.

2014-08-01

A critical problem in understanding active galaxies (AGN) is the separation of intrinsic physical differences from observed differences that are due to orientation. Obscuration of the active nucleus is anisotropic and strongly frequency dependent leading to complex selection effects for observations in most wavebands. These can only be quantified using a sample that is sufficiently unbiased to test orientation effects. Low-frequency radio emission is one way to select a close-to orientation-unbiased sample, albeit limited to the minority of AGN with strong radio emission.Recent Chandra, Spitzer and Herschel observations combined with multi-wavelength data for a complete sample of high-redshift (1half the sample is significantly obscured with ratios of unobscured: Compton thin (22 24.2) = 2.5:1.4:1 in these high-luminosity (log L(0.3-8keV) ~ 44-46) sources. These ratios are consistent with current expectations based on modelingthe Cosmic X-ray Background. A strong correlation with radio orientation constrains the geometry of the obscuring disk/torus to have a ~60 degree opening angle and ~12 degree Compton-thick cross-section. The deduced ~50% obscured fraction of the population contrasts with typical estimates of ~20% obscured in optically- and X-ray-selected high-luminosity samples. Once the primary nuclear emission is obscured, AGN X-ray spectra are frequently dominated by unobscured non-nuclear or scattered nuclear emission which cannot be distinguished from direct nuclear emission with a lower obscuration level unless high quality data is available. As a result, both the level of obscuration and the estimated instrinsic luminosities of highly-obscured AGN are likely to be significantly (*10-1000) underestimated for 25-50% of the population. This may explain the lower obscured fractions reported for optical and X-ray samples which have no independent measure of the AGN luminosity. Correcting AGN samples for these underestimated luminosities would result in

Unbiased survival estimates and evidence for skipped breeding opportunities in females

Science.gov (United States)

Muths, Erin L.; Scherer, Rick D.; Lambert, Brad A.

2010-01-01

1. Estimates of demographic parameters for females, in many organisms, are sparse. This is particularly worrisome as more and more species are faced with high extinction probabilities and conservation increasingly depends on actions dictated by complex predictive models that require accurate estimates of demographic parameters for each sex and species.

Three-dimensional stereology as a tool for evaluating bladder outlet obstruction

DEFF Research Database (Denmark)

Van Der Wijk, Jasper; Van Der Wijk, Jan; Horn, Thomas

2008-01-01

Objective. In a pilot study we evaluated whether implementation of a novel 3D stereologic technique can prove that bladder outlet obstruction (BOO) is associated with morphologic changes in the bladder wall. Material and methods. Ten males (mean age 69.7 years; range 58-84 years) with lower urinary...... tract symptoms (LUTS) suggestive of BOO and five controls (mean age 48.6 years; range 43-53 years) without LUTS were studied. All participants underwent a full examination, including determination of the International Prostate Symptom Score, laboratory analysis and a urodynamic evaluation. A cold....... Conclusions. This pilot study shows that, even with the implementation of subtle morphometric techniques, there seems to be no relationship between the severity of BOO and bladder wall morphology. It is possible that interstitial collagen in the bladder wall increases with age. It seems that bladder wall...

Biased and unbiased perceptual decision-making on vocal emotions.

Science.gov (United States)

Dricu, Mihai; Ceravolo, Leonardo; Grandjean, Didier; Frühholz, Sascha

2017-11-24

Perceptual decision-making on emotions involves gathering sensory information about the affective state of another person and forming a decision on the likelihood of a particular state. These perceptual decisions can be of varying complexity as determined by different contexts. We used functional magnetic resonance imaging and a region of interest approach to investigate the brain activation and functional connectivity behind two forms of perceptual decision-making. More complex unbiased decisions on affective voices recruited an extended bilateral network consisting of the posterior inferior frontal cortex, the orbitofrontal cortex, the amygdala, and voice-sensitive areas in the auditory cortex. Less complex biased decisions on affective voices distinctly recruited the right mid inferior frontal cortex, pointing to a functional distinction in this region following decisional requirements. Furthermore, task-induced neural connectivity revealed stronger connections between these frontal, auditory, and limbic regions during unbiased relative to biased decision-making on affective voices. Together, the data shows that different types of perceptual decision-making on auditory emotions have distinct patterns of activations and functional coupling that follow the decisional strategies and cognitive mechanisms involved during these perceptual decisions.

On the degrees of freedom of reduced-rank estimators in multivariate regression.

Science.gov (United States)

Mukherjee, A; Chen, K; Wang, N; Zhu, J

We study the effective degrees of freedom of a general class of reduced-rank estimators for multivariate regression in the framework of Stein's unbiased risk estimation. A finite-sample exact unbiased estimator is derived that admits a closed-form expression in terms of the thresholded singular values of the least-squares solution and hence is readily computable. The results continue to hold in the high-dimensional setting where both the predictor and the response dimensions may be larger than the sample size. The derived analytical form facilitates the investigation of theoretical properties and provides new insights into the empirical behaviour of the degrees of freedom. In particular, we examine the differences and connections between the proposed estimator and a commonly-used naive estimator. The use of the proposed estimator leads to efficient and accurate prediction risk estimation and model selection, as demonstrated by simulation studies and a data example.

Fast and unbiased estimator of the time-dependent Hurst exponent

Science.gov (United States)

Pianese, Augusto; Bianchi, Sergio; Palazzo, Anna Maria

2018-03-01

We combine two existing estimators of the local Hurst exponent to improve both the goodness of fit and the computational speed of the algorithm. An application with simulated time series is implemented, and a Monte Carlo simulation is performed to provide evidence of the improvement.

Stereological measures of trabecular bone structure: comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies

DEFF Research Database (Denmark)

Thomsen, Jesper Skovhus; Laib, A.; Koller, B.

2005-01-01

Stereology applied on histological sections is the 'gold standard' for obtaining quantitative information on cancellous bone structure. Recent advances in micro computed tomography (microCT) have made it possible to acquire three-dimensional (3D) data non-destructively. However, before the 3D...... methods can be used as a substitute for the current 'gold standard' they have to be verified against the existing standard. The aim of this study was to compare bone structural measures obtained from 3D microCT data sets with those obtained by stereology performed on conventional histological sections...... tibial metaphysis. The biopsies were embedded in methylmetacrylate before microCT scanning in a Scanco microCT 40 scanner at a resolution of 20 x 20 x 20 microm3, and the 3D data sets were analysed with a computer program. After microCT scanning, 16 sections were cut from the central 2 mm of each biopsy...

A novel SURE-based criterion for parametric PSF estimation.

Science.gov (United States)

Xue, Feng; Blu, Thierry

2015-02-01

We propose an unbiased estimate of a filtered version of the mean squared error--the blur-SURE (Stein's unbiased risk estimate)--as a novel criterion for estimating an unknown point spread function (PSF) from the degraded image only. The PSF is obtained by minimizing this new objective functional over a family of Wiener processings. Based on this estimated blur kernel, we then perform nonblind deconvolution using our recently developed algorithm. The SURE-based framework is exemplified with a number of parametric PSF, involving a scaling factor that controls the blur size. A typical example of such parametrization is the Gaussian kernel. The experimental results demonstrate that minimizing the blur-SURE yields highly accurate estimates of the PSF parameters, which also result in a restoration quality that is very similar to the one obtained with the exact PSF, when plugged into our recent multi-Wiener SURE-LET deconvolution algorithm. The highly competitive results obtained outline the great potential of developing more powerful blind deconvolution algorithms based on SURE-like estimates.

Efficient, Differentially Private Point Estimators

OpenAIRE

Smith, Adam

2008-01-01

Differential privacy is a recent notion of privacy for statistical databases that provides rigorous, meaningful confidentiality guarantees, even in the presence of an attacker with access to arbitrary side information. We show that for a large class of parametric probability models, one can construct a differentially private estimator whose distribution converges to that of the maximum likelihood estimator. In particular, it is efficient and asymptotically unbiased. This result provides (furt...

Quantum circuit implementation of cyclic mutually unbiased bases

Energy Technology Data Exchange (ETDEWEB)

Seyfarth, Ulrich; Dittmann, Niklas; Alber, Gernot [Institut fuer Angewandte Physik, Technische Universitaet Darmstadt, 64289 Darmstadt (Germany)

2013-07-01

Complete sets of mutually unbiased bases (MUBs) play an important role in the areas of quantum state tomography and quantum cryptography. Sets which can be generated cyclically may eliminate certain side-channel attacks. To profit from the advantages of these MUBs we propose a method for deriving a quantum circuit that implements the generator of a set into an experimental setup. For some dimensions this circuit is minimal. The presented method is in principle applicable for a larger set of operations and generalizes recently published results.

Characteristic properties of Fibonacci-based mutually unbiased bases

Energy Technology Data Exchange (ETDEWEB)

Seyfarth, Ulrich; Alber, Gernot [Institut fuer Angewandte Physik, Technische Universitaet Darmstadt, 64289 Darmstadt (Germany); Ranade, Kedar [Institut fuer Quantenphysik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany)

2012-07-01

Complete sets of mutually unbiased bases (MUBs) offer interesting applications in quantum information processing ranging from quantum cryptography to quantum state tomography. Different construction schemes provide different perspectives on these bases which are typically also deeply connected to various mathematical research areas. In this talk we discuss characteristic properties resulting from a recently established connection between construction methods for cyclic MUBs and Fibonacci polynomials. As a remarkable fact this connection leads to construction methods which do not involve any relations to mathematical properties of finite fields.

Empirical estimates of the NAIRU

DEFF Research Database (Denmark)

Madsen, Jakob Brøchner

2005-01-01

equations. In this paper it is shown that a high proportion of the constant term is a statistical artefact and suggests a new method which yields approximately unbiased estimates of the time-invariant NAIRU. Using data for OECD countries it is shown that the constant-term correction lowers the unadjusted...

Time Domain Frequency Stability Estimation Based On FFT Measurements

National Research Council Canada - National Science Library

Chang, P

2004-01-01

.... In this paper, the biases of the Fast Fourier transform (FFT) spectral estimate with Hanning window are checked and the resulting unbiased spectral density are used to calculate the Allan variance...

Unbiased classification of spatial strategies in the Barnes maze.

Science.gov (United States)

Illouz, Tomer; Madar, Ravit; Clague, Charlotte; Griffioen, Kathleen J; Louzoun, Yoram; Okun, Eitan

2016-11-01

Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze. Here, we offer a support vector machine-based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis. Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application. eitan.okun@biu.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Data-Constrained Generalized Maximum Entropy Estimator of the GLM: Asymptotic Theory and Inference

Directory of Open Access Journals (Sweden)

Nicholas Scott Cardell

2013-05-01

Full Text Available Maximum entropy methods of parameter estimation are appealing because they impose no additional structure on the data, other than that explicitly assumed by the analyst. In this paper we prove that the data constrained GME estimator of the general linear model is consistent and asymptotically normal. The approach we take in establishing the asymptotic properties concomitantly identifies a new computationally efficient method for calculating GME estimates. Formulae are developed to compute asymptotic variances and to perform Wald, likelihood ratio, and Lagrangian multiplier statistical tests on model parameters. Monte Carlo simulations are provided to assess the performance of the GME estimator in both large and small sample situations. Furthermore, we extend our results to maximum cross-entropy estimators and indicate a variant of the GME estimator that is unbiased. Finally, we discuss the relationship of GME estimators to Bayesian estimators, pointing out the conditions under which an unbiased GME estimator would be efficient.

Encoding mutually unbiased bases in orbital angular momentum for quantum key distribution

CSIR Research Space (South Africa)

Dudley, Angela L

2013-07-01

Full Text Available We encode mutually unbiased bases (MUBs) using the higher-dimensional orbital angular momentum (OAM) degree of freedom associated with optical fields. We illustrate how these states are encoded with the use of a spatial light modulator (SLM). We...

Experimental studies of unbiased gluon jets from $e^{+}e^{-}$ annihilations using the jet boost algorithm

CERN Document Server

Abbiendi, G.; Akesson, P.F.; Alexander, G.; Allison, John; Amaral, P.; Anagnostou, G.; Anderson, K.J.; Arcelli, S.; Asai, S.; Axen, D.; Azuelos, G.; Bailey, I.; Barberio, E.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brigliadori, L.; Brown, Robert M.; Buesser, K.; Burckhart, H.J.; Campana, S.; Carnegie, R.K.; Caron, B.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Feld, L.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Furtjes, A.; Gagnon, P.; Gary, John William; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harder, K.; Harel, A.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Hensel, C.; Herten, G.; Heuer, R.D.; Hill, J.C.; Hoffman, Kara Dion; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karapetian, G.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klein, K.; Klier, A.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kormos, Laura L.; Kramer, T.; Krieger, P.; von Krogh, J.; Kruger, K.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Layter, J.G.; Leins, A.; Lellouch, D.; Letts, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, J.; Macpherson, A.; Mader, W.; Marcellini, S.; Martin, A.J.; Masetti, G.; Mashimo, T.; Mattig, Peter; McDonald, W.J.; McKenna, J.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Moed, S.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Polok, J.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Rick, H.; Roney, J.M.; Rosati, S.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schoerner-Sadenius, Thomas; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Siroli, G.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Stephens, K.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Taylor, R.J.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Waller, D.; Ward, C.P.; Ward, D.R.; Warsinsky, M.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wetterling, D.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

2004-01-01

We present the first experimental results based on the jet boost algorithm, a technique to select unbiased samples of gluon jets in e+e- annihilations, i.e. gluon jets free of biases introduced by event selection or jet finding criteria. Our results are derived from hadronic Z0 decays observed with the OPAL detector at the LEP e+e- collider at CERN. First, we test the boost algorithm through studies with Herwig Monte Carlo events and find that it provides accurate measurements of the charged particle multiplicity distributions of unbiased gluon jets for jet energies larger than about 5 GeV, and of the jet particle energy spectra (fragmentation functions) for jet energies larger than about 14 GeV. Second, we apply the boost algorithm to our data to derive unbiased measurements of the gluon jet multiplicity distribution for energies between about 5 and 18 GeV, and of the gluon jet fragmentation function at 14 and 18 GeV. In conjunction with our earlier results at 40 GeV, we then test QCD calculations for the en...

Unbiased water and methanol maser surveys of NGC 1333

Energy Technology Data Exchange (ETDEWEB)

Lyo, A-Ran; Kim, Jongsoo; Byun, Do-Young; Lee, Ho-Gyu, E-mail: arl@kasi.re.kr [Korea Astronomy and Space Science Institute, 776, Daedeokdae-ro Yuseong-gu, Daejeon 305-348 (Korea, Republic of)

2014-11-01

We present the results of unbiased 22 GHz H{sub 2}O water and 44 GHz class I CH{sub 3}OH methanol maser surveys in the central 7' × 10' area of NGC 1333 and two additional mapping observations of a 22 GHz water maser in a ∼3' × 3' area of the IRAS4A region. In the 22 GHz water maser survey of NGC 1333 with a sensitivity of σ ∼ 0.3 Jy, we confirmed the detection of masers toward H{sub 2}O(B) in the region of HH 7-11 and IRAS4B. We also detected new water masers located ∼20'' away in the western direction of IRAS4B or ∼25'' away in the southern direction of IRAS4A. We could not, however, find young stellar objects or molecular outflows associated with them. They showed two different velocity components of ∼0 and ∼16 km s{sup –1}, which are blue- and redshifted relative to the adopted systemic velocity of ∼7 km s{sup –1} for NGC 1333. They also showed time variabilities in both intensity and velocity from multi-epoch observations and an anti-correlation between the intensities of the blue- and redshifted velocity components. We suggest that the unidentified power source of these masers might be found in the earliest evolutionary stage of star formation, before the onset of molecular outflows. Finding this kind of water maser is only possible through an unbiased blind survey. In the 44 GHz methanol maser survey with a sensitivity of σ ∼ 0.5 Jy, we confirmed masers toward IRAS4A2 and the eastern shock region of IRAS2A. Both sources are also detected in 95 and 132 GHz methanol maser lines. In addition, we had new detections of methanol masers at 95 and 132 GHz toward IRAS4B. In terms of the isotropic luminosity, we detected methanol maser sources brighter than ∼5 × 10{sup 25} erg s{sup –1} from our unbiased survey.

Robust and bias-corrected estimation of the coefficient of tail dependence

DEFF Research Database (Denmark)

Dutang, C.; Goegebeur, Y.; Guillou, A.

2014-01-01

We introduce a robust and asymptotically unbiased estimator for the coefficient of tail dependence in multivariate extreme value statistics. The estimator is obtained by fitting a second order model to the data by means of the minimum density power divergence criterion. The asymptotic properties ...

Mutually unbiased coarse-grained measurements of two or more phase-space variables

Science.gov (United States)

Paul, E. C.; Walborn, S. P.; Tasca, D. S.; Rudnicki, Łukasz

2018-05-01

Mutual unbiasedness of the eigenstates of phase-space operators—such as position and momentum, or their standard coarse-grained versions—exists only in the limiting case of infinite squeezing. In Phys. Rev. Lett. 120, 040403 (2018), 10.1103/PhysRevLett.120.040403, it was shown that mutual unbiasedness can be recovered for periodic coarse graining of these two operators. Here we investigate mutual unbiasedness of coarse-grained measurements for more than two phase-space variables. We show that mutual unbiasedness can be recovered between periodic coarse graining of any two nonparallel phase-space operators. We illustrate these results through optics experiments, using the fractional Fourier transform to prepare and measure mutually unbiased phase-space variables. The differences between two and three mutually unbiased measurements is discussed. Our results contribute to bridging the gap between continuous and discrete quantum mechanics, and they could be useful in quantum-information protocols.

Development of an unbiased statistical method for the analysis of unigenic evolution

Directory of Open Access Journals (Sweden)

Shilton Brian H

2006-03-01

Full Text Available Abstract Background Unigenic evolution is a powerful genetic strategy involving random mutagenesis of a single gene product to delineate functionally important domains of a protein. This method involves selection of variants of the protein which retain function, followed by statistical analysis comparing expected and observed mutation frequencies of each residue. Resultant mutability indices for each residue are averaged across a specified window of codons to identify hypomutable regions of the protein. As originally described, the effect of changes to the length of this averaging window was not fully eludicated. In addition, it was unclear when sufficient functional variants had been examined to conclude that residues conserved in all variants have important functional roles. Results We demonstrate that the length of averaging window dramatically affects identification of individual hypomutable regions and delineation of region boundaries. Accordingly, we devised a region-independent chi-square analysis that eliminates loss of information incurred during window averaging and removes the arbitrary assignment of window length. We also present a method to estimate the probability that conserved residues have not been mutated simply by chance. In addition, we describe an improved estimation of the expected mutation frequency. Conclusion Overall, these methods significantly extend the analysis of unigenic evolution data over existing methods to allow comprehensive, unbiased identification of domains and possibly even individual residues that are essential for protein function.

Integrated covariance estimation using high-frequency data in the presence of noise

DEFF Research Database (Denmark)

Voev, Valeri; Lunde, Asger

2007-01-01

We analyze the effects of nonsynchronicity and market microstructure noise on realized covariance type estimators. Hayashi and Yoshida (2005) propose a simple estimator that resolves the problem of nonsynchronicity and is unbiased and consistent for the integrated covariance in the absence of noise...

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

Science.gov (United States)

Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J

2018-04-01

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

A comparison of porosity analysis using 2D stereology estimates and 3D serial sectioning for additively manufactured Ti 6Al 2Sn 4Zr 2Mo alloy; Vergleich der Porositaetsanalyse einer Ti 6Al 2Sn 4Zr 2Mo-Legierung aus additiver Fertigung mittels stereologischer Schaetzungen (2D) und mit Serienschnitten (3D)

Energy Technology Data Exchange (ETDEWEB)

Ganti, Satya R.; Velez, Michael A.; Geier, Brian A.; Hayes, Brian J.; Turner, Bryan J.; Jenkins, Elizabeth J. [UES Inc., Dayton, OH (United States)

2017-02-15

Porosity is a typical defect in additively manufactured (AM) parts. Such defects limit the properties and performance of AM parts, and therefore need to be characterized accurately. Current methods for characterization of defects and microstructure rely on classical stereological methods that extrapolate information from two dimensional images. The automation of serial sectioning provides an opportunity to precisely and accurately quantify porosity in three dimensions in materials. In this work, we analyzed the porosity of an additively manufactured Ti 6Al 2Sn 4Zr 2Mo sample using Robo-Met.3D {sup registered}, an automated serial sectioning system. Image processing for three dimensional reconstruction of the serial-sectioned two dimensional images was performed using open source image analysis software (Fiji/ImageJ, Dream.3D, Paraview). The results from this 3D serial sectioning analysis were then compared to classical 2D stereological methods (Saltykov stereological theory). We found that for this dataset, the classical 2D methods underestimated the porosity size and distributions of the larger pores; a critical attribute to fatigue behavior of the AM part. The results suggest that acquiring experimental data with equipment such as Robo-Met.3D {sup registered} to measure the number and size of particles such as pores in a volume irrespective of knowing their shape is a better choice.

On Estimating Quantiles Using Auxiliary Information

Directory of Open Access Journals (Sweden)

Berger Yves G.

2015-03-01

Full Text Available We propose a transformation-based approach for estimating quantiles using auxiliary information. The proposed estimators can be easily implemented using a regression estimator. We show that the proposed estimators are consistent and asymptotically unbiased. The main advantage of the proposed estimators is their simplicity. Despite the fact the proposed estimators are not necessarily more efficient than their competitors, they offer a good compromise between accuracy and simplicity. They can be used under single and multistage sampling designs with unequal selection probabilities. A simulation study supports our finding and shows that the proposed estimators are robust and of an acceptable accuracy compared to alternative estimators, which can be more computationally intensive.

Ultrastructural and stereological analysis of trypanosomatidis of the genus Endotrypanum

Directory of Open Access Journals (Sweden)

Maurílio J. Soares

1991-06-01

Full Text Available Culture forms of four strains of Endotrypanum (E. schaudinni and E. monterogeii were processed for transmission electron microscopy and analyzed at the ultrastructural level. Quantitative data about some cytoplasmic organelles were obeined by stereology. All culture forms were promastigotes. In their cytoplasm four different organelles could be found: lipid inclusions (0,2-0,4 µm in diameter, mebrane-bounded vacuoles (0.10-0,28 µm in diameter, glycosomes (0,2-0,3 µm in diameter, and the mitochondrion. The kenetoplast appears as a thin band, except for the strain IM201, which possesses a broader structure, and possibly is not a member of this genus. Clusters of virus-like particles were seen in the cytoplasm of the strain LV88. The data obtained show that all strains have the typical morphological feature of the trypanosomatids. Only strain IM201 could be differentiated from the others, due to its larger kenetoplast-DNA network and its large mitochondrial and glycosomal relative volume. The morphometrical data did not allow the differentiation between E. schaudinni (strains IM217 and M6226 and E. monterogeii (strain LV88.

A new fractionator principle with varying sampling fractions: exemplified by estimation of synapse number using electron microscopy

DEFF Research Database (Denmark)

Witgen, Brent Marvin; Grady, M. Sean; Nyengaard, Jens Randel

2006-01-01

The quantification of ultrastructure has been permanently improved by the application of new stereological principles. Both precision and efficiency have been enhanced. Here we report for the first time a fractionator method that can be applied at the electron microscopy level. This new design...... the total object number using section sampling fractions based on the average thickness of sections of variable thicknesses. As an alternative, this approach estimates the correct particle section sampling probability based on an estimator of the Horvitz-Thompson type, resulting in a theoretically more...

Black-Box Search by Unbiased Variation

DEFF Research Database (Denmark)

Lehre, Per Kristian; Witt, Carsten

2012-01-01

The complexity theory for black-box algorithms, introduced by Droste, Jansen, and Wegener (Theory Comput. Syst. 39:525–544, 2006), describes common limits on the efficiency of a broad class of randomised search heuristics. There is an obvious trade-off between the generality of the black-box model...... and the strength of the bounds that can be proven in such a model. In particular, the original black-box model provides for well-known benchmark problems relatively small lower bounds, which seem unrealistic in certain cases and are typically not met by popular search heuristics.In this paper, we introduce a more...... restricted black-box model for optimisation of pseudo-Boolean functions which we claim captures the working principles of many randomised search heuristics including simulated annealing, evolutionary algorithms, randomised local search, and others. The key concept worked out is an unbiased variation operator...

Multilevel systematic sampling to estimate total fruit number for yield forecasts

DEFF Research Database (Denmark)

Wulfsohn, Dvora-Laio; Zamora, Felipe Aravena; Tellez, Camilla Potin

2012-01-01

procedure for unbiased estimation of fruit number for yield forecasts. In the Spring of 2009 we estimated the total number of fruit in several rows of each of 14 commercial fruit orchards growing apple (11 groves), kiwifruit (two groves), and table grapes (one grove) in central Chile. Survey times were 10...

Combining within and between instrument information to estimate precision

International Nuclear Information System (INIS)

Jost, J.W.; Devary, J.L.; Ward, J.E.

1980-01-01

When two instruments, both having replicated measurements, are used to measure the same set of items, between instrument information may be used to augment the within instrument precision estimate. A method is presented which combines the within and between instrument information to obtain an unbiased and minimum variance estimate of instrument precision. The method does not assume the instruments have equal precision

Pyroelectric photovoltaic spatial solitons in unbiased photorefractive crystals

International Nuclear Information System (INIS)

Jiang, Qichang; Su, Yanli; Ji, Xuanmang

2012-01-01

A new type of spatial solitons i.e. pyroelectric photovoltaic spatial solitons based on the combination of pyroelectric and photovoltaic effect is predicted theoretically. It shows that bright, dark and grey spatial solitons can exist in unbiased photovoltaic photorefractive crystals with appreciable pyroelectric effect. Especially, the bright soliton can form in self-defocusing photovoltaic crystals if it gives larger self-focusing pyroelectric effect. -- Highlights: ► A new type of spatial soliton i.e. pyroelectric photovoltaic spatial soliton is predicted. ► The bright, dark and grey pyroelectric photovoltaic spatial soliton can form. ► The bright soliton can also exist in self-defocusing photovoltaic crystals.

On the mathematical foundations of mutually unbiased bases

Science.gov (United States)

Thas, Koen

2018-02-01

In order to describe a setting to handle Zauner's conjecture on mutually unbiased bases (MUBs) (stating that in C^d, a set of MUBs of the theoretical maximal size d + 1 exists only if d is a prime power), we pose some fundamental questions which naturally arise. Some of these questions have important consequences for the construction theory of (new) sets of maximal MUBs. Partial answers will be provided in particular cases; more specifically, we will analyze MUBs with associated operator groups that have nilpotence class 2, and consider MUBs of height 1. We will also confirm Zauner's conjecture for MUBs with associated finite nilpotent operator groups.

Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons

DEFF Research Database (Denmark)

Kragsnaes, Maja Skov; Fredberg, Ulrich; Stribolt, Katrine

2014-01-01

BACKGROUND: Limited data exist on the presence and function of immune-competent cells in chronic tendinopathic tendons and their potential role in inflammation and tissue healing as well as in predicting long-term outcome. PURPOSE: To quantify subtypes of immune-competent cells in biopsy specimens...... immunohistochemically by quantifying the presence of macrophages (CD68-PGM1(+), CD68-KP1(+)), hemosiderophages (Perls blue), T lymphocytes (CD2(+), CD3(+), CD4(+), CD7(+), CD8(+)), B lymphocytes (CD20(+)), natural killer cells (CD56(+)), mast cells (NaSDCl(+)), Schwann cells (S100(+)), and endothelial cells (CD34......(+)) using a stereological technique. A follow-up examination was conducted more than 4 years (range, 4-9 years) after the biopsy procedure to evaluate the long-term presence of Achilles tendon symptoms. RESULTS: Macrophages, T lymphocytes, mast cells, and natural killer cells were observed in the majority...

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas

DEFF Research Database (Denmark)

Bundgaard, T; Sørensen, Flemming Brandt; Gaihede, M

1992-01-01

, tumor size, and the TNM classification. RESULTS: The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival......BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology...

Circulating tumor cell detection: A direct comparison between negative and unbiased enrichment in lung cancer.

Science.gov (United States)

Xu, Yan; Liu, Biao; Ding, Fengan; Zhou, Xiaodie; Tu, Pin; Yu, Bo; He, Yan; Huang, Peilin

2017-06-01

Circulating tumor cells (CTCs), isolated as a 'liquid biopsy', may provide important diagnostic and prognostic information. Therefore, rapid, reliable and unbiased detection of CTCs are required for routine clinical analyses. It was demonstrated that negative enrichment, an epithelial marker-independent technique for isolating CTCs, exhibits a better efficiency in the detection of CTCs compared with positive enrichment techniques that only use specific anti-epithelial cell adhesion molecules. However, negative enrichment techniques incur significant cell loss during the isolation procedure, and as it is a method that uses only one type of antibody, it is inherently biased. The detection procedure and identification of cell types also relies on skilled and experienced technicians. In the present study, the detection sensitivity of using negative enrichment and a previously described unbiased detection method was compared. The results revealed that unbiased detection methods may efficiently detect >90% of cancer cells in blood samples containing CTCs. By contrast, only 40-60% of CTCs were detected by negative enrichment. Additionally, CTCs were identified in >65% of patients with stage I/II lung cancer. This simple yet efficient approach may achieve a high level of sensitivity. It demonstrates a potential for the large-scale clinical implementation of CTC-based diagnostic and prognostic strategies.

Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats--a stereological study.

Science.gov (United States)

Golalipour, Mohammad Jafar; Gharravi, Anneh Mohammad; Ghafari, Sorya; Afshar, Mohammad

2007-11-01

The aim of the present study was to investigate the effect of Urtica dioica on Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar rats of 125-175 g divided into control, diabetic and Urtica dioica treatment groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the animals had been sacrified, the kidneys were removed and fixed by formaldehyde, cut horizontally into 1 mm slices and processed, Stained with H and E. Stereological study performed using light microscope and the image projected on a table of olysa software. Cavalieri principle was used to estimate the volume of cortex, medulla and whole kidney. All the grouped data statistically evaluated using Student's t-test, expressed as the Mean +/- SE. Ration of kidney weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were higher then control group (0.42). Ratio of kidney volume/body weight in diabetes (350) and diabetes-extract group (348) were higher then control group (323). Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then control (1.34) and diabetes group (1.33). Glomerular area and diameter and proximal tubule diameter in diabetes-Extract group was higher than control and diabetes groups. This study revealed that Urtica dioica has no effect on renal morphometric indices in induced diabetic rats.

Inverse sampled Bernoulli (ISB) procedure for estimating a population proportion, with nuclear material applications

International Nuclear Information System (INIS)

Wright, T.

1982-01-01

A new sampling procedure is introduced for estimating a population proportion. The procedure combines the ideas of inverse binomial sampling and Bernoulli sampling. An unbiased estimator is given with its variance. The procedure can be viewed as a generalization of inverse binomial sampling

x-y-recording in transmission electron microscopy. A versatile and inexpensive interface to personal computers with application to stereology.

Science.gov (United States)

Rickmann, M; Siklós, L; Joó, F; Wolff, J R

1990-09-01

An interface for IBM XT/AT-compatible computers is described which has been designed to read the actual specimen stage position of electron microscopes. The complete system consists of (i) optical incremental encoders attached to the x- and y-stage drivers of the microscope, (ii) two keypads for operator input, (iii) an interface card fitted to the bus of the personal computer, (iv) a standard configuration IBM XT (or compatible) personal computer optionally equipped with a (v) HP Graphic Language controllable colour plotter. The small size of the encoders and their connection to the stage drivers by simple ribbed belts allows an easy adaptation of the system to most electron microscopes. Operation of the interface card itself is supported by any high-level language available for personal computers. By the modular concept of these languages, the system can be customized to various applications, and no computer expertise is needed for actual operation. The present configuration offers an inexpensive attachment, which covers a wide range of applications from a simple notebook to high-resolution (200-nm) mapping of tissue. Since section coordinates can be processed in real-time, stereological estimations can be derived directly "on microscope". This is exemplified by an application in which particle numbers were determined by the disector method.

Immunocytochemical and stereological analysis of GABA(B) receptor subunit expression in the rat vestibular nucleus following unilateral vestibular deafferentation.

Science.gov (United States)

Zhang, Rong; Ashton, John; Horii, Arata; Darlington, Cynthia L; Smith, Paul F

2005-03-10

The process of behavioral recovery that occurs following damage to one vestibular labyrinth, vestibular compensation, has been attributed in part to a down-regulation of GABA(B) receptors in the vestibular nucleus complex (VNC) ipsilateral to the lesion, which could potentially reduce commissural inhibition from the contralateral VNC. In this study, we tested the possibility that this occurs through a decrease in the expression of either the GABA(B1) or GABA(B2) subunits of the GABA(B) receptor. We used Western blotting to quantify the expression of these subunits in the VNC at 10 h and 50 h following unilateral vestibular deafferentation (UVD) or sham surgery in rats. We then used immunocytochemistry and stereological counting methods to estimate the number of neurons expressing these subunits in the MVN at 10 h and 2 weeks following UVD or sham surgery. Compared to sham controls, we found no significant changes in either the expression of the two GABA(B) receptor subunits in the VNC or in the number of MVN neurons expressing these GABA(B) receptor subunits post-UVD. These results suggest that GABA(B) receptor expression does not change substantially in the VNC during the process of vestibular compensation.

Simple, efficient estimators of treatment effects in randomized trials using generalized linear models to leverage baseline variables.

Science.gov (United States)

Rosenblum, Michael; van der Laan, Mark J

2010-04-01

Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation.

Simple, Efficient Estimators of Treatment Effects in Randomized Trials Using Generalized Linear Models to Leverage Baseline Variables

Science.gov (United States)

Rosenblum, Michael; van der Laan, Mark J.

2010-01-01

Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation. PMID:20628636

Collision energy alteration during mass spectrometric acquisition is essential to ensure unbiased metabolomic analysis

CSIR Research Space (South Africa)

Madala, NE

2012-08-01

Full Text Available Metabolomics entails identification and quantification of all metabolites within a biological system with a given physiological status; as such, it should be unbiased. A variety of techniques are used to measure the metabolite content of living...

Linear Estimation of Standard Deviation of Logistic Distribution ...

African Journals Online (AJOL)

The paper presents a theoretical method based on order statistics and a FORTRAN program for computing the variance and relative efficiencies of the standard deviation of the logistic population with respect to the Cramer-Rao lower variance bound and the best linear unbiased estimators (BLUE\\'s) when the mean is ...

Reconstruction of high-dimensional states entangled in orbital angular momentum using mutually unbiased measurements

CSIR Research Space (South Africa)

Giovannini, D

2013-06-01

Full Text Available : QELS_Fundamental Science, San Jose, California United States, 9-14 June 2013 Reconstruction of High-Dimensional States Entangled in Orbital Angular Momentum Using Mutually Unbiased Measurements D. Giovannini1, ⇤, J. Romero1, 2, J. Leach3, A...

Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt

1989-01-01

a favorable prognosis. No significant differences in vV could be demonstrated among different noninvasive tumor types. Two-dimensional estimates only distinguished benign from malignant tumors with considerable overlap and with significantly varying influence from other factors among different benign lesional...

Novel efficient methods for measuring mesophyll anatomical characteristics from fresh thick sections using stereology and confocal microscopy: application on acid rain-treated Norway spruce needles

Czech Academy of Sciences Publication Activity Database

Albrechtová, Jana; Janáček, Jiří; Lhotáková, Zuzana; Radochová, Barbora; Kubínová, Lucie

2007-01-01

Roč. 58, č. 6 (2007), s. 1451-1461 ISSN 0022-0957 R&D Projects: GA AV ČR IAA5011810; GA AV ČR(CZ) IAA600110507; GA MŠk(CZ) LC06063 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60050516 Keywords : mesophyll * stereology * confocal microscopy Subject RIV: EA - Cell Biology Impact factor: 3.917, year: 2007

Accurate and quantitative polarization-sensitive OCT by unbiased birefringence estimator with noise-stochastic correction

Science.gov (United States)

Kasaragod, Deepa; Sugiyama, Satoshi; Ikuno, Yasushi; Alonso-Caneiro, David; Yamanari, Masahiro; Fukuda, Shinichi; Oshika, Tetsuro; Hong, Young-Joo; Li, En; Makita, Shuichi; Miura, Masahiro; Yasuno, Yoshiaki

2016-03-01

Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT that contrasts the polarization properties of tissues. It has been applied to ophthalmology, cardiology, etc. Proper quantitative imaging is required for a widespread clinical utility. However, the conventional method of averaging to improve the signal to noise ratio (SNR) and the contrast of the phase retardation (or birefringence) images introduce a noise bias offset from the true value. This bias reduces the effectiveness of birefringence contrast for a quantitative study. Although coherent averaging of Jones matrix tomography has been widely utilized and has improved the image quality, the fundamental limitation of nonlinear dependency of phase retardation and birefringence to the SNR was not overcome. So the birefringence obtained by PS-OCT was still not accurate for a quantitative imaging. The nonlinear effect of SNR to phase retardation and birefringence measurement was previously formulated in detail for a Jones matrix OCT (JM-OCT) [1]. Based on this, we had developed a maximum a-posteriori (MAP) estimator and quantitative birefringence imaging was demonstrated [2]. However, this first version of estimator had a theoretical shortcoming. It did not take into account the stochastic nature of SNR of OCT signal. In this paper, we present an improved version of the MAP estimator which takes into account the stochastic property of SNR. This estimator uses a probability distribution function (PDF) of true local retardation, which is proportional to birefringence, under a specific set of measurements of the birefringence and SNR. The PDF was pre-computed by a Monte-Carlo (MC) simulation based on the mathematical model of JM-OCT before the measurement. A comparison between this new MAP estimator, our previous MAP estimator [2], and the standard mean estimator is presented. The comparisons are performed both by numerical simulation and in vivo measurements of anterior and

Validation of abundance estimates from mark–recapture and removal techniques for rainbow trout captured by electrofishing in small streams

Science.gov (United States)

Rosenberger, Amanda E.; Dunham, Jason B.

2005-01-01

Estimation of fish abundance in streams using the removal model or the Lincoln - Peterson mark - recapture model is a common practice in fisheries. These models produce misleading results if their assumptions are violated. We evaluated the assumptions of these two models via electrofishing of rainbow trout Oncorhynchus mykiss in central Idaho streams. For one-, two-, three-, and four-pass sampling effort in closed sites, we evaluated the influences of fish size and habitat characteristics on sampling efficiency and the accuracy of removal abundance estimates. We also examined the use of models to generate unbiased estimates of fish abundance through adjustment of total catch or biased removal estimates. Our results suggested that the assumptions of the mark - recapture model were satisfied and that abundance estimates based on this approach were unbiased. In contrast, the removal model assumptions were not met. Decreasing sampling efficiencies over removal passes resulted in underestimated population sizes and overestimates of sampling efficiency. This bias decreased, but was not eliminated, with increased sampling effort. Biased removal estimates based on different levels of effort were highly correlated with each other but were less correlated with unbiased mark - recapture estimates. Stream size decreased sampling efficiency, and stream size and instream wood increased the negative bias of removal estimates. We found that reliable estimates of population abundance could be obtained from models of sampling efficiency for different levels of effort. Validation of abundance estimates requires extra attention to routine sampling considerations but can help fisheries biologists avoid pitfalls associated with biased data and facilitate standardized comparisons among studies that employ different sampling methods.

An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

Science.gov (United States)

Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon

2014-05-27

Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.

Automated and unbiased classification of chemical profiles from fungi using high performance liquid chromatography

DEFF Research Database (Denmark)

Hansen, Michael Edberg; Andersen, Birgitte; Smedsgaard, Jørn

2005-01-01

In this paper we present a method for unbiased/unsupervised classification and identification of closely related fungi, using chemical analysis of secondary metabolite profiles created by HPLC with UV diode array detection. For two chromatographic data matrices a vector of locally aligned full sp...

An Unbiased Distance-based Outlier Detection Approach for High-dimensional Data

DEFF Research Database (Denmark)

Nguyen, Hoang Vu; Gopalkrishnan, Vivekanand; Assent, Ira

2011-01-01

than a global property. Different from existing approaches, it is not grid-based and dimensionality unbiased. Thus, its performance is impervious to grid resolution as well as the curse of dimensionality. In addition, our approach ranks the outliers, allowing users to select the number of desired...... outliers, thus mitigating the issue of high false alarm rate. Extensive empirical studies on real datasets show that our approach efficiently and effectively detects outliers, even in high-dimensional spaces....

Monofunctional stealth nanoparticle for unbiased single molecule tracking inside living cells.

Science.gov (United States)

Lisse, Domenik; Richter, Christian P; Drees, Christoph; Birkholz, Oliver; You, Changjiang; Rampazzo, Enrico; Piehler, Jacob

2014-01-01

On the basis of a protein cage scaffold, we have systematically explored intracellular application of nanoparticles for single molecule studies and discovered that recognition by the autophagy machinery plays a key role for rapid metabolism in the cytosol. Intracellular stealth nanoparticles were achieved by heavy surface PEGylation. By combination with a generic approach for nanoparticle monofunctionalization, efficient labeling of intracellular proteins with high fidelity was accomplished, allowing unbiased long-term tracking of proteins in the outer mitochondrial membrane.

Differential estimates of southern flying squirrel (Glaucomys volans) population structure based on capture method

Science.gov (United States)

Kevin S. Laves; Susan C. Loeb

2005-01-01

It is commonly assumed that population estimates derived from trapping small mammals are accurate and unbiased or that estimates derived from different capture methods are comparable. We captured southern flying squirrels (Glaucmrtys volam) using two methods to study their effect on red-cockaded woodpecker (Picoides bumah) reproductive success. Southern flying...

Monte Carlo-based tail exponent estimator

Science.gov (United States)

Barunik, Jozef; Vacha, Lukas

2010-11-01

In this paper we propose a new approach to estimation of the tail exponent in financial stock markets. We begin the study with the finite sample behavior of the Hill estimator under α-stable distributions. Using large Monte Carlo simulations, we show that the Hill estimator overestimates the true tail exponent and can hardly be used on samples with small length. Utilizing our results, we introduce a Monte Carlo-based method of estimation for the tail exponent. Our proposed method is not sensitive to the choice of tail size and works well also on small data samples. The new estimator also gives unbiased results with symmetrical confidence intervals. Finally, we demonstrate the power of our estimator on the international world stock market indices. On the two separate periods of 2002-2005 and 2006-2009, we estimate the tail exponent.

Proliferation of Sertoli cells during development of the human testis assessed by stereological methods

DEFF Research Database (Denmark)

Cortes, D; Müller, J; Skakkebaek, N E

1987-01-01

Sertoli cells were studied using stereological methods in testes obtained from five children who were stillborn, and 31 individuals between 3 months and 40 years of age, who had suffered from sudden, unexpected death. The mean nuclear volume of the Sertoli cells, the numerical density of Sertoli...... cells, and the total number of Sertoli cells per individual were determined by point- and profile-counting of 0.5 micron sections. The nuclear volume of Sertoli cells increased from a median of 120 microns3 (range 53-130) during the period of 3 months to 10 years to 210 microns3 (170-260) in adults...... (greater than 25 years). The numerical density of Sertoli cells decreased from a median of 1200 X 10(6)/cm3 (870-1400) during childhood (3 months to 10 years) to 140 X 10(6)/cm3 (110-260) in adults (greater than 25 years). The total number of Sertoli cells per individual increased significantly from...

Rethinking economy-wide rebound measures: An unbiased proposal

International Nuclear Information System (INIS)

Guerra, Ana-Isabel; Sancho, Ferran

2010-01-01

In spite of having been first introduced in the last half of the ninetieth century, the debate about the possible rebound effects from energy efficiency improvements is still an open question in the economic literature. This paper contributes to the existing research on this issue proposing an unbiased measure for economy-wide rebound effects. The novelty of this economy-wide rebound measure stems from the fact that not only actual energy savings but also potential energy savings are quantified under general equilibrium conditions. Our findings indicate that the use of engineering savings instead of general equilibrium potential savings downward biases economy-wide rebound effects and upward-biases backfire effects. The discrepancies between the traditional indicator and our proposed measure are analysed in the context of the Spanish economy.

FIRST USE OF STEREOLOGY TO QUANTIFY THE SURVIVAL OF FAT AUTOGRAFTS

Directory of Open Access Journals (Sweden)

Eduardo Serna Cuéllar

2011-05-01

Full Text Available It is not usual to perform quantitative analyses on surgical materials. Rather, they are evaluated clinically, through qualitative methods, and if quantitation is done, it is on a 2-dimensional basis. In this study, the long-term survival of fat autografts (FAG in 40 subjects with facial soft tissue defects is quantified. An adipose tissue preparation from the abdomen obtained through liposuction and centrifugation is injected subcutaneously. Approximately 14 months later, the treated area is biopsied. Extensive computer-based histological analyses were performed using the stereological method in order to directly obtain three parameters: volume fraction of adipocytes in the fat tissue (VV, density (number per volume of adipocytes in the fat tissue (NV, and the mean cell volume of adipocytes (VA in each tissue sample. A set of equations based on these three quantitative parameters is produced for evaluation of the volumetric survival fraction (VSF of FAG. The presented data evidenced a 66% survival fraction at the 14-month follow-up. In routine practice, it would be sufficient to perform this volumetric analysis on the injected and biopsied fat samples to know what fraction of the FAG has survived. This is an objective method for quantifying FAG survival and will allow a standardized comparison between different research series and authors.

Estimation of the location parameter of distributions with known coefficient of variation by record values

Directory of Open Access Journals (Sweden)

N. K. Sajeevkumar

2014-09-01

Full Text Available In this article, we derived the Best Linear Unbiased Estimator (BLUE of the location parameter of certain distributions with known coefficient of variation by record values. Efficiency comparisons are also made on the proposed estimator with some of the usual estimators. Finally we give a real life data to explain the utility of results developed in this article.

An Unbiased Survey of 500 Nearby Stars for Debris Disks: A JCMT Legacy Program

NARCIS (Netherlands)

Matthews, B.C.; Greaves, J.S.; Holland, W.S.; Wyatt, M.C.; Barlow, M.J.; Bastien, P.; Beichman, C.A.; Biggs, A.; Butner, H.M.; Dent, W.R.F.; Francesco, J. Di; Dominik, C.; Fissel, L.; Friberg, P.; Gibb, A.G.; Halpern, M.; Ivison, R.J.; Jayawardhana, R.; Jenness, T.; Johnstone, D.; Kavelaars, J.J.; Marshall, J.L.; Phillips, N.; Schieven, G.; Snellen, I.A.G.; Walker, H.J.; Ward-Thompson, D.; Weferling, B.; White, G.J.; Yates, J.; Zhu, M.; Craigon, A.

2007-01-01

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA-2 Unbiased Nearby Stars (SUNS) survey will observe 500 nearby main-sequence and subgiant stars (100 of each of the A, F, G, K, and M spectral

Automated and unbiased image analyses as tools in phenotypic classification of small-spored Alternaria species

DEFF Research Database (Denmark)

Andersen, Birgitte; Hansen, Michael Edberg; Smedsgaard, Jørn

2005-01-01

often has been broadly applied to various morphologically and chemically distinct groups of isolates from different hosts. The purpose of this study was to develop and evaluate automated and unbiased image analysis systems that will analyze different phenotypic characters and facilitate testing...

Stereological study of the effect of ginger's alcoholic extract on the testis in busulfan-induced infertility in rats

Directory of Open Access Journals (Sweden)

Hossein Bordbar

2013-06-01

Full Text Available Background: In traditional medicine zingiber officinale used to regulate female menstural cycle and treat male infertility. Recent studies have suggested the possible role of ginger extract in improving the testicular damage of busulfan. Objective: The aim of this study was to evaluate the effects of zingiber officinale on the sperm parameters, testosterone level and the volume of the testes and seminiferous tubules by stereological methods. Materials and Methods: Fifty rats were divided into four groups. All the rats were given a single intraperitoneally injection of 5mg/kg busulfan solution. The first group was kept as busulfan control, while the other groups were orally administrated ginger extract in graded doses of 50, 100 and 150mg/kg b.wt, for 48 consecutive days. At the end, all animals were anesthetized and their testes and vas deference were removed, fixed, embedded, and stained. The volume of testes and seminiferous tubules were estimated by cavalieri methods. Results: The result showed, that zingiber officinale increased the volumes of seminiferous tubule in 100mg/kg treated group compared to control group. Sperm count (706×105 and 682×105 and the level of testosterone (50.90 ng/mL and 54.10 ng/mL enhanced in 100 mg/kg and 150 mg/kg treated groups compared to control group (p=0.00. Conclusion: It seems that zingiber officinale stimulate male reproductive system in induce busulfan infertility

Using small area estimation and Lidar-derived variables for multivariate prediction of forest attributes

Science.gov (United States)

F. Mauro; Vicente Monleon; H. Temesgen

2015-01-01

Small area estimation (SAE) techniques have been successfully applied in forest inventories to provide reliable estimates for domains where the sample size is small (i.e. small areas). Previous studies have explored the use of either Area Level or Unit Level Empirical Best Linear Unbiased Predictors (EBLUPs) in a univariate framework, modeling each variable of interest...

Creel survey sampling designs for estimating effort in short-duration Chinook salmon fisheries

Science.gov (United States)

McCormick, Joshua L.; Quist, Michael C.; Schill, Daniel J.

2013-01-01

Chinook Salmon Oncorhynchus tshawytscha sport fisheries in the Columbia River basin are commonly monitored using roving creel survey designs and require precise, unbiased catch estimates. The objective of this study was to examine the relative bias and precision of total catch estimates using various sampling designs to estimate angling effort under the assumption that mean catch rate was known. We obtained information on angling populations based on direct visual observations of portions of Chinook Salmon fisheries in three Idaho river systems over a 23-d period. Based on the angling population, Monte Carlo simulations were used to evaluate the properties of effort and catch estimates for each sampling design. All sampling designs evaluated were relatively unbiased. Systematic random sampling (SYS) resulted in the most precise estimates. The SYS and simple random sampling designs had mean square error (MSE) estimates that were generally half of those observed with cluster sampling designs. The SYS design was more efficient (i.e., higher accuracy per unit cost) than a two-cluster design. Increasing the number of clusters available for sampling within a day decreased the MSE of estimates of daily angling effort, but the MSE of total catch estimates was variable depending on the fishery. The results of our simulations provide guidelines on the relative influence of sample sizes and sampling designs on parameters of interest in short-duration Chinook Salmon fisheries.

Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes Enabled by a Nitrite Co-Catalyst

KAUST Repository

Wickens, Zachary K.; Morandi, Bill; Grubbs, Robert H.

2013-01-01

Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with high yield and aldehyde selectivity, and several functional groups are tolerated. 18O-labeling experiments indicate that the aldehydic O atom is derived from the nitrite salt.

Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes Enabled by a Nitrite Co-Catalyst

KAUST Repository

Wickens, Zachary K.

2013-09-13

Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with high yield and aldehyde selectivity, and several functional groups are tolerated. 18O-labeling experiments indicate that the aldehydic O atom is derived from the nitrite salt.

Multi-level restricted maximum likelihood covariance estimation and kriging for large non-gridded spatial datasets

KAUST Repository

Castrillon, Julio; Genton, Marc G.; Yokota, Rio

2015-01-01

We develop a multi-level restricted Gaussian maximum likelihood method for estimating the covariance function parameters and computing the best unbiased predictor. Our approach produces a new set of multi-level contrasts where the deterministic

Signal detection theory and vestibular perception: III. Estimating unbiased fit parameters for psychometric functions.

Science.gov (United States)

Chaudhuri, Shomesh E; Merfeld, Daniel M

2013-03-01

Psychophysics generally relies on estimating a subject's ability to perform a specific task as a function of an observed stimulus. For threshold studies, the fitted functions are called psychometric functions. While fitting psychometric functions to data acquired using adaptive sampling procedures (e.g., "staircase" procedures), investigators have encountered a bias in the spread ("slope" or "threshold") parameter that has been attributed to the serial dependency of the adaptive data. Using simulations, we confirm this bias for cumulative Gaussian parametric maximum likelihood fits on data collected via adaptive sampling procedures, and then present a bias-reduced maximum likelihood fit that substantially reduces the bias without reducing the precision of the spread parameter estimate and without reducing the accuracy or precision of the other fit parameters. As a separate topic, we explain how to implement this bias reduction technique using generalized linear model fits as well as other numeric maximum likelihood techniques such as the Nelder-Mead simplex. We then provide a comparison of the iterative bootstrap and observed information matrix techniques for estimating parameter fit variance from adaptive sampling procedure data sets. The iterative bootstrap technique is shown to be slightly more accurate; however, the observed information technique executes in a small fraction (0.005 %) of the time required by the iterative bootstrap technique, which is an advantage when a real-time estimate of parameter fit variance is required.

Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum

DEFF Research Database (Denmark)

Licht, R W; Larsen, Jytte Overgaard; Smith, D

2003-01-01

We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were...... randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were...

Transport-constrained extensions of collision and track length estimators for solutions of radiative transport problems

International Nuclear Information System (INIS)

Kong, Rong; Spanier, Jerome

2013-01-01

In this paper we develop novel extensions of collision and track length estimators for the complete space-angle solutions of radiative transport problems. We derive the relevant equations, prove that our new estimators are unbiased, and compare their performance with that of more conventional estimators. Such comparisons based on numerical solutions of simple one dimensional slab problems indicate the the potential superiority of the new estimators for a wide variety of more general transport problems

RandomSpot: A web-based tool for systematic random sampling of virtual slides.

Science.gov (United States)

Wright, Alexander I; Grabsch, Heike I; Treanor, Darren E

2015-01-01

This paper describes work presented at the Nordic Symposium on Digital Pathology 2014, Linköping, Sweden. Systematic random sampling (SRS) is a stereological tool, which provides a framework to quickly build an accurate estimation of the distribution of objects or classes within an image, whilst minimizing the number of observations required. RandomSpot is a web-based tool for SRS in stereology, which systematically places equidistant points within a given region of interest on a virtual slide. Each point can then be visually inspected by a pathologist in order to generate an unbiased sample of the distribution of classes within the tissue. Further measurements can then be derived from the distribution, such as the ratio of tumor to stroma. RandomSpot replicates the fundamental principle of traditional light microscope grid-shaped graticules, with the added benefits associated with virtual slides, such as facilitated collaboration and automated navigation between points. Once the sample points have been added to the region(s) of interest, users can download the annotations and view them locally using their virtual slide viewing software. Since its introduction, RandomSpot has been used extensively for international collaborative projects, clinical trials and independent research projects. So far, the system has been used to generate over 21,000 sample sets, and has been used to generate data for use in multiple publications, identifying significant new prognostic markers in colorectal, upper gastro-intestinal and breast cancer. Data generated using RandomSpot also has significant value for training image analysis algorithms using sample point coordinates and pathologist classifications.

Fixed-location hydroacoustic monitoring designs for estimating fish passage using stratified random and systematic sampling

International Nuclear Information System (INIS)

Skalski, J.R.; Hoffman, A.; Ransom, B.H.; Steig, T.W.

1993-01-01

Five alternate sampling designs are compared using 15 d of 24-h continuous hydroacoustic data to identify the most favorable approach to fixed-location hydroacoustic monitoring of salmonid outmigrants. Four alternative aproaches to systematic sampling are compared among themselves and with stratified random sampling (STRS). Stratifying systematic sampling (STSYS) on a daily basis is found to reduce sampling error in multiday monitoring studies. Although sampling precision was predictable with varying levels of effort in STRS, neither magnitude nor direction of change in precision was predictable when effort was varied in systematic sampling (SYS). Furthermore, modifying systematic sampling to include replicated (e.g., nested) sampling (RSYS) is further shown to provide unbiased point and variance estimates as does STRS. Numerous short sampling intervals (e.g., 12 samples of 1-min duration per hour) must be monitored hourly using RSYS to provide efficient, unbiased point and interval estimates. For equal levels of effort, STRS outperformed all variations of SYS examined. Parametric approaches to confidence interval estimates are found to be superior to nonparametric interval estimates (i.e., bootstrap and jackknife) in estimating total fish passage. 10 refs., 1 fig., 8 tabs

Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

DEFF Research Database (Denmark)

Jung, A; Allen, L; Nyengaard, Jens Randel

2005-01-01

Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach...

Stereological estimation of total cell numbers in the young human utricular macula

DEFF Research Database (Denmark)

Severinsen, Stig Avall; Sørensen, Mads Sølvsten; Kirkegaard, Mette

2010-01-01

Abstract Conclusion: There is no change in the total cell population and hair cell:supporting cell ratio in the human utricular macula from gestational week 16 and onwards, whereas the lower hair cell:supporting cell ratio and lower total number of cells in the youngest specimens indicate...... that the utricle is still differentiating and adding new cells at the 10th to 12th gestational week. Objectives: Archival temporal bones were investigated to quantify cell numbers in the utricular macula in fetuses and children. Methods: The age of the subjects ranged from gestational week 10 to 15 years....... The optical fractionator was used to estimate the total number of cells in the utricular macula. Results: The total cell number was found to be 143 000 in subjects older than gestational week 16. The number of hair cells and supporting cells did not change between the 16th gestational week and 15 years...

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

DEFF Research Database (Denmark)

Damsgaard, T E; Olesen, A B; Sørensen, Flemming Brandt

1997-01-01

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results...... of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out...... yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found...

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

DEFF Research Database (Denmark)

Damsgaard, T E; Olesen, A B; Sørensen, Flemming Brandt

1997-01-01

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results...... of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out...... at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 microns serial sections. Ten sections, 30 microns apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study...

Empirically Driven Variable Selection for the Estimation of Causal Effects with Observational Data

Science.gov (United States)

Keller, Bryan; Chen, Jianshen

2016-01-01

Observational studies are common in educational research, where subjects self-select or are otherwise non-randomly assigned to different interventions (e.g., educational programs, grade retention, special education). Unbiased estimation of a causal effect with observational data depends crucially on the assumption of ignorability, which specifies…

A statistical model for estimation of fish density including correlation in size, space, time and between species from research survey data

DEFF Research Database (Denmark)

Nielsen, J. Rasmus; Kristensen, Kasper; Lewy, Peter

2014-01-01

Trawl survey data with high spatial and seasonal coverage were analysed using a variant of the Log Gaussian Cox Process (LGCP) statistical model to estimate unbiased relative fish densities. The model estimates correlations between observations according to time, space, and fish size and includes...

Applied tensor stereology

DEFF Research Database (Denmark)

Ziegel, Johanna; Nyengaard, Jens Randel; Jensen, Eva B. Vedel

In the present paper, statistical procedures for estimating shape and orientation of arbitrary three-dimensional particles are developed. The focus of this work is on the case where the particles cannot be observed directly, but only via sections. Volume tensors are used for describing particle s...

The Effects of Acoustic White Noise on the Rat Central Auditory System During the Fetal and Critical Neonatal Periods: A Stereological Study.

Science.gov (United States)

Salehi, Mohammad Saied; Namavar, Mohammad Reza; Tamadon, Amin; Bahmani, Raziyeh; Jafarzadeh Shirazi, Mohammad Reza; Khazali, Homayoun; Dargahi, Leila; Pandamooz, Sareh; Mohammad-Rezazadeh, Farzad; Rashidi, Fatemeh Sadat

2017-01-01

To evaluate the effects of long-term, moderate level noise exposure during crucial periods of rat infants on stereological parameters of medial geniculate body (MGB) and auditory cortex. Twenty-four male offspring of 12 pregnant rats were divided into four groups: fetal-to-critical period group, which were exposed to noise from the last 10 days of fetal life till postnatal day (PND) 29; fetal period group that exposed to noise during the last 10 days of fetal life; critical period group, exposed to noise from PND 15 till PND 29, and control group. White noise at 90 dB for 2 h per day was used. Variance for variables was performed using Proc GLM followed by mean comparison by Duncan's multiple range test. Numerical density of neurons in MGB of fetal-to-critical period group was lower than control group. Similar results were seen in numerical density of neurons in layers IV and VI of auditory cortex. Furthermore, no significant difference was observed in the volume of auditory cortex among groups, and only MGB volume in fetal-to-critical period group was higher than other groups. Estimated total number of neurons in MGB was not significantly different among groups. It seems necessary to prevent long-term moderate level noise exposure during fetal-to-critical neonatal period.

MRI volumetry of prefrontal cortex

Science.gov (United States)

Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

1995-05-01

Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Science.gov (United States)

Craggs, Lucinda J L; Yamamoto, Yumi; Ihara, Masafumi; Fenwick, Richard; Burke, Matthew; Oakley, Arthur E; Roeber, Sigrun; Duering, Marco; Kretzschmar, Hans; Kalaria, Raj N

2014-08-01

Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (Pneurones connecting to targets in the subcortical structures. © 2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

Science.gov (United States)

Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi

2015-04-28

Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.

A characteristic ventricular shape in myelomeningocele-associated hydrocephalus? A CT stereology study

International Nuclear Information System (INIS)

Roost, D. van; Solymosi, L.; Funke, K.

1995-01-01

We measured the volume of the supratentorial ventricles in 39 consecutive children with myelomeningocele (MMC) and associated hydrocephalus, using a stereological method based on the Cavalieri theorem of systematic sampling. We distinguished the following groups: newborns before and after cerebrospinal fluid shunting (14), a somewhat larger group of newborns with an untreated MMC-associated hydrocephalus (25) and a group of shunted children at a mean age of 1.5 years (28). We paid special attention to the shape of the lateral ventricles, looking separately at the anterior and posterior halves. The measurements were compared with a healthy control group (10) and with children with hydrocephalus unrelated to MMC (15). The average volume ratio of the posterior to the anterior half of the lateral ventricles was 1.05 ± 0.39 in non-hydrocephalic children, 1.11 ± 0.55 in untreated hydrocephalic children without MMC, and 2.15 ± 0.65 in MMC-associated hydrocephalus prior to shunting. These ratios did not change significantly after shunting. This confirms our impression that MMC-associated hydrocephalus shows a characteristic shape, with a disproportionate enlargement of the posterior part of the lateral ventricles, in clear contrast to the normal-width frontal horns. This shape is reminiscent of the fetal ventricular shape. It reveals disturbance of brain development in children with MMC, which goes beyond the classic description of the Chiari malformation. (orig.)

Improved linear least squares estimation using bounded data uncertainty

KAUST Repository

Ballal, Tarig

2015-04-01

This paper addresses the problemof linear least squares (LS) estimation of a vector x from linearly related observations. In spite of being unbiased, the original LS estimator suffers from high mean squared error, especially at low signal-to-noise ratios. The mean squared error (MSE) of the LS estimator can be improved by introducing some form of regularization based on certain constraints. We propose an improved LS (ILS) estimator that approximately minimizes the MSE, without imposing any constraints. To achieve this, we allow for perturbation in the measurement matrix. Then we utilize a bounded data uncertainty (BDU) framework to derive a simple iterative procedure to estimate the regularization parameter. Numerical results demonstrate that the proposed BDU-ILS estimator is superior to the original LS estimator, and it converges to the best linear estimator, the linear-minimum-mean-squared error estimator (LMMSE), when the elements of x are statistically white.

Improved linear least squares estimation using bounded data uncertainty

KAUST Repository

Ballal, Tarig; Al-Naffouri, Tareq Y.

2015-01-01

This paper addresses the problemof linear least squares (LS) estimation of a vector x from linearly related observations. In spite of being unbiased, the original LS estimator suffers from high mean squared error, especially at low signal-to-noise ratios. The mean squared error (MSE) of the LS estimator can be improved by introducing some form of regularization based on certain constraints. We propose an improved LS (ILS) estimator that approximately minimizes the MSE, without imposing any constraints. To achieve this, we allow for perturbation in the measurement matrix. Then we utilize a bounded data uncertainty (BDU) framework to derive a simple iterative procedure to estimate the regularization parameter. Numerical results demonstrate that the proposed BDU-ILS estimator is superior to the original LS estimator, and it converges to the best linear estimator, the linear-minimum-mean-squared error estimator (LMMSE), when the elements of x are statistically white.

An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

DEFF Research Database (Denmark)

Lyck, L.; Santamaria, I.D.; Pakkenberg, B.

2009-01-01

Improving histomorphometric analysis of the human neocortex by combining stereological cell counting with immunchistochemical visualisation of specific neuronal and glial cell populations is a methodological challenge. To enable standardized immunohistochemical staining, the amount of brain tissue...... at each level of sampling was determined empirically. The methodology was tested in three brains analysing the contribution of the multi-step sampling procedure to the precision on the estimated total numbers of immunohistochemically defined NeuN expressing (NeuN(+)) neurons and CD45(+) microglia...

Unbiased determination of polarized parton distributions and their uncertainties

CERN Document Server

Ball, Richard D.; Guffanti, Alberto; Nocera, Emanuele R.; Ridolfi, Giovanni; Rojo, Juan

2013-01-01

We present a determination of a set of polarized parton distributions (PDFs) of the nucleon, at next-to-leading order, from a global set of longitudinally polarized deep-inelastic scattering data: NNPDFpol1.0. The determination is based on the NNPDF methodology: a Monte Carlo approach, with neural networks used as unbiased interpolants, previously applied to the determination of unpolarized parton distributions, and designed to provide a faithful and statistically sound representation of PDF uncertainties. We present our dataset, its statistical features, and its Monte Carlo representation. We summarize the technique used to solve the polarized evolution equations and its benchmarking, and the method used to compute physical observables. We review the NNPDF methodology for parametrization and fitting of neural networks, the algorithm used to determine the optimal fit, and its adaptation to the polarized case. We finally present our set of polarized parton distributions. We discuss its statistical properties, ...

Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.

Science.gov (United States)

Chen, Charles H; Wiedman, Gregory; Khan, Ayesha; Ulmschneider, Martin B

2014-09-01

Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014. Published by Elsevier B.V.

Estimating the Quadratic Variation Spectrum of Noisy Asset Prices Using Generalized Flat-top Realized Kernels

DEFF Research Database (Denmark)

Varneskov, Rasmus T.

2014-01-01

-top estimators are shown to be consistent, asymptotically unbiased, and mixed Gaussian at the optimal rate of convergence, n1/4. Exact bound on lower order terms are obtained using maximal inequalities and these are used to derive a conservative, MSE-optimal flat-top shrinkage. Additionally, bounds...

Weighted Moments Estimators of the Parameters for the Extreme Value Distribution Based on the Multiply Type II Censored Sample

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Jong-Wuu Wu

2013-01-01

Full Text Available We propose the weighted moments estimators (WMEs of the location and scale parameters for the extreme value distribution based on the multiply type II censored sample. Simulated mean squared errors (MSEs of best linear unbiased estimator (BLUE and exact MSEs of WMEs are compared to study the behavior of different estimation methods. The results show the best estimator among the WMEs and BLUE under different combinations of censoring schemes.

An Introduction to Generalized Estimating Equations and an Application to Assess Selectivity Effects in a Longitudinal Study on Very Old Individuals

Science.gov (United States)

Ghisletta, Paolo; Spini, Dario

2004-01-01

Correlated data are very common in the social sciences. Most common applications include longitudinal and hierarchically organized (or clustered) data. Generalized estimating equations (GEE) are a convenient and general approach to the analysis of several kinds of correlated data. The main advantage of GEE resides in the unbiased estimation of…

Unextendible Mutually Unbiased Bases (after Mandayam, Bandyopadhyay, Grassl and Wootters

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Koen Thas

2016-11-01

Full Text Available We consider questions posed in a recent paper of Mandayam et al. (2014 on the nature of “unextendible mutually unbiased bases.” We describe a conceptual framework to study these questions, using a connection proved by the author in Thas (2009 between the set of nonidentity generalized Pauli operators on the Hilbert space of N d-level quantum systems, d a prime, and the geometry of non-degenerate alternating bilinear forms of rank N over finite fields F d . We then supply alternative and short proofs of results obtained in Mandayam et al. (2014, as well as new general bounds for the problems considered in loc. cit. In this setting, we also solve Conjecture 1 of Mandayam et al. (2014 and speculate on variations of this conjecture.

Is length an appropriate estimator to characterize pulmonary alveolar capillaries? A critical evaluation in the human lung

DEFF Research Database (Denmark)

Mühlfeld, Christian; Weibel, Ewald R.; Hahn, Ute

2010-01-01

Stereological estimations of total capillary length have been used to characterize changes in the alveolar capillary network (ACN) during developmental processes or pathophysiological conditions. Here, we analyzed whether length estimations are appropriate to describe the 3D nature of the ACN. Semi...... resulted in a mean of 2,746 km (SD: 722 km). Because of the geometry of the ACN both approaches carry an unpredictable bias. The bias incurred by the design-based approach is proportional to the ratio between radius and length of the capillary segments in the ACN, the number of branching points...... and the winding of the capillaries. The model-based approach is biased because of the real noncylindrical shape of capillaries and the network structure. In conclusion, the estimation of the total length of capillaries in the ACN cannot be recommended as the geometry of the ACN does not fulfill the requirements...

Estimation of otitis media in ancient populations: A study of past and present Greenlandic Inuit

DEFF Research Database (Denmark)

Homøe, P; Lynnerup, N; Skovgaard, Lene Theil

1996-01-01

Examination of disease patterns in the past has often been difficult due to lack of morphological evidence. This study presents a new unbiased method for estimation of occurrence of infectious middle ear disease (IMED) in childhood. The method is based on the relation between IMED in childhood an...

Landslide susceptibility assessment in the Upper Orcia Valley (Southern Tuscany, Italy through conditional analysis: a contribution to the unbiased selection of causal factors

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F. Vergari

2011-05-01

Full Text Available In this work the conditional multivariate analysis was applied to evaluate landslide susceptibility in the Upper Orcia River Basin (Tuscany, Italy, where widespread denudation processes and agricultural practices have a mutual impact. We introduced an unbiased procedure for causal factor selection based on some intuitive statistical indices. This procedure is aimed at detecting among different potential factors the most discriminant ones in a given study area. Moreover, this step avoids generating too small and statistically insignificant spatial units by intersecting the factor maps. Finally, a validation procedure was applied based on the partition of the landslide inventory from multi-temporal aerial photo interpretation.

Although encompassing some sources of uncertainties, the applied susceptibility assessment method provided a satisfactory and unbiased prediction for the Upper Orcia Valley. The results confirmed the efficiency of the selection procedure, as an unbiased step of the landslide susceptibility evaluation. Furthermore, we achieved the purpose of presenting a conceptually simple but, at the same time, effective statistical procedure for susceptibility analysis to be used as well by decision makers in land management.

STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

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Terry M Mayhew

2011-05-01

Full Text Available In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area. Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios or progressive (volume, surface and length densities increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter. In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced

Accurate estimation of the RMS emittance from single current amplifier data

International Nuclear Information System (INIS)

Stockli, Martin P.; Welton, R.F.; Keller, R.; Letchford, A.P.; Thomae, R.W.; Thomason, J.W.G.

2002-01-01

This paper presents the SCUBEEx rms emittance analysis, a self-consistent, unbiased elliptical exclusion method, which combines traditional data-reduction methods with statistical methods to obtain accurate estimates for the rms emittance. Rather than considering individual data, the method tracks the average current density outside a well-selected, variable boundary to separate the measured beam halo from the background. The average outside current density is assumed to be part of a uniform background and not part of the particle beam. Therefore the average outside current is subtracted from the data before evaluating the rms emittance within the boundary. As the boundary area is increased, the average outside current and the inside rms emittance form plateaus when all data containing part of the particle beam are inside the boundary. These plateaus mark the smallest acceptable exclusion boundary and provide unbiased estimates for the average background and the rms emittance. Small, trendless variations within the plateaus allow for determining the uncertainties of the estimates caused by variations of the measured background outside the smallest acceptable exclusion boundary. The robustness of the method is established with complementary variations of the exclusion boundary. This paper presents a detailed comparison between traditional data reduction methods and SCUBEEx by analyzing two complementary sets of emittance data obtained with a Lawrence Berkeley National Laboratory and an ISIS H - ion source

Finite mixture model: A maximum likelihood estimation approach on time series data

Science.gov (United States)

Yen, Phoong Seuk; Ismail, Mohd Tahir; Hamzah, Firdaus Mohamad

2014-09-01

Recently, statistician emphasized on the fitting of finite mixture model by using maximum likelihood estimation as it provides asymptotic properties. In addition, it shows consistency properties as the sample sizes increases to infinity. This illustrated that maximum likelihood estimation is an unbiased estimator. Moreover, the estimate parameters obtained from the application of maximum likelihood estimation have smallest variance as compared to others statistical method as the sample sizes increases. Thus, maximum likelihood estimation is adopted in this paper to fit the two-component mixture model in order to explore the relationship between rubber price and exchange rate for Malaysia, Thailand, Philippines and Indonesia. Results described that there is a negative effect among rubber price and exchange rate for all selected countries.

Optimal estimations of random fields using kriging

International Nuclear Information System (INIS)

Barua, G.

2004-01-01

Kriging is a statistical procedure of estimating the best weights of a linear estimator. Suppose there is a point or an area or a volume of ground over which we do not know a hydrological variable and wish to estimate it. In order to produce an estimator, we need some information to work on, usually available in the form of samples. There can, be an infinite number of linear unbiased estimators for which the weights sum up to one. The problem is how to determine the best weights for which the estimation variance is the least. The system of equations as shown above is generally known as the kriging system and the estimator produced is the kriging estimator. The variance of the kriging estimator can be found by substitution of the weights in the general estimation variance equation. We assume here a linear model for the semi-variogram. Applying the model to the equation, we obtain a set of kriging equations. By solving these equations, we obtain the kriging variance. Thus, for the one-dimensional problem considered, kriging definitely gives a better estimation variance than the extension variance

Cokriging model for estimation of water table elevation

International Nuclear Information System (INIS)

Hoeksema, R.J.; Clapp, R.B.; Thomas, A.L.; Hunley, A.E.; Farrow, N.D.; Dearstone, K.C.

1989-01-01

In geological settings where the water table is a subdued replica of the ground surface, cokriging can be used to estimate the water table elevation at unsampled locations on the basis of values of water table elevation and ground surface elevation measured at wells and at points along flowing streams. The ground surface elevation at the estimation point must also be determined. In the proposed method, separate models are generated for the spatial variability of the water table and ground surface elevation and for the dependence between these variables. After the models have been validated, cokriging or minimum variance unbiased estimation is used to obtain the estimated water table elevations and their estimation variances. For the Pits and Trenches area (formerly a liquid radioactive waste disposal facility) near Oak Ridge National Laboratory, water table estimation along a linear section, both with and without the inclusion of ground surface elevation as a statistical predictor, illustrate the advantages of the cokriging model

Estimation of equivalent dose and its uncertainty in the OSL SAR protocol when count numbers do not follow a Poisson distribution

International Nuclear Information System (INIS)

Bluszcz, Andrzej; Adamiec, Grzegorz; Heer, Aleksandra J.

2015-01-01

The current work focuses on the estimation of equivalent dose and its uncertainty using the single aliquot regenerative protocol in optically stimulated luminescence measurements. The authors show that the count numbers recorded with the use of photomultiplier tubes are well described by negative binomial distributions, different ones for background counts and photon induced counts. This fact is then exploited in pseudo-random count number generation and simulations of D e determination assuming a saturating exponential growth. A least squares fitting procedure is applied using different types of weights to determine whether the obtained D e 's and their error estimates are unbiased and accurate. A weighting procedure is suggested that leads to almost unbiased D e estimates. It is also shown that the assumption of Poisson distribution in D e estimation may lead to severe underestimation of the D e error. - Highlights: • Detailed analysis of statistics of count numbers in luminescence readers. • Generation of realistically scattered pseudo-random numbers of counts in luminescence measurements. • A practical guide for stringent analysis of D e values and errors assessment.

FIBRIN-TYPE FIBRINOID IN HUMAN PLACENTA: A STEREOLOGICAL ANALYSIS OF ITS ASSOCIATION WITH INTERVILLOUS VOLUME AND VILLOUS SURFACE AREA

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Terry M Mayhew

2011-05-01

Full Text Available Stereological methods were used to examine fibrin-type fibrinoid deposition in the intervillous spaces of human placentas collected during gestation (12-41 weeks and from term pregnancies at low (400 m and high (3.6 km altitude. The main aim was to test predictions about the relationships between fibrinoid deposits and either the volume of intervillous space or the surface area of (intermediate + terminal villi. Fields of view on Masson trichrome-stained paraffin sections were selected as part of a systematic sampling design which randomised section location and orientation. Relative and absolute volumes were estimated by test point counting and surfaces by intersection counting. Apparent differences were tested by analyses of variance and relationships by correlation and regression analysis. Fibrinoid volume increased during gestation and correlated positively with intervillous volume and villous surface area. However, relative to intervillous volume, the main increase in fibrinoid occurred towards term (36-41 weeks. At high altitude, placentas contained more intervillous space but less fibrinoid. At both altitudes, there were significant correlations between fibrinoid volume and villous surface area. In all cases, changes in fibrinoid volume were commensurate with changes in villous surface area. Whilst findings lend support to the notion that fibrinoid deposition during normal gestation is influenced by the quality of vascular perfusion, they also emphasise that the extent of the villous surface is a more generally important factor. The villous surface may influence the steady state between coagulation and fibrinolysis since some pro-coagulatory events operate at the trophoblastic epithelium. They occur notably at sites of trophoblast de-epithelialisation and these arise following trauma or during the extrusion phase of normal epithelial turnover.

Crataegus Monogyna Aqueous Extract Ameliorates Cyclophosphamide-Induced Toxicity in Rat Testis: Stereological Evidences

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Hassan Malekinejad

2012-01-01

Full Text Available Cyclophosphamide (CP is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

Effects of social organization, trap arrangement and density, sampling scale, and population density on bias in population size estimation using some common mark-recapture estimators.

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Manan Gupta

Full Text Available Mark-recapture estimators are commonly used for population size estimation, and typically yield unbiased estimates for most solitary species with low to moderate home range sizes. However, these methods assume independence of captures among individuals, an assumption that is clearly violated in social species that show fission-fusion dynamics, such as the Asian elephant. In the specific case of Asian elephants, doubts have been raised about the accuracy of population size estimates. More importantly, the potential problem for the use of mark-recapture methods posed by social organization in general has not been systematically addressed. We developed an individual-based simulation framework to systematically examine the potential effects of type of social organization, as well as other factors such as trap density and arrangement, spatial scale of sampling, and population density, on bias in population sizes estimated by POPAN, Robust Design, and Robust Design with detection heterogeneity. In the present study, we ran simulations with biological, demographic and ecological parameters relevant to Asian elephant populations, but the simulation framework is easily extended to address questions relevant to other social species. We collected capture history data from the simulations, and used those data to test for bias in population size estimation. Social organization significantly affected bias in most analyses, but the effect sizes were variable, depending on other factors. Social organization tended to introduce large bias when trap arrangement was uniform and sampling effort was low. POPAN clearly outperformed the two Robust Design models we tested, yielding close to zero bias if traps were arranged at random in the study area, and when population density and trap density were not too low. Social organization did not have a major effect on bias for these parameter combinations at which POPAN gave more or less unbiased population size estimates

Unbiased Strain-Typing of Arbovirus Directly from Mosquitoes Using Nanopore Sequencing: A Field-forward Biosurveillance Protocol.

Science.gov (United States)

Russell, Joseph A; Campos, Brittany; Stone, Jennifer; Blosser, Erik M; Burkett-Cadena, Nathan; Jacobs, Jonathan L

2018-04-03

The future of infectious disease surveillance and outbreak response is trending towards smaller hand-held solutions for point-of-need pathogen detection. Here, samples of Culex cedecei mosquitoes collected in Southern Florida, USA were tested for Venezuelan Equine Encephalitis Virus (VEEV), a previously-weaponized arthropod-borne RNA-virus capable of causing acute and fatal encephalitis in animal and human hosts. A single 20-mosquito pool tested positive for VEEV by quantitative reverse transcription polymerase chain reaction (RT-qPCR) on the Biomeme two3. The virus-positive sample was subjected to unbiased metatranscriptome sequencing on the Oxford Nanopore MinION and shown to contain Everglades Virus (EVEV), an alphavirus in the VEEV serocomplex. Our results demonstrate, for the first time, the use of unbiased sequence-based detection and subtyping of a high-consequence biothreat pathogen directly from an environmental sample using field-forward protocols. The development and validation of methods designed for field-based diagnostic metagenomics and pathogen discovery, such as those suitable for use in mobile "pocket laboratories", will address a growing demand for public health teams to carry out their mission where it is most urgent: at the point-of-need.

Estimation of the reliability function for two-parameter exponentiated Rayleigh or Burr type X distribution

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Anupam Pathak

2014-11-01

Full Text Available Abstract: Problem Statement: The two-parameter exponentiated Rayleigh distribution has been widely used especially in the modelling of life time event data. It provides a statistical model which has a wide variety of application in many areas and the main advantage is its ability in the context of life time event among other distributions. The uniformly minimum variance unbiased and maximum likelihood estimation methods are the way to estimate the parameters of the distribution. In this study we explore and compare the performance of the uniformly minimum variance unbiased and maximum likelihood estimators of the reliability function R(t=P(X>t and P=P(X>Y for the two-parameter exponentiated Rayleigh distribution. Approach: A new technique of obtaining these parametric functions is introduced in which major role is played by the powers of the parameter(s and the functional forms of the parametric functions to be estimated are not needed.  We explore the performance of these estimators numerically under varying conditions. Through the simulation study a comparison are made on the performance of these estimators with respect to the Biasness, Mean Square Error (MSE, 95% confidence length and corresponding coverage percentage. Conclusion: Based on the results of simulation study the UMVUES of R(t and ‘P’ for the two-parameter exponentiated Rayleigh distribution found to be superior than MLES of R(t and ‘P’.

Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

Science.gov (United States)

Marcos, Ricardo; Correia-Gomes, Carla

2016-12-01

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

Systematic sampling of discrete and continuous populations: sample selection and the choice of estimator

Science.gov (United States)

Harry T. Valentine; David L. R. Affleck; Timothy G. Gregoire

2009-01-01

Systematic sampling is easy, efficient, and widely used, though it is not generally recognized that a systematic sample may be drawn from the population of interest with or without restrictions on randomization. The restrictions or the lack of them determine which estimators are unbiased, when using the sampling design as the basis for inference. We describe the...

Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice.

Science.gov (United States)

Chao, Fenglei; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Zhang, Lei; Tang, Jing; Liang, Xin; Qi, Yingqiang; Zhu, Yanqing; Ma, Jing; Tang, Yong

2018-01-01

The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.

Computer-generated ovaries to assist follicle counting experiments.

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Angelos Skodras

Full Text Available Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries, with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units.

Nearest Neighbor Estimates of Entropy for Multivariate Circular Distributions

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Neeraj Misra

2010-05-01

Full Text Available In molecular sciences, the estimation of entropies of molecules is important for the understanding of many chemical and biological processes. Motivated by these applications, we consider the problem of estimating the entropies of circular random vectors and introduce non-parametric estimators based on circular distances between n sample points and their k th nearest neighbors (NN, where k (≤ n – 1 is a fixed positive integer. The proposed NN estimators are based on two different circular distances, and are proven to be asymptotically unbiased and consistent. The performance of one of the circular-distance estimators is investigated and compared with that of the already established Euclidean-distance NN estimator using Monte Carlo samples from an analytic distribution of six circular variables of an exactly known entropy and a large sample of seven internal-rotation angles in the molecule of tartaric acid, obtained by a realistic molecular-dynamics simulation.

Uncertainty estimation with a small number of measurements, part II: a redefinition of uncertainty and an estimator method

Science.gov (United States)

Huang, Hening

2018-01-01

This paper is the second (Part II) in a series of two papers (Part I and Part II). Part I has quantitatively discussed the fundamental limitations of the t-interval method for uncertainty estimation with a small number of measurements. This paper (Part II) reveals that the t-interval is an ‘exact’ answer to a wrong question; it is actually misused in uncertainty estimation. This paper proposes a redefinition of uncertainty, based on the classical theory of errors and the theory of point estimation, and a modification of the conventional approach to estimating measurement uncertainty. It also presents an asymptotic procedure for estimating the z-interval. The proposed modification is to replace the t-based uncertainty with an uncertainty estimator (mean- or median-unbiased). The uncertainty estimator method is an approximate answer to the right question to uncertainty estimation. The modified approach provides realistic estimates of uncertainty, regardless of whether the population standard deviation is known or unknown, or if the sample size is small or large. As an application example of the modified approach, this paper presents a resolution to the Du-Yang paradox (i.e. Paradox 2), one of the three paradoxes caused by the misuse of the t-interval in uncertainty estimation.

Long lasting structural changes in primary motor cortex after motor skill learning: a behavioural and stereological study

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PAOLA MORALES

2008-12-01

Full Text Available Many motor skills, once acquired, are stored over a long time period, probably sustained by permanent neuronal changes. Thus, in this paper we have investigated with quantitative stereology the generation and persistence of neuronal density changes in primary motor cortex (MI following motor skill learning (skilled reaching task. Rats were trained a lateralised reaching task during an "early" (22-31 days oíd or "late" (362-371 days oíd postnatal period. The trained and corresponding control rats were sacrificed at day 372, immediately after the behavioural testing. The "early" trained group preserved the learned skilled reaching task when tested at day 372, without requiring any additional training. The "late" trained group showed a similar capacity to that of the "early" trained group for learning the skilled reaching task. All trained animáis ("early" and "late" trained groups showed a significant Ínter hemispheric decrease of neuronal density in the corresponding motor forelimb representation área of MI (cortical layers II-III

Towards an unbiased comparison of CC, BCC, and FCC lattices in terms of prealiasing

KAUST Repository

Vad, Viktor

2014-06-01

In the literature on optimal regular volume sampling, the Body-Centered Cubic (BCC) lattice has been proven to be optimal for sampling spherically band-limited signals above the Nyquist limit. On the other hand, if the sampling frequency is below the Nyquist limit, the Face-Centered Cubic (FCC) lattice was demonstrated to be optimal in reducing the prealiasing effect. In this paper, we confirm that the FCC lattice is indeed optimal in this sense in a certain interval of the sampling frequency. By theoretically estimating the prealiasing error in a realistic range of the sampling frequency, we show that in other frequency intervals, the BCC lattice and even the traditional Cartesian Cubic (CC) lattice are expected to minimize the prealiasing. The BCC lattice is superior over the FCC lattice if the sampling frequency is not significantly below the Nyquist limit. Interestingly, if the original signal is drastically undersampled, the CC lattice is expected to provide the lowest prealiasing error. Additionally, we give a comprehensible clarification that the sampling efficiency of the FCC lattice is lower than that of the BCC lattice. Although this is a well-known fact, the exact percentage has been erroneously reported in the literature. Furthermore, for the sake of an unbiased comparison, we propose to rotate the Marschner-Lobb test signal such that an undue advantage is not given to either lattice. © 2014 The Eurographics Association and John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd.

Towards an unbiased comparison of CC, BCC, and FCC lattices in terms of prealiasing

KAUST Repository

Vad, Viktor; Csé bfalvi, Balá zs; Rautek, Peter; Grö ller, Eduard M.

2014-01-01

In the literature on optimal regular volume sampling, the Body-Centered Cubic (BCC) lattice has been proven to be optimal for sampling spherically band-limited signals above the Nyquist limit. On the other hand, if the sampling frequency is below the Nyquist limit, the Face-Centered Cubic (FCC) lattice was demonstrated to be optimal in reducing the prealiasing effect. In this paper, we confirm that the FCC lattice is indeed optimal in this sense in a certain interval of the sampling frequency. By theoretically estimating the prealiasing error in a realistic range of the sampling frequency, we show that in other frequency intervals, the BCC lattice and even the traditional Cartesian Cubic (CC) lattice are expected to minimize the prealiasing. The BCC lattice is superior over the FCC lattice if the sampling frequency is not significantly below the Nyquist limit. Interestingly, if the original signal is drastically undersampled, the CC lattice is expected to provide the lowest prealiasing error. Additionally, we give a comprehensible clarification that the sampling efficiency of the FCC lattice is lower than that of the BCC lattice. Although this is a well-known fact, the exact percentage has been erroneously reported in the literature. Furthermore, for the sake of an unbiased comparison, we propose to rotate the Marschner-Lobb test signal such that an undue advantage is not given to either lattice. © 2014 The Eurographics Association and John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd.

Mutually unbiased bases and trinary operator sets for N qutrits

International Nuclear Information System (INIS)

Lawrence, Jay

2004-01-01

A compete orthonormal basis of N-qutrit unitary operators drawn from the Pauli group consists of the identity and 9 N -1 traceless operators. The traceless ones partition into 3 N +1 maximally commuting subsets (MCS's) of 3 N -1 operators each, whose joint eigenbases are mutually unbiased. We prove that Pauli factor groups of order 3 N are isomorphic to all MCS's and show how this result applies in specific cases. For two qutrits, the 80 traceless operators partition into 10 MCS's. We prove that 4 of the corresponding basis sets must be separable, while 6 must be totally entangled (and Bell-like). For three qutrits, 728 operators partition into 28 MCS's with less rigid structure, allowing for the coexistence of separable, partially entangled, and totally entangled (GHZ-like) bases. However a minimum of 16 GHZ-like bases must occur. Every basis state is described by an N-digit trinary number consisting of the eigenvalues of N observables constructed from the corresponding MCS

Towards an unbiased, full-sky clustering search with IceCube in real time

Energy Technology Data Exchange (ETDEWEB)

Bernardini, Elisa; Franckowiak, Anna; Kintscher, Thomas; Kowalski, Marek; Stasik, Alexander [DESY, Zeuthen (Germany); Collaboration: IceCube-Collaboration

2016-07-01

The IceCube neutrino observatory is a 1 km{sup 3} detector for Cherenkov light in the ice at the South Pole. Having observed the presence of a diffuse astrophysical neutrino flux, static point source searches have come up empty handed. Thus, transient and variable objects emerge as promising, detectable source candidates. An unbiased, full-sky clustering search - run in real time - can find neutrino events with close temporal and spatial proximity. The most significant of these clusters serve as alerts to third-party observatories in order to obtain a complete picture of cosmic accelerators. The talk showcases the status and prospects of this project.

Estimation after classification using lot quality assurance sampling: corrections for curtailed sampling with application to evaluating polio vaccination campaigns.

Science.gov (United States)

Olives, Casey; Valadez, Joseph J; Pagano, Marcello

2014-03-01

To assess the bias incurred when curtailment of Lot Quality Assurance Sampling (LQAS) is ignored, to present unbiased estimators, to consider the impact of cluster sampling by simulation and to apply our method to published polio immunization data from Nigeria. We present estimators of coverage when using two kinds of curtailed LQAS strategies: semicurtailed and curtailed. We study the proposed estimators with independent and clustered data using three field-tested LQAS designs for assessing polio vaccination coverage, with samples of size 60 and decision rules of 9, 21 and 33, and compare them to biased maximum likelihood estimators. Lastly, we present estimates of polio vaccination coverage from previously published data in 20 local government authorities (LGAs) from five Nigerian states. Simulations illustrate substantial bias if one ignores the curtailed sampling design. Proposed estimators show no bias. Clustering does not affect the bias of these estimators. Across simulations, standard errors show signs of inflation as clustering increases. Neither sampling strategy nor LQAS design influences estimates of polio vaccination coverage in 20 Nigerian LGAs. When coverage is low, semicurtailed LQAS strategies considerably reduces the sample size required to make a decision. Curtailed LQAS designs further reduce the sample size when coverage is high. Results presented dispel the misconception that curtailed LQAS data are unsuitable for estimation. These findings augment the utility of LQAS as a tool for monitoring vaccination efforts by demonstrating that unbiased estimation using curtailed designs is not only possible but these designs also reduce the sample size. © 2014 John Wiley & Sons Ltd.

Bipartite entangled stabilizer mutually unbiased bases as maximum cliques of Cayley graphs

Science.gov (United States)

van Dam, Wim; Howard, Mark

2011-07-01

We examine the existence and structure of particular sets of mutually unbiased bases (MUBs) in bipartite qudit systems. In contrast to well-known power-of-prime MUB constructions, we restrict ourselves to using maximally entangled stabilizer states as MUB vectors. Consequently, these bipartite entangled stabilizer MUBs (BES MUBs) provide no local information, but are sufficient and minimal for decomposing a wide variety of interesting operators including (mixtures of) Jamiołkowski states, entanglement witnesses, and more. The problem of finding such BES MUBs can be mapped, in a natural way, to that of finding maximum cliques in a family of Cayley graphs. Some relationships with known power-of-prime MUB constructions are discussed, and observables for BES MUBs are given explicitly in terms of Pauli operators.

Bipartite entangled stabilizer mutually unbiased bases as maximum cliques of Cayley graphs

International Nuclear Information System (INIS)

Dam, Wim van; Howard, Mark

2011-01-01

We examine the existence and structure of particular sets of mutually unbiased bases (MUBs) in bipartite qudit systems. In contrast to well-known power-of-prime MUB constructions, we restrict ourselves to using maximally entangled stabilizer states as MUB vectors. Consequently, these bipartite entangled stabilizer MUBs (BES MUBs) provide no local information, but are sufficient and minimal for decomposing a wide variety of interesting operators including (mixtures of) Jamiolkowski states, entanglement witnesses, and more. The problem of finding such BES MUBs can be mapped, in a natural way, to that of finding maximum cliques in a family of Cayley graphs. Some relationships with known power-of-prime MUB constructions are discussed, and observables for BES MUBs are given explicitly in terms of Pauli operators.

Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

Science.gov (United States)

2009-02-05

22 CHAPTER 2 TABLE 1 Stereological estimation of total Nissl - stained and GAD67-positive neurons in the BLA of sham control rats and KA-SE rats... Nissl - stained sections……………….... FIGURE 2 Counting site for stereological quantification of Nissl - stained neurons...FIGURE 3 Counting grid superimposed over tracing of BLA………………... 142 143 144 xii FIGURE 4 Disector height and guard zones in Nissl - stained

A simple method for estimating the length density of convoluted tubular systems.

Science.gov (United States)

Ferraz de Carvalho, Cláudio A; de Campos Boldrini, Silvia; Nishimaru, Flávio; Liberti, Edson A

2008-10-01

We present a new method for estimating the length density (Lv) of convoluted tubular structures exhibiting an isotropic distribution. Although the traditional equation Lv=2Q/A is used, the parameter Q is obtained by considering the collective perimeters of tubular sections. This measurement is converted to a standard model of the structure, assuming that all cross-sections are approximately circular and have an average perimeter similar to that of actual circular cross-sections observed in the same material. The accuracy of this method was tested in eight experiments using hollow macaroni bent into helical shapes. After measuring the length of the macaroni segments, they were boiled and randomly packed into cylindrical volumes along with an aqueous suspension of gelatin and India ink. The solidified blocks were cut into slices 1.0 cm thick and 33.2 cm2 in area (A). The total perimeter of the macaroni cross-sections so revealed was stereologically estimated using a test system of straight parallel lines. Given Lv and the reference volume, the total length of macaroni in each section could be estimated. Additional corrections were made for the changes induced by boiling, and the off-axis position of the thread used to measure length. No statistical difference was observed between the corrected estimated values and the actual lengths. This technique is useful for estimating the length of capillaries, renal tubules, and seminiferous tubules.

Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves

DEFF Research Database (Denmark)

Barghash, Ziad; Larsen, Jytte Overgaard; Al-Bishri, Awad

2013-01-01

The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod...... for 30 s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both...... in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed...

Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia

Directory of Open Access Journals (Sweden)

Robert Sweet

2010-06-01

Full Text Available Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g. dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin, or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article we consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, we provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex.

Effects of sample size on estimates of population growth rates calculated with matrix models.

Directory of Open Access Journals (Sweden)

Ian J Fiske

Full Text Available BACKGROUND: Matrix models are widely used to study the dynamics and demography of populations. An important but overlooked issue is how the number of individuals sampled influences estimates of the population growth rate (lambda calculated with matrix models. Even unbiased estimates of vital rates do not ensure unbiased estimates of lambda-Jensen's Inequality implies that even when the estimates of the vital rates are accurate, small sample sizes lead to biased estimates of lambda due to increased sampling variance. We investigated if sampling variability and the distribution of sampling effort among size classes lead to biases in estimates of lambda. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a long-term field study of plant demography, we simulated the effects of sampling variance by drawing vital rates and calculating lambda for increasingly larger populations drawn from a total population of 3842 plants. We then compared these estimates of lambda with those based on the entire population and calculated the resulting bias. Finally, we conducted a review of the literature to determine the sample sizes typically used when parameterizing matrix models used to study plant demography. CONCLUSIONS/SIGNIFICANCE: We found significant bias at small sample sizes when survival was low (survival = 0.5, and that sampling with a more-realistic inverse J-shaped population structure exacerbated this bias. However our simulations also demonstrate that these biases rapidly become negligible with increasing sample sizes or as survival increases. For many of the sample sizes used in demographic studies, matrix models are probably robust to the biases resulting from sampling variance of vital rates. However, this conclusion may depend on the structure of populations or the distribution of sampling effort in ways that are unexplored. We suggest more intensive sampling of populations when individual survival is low and greater sampling of stages with high

Effects of sample size on estimates of population growth rates calculated with matrix models.

Science.gov (United States)

Fiske, Ian J; Bruna, Emilio M; Bolker, Benjamin M

2008-08-28

Matrix models are widely used to study the dynamics and demography of populations. An important but overlooked issue is how the number of individuals sampled influences estimates of the population growth rate (lambda) calculated with matrix models. Even unbiased estimates of vital rates do not ensure unbiased estimates of lambda-Jensen's Inequality implies that even when the estimates of the vital rates are accurate, small sample sizes lead to biased estimates of lambda due to increased sampling variance. We investigated if sampling variability and the distribution of sampling effort among size classes lead to biases in estimates of lambda. Using data from a long-term field study of plant demography, we simulated the effects of sampling variance by drawing vital rates and calculating lambda for increasingly larger populations drawn from a total population of 3842 plants. We then compared these estimates of lambda with those based on the entire population and calculated the resulting bias. Finally, we conducted a review of the literature to determine the sample sizes typically used when parameterizing matrix models used to study plant demography. We found significant bias at small sample sizes when survival was low (survival = 0.5), and that sampling with a more-realistic inverse J-shaped population structure exacerbated this bias. However our simulations also demonstrate that these biases rapidly become negligible with increasing sample sizes or as survival increases. For many of the sample sizes used in demographic studies, matrix models are probably robust to the biases resulting from sampling variance of vital rates. However, this conclusion may depend on the structure of populations or the distribution of sampling effort in ways that are unexplored. We suggest more intensive sampling of populations when individual survival is low and greater sampling of stages with high elasticities.

Directed transport in a periodic tube driven by asymmetric unbiased forces coexisting with spatially modulated noises

International Nuclear Information System (INIS)

Li Fengguo; Ai Baoquan

2011-01-01

Graphical abstract: The current J as a function of the phase shift φ and ε at a = 1/2π, b = 0.5/2π, k B T = 0.5, α = 0.1, and F 0 = 0.5. Highlights: → Unbiased forces and spatially modulated white noises affect the current. → In the adiabatic limit, the analytical expression of directed current is obtained. → Their competition will induce current reversals. → For negative asymmetric parameters of the force, there exists an optimum parameter. → The current increases monotonously for positive asymmetric parameters. - Abstract: Transport of Brownian particles in a symmetrically periodic tube is investigated in the presence of asymmetric unbiased external forces and spatially modulated Gaussian white noises. In the adiabatic limit, we obtain the analytical expression of the directed current. It is found that the temporal asymmetry can break thermodynamic equilibrium and induce a net current. Their competition between the temporal asymmetry force and the phase shift between the noise modulation and the tube shape will induce some peculiar phenomena, for example, current reversals. The current changes with the phase shift in the form of the sine function. For negative asymmetric parameters of the force, there exists an optimum parameter at which the current takes its maximum value. However, the current increases monotonously for positive asymmetric parameters.

Estimating Gravity Biases with Wavelets in Support of a 1-cm Accurate Geoid Model

Science.gov (United States)

Ahlgren, K.; Li, X.

2017-12-01

Systematic errors that reside in surface gravity datasets are one of the major hurdles in constructing a high-accuracy geoid model at high resolutions. The National Oceanic and Atmospheric Administration's (NOAA) National Geodetic Survey (NGS) has an extensive historical surface gravity dataset consisting of approximately 10 million gravity points that are known to have systematic biases at the mGal level (Saleh et al. 2013). As most relevant metadata is absent, estimating and removing these errors to be consistent with a global geopotential model and airborne data in the corresponding wavelength is quite a difficult endeavor. However, this is crucial to support a 1-cm accurate geoid model for the United States. With recently available independent gravity information from GRACE/GOCE and airborne gravity from the NGS Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project, several different methods of bias estimation are investigated which utilize radial basis functions and wavelet decomposition. We estimate a surface gravity value by incorporating a satellite gravity model, airborne gravity data, and forward-modeled topography at wavelet levels according to each dataset's spatial wavelength. Considering the estimated gravity values over an entire gravity survey, an estimate of the bias and/or correction for the entire survey can be found and applied. In order to assess the accuracy of each bias estimation method, two techniques are used. First, each bias estimation method is used to predict the bias for two high-quality (unbiased and high accuracy) geoid slope validation surveys (GSVS) (Smith et al. 2013 & Wang et al. 2017). Since these surveys are unbiased, the various bias estimation methods should reflect that and provide an absolute accuracy metric for each of the bias estimation methods. Secondly, the corrected gravity datasets from each of the bias estimation methods are used to build a geoid model. The accuracy of each geoid model

Ultrastructure and mitochondrial numbers in pre- and postpubertal pig oocytes

DEFF Research Database (Denmark)

Pedersen, Hanne Skovsgaard; Callesen, Henrik; Løvendahl, Peter

2016-01-01

Prepubertal pig oocytes are associated with lower developmental competence. The aim of this experiment was to conduct an exhaustive survey of oocyte ultrastructure and to use a design-unbiased stereological approach to quantify the numerical density and total number of mitochondria in oocytes...... with different diameters from pre- and postpubertal pigs. The ultrastructure of smaller prepubertal immature oocytes indicated active cells in close contact with cumulus cells. The postpubertal oocytes were more quiescent cell types. The small prepubertal oocytes had a lower total mitochondrial number......, but no differences were observed in mitochondrial densities between groups. Mature postpubertal oocytes adhered to the following characteristics: presence of metaphase II, lack of contact between cumulus cells and oocyte, absence of rough endoplasmic reticulum and Golgi complexes, peripheral location of cortical...

Estimation of group means when adjusting for covariates in generalized linear models.

Science.gov (United States)

Qu, Yongming; Luo, Junxiang

2015-01-01

Generalized linear models are commonly used to analyze categorical data such as binary, count, and ordinal outcomes. Adjusting for important prognostic factors or baseline covariates in generalized linear models may improve the estimation efficiency. The model-based mean for a treatment group produced by most software packages estimates the response at the mean covariate, not the mean response for this treatment group for the studied population. Although this is not an issue for linear models, the model-based group mean estimates in generalized linear models could be seriously biased for the true group means. We propose a new method to estimate the group mean consistently with the corresponding variance estimation. Simulation showed the proposed method produces an unbiased estimator for the group means and provided the correct coverage probability. The proposed method was applied to analyze hypoglycemia data from clinical trials in diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Distortion of online reputation by excess reciprocity: quantification and estimation of unbiased reputation

Science.gov (United States)

Aste, Tomaso; Livan, Giacomo; Caccioli, Fabio

The peer-to-peer (P2P) economy relies on establishing trust in distributed networked systems, where the reliability of a user is assessed through digital peer-review processes that aggregate ratings into reputation scores. Here we present evidence of a network effect which biases digital reputations, revealing that P2P networks display exceedingly high levels of reciprocity. In fact, these are so large that they are close to the highest levels structurally compatible with the networks reputation landscape. This indicates that the crowdsourcing process underpinning digital reputation is significantly distorted by the attempt of users to mutually boost reputation, or to retaliate, through the exchange of ratings. We uncover that the least active users are predominantly responsible for such reciprocity-induced bias, and that this fact can be exploited to obtain more reliable reputation estimates. Our findings are robust across different P2P platforms, including both cases where ratings are used to vote on the content produced by users and to vote on user profiles.

SU2 nonstandard bases: the case of mutually unbiased bases

International Nuclear Information System (INIS)

Olivier, Albouy; Kibler, Maurice R.

2007-02-01

This paper deals with bases in a finite-dimensional Hilbert space. Such a space can be realized as a subspace of the representation space of SU 2 corresponding to an irreducible representation of SU 2 . The representation theory of SU 2 is reconsidered via the use of two truncated deformed oscillators. This leads to replace the familiar scheme [j 2 , j z ] by a scheme [j 2 , v ra ], where the two-parameter operator v ra is defined in the universal enveloping algebra of the Lie algebra su 2 . The eigenvectors of the commuting set of operators [j 2 , v ra ] are adapted to a tower of chains SO 3 includes C 2j+1 (2j belongs to N * ), where C 2j+1 is the cyclic group of order 2j + 1. In the case where 2j + 1 is prime, the corresponding eigenvectors generate a complete set of mutually unbiased bases. Some useful relations on generalized quadratic Gauss sums are exposed in three appendices. (authors)

Cardinality Estimation Algorithm in Large-Scale Anonymous Wireless Sensor Networks

KAUST Repository

Douik, Ahmed

2017-08-30

Consider a large-scale anonymous wireless sensor network with unknown cardinality. In such graphs, each node has no information about the network topology and only possesses a unique identifier. This paper introduces a novel distributed algorithm for cardinality estimation and topology discovery, i.e., estimating the number of node and structure of the graph, by querying a small number of nodes and performing statistical inference methods. While the cardinality estimation allows the design of more efficient coding schemes for the network, the topology discovery provides a reliable way for routing packets. The proposed algorithm is shown to produce a cardinality estimate proportional to the best linear unbiased estimator for dense graphs and specific running times. Simulation results attest the theoretical results and reveal that, for a reasonable running time, querying a small group of nodes is sufficient to perform an estimation of 95% of the whole network. Applications of this work include estimating the number of Internet of Things (IoT) sensor devices, online social users, active protein cells, etc.

Human dental age estimation using third molar developmental stages: does a Bayesian approach outperform regression models to discriminate between juveniles and adults?

OpenAIRE

Thevissen, P. W.; FIEUWS, Steffen; Willems, G.

2010-01-01

Dental age estimation methods based on the radiologically detected third molar developmental stages are implemented in forensic age assessments to discriminate between juveniles and adults considering the judgment of young unaccompanied asylum seekers. Accurate and unbiased age estimates combined with appropriate quantified uncertainties are the required properties for accurate forensic reporting. In this study, a subset of 910 individuals uniformly distributed in age between 16 and 22 years ...

In search of a corrected prescription drug elasticity estimate: a meta-regression approach.

Science.gov (United States)

Gemmill, Marin C; Costa-Font, Joan; McGuire, Alistair

2007-06-01

An understanding of the relationship between cost sharing and drug consumption depends on consistent and unbiased price elasticity estimates. However, there is wide heterogeneity among studies, which constrains the applicability of elasticity estimates for empirical purposes and policy simulation. This paper attempts to provide a corrected measure of the drug price elasticity by employing meta-regression analysis (MRA). The results indicate that the elasticity estimates are significantly different from zero, and the corrected elasticity is -0.209 when the results are made robust to heteroskedasticity and clustering of observations. Elasticity values are higher when the study was published in an economic journal, when the study employed a greater number of observations, and when the study used aggregate data. Elasticity estimates are lower when the institutional setting was a tax-based health insurance system.

Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor

DEFF Research Database (Denmark)

de los Campos, Gustavo; Vazquez, Ana I; Fernando, Rohan

2013-01-01

Despite important advances from Genome Wide Association Studies (GWAS), for most complex human traits and diseases, a sizable proportion of genetic variance remains unexplained and prediction accuracy (PA) is usually low. Evidence suggests that PA can be improved using Whole-Genome Regression (WGR......) models where phenotypes are regressed on hundreds of thousands of variants simultaneously. The Genomic Best Linear Unbiased Prediction G-BLUP, a ridge-regression type method) is a commonly used WGR method and has shown good predictive performance when applied to plant and animal breeding populations....... However, breeding and human populations differ greatly in a number of factors that can affect the predictive performance of G-BLUP. Using theory, simulations, and real data analysis, we study the erformance of G-BLUP when applied to data from related and unrelated human subjects. Under perfect linkage...

Unbiased determination of polarized parton distributions and their uncertainties

Energy Technology Data Exchange (ETDEWEB)

Ball, Richard D. [Tait Institute, University of Edinburgh, JCMB, KB, Mayfield Rd, Edinburgh EH9 3JZ, Scotland (United Kingdom); Forte, Stefano, E-mail: forte@mi.infn.it [Dipartimento di Fisica, Università di Milano and INFN, Sezione di Milano, Via Celoria 16, I-20133 Milano (Italy); Guffanti, Alberto [The Niels Bohr International Academy and Discovery Center, The Niels Bohr Institute, Blegdamsvej 17, DK-2100 Copenhagen (Denmark); Nocera, Emanuele R. [Dipartimento di Fisica, Università di Milano and INFN, Sezione di Milano, Via Celoria 16, I-20133 Milano (Italy); Ridolfi, Giovanni [Dipartimento di Fisica, Università di Genova and INFN, Sezione di Genova, Genova (Italy); Rojo, Juan [PH Department, TH Unit, CERN, CH-1211 Geneva 23 (Switzerland)

2013-09-01

We present a determination of a set of polarized parton distributions (PDFs) of the nucleon, at next-to-leading order, from a global set of longitudinally polarized deep-inelastic scattering data: NNPDFpol1.0. The determination is based on the NNPDF methodology: a Monte Carlo approach, with neural networks used as unbiased interpolants, previously applied to the determination of unpolarized parton distributions, and designed to provide a faithful and statistically sound representation of PDF uncertainties. We present our dataset, its statistical features, and its Monte Carlo representation. We summarize the technique used to solve the polarized evolution equations and its benchmarking, and the method used to compute physical observables. We review the NNPDF methodology for parametrization and fitting of neural networks, the algorithm used to determine the optimal fit, and its adaptation to the polarized case. We finally present our set of polarized parton distributions. We discuss its statistical properties, test for its stability upon various modifications of the fitting procedure, and compare it to other recent polarized parton sets, and in particular obtain predictions for polarized first moments of PDFs based on it. We find that the uncertainties on the gluon, and to a lesser extent the strange PDF, were substantially underestimated in previous determinations.

Unbiased determination of polarized parton distributions and their uncertainties

International Nuclear Information System (INIS)

Ball, Richard D.; Forte, Stefano; Guffanti, Alberto; Nocera, Emanuele R.; Ridolfi, Giovanni; Rojo, Juan

2013-01-01

We present a determination of a set of polarized parton distributions (PDFs) of the nucleon, at next-to-leading order, from a global set of longitudinally polarized deep-inelastic scattering data: NNPDFpol1.0. The determination is based on the NNPDF methodology: a Monte Carlo approach, with neural networks used as unbiased interpolants, previously applied to the determination of unpolarized parton distributions, and designed to provide a faithful and statistically sound representation of PDF uncertainties. We present our dataset, its statistical features, and its Monte Carlo representation. We summarize the technique used to solve the polarized evolution equations and its benchmarking, and the method used to compute physical observables. We review the NNPDF methodology for parametrization and fitting of neural networks, the algorithm used to determine the optimal fit, and its adaptation to the polarized case. We finally present our set of polarized parton distributions. We discuss its statistical properties, test for its stability upon various modifications of the fitting procedure, and compare it to other recent polarized parton sets, and in particular obtain predictions for polarized first moments of PDFs based on it. We find that the uncertainties on the gluon, and to a lesser extent the strange PDF, were substantially underestimated in previous determinations

AN UNBIASED 1.3 mm EMISSION LINE SURVEY OF THE PROTOPLANETARY DISK ORBITING LkCa 15

Energy Technology Data Exchange (ETDEWEB)

Punzi, K. M.; Kastner, J. H. [Center for Imaging Science, School of Physics and Astronomy, and Laboratory for Multiwavelength Astrophysics, Rochester Institute of Technology, 54 Lomb Memorial Drive, Rochester, NY 14623 (United States); Hily-Blant, P.; Forveille, T. [UJF—Grenoble 1/CNRS-INSU, Institut de Planétologie et d’Astrophysique de Grenoble (IPAG) UMR 5274, F-38041, Grenoble (France); Sacco, G. G. [INAF—Osservatorio Astrofisico di Arcetri, Largo E. Fermi 5, I-50125, Firenze (Italy)

2015-06-01

The outer (>30 AU) regions of the dusty circumstellar disk orbiting the ∼2–5 Myr old, actively accreting solar analog LkCa 15 are known to be chemically rich, and the inner disk may host a young protoplanet within its central cavity. To obtain a complete census of the brightest molecular line emission emanating from the LkCa 15 disk over the 210–270 GHz (1.4–1.1 mm) range, we have conducted an unbiased radio spectroscopic survey with the Institute de Radioastronomie Millimétrique (IRAM) 30 m telescope. The survey demonstrates that in this spectral region, the most readily detectable lines are those of CO and its isotopologues {sup 13}CO and C{sup 18}O, as well as HCO{sup +}, HCN, CN, C{sub 2}H, CS, and H{sub 2}CO. All of these species had been previously detected in the LkCa 15 disk; however, the present survey includes the first complete coverage of the CN (2–1) and C{sub 2}H (3–2) hyperfine complexes. Modeling of these emission complexes indicates that the CN and C{sub 2}H either reside in the coldest regions of the disk or are subthermally excited, and that their abundances are enhanced relative to molecular clouds and young stellar object environments. These results highlight the value of unbiased single-dish line surveys in guiding future high-resolution interferometric imaging of disks.

Identification and characterization of Highlands J virus from a Mississippi sandhill crane using unbiased next-generation sequencing

Science.gov (United States)

Ip, Hon S.; Wiley, Michael R.; Long, Renee; Gustavo, Palacios; Shearn-Bochsler, Valerie; Whitehouse, Chris A.

2014-01-01

Advances in massively parallel DNA sequencing platforms, commonly termed next-generation sequencing (NGS) technologies, have greatly reduced time, labor, and cost associated with DNA sequencing. Thus, NGS has become a routine tool for new viral pathogen discovery and will likely become the standard for routine laboratory diagnostics of infectious diseases in the near future. This study demonstrated the application of NGS for the rapid identification and characterization of a virus isolated from the brain of an endangered Mississippi sandhill crane. This bird was part of a population restoration effort and was found in an emaciated state several days after Hurricane Isaac passed over the refuge in Mississippi in 2012. Post-mortem examination had identified trichostrongyliasis as the possible cause of death, but because a virus with morphology consistent with a togavirus was isolated from the brain of the bird, an arboviral etiology was strongly suspected. Because individual molecular assays for several known arboviruses were negative, unbiased NGS by Illumina MiSeq was used to definitively identify and characterize the causative viral agent. Whole genome sequencing and phylogenetic analysis revealed the viral isolate to be the Highlands J virus, a known avian pathogen. This study demonstrates the use of unbiased NGS for the rapid detection and characterization of an unidentified viral pathogen and the application of this technology to wildlife disease diagnostics and conservation medicine.

Systematic Testing of Belief-Propagation Estimates for Absolute Free Energies in Atomistic Peptides and Proteins.

Science.gov (United States)

Donovan-Maiye, Rory M; Langmead, Christopher J; Zuckerman, Daniel M

2018-01-09

Motivated by the extremely high computing costs associated with estimates of free energies for biological systems using molecular simulations, we further the exploration of existing "belief propagation" (BP) algorithms for fixed-backbone peptide and protein systems. The precalculation of pairwise interactions among discretized libraries of side-chain conformations, along with representation of protein side chains as nodes in a graphical model, enables direct application of the BP approach, which requires only ∼1 s of single-processor run time after the precalculation stage. We use a "loopy BP" algorithm, which can be seen as an approximate generalization of the transfer-matrix approach to highly connected (i.e., loopy) graphs, and it has previously been applied to protein calculations. We examine the application of loopy BP to several peptides as well as the binding site of the T4 lysozyme L99A mutant. The present study reports on (i) the comparison of the approximate BP results with estimates from unbiased estimators based on the Amber99SB force field; (ii) investigation of the effects of varying library size on BP predictions; and (iii) a theoretical discussion of the discretization effects that can arise in BP calculations. The data suggest that, despite their approximate nature, BP free-energy estimates are highly accurate-indeed, they never fall outside confidence intervals from unbiased estimators for the systems where independent results could be obtained. Furthermore, we find that libraries of sufficiently fine discretization (which diminish library-size sensitivity) can be obtained with standard computing resources in most cases. Altogether, the extremely low computing times and accurate results suggest the BP approach warrants further study.

Verifying mixing in dilution tunnels How to ensure cookstove emissions samples are unbiased

Energy Technology Data Exchange (ETDEWEB)

Wilson, Daniel L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rapp, Vi H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Caubel, Julien J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chen, Sharon S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gadgil, Ashok J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-12-15

A well-mixed diluted sample is essential for unbiased measurement of cookstove emissions. Most cookstove testing labs employ a dilution tunnel, also referred to as a “duct,” to mix clean dilution air with cookstove emissions before sampling. It is important that the emissions be well-mixed and unbiased at the sampling port so that instruments can take representative samples of the emission plume. Some groups have employed mixing baffles to ensure the gaseous and aerosol emissions from cookstoves are well-mixed before reaching the sampling location [2, 4]. The goal of these baffles is to to dilute and mix the emissions stream with the room air entering the fume hood by creating a local zone of high turbulence. However, potential drawbacks of mixing baffles include increased flow resistance (larger blowers needed for the same exhaust flow), nuisance cleaning of baffles as soot collects, and, importantly, the potential for loss of PM2.5 particles on the baffles themselves, thus biasing results. A cookstove emission monitoring system with baffles will collect particles faster than the duct’s walls alone. This is mostly driven by the available surface area for deposition by processes of Brownian diffusion (through the boundary layer) and turbophoresis (i.e. impaction). The greater the surface area available for diffusive and advection-driven deposition to occur, the greater the particle loss will be at the sampling port. As a layer of larger particle “fuzz” builds on the mixing baffles, even greater PM2.5 loss could occur. The micro structure of the deposited aerosol will lead to increased rates of particle loss by interception and a tendency for smaller particles to deposit due to impaction on small features of the micro structure. If the flow stream could be well-mixed without the need for baffles, these drawbacks could be avoided and the cookstove emissions sampling system would be more robust.

Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

DEFF Research Database (Denmark)

Lyck, Lise; Krøigård, Thomas; Finsen, Bente

2007-01-01

The post-natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post...

Stereological estimates of nuclear volume in thin malignant melanomas

DEFF Research Database (Denmark)

Björnhagen, V; Månsson-Brahme, E; Lindholm, J

1998-01-01

melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed...

Unbiased in-depth characterization of CEX fractions from a stressed monoclonal antibody by mass spectrometry.

Science.gov (United States)

Griaud, François; Denefeld, Blandine; Lang, Manuel; Hensinger, Héloïse; Haberl, Peter; Berg, Matthias

2017-07-01

Characterization of charge-based variants by mass spectrometry (MS) is required for the analytical development of a new biologic entity and its marketing approval by health authorities. However, standard peak-based data analysis approaches are time-consuming and biased toward the detection, identification, and quantification of main variants only. The aim of this study was to characterize in-depth acidic and basic species of a stressed IgG1 monoclonal antibody using comprehensive and unbiased MS data evaluation tools. Fractions collected from cation ion exchange (CEX) chromatography were analyzed as intact, after reduction of disulfide bridges, and after proteolytic cleavage using Lys-C. Data of both intact and reduced samples were evaluated consistently using a time-resolved deconvolution algorithm. Peptide mapping data were processed simultaneously, quantified and compared in a systematic manner for all MS signals and fractions. Differences observed between the fractions were then further characterized and assigned. Time-resolved deconvolution enhanced pattern visualization and data interpretation of main and minor modifications in 3-dimensional maps across CEX fractions. Relative quantification of all MS signals across CEX fractions before peptide assignment enabled the detection of fraction-specific chemical modifications at abundances below 1%. Acidic fractions were shown to be heterogeneous, containing antibody fragments, glycated as well as deamidated forms of the heavy and light chains. In contrast, the basic fractions contained mainly modifications of the C-terminus and pyroglutamate formation at the N-terminus of the heavy chain. Systematic data evaluation was performed to investigate multiple data sets and comprehensively extract main and minor differences between each CEX fraction in an unbiased manner.

Using a Regression Method for Estimating Performance in a Rapid Serial Visual Presentation Target-Detection Task

Science.gov (United States)

2017-12-01

Fig. 2 Simulation method; the process for one iteration of the simulation . It was repeated 250 times per combination of HR and FAR. Analysis was...distribution is unlimited. 8 Fig. 2 Simulation method; the process for one iteration of the simulation . It was repeated 250 times per combination of HR...stimuli. Simulations show that this regression method results in an unbiased and accurate estimate of target detection performance. The regression

Estimating rate of occurrence of rare events with empirical bayes: A railway application

International Nuclear Information System (INIS)

Quigley, John; Bedford, Tim; Walls, Lesley

2007-01-01

Classical approaches to estimating the rate of occurrence of events perform poorly when data are few. Maximum likelihood estimators result in overly optimistic point estimates of zero for situations where there have been no events. Alternative empirical-based approaches have been proposed based on median estimators or non-informative prior distributions. While these alternatives offer an improvement over point estimates of zero, they can be overly conservative. Empirical Bayes procedures offer an unbiased approach through pooling data across different hazards to support stronger statistical inference. This paper considers the application of Empirical Bayes to high consequence low-frequency events, where estimates are required for risk mitigation decision support such as as low as reasonably possible. A summary of empirical Bayes methods is given and the choices of estimation procedures to obtain interval estimates are discussed. The approaches illustrated within the case study are based on the estimation of the rate of occurrence of train derailments within the UK. The usefulness of empirical Bayes within this context is discussed

SU{sub 2} nonstandard bases: the case of mutually unbiased bases

Energy Technology Data Exchange (ETDEWEB)

Olivier, Albouy; Kibler, Maurice R. [Universite de Lyon, Institut de Physique Nucleaire de Lyon, Universite Lyon, CNRS/IN2P3, 43 bd du 11 novembre 1918, F-69622 Villeurbanne Cedex (France)

2007-02-15

This paper deals with bases in a finite-dimensional Hilbert space. Such a space can be realized as a subspace of the representation space of SU{sub 2} corresponding to an irreducible representation of SU{sub 2}. The representation theory of SU{sub 2} is reconsidered via the use of two truncated deformed oscillators. This leads to replace the familiar scheme [j{sub 2}, j{sub z}] by a scheme [j{sup 2}, v{sub ra}], where the two-parameter operator v{sub ra} is defined in the universal enveloping algebra of the Lie algebra su{sub 2}. The eigenvectors of the commuting set of operators [j{sup 2}, v{sub ra}] are adapted to a tower of chains SO{sub 3} includes C{sub 2j+1} (2j belongs to N{sup *}), where C{sub 2j+1} is the cyclic group of order 2j + 1. In the case where 2j + 1 is prime, the corresponding eigenvectors generate a complete set of mutually unbiased bases. Some useful relations on generalized quadratic Gauss sums are exposed in three appendices. (authors)

The New Peabody Picture Vocabulary Test-III: An Illusion of Unbiased Assessment?

Science.gov (United States)

Stockman, Ida J

2000-10-01

This article examines whether changes in the ethnic minority composition of the standardization sample for the latest edition of the Peabody Picture Vocabulary Test (PPVT-III, Dunn & Dunn, 1997) can be used as the sole explanation for children's better test scores when compared to an earlier edition, the Peabody Picture Vocabulary Test-Revised (PPVT-R, Dunn & Dunn, 1981). Results from a comparative analysis of these two test editions suggest that other factors may explain improved performances. Among these factors are the number of words and age levels sampled, the types of words and pictures used, and characteristics of the standardization sample other than its ethnic minority composition. This analysis also raises questions regarding the usefulness of converting scores from one edition to the other and the type of criteria that could be used to evaluate whether the PPVT-III is an unbiased test of vocabulary for children from diverse cultural and linguistic backgrounds.

Interplanetary scintillation observations of an unbiased sample of 90 Ooty occultation radio sources at 326.5 MHz

International Nuclear Information System (INIS)

Banhatti, D.G.; Ananthakrishnan, S.

1989-01-01

We present 327-MHz interplanetary scintillation (IPS) observations of an unbiased sample of 90 extragalactic radio sources selected from the ninth Ooty lunar occultation list. The sources are brighter than 0.75 Jy at 327 MHz and lie outside the galactic plane. We derive values, the fraction of scintillating flux density, and the equivalent Gaussian diameter for the scintillating structure. Various correlations are found between the observed parameters. In particular, the scintillating component weakens and broadens with increasing largest angular size, and stronger scintillators have more compact scintillating components. (author)

Systematic random sampling of the comet assay.

Science.gov (United States)

McArt, Darragh G; Wasson, Gillian R; McKerr, George; Saetzler, Kurt; Reed, Matt; Howard, C Vyvyan

2009-07-01

The comet assay is a technique used to quantify DNA damage and repair at a cellular level. In the assay, cells are embedded in agarose and the cellular content is stripped away leaving only the DNA trapped in an agarose cavity which can then be electrophoresed. The damaged DNA can enter the agarose and migrate while the undamaged DNA cannot and is retained. DNA damage is measured as the proportion of the migratory 'tail' DNA compared to the total DNA in the cell. The fundamental basis of these arbitrary values is obtained in the comet acquisition phase using fluorescence microscopy with a stoichiometric stain in tandem with image analysis software. Current methods deployed in such an acquisition are expected to be both objectively and randomly obtained. In this paper we examine the 'randomness' of the acquisition phase and suggest an alternative method that offers both objective and unbiased comet selection. In order to achieve this, we have adopted a survey sampling approach widely used in stereology, which offers a method of systematic random sampling (SRS). This is desirable as it offers an impartial and reproducible method of comet analysis that can be used both manually or automated. By making use of an unbiased sampling frame and using microscope verniers, we are able to increase the precision of estimates of DNA damage. Results obtained from a multiple-user pooled variation experiment showed that the SRS technique attained a lower variability than that of the traditional approach. The analysis of a single user with repetition experiment showed greater individual variances while not being detrimental to overall averages. This would suggest that the SRS method offers a better reflection of DNA damage for a given slide and also offers better user reproducibility.

Kinetic parameter estimation from attenuated SPECT projection measurements

International Nuclear Information System (INIS)

Reutter, B.W.; Gullberg, G.T.

1998-01-01

Conventional analysis of dynamically acquired nuclear medicine data involves fitting kinetic models to time-activity curves generated from regions of interest defined on a temporal sequence of reconstructed images. However, images reconstructed from the inconsistent projections of a time-varying distribution of radiopharmaceutical acquired by a rotating SPECT system can contain artifacts that lead to biases in the estimated kinetic parameters. To overcome this problem the authors investigated the estimation of kinetic parameters directly from projection data by modeling the data acquisition process. To accomplish this it was necessary to parametrize the spatial and temporal distribution of the radiopharmaceutical within the SPECT field of view. In a simulated transverse slice, kinetic parameters were estimated for simple one compartment models for three myocardial regions of interest, as well as for the liver. Myocardial uptake and washout parameters estimated by conventional analysis of noiseless simulated data had biases ranging between 1--63%. Parameters estimated directly from the noiseless projection data were unbiased as expected, since the model used for fitting was faithful to the simulation. Predicted uncertainties (standard deviations) of the parameters obtained for 500,000 detected events ranged between 2--31% for the myocardial uptake parameters and 2--23% for the myocardial washout parameters

Independent contrasts and PGLS regression estimators are equivalent.

Science.gov (United States)

Blomberg, Simon P; Lefevre, James G; Wells, Jessie A; Waterhouse, Mary

2012-05-01

We prove that the slope parameter of the ordinary least squares regression of phylogenetically independent contrasts (PICs) conducted through the origin is identical to the slope parameter of the method of generalized least squares (GLSs) regression under a Brownian motion model of evolution. This equivalence has several implications: 1. Understanding the structure of the linear model for GLS regression provides insight into when and why phylogeny is important in comparative studies. 2. The limitations of the PIC regression analysis are the same as the limitations of the GLS model. In particular, phylogenetic covariance applies only to the response variable in the regression and the explanatory variable should be regarded as fixed. Calculation of PICs for explanatory variables should be treated as a mathematical idiosyncrasy of the PIC regression algorithm. 3. Since the GLS estimator is the best linear unbiased estimator (BLUE), the slope parameter estimated using PICs is also BLUE. 4. If the slope is estimated using different branch lengths for the explanatory and response variables in the PIC algorithm, the estimator is no longer the BLUE, so this is not recommended. Finally, we discuss whether or not and how to accommodate phylogenetic covariance in regression analyses, particularly in relation to the problem of phylogenetic uncertainty. This discussion is from both frequentist and Bayesian perspectives.

Downlink Channel Estimation in Cellular Systems with Antenna Arrays at Base Stations Using Channel Probing with Feedback

Directory of Open Access Journals (Sweden)

Biguesh Mehrzad

2004-01-01

Full Text Available In mobile communication systems with multisensor antennas at base stations, downlink channel estimation plays a key role because accurate channel estimates are needed for transmit beamforming. One efficient approach to this problem is channel probing with feedback. In this method, the base station array transmits probing (training signals. The channel is then estimated from feedback reports provided by the users. This paper studies the performance of the channel probing method with feedback using a multisensor base station antenna array and single-sensor users. The least squares (LS, linear minimum mean square error (LMMSE, and a new scaled LS (SLS approaches to the channel estimation are studied. Optimal choice of probing signals is investigated for each of these techniques and their channel estimation performances are analyzed. In the case of multiple LS channel estimates, the best linear unbiased estimation (BLUE scheme for their linear combining is developed and studied.

Sieve estimation in a Markov illness-death process under dual censoring.

Science.gov (United States)

Boruvka, Audrey; Cook, Richard J

2016-04-01

Semiparametric methods are well established for the analysis of a progressive Markov illness-death process observed up to a noninformative right censoring time. However, often the intermediate and terminal events are censored in different ways, leading to a dual censoring scheme. In such settings, unbiased estimation of the cumulative transition intensity functions cannot be achieved without some degree of smoothing. To overcome this problem, we develop a sieve maximum likelihood approach for inference on the hazard ratio. A simulation study shows that the sieve estimator offers improved finite-sample performance over common imputation-based alternatives and is robust to some forms of dependent censoring. The proposed method is illustrated using data from cancer trials. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Bracken: estimating species abundance in metagenomics data

Directory of Open Access Journals (Sweden)

Jennifer Lu

2017-01-01

Full Text Available Metagenomic experiments attempt to characterize microbial communities using high-throughput DNA sequencing. Identification of the microorganisms in a sample provides information about the genetic profile, population structure, and role of microorganisms within an environment. Until recently, most metagenomics studies focused on high-level characterization at the level of phyla, or alternatively sequenced the 16S ribosomal RNA gene that is present in bacterial species. As the cost of sequencing has fallen, though, metagenomics experiments have increasingly used unbiased shotgun sequencing to capture all the organisms in a sample. This approach requires a method for estimating abundance directly from the raw read data. Here we describe a fast, accurate new method that computes the abundance at the species level using the reads collected in a metagenomics experiment. Bracken (Bayesian Reestimation of Abundance after Classification with KrakEN uses the taxonomic assignments made by Kraken, a very fast read-level classifier, along with information about the genomes themselves to estimate abundance at the species level, the genus level, or above. We demonstrate that Bracken can produce accurate species- and genus-level abundance estimates even when a sample contains multiple near-identical species.

The Cellular Composition and Glia-Neuron Ratio in the Spinal Cord of a Human and a Nonhuman Primate: Comparison With Other Species and Brain Regions.

Science.gov (United States)

Bahney, Jami; von Bartheld, Christopher S

2018-04-01

The cellular composition of brains shows largely conserved, gradual evolutionary trends between species. In the primate spinal cord, however, the glia-neuron ratio was reported to be greatly increased over that in the rodent spinal cord. Here, we re-examined the cellular composition of the spinal cord of one human and one nonhuman primate species by employing two different counting methods, the isotropic fractionator and stereology. We also determined whether segmental differences in cellular composition, possibly reflecting increased fine motor control of the upper extremities, may explain a sharply increased glia-neuron ratio in primates. In the cynomolgus monkey spinal cord, the isotropic fractionator and stereology yielded 206-275 million cells, of which 13.3-25.1% were neurons (28-69 million). Stereological estimates yielded 21.1% endothelial cells and 65.5% glial cells (glia-neuron ratio of 4.9-5.6). In human spinal cords, the isotropic fractionator and stereology generated estimates of 1.5-1.7 billion cells and 197-222 million neurons (13.4% neurons, 12.2% endothelial cells, 74.8% glial cells), and a glia-neuron ratio of 5.6-7.1, with estimates of neuron numbers in the human spinal cord based on morphological criteria. The non-neuronal to neuron ratios in human and cynomolgus monkey spinal cords were 6.5 and 3.2, respectively, suggesting that previous reports overestimated this ratio. We did not find significant segmental differences in the cellular composition between cervical, thoracic and lumbar levels. When compared with brain regions, the spinal cord showed gradual increases of the glia-neuron ratio with increasing brain mass, similar to the cerebral cortex and the brainstem. Anat Rec, 301:697-710, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

On Kolmogorov asymptotics of estimators of the misclassification error rate in linear discriminant analysis

KAUST Repository

Zollanvari, Amin

2013-05-24

We provide a fundamental theorem that can be used in conjunction with Kolmogorov asymptotic conditions to derive the first moments of well-known estimators of the actual error rate in linear discriminant analysis of a multivariate Gaussian model under the assumption of a common known covariance matrix. The estimators studied in this paper are plug-in and smoothed resubstitution error estimators, both of which have not been studied before under Kolmogorov asymptotic conditions. As a result of this work, we present an optimal smoothing parameter that makes the smoothed resubstitution an unbiased estimator of the true error. For the sake of completeness, we further show how to utilize the presented fundamental theorem to achieve several previously reported results, namely the first moment of the resubstitution estimator and the actual error rate. We provide numerical examples to show the accuracy of the succeeding finite sample approximations in situations where the number of dimensions is comparable or even larger than the sample size.

On Kolmogorov asymptotics of estimators of the misclassification error rate in linear discriminant analysis

KAUST Repository

Zollanvari, Amin; Genton, Marc G.

2013-01-01

We provide a fundamental theorem that can be used in conjunction with Kolmogorov asymptotic conditions to derive the first moments of well-known estimators of the actual error rate in linear discriminant analysis of a multivariate Gaussian model under the assumption of a common known covariance matrix. The estimators studied in this paper are plug-in and smoothed resubstitution error estimators, both of which have not been studied before under Kolmogorov asymptotic conditions. As a result of this work, we present an optimal smoothing parameter that makes the smoothed resubstitution an unbiased estimator of the true error. For the sake of completeness, we further show how to utilize the presented fundamental theorem to achieve several previously reported results, namely the first moment of the resubstitution estimator and the actual error rate. We provide numerical examples to show the accuracy of the succeeding finite sample approximations in situations where the number of dimensions is comparable or even larger than the sample size.

Efficacy of calf:cow ratios for estimating calf production of arctic caribou

Science.gov (United States)

Cameron, R.D.; Griffith, B.; Parrett, L.S.; White, R.G.

2013-01-01

Caribou (Rangifer tarandus granti) calf:cow ratios (CCR) computed from composition counts obtained on arctic calving grounds are biased estimators of net calf production (NCP, the product of parturition rate and early calf survival) for sexually-mature females. Sexually-immature 2-year-old females, which are indistinguishable from sexually-mature females without calves, are included in the denominator, thereby biasing the calculated ratio low. This underestimate increases with the proportion of 2-year-old females in the population. We estimated the magnitude of this error with deterministic simulations under three scenarios of calf and yearling annual survival (respectively: low, 60 and 70%; medium, 70 and 80%; high, 80 and 90%) for five levels of unbiased NCP: 20, 40, 60, 80, and 100%. We assumed a survival rate of 90% for both 2-year-old and mature females. For each NCP, we computed numbers of 2-year-old females surviving annually and increased the denominator of CCR accordingly. We then calculated a series of hypothetical “observed” CCRs, which stabilized during the last 6 years of the simulations, and documented the degree to which each 6-year mean CCR differed from the corresponding NCP. For the three calf and yearling survival scenarios, proportional underestimates of NCP by CCR ranged 0.046–0.156, 0.058–0.187, and 0.071–0.216, respectively. Unfortunately, because parturition and survival rates are typically variable (i.e., age distribution is unstable), the magnitude of the error is not predictable without substantial supporting information. We recommend maintaining a sufficient sample of known-age radiocollared females in each herd and implementing a regular relocation schedule during the calving period to obtain unbiased estimates of both parturition rate and NCP.

Annual survival estimation of migratory songbirds confounded by incomplete breeding site-fidelity: study designs that may help

Directory of Open Access Journals (Sweden)

Marshall, M. R.

2004-06-01

surrounding areas to minimize bias. Therefore, as an alternative protocol, we analyzed the data with subsets of three progressively larger areas surrounding the core. The data subsets provided four estimates of apparent survival that asymptotically approached true survival. This study design and analytical approach is likely to be logistically feasible in field settings and yields estimates of true survival unbiased (bias < 0.03 by incomplete breeding site–fidelity over a range of inter–annual territory movement patterns. The third approach we investigated used a robust design data collection and analysis approach. This approach resulted in estimates of survival that were unbiased (bias < 0.02, but were very imprecise and likely would not yield reliable estimates in field situations. The fourth approach utilized a fixed study area size, but modeled detection probability as a function of bird proximity to the study plot boundary (e.g., those birds closest to the edge are more likely to emigrate. This approach also resulted in estimates of survival that were unbiased (bias < 0.02, but because the individual covariates were normalized, the average capture probability was 0.50, and thus did not provide an accurate estimate of the true capture probability. Our results show that the core–area with surrounding resight–only can provide estimates of survival that are not biased by the effects of incomplete breeding site–fidelity.

Combined Radar-Radiometer Surface Soil Moisture and Roughness Estimation

Science.gov (United States)

Akbar, Ruzbeh; Cosh, Michael H.; O'Neill, Peggy E.; Entekhabi, Dara; Moghaddam, Mahta

2017-01-01

A robust physics-based combined radar-radiometer, or Active-Passive, surface soil moisture and roughness estimation methodology is presented. Soil moisture and roughness retrieval is performed via optimization, i.e., minimization, of a joint objective function which constrains similar resolution radar and radiometer observations simultaneously. A data-driven and noise-dependent regularization term has also been developed to automatically regularize and balance corresponding radar and radiometer contributions to achieve optimal soil moisture retrievals. It is shown that in order to compensate for measurement and observation noise, as well as forward model inaccuracies, in combined radar-radiometer estimation surface roughness can be considered a free parameter. Extensive Monte-Carlo numerical simulations and assessment using field data have been performed to both evaluate the algorithms performance and to demonstrate soil moisture estimation. Unbiased root mean squared errors (RMSE) range from 0.18 to 0.03 cm3cm3 for two different land cover types of corn and soybean. In summary, in the context of soil moisture retrieval, the importance of consistent forward emission and scattering development is discussed and presented.

Minimum Energy Decentralized Estimation in a Wireless Sensor Network with Correlated Sensor Noises

Directory of Open Access Journals (Sweden)

Krasnopeev Alexey

2005-01-01

Full Text Available Consider the problem of estimating an unknown parameter by a sensor network with a fusion center (FC. Sensor observations are corrupted by additive noises with an arbitrary spatial correlation. Due to bandwidth and energy limitation, each sensor is only able to transmit a finite number of bits to the FC, while the latter must combine the received bits to estimate the unknown parameter. We require the decentralized estimator to have a mean-squared error ( that is within a constant factor to that of the best linear unbiased estimator (BLUE. We minimize the total sensor transmitted energy by selecting sensor quantization levels using the knowledge of noise covariance matrix while meeting the target requirement. Computer simulations show that our designs can achieve energy savings up to when compared to the uniform quantization strategy whereby each sensor generates the same number of bits, irrespective of the quality of its observation and the condition of its channel to the FC.

Doubly robust estimation of generalized partial linear models for longitudinal data with dropouts.

Science.gov (United States)

Lin, Huiming; Fu, Bo; Qin, Guoyou; Zhu, Zhongyi

2017-12-01

We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation. We establish the asymptotic theory for the proposed method and use simulation studies to compare its finite sample performance with that of Qu's method, the complete-case generalized estimating equation (GEE) and the inverse-probability weighted GEE. The proposed method is finally illustrated using data from a longitudinal cohort study. © 2017, The International Biometric Society.

Minimum Energy Decentralized Estimation in a Wireless Sensor Network with Correlated Sensor Noises

Directory of Open Access Journals (Sweden)

Krasnopeev Alexey

2005-01-01

Full Text Available Consider the problem of estimating an unknown parameter by a sensor network with a fusion center (FC. Sensor observations are corrupted by additive noises with an arbitrary spatial correlation. Due to bandwidth and energy limitation, each sensor is only able to transmit a finite number of bits to the FC, while the latter must combine the received bits to estimate the unknown parameter. We require the decentralized estimator to have a mean-squared error (MSE that is within a constant factor to that of the best linear unbiased estimator (BLUE. We minimize the total sensor transmitted energy by selecting sensor quantization levels using the knowledge of noise covariance matrix while meeting the target MSE requirement. Computer simulations show that our designs can achieve energy savings up to 70 % when compared to the uniform quantization strategy whereby each sensor generates the same number of bits, irrespective of the quality of its observation and the condition of its channel to the FC.

Bias and efficiency loss in regression estimates due to duplicated observations: a Monte Carlo simulation

Directory of Open Access Journals (Sweden)

Francesco Sarracino

2017-04-01

Full Text Available Recent studies documented that survey data contain duplicate records. We assess how duplicate records affect regression estimates, and we evaluate the effectiveness of solutions to deal with duplicate records. Results show that the chances of obtaining unbiased estimates when data contain 40 doublets (about 5% of the sample range between 3.5% and 11.5% depending on the distribution of duplicates. If 7 quintuplets are present in the data (2% of the sample, then the probability of obtaining biased estimates ranges between 11% and 20%. Weighting the duplicate records by the inverse of their multiplicity, or dropping superfluous duplicates outperform other solutions in all considered scenarios. Our results illustrate the risk of using data in presence of duplicate records and call for further research on strategies to analyze affected data.

Noise Estimation for Single-Slice Sinogram of Low-Dose X-Ray Computed Tomography Using Homogenous Patch

Directory of Open Access Journals (Sweden)

Zhiwu Liao

2012-01-01

Full Text Available We present a new method to estimate noise for a single-slice sinogram of low-dose CT based on the homogenous patches centered at a special pixel, called center point, which has the smallest variance among all sinogram pixels. The homogenous patch, composed by homogenous points, is formed by the points similar to the center point using similarity sorting, similarity decreasing searching, and variance analysis in a very large neighborhood (VLN to avoid manual selection of parameter for similarity measures.Homogenous pixels in the VLN allow us find the largest number of samples, who have the highest similarities to the center point, for noise estimation, and the noise level can be estimated according to unbiased estimation.Experimental results show that for the simulated noisy sinograms, the method proposed in this paper can obtain satisfied noise estimation results, especially for sinograms with relatively serious noises.

Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

DEFF Research Database (Denmark)

Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

2015-01-01

The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress...

UNBIASED INCLINATION DISTRIBUTIONS FOR OBJECTS IN THE KUIPER BELT

International Nuclear Information System (INIS)

Gulbis, A. A. S.; Elliot, J. L.; Adams, E. R.; Benecchi, S. D.; Buie, M. W.; Trilling, D. E.; Wasserman, L. H.

2010-01-01

Using data from the Deep Ecliptic Survey (DES), we investigate the inclination distributions of objects in the Kuiper Belt. We present a derivation for observational bias removal and use this procedure to generate unbiased inclination distributions for Kuiper Belt objects (KBOs) of different DES dynamical classes, with respect to the Kuiper Belt plane. Consistent with previous results, we find that the inclination distribution for all DES KBOs is well fit by the sum of two Gaussians, or a Gaussian plus a generalized Lorentzian, multiplied by sin i. Approximately 80% of KBOs are in the high-inclination grouping. We find that Classical object inclinations are well fit by sin i multiplied by the sum of two Gaussians, with roughly even distribution between Gaussians of widths 2.0 +0.6 -0.5 0 and 8.1 +2.6 -2.1 0 . Objects in different resonances exhibit different inclination distributions. The inclinations of Scattered objects are best matched by sin i multiplied by a single Gaussian that is centered at 19.1 +3.9 -3.6 0 with a width of 6.9 +4.1 -2.7 0 . Centaur inclinations peak just below 20 0 , with one exceptionally high-inclination object near 80 0 . The currently observed inclination distribution of the Centaurs is not dissimilar to that of the Scattered Extended KBOs and Jupiter-family comets, but is significantly different from the Classical and Resonant KBOs. While the sample sizes of some dynamical classes are still small, these results should begin to serve as a critical diagnostic for models of solar system evolution.

An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

DEFF Research Database (Denmark)

Lyck, L.; Santamaria, I.D.; Pakkenberg, B.

2009-01-01

Improving histomorphometric analysis of the human neocortex by combining stereological cell counting with immunchistochemical visualisation of specific neuronal and glial cell populations is a methodological challenge. To enable standardized immunohistochemical staining, the amount of brain tissue...... to be stained and analysed by cell counting was efficiently reduced using a fractionator protocol involving several steps of sub-sampling. Since no mathematical or statistical tools exist to predict the variance originating from repeated sampling in complex structures like the human neocortex, the variance....... The results showed that it was possible, but not straight forward, to combine immunohistochemistry and the optical fractionator for estimation of specific subpopulations of brain cells in human neocortex. (C) 2009 Elsevier B.V. All rights reserved Udgivelsesdato: 2009/9/15...

Statistical properties of the anomalous scaling exponent estimator based on time-averaged mean-square displacement

Science.gov (United States)

Sikora, Grzegorz; Teuerle, Marek; Wyłomańska, Agnieszka; Grebenkov, Denis

2017-08-01

The most common way of estimating the anomalous scaling exponent from single-particle trajectories consists of a linear fit of the dependence of the time-averaged mean-square displacement on the lag time at the log-log scale. We investigate the statistical properties of this estimator in the case of fractional Brownian motion (FBM). We determine the mean value, the variance, and the distribution of the estimator. Our theoretical results are confirmed by Monte Carlo simulations. In the limit of long trajectories, the estimator is shown to be asymptotically unbiased, consistent, and with vanishing variance. These properties ensure an accurate estimation of the scaling exponent even from a single (long enough) trajectory. As a consequence, we prove that the usual way to estimate the diffusion exponent of FBM is correct from the statistical point of view. Moreover, the knowledge of the estimator distribution is the first step toward new statistical tests of FBM and toward a more reliable interpretation of the experimental histograms of scaling exponents in microbiology.

Direct metagenomic detection of viral pathogens in nasal and fecal specimens using an unbiased high-throughput sequencing approach.

Directory of Open Access Journals (Sweden)

Shota Nakamura

Full Text Available With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a "next-generation" parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1-0.25 ml of nasopharyngeal aspirates (N = 3 and fecal specimens (N = 5, and more than 10 microg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298-32,335 (average 24,738 reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90% of reads were host genome-derived, 20-460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484-15,260 reads of norovirus sequence (78-98% of the whole genome was covered, except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.

Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study).

Science.gov (United States)

Dursun, Hakan; Albayrak, Fatih; Uyanik, Abdullah; Keleş, Nuri Osman; Beyzagül, Polat; Bayram, Ednan; Halici, Zekai; Altunkaynak, Zuhal Berrin; Süleyman, Halis; Okçu, Nihat; Ünal, Bünyamin

2010-12-01

Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats. In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined. The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 μm3, respectively. Significant differences were found between values of all groups (phypertension in Groups 5 and 6. Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.

Use of flow cytometry for high-throughput cell population estimates in fixed brain tissue

Directory of Open Access Journals (Sweden)

Nicole A Young

2012-07-01

Full Text Available The numbers and types of cells in an area of cortex define its function. Therefore it is essential to characterize the numbers and distributions of total cells in areas of the cortex, as well as to identify numbers of subclasses of neurons and glial cells. To date, the large size of the primate brain and the lack of innovation in cell counting methods have been a roadblock to obtaining high-resolution maps of cell and neuron density across the cortex in humans and non-human primates. Stereological counting methods and the isotropic fractionator are valuable tools for estimating cell numbers, but are better suited to smaller, well-defined brain structures or to cortex as a whole. In the present study, we have extended our flow-cytometry based counting method, the flow fractionator (Collins et al., 2010a, to include high-throughput total cell population estimates in homogenized cortical samples. We demonstrate that our method produces consistent, accurate and repeatable cell estimates quickly. The estimates we report are in excellent agreement with estimates for the same samples obtained using a Neubauer chamber and a fluorescence microscope. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue is more efficient and more precise than manual counting methods. The addition of automated nuclei counting to our flow fractionator method allows for a fully automated, rapid characterization of total cells and neuronal and non-neuronal populations in human and non-human primate brains, providing valuable data to further our understanding of the functional organization of normal, aging and diseased brains.

Unbiased, complete solar charging of a neutral flow battery by a single Si photocathode

DEFF Research Database (Denmark)

Wedege, Kristina; Bae, Dowon; Dražević, Emil

2018-01-01

Solar redox flow batteries have attracted attention as a possible integrated technology for simultaneous conversion and storage of solar energy. In this work, we review current efforts to design aqueous solar flow batteries in terms of battery electrolyte capacity, solar conversion efficiency...... and depth of solar charge. From a materials cost and design perspective, a simple, cost-efficient, aqueous solar redox flow battery will most likely incorporate only one semiconductor, and we demonstrate here a system where a single photocathode is accurately matched to the redox couples to allow...... for a complete solar charge. The single TiO2 protected Si photocathode with a catalytic Pt layer can fully solar charge a neutral TEMPO-sulfate/ferricyanide battery with a cell voltage of 0.35 V. An unbiased solar conversion efficiency of 1.6% is obtained and this system represents a new strategy in solar RFBs...

Bayesian estimates of male and female African lion mortality for future use in population management

DEFF Research Database (Denmark)

Barthold, Julia A; Loveridge, Andrew; Macdonald, David

2016-01-01

1. The global population size of African lions is plummeting, and many small fragmented populations face local extinction. Extinction risks are amplified through the common practice of trophy hunting for males, which makes setting sustainable hunting quotas a vital task. 2. Various demographic...... models evaluate consequences of hunting on lion population growth. However, none of the models use unbiased estimates of male age-specific mortality because such estimates do not exist. Until now, estimating mortality from resighting records of marked males has been impossible due to the uncertain fates...... of disappeared individuals: dispersal or death. 3. We develop a new method and infer mortality for male and female lions from two popula- tions that are typical with respect to their experienced levels of human impact. 4. We found that mortality of both sexes differed between the populations and that males had...

Estimates of the abundance of minke whales (Balaenoptera acutorostrata from Faroese and Icelandic NASS shipboard surveys

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Daniel G Pike

2009-09-01

Full Text Available North Atlantic Sightings Surveys for cetaceans were carried out Northeast and Central Atlantic in 1987, 1989, 1995 and 2001. Here we provide estimates of density and abundance for minke whales from the Faroese and Icelandic ship surveys. The estimates are not corrected for availability or perception biases. Double platform data collected in 2001 indicates that perception bias is likely considerable for this species. However comparison of corrected estimates of densityfrom aerial surveys with a ship survey estimate from the same area suggests that ship surveys can be nearly unbiased under optimal survey conditions with high searching effort. There were some regional changes in density over the period but no overall changes in density and abundance. Given the recent catch history for minke whales in this area, we would not expect to see changes in abundance due to exploitation that would be detectable with these surveys.

Estimation of the number of angiotensin II AT1 receptors in rat kidney afferent and efferent arterioles

DEFF Research Database (Denmark)

Razga, Zsolt; Nyengaard, Jens Randel

2007-01-01

of angiotensin II AT1 receptors along the length of the arterioles and per arteriole, we combined immunoelectron microscopy with stereology. RESULTS: The number of AT1 receptor molecules was significantly lower in the renin-positive smooth muscle cells (SMCs) than in the renin-negative SMCs of the afferent...

Fourier band-power E/B-mode estimators for cosmic shear

Energy Technology Data Exchange (ETDEWEB)

Becker, Matthew R.; Rozo, Eduardo

2016-01-20

We introduce new Fourier band-power estimators for cosmic shear data analysis and E/B-mode separation. We consider both the case where one performs E/B-mode separation and the case where one does not. The resulting estimators have several nice properties which make them ideal for cosmic shear data analysis. First, they can be written as linear combinations of the binned cosmic shear correlation functions. Secondly, they account for the survey window function in real-space. Thirdly, they are unbiased by shape noise since they do not use correlation function data at zero separation. Fourthly, the band-power window functions in Fourier space are compact and largely non-oscillatory. Fifthly, they can be used to construct band-power estimators with very efficient data compression properties. In particular, we find that all of the information on the parameters Ωm, σ8 and ns in the shear correlation functions in the range of ~10–400 arcmin for single tomographic bin can be compressed into only three band-power estimates. Finally, we can achieve these rates of data compression while excluding small-scale information where the modelling of the shear correlation functions and power spectra is very difficult. Given these desirable properties, these estimators will be very useful for cosmic shear data analysis.

Revisiting AFLP fingerprinting for an unbiased assessment of genetic structure and differentiation of taurine and zebu cattle

Science.gov (United States)

2014-01-01

Background Descendants from the extinct aurochs (Bos primigenius), taurine (Bos taurus) and zebu cattle (Bos indicus) were domesticated 10,000 years ago in Southwestern and Southern Asia, respectively, and colonized the world undergoing complex events of admixture and selection. Molecular data, in particular genome-wide single nucleotide polymorphism (SNP) markers, can complement historic and archaeological records to elucidate these past events. However, SNP ascertainment in cattle has been optimized for taurine breeds, imposing limitations to the study of diversity in zebu cattle. As amplified fragment length polymorphism (AFLP) markers are discovered and genotyped as the samples are assayed, this type of marker is free of ascertainment bias. In order to obtain unbiased assessments of genetic differentiation and structure in taurine and zebu cattle, we analyzed a dataset of 135 AFLP markers in 1,593 samples from 13 zebu and 58 taurine breeds, representing nine continental areas. Results We found a geographical pattern of expected heterozygosity in European taurine breeds decreasing with the distance from the domestication centre, arguing against a large-scale introgression from European or African aurochs. Zebu cattle were found to be at least as diverse as taurine cattle. Western African zebu cattle were found to have diverged more from Indian zebu than South American zebu. Model-based clustering and ancestry informative markers analyses suggested that this is due to taurine introgression. Although a large part of South American zebu cattle also descend from taurine cows, we did not detect significant levels of taurine ancestry in these breeds, probably because of systematic backcrossing with zebu bulls. Furthermore, limited zebu introgression was found in Podolian taurine breeds in Italy. Conclusions The assessment of cattle diversity reported here contributes an unbiased global view to genetic differentiation and structure of taurine and zebu cattle

Large-scale Reconstructions and Independent, Unbiased Clustering Based on Morphological Metrics to Classify Neurons in Selective Populations.

Science.gov (United States)

Bragg, Elise M; Briggs, Farran

2017-02-15

This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population. The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills. Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus

Sensitivity of Hurst parameter estimation to periodic signals in time series and filtering approaches

Science.gov (United States)

Marković, D.; Koch, M.

2005-09-01

The influence of the periodic signals in time series on the Hurst parameter estimate is investigated with temporal, spectral and time-scale methods. The Hurst parameter estimates of the simulated periodic time series with a white noise background show a high sensitivity on the signal to noise ratio and for some methods, also on the data length used. The analysis is then carried on to the investigation of extreme monthly river flows of the Elbe River (Dresden) and of the Rhine River (Kaub). Effects of removing the periodic components employing different filtering approaches are discussed and it is shown that such procedures are a prerequisite for an unbiased estimation of H. In summary, our results imply that the first step in a time series long-correlation study should be the separation of the deterministic components from the stochastic ones. Otherwise wrong conclusions concerning possible memory effects may be drawn.

On Compressed Sensing and the Estimation of Continuous Parameters From Noisy Observations

DEFF Research Database (Denmark)

Nielsen, Jesper Kjær; Christensen, Mads Græsbøll; Jensen, Søren Holdt

2012-01-01

Compressed sensing (CS) has in recent years become a very popular way of sampling sparse signals. This sparsity is measured with respect to some known dictionary consisting of a finite number of atoms. Most models for real world signals, however, are parametrised by continuous parameters correspo......Compressed sensing (CS) has in recent years become a very popular way of sampling sparse signals. This sparsity is measured with respect to some known dictionary consisting of a finite number of atoms. Most models for real world signals, however, are parametrised by continuous parameters...... corresponding to a dictionary with an infinite number of atoms. Examples of such parameters are the temporal and spatial frequency. In this paper, we analyse how CS affects the estimation performance of any unbiased estimator when we assume such infinite dictionaries. We base our analysis on the Cramer...

High Efficient THz Emission From Unbiased and Biased Semiconductor Nanowires Fabricated Using Electron Beam Lithography

Energy Technology Data Exchange (ETDEWEB)

Balci, Soner; Czaplewski, David A.; Jung, Il Woong; Kim, Ju-Hyung; Hatami, Fariba; Kung, Patrick; Kim, Seongsin Margaret

2017-07-01

Besides having perfect control on structural features, such as vertical alignment and uniform distribution by fabricating the wires via e-beam lithography and etching process, we also investigated the THz emission from these fabricated nanowires when they are applied DC bias voltage. To be able to apply a voltage bias, an interdigitated gold (Au) electrode was patterned on the high-quality InGaAs epilayer grown on InP substrate bymolecular beam epitaxy. Afterwards, perfect vertically aligned and uniformly distributed nanowires were fabricated in between the electrodes of this interdigitated pattern so that we could apply voltage bias to improve the THz emission. As a result, we achieved enhancement in the emitted THz radiation by ~four times, about 12 dB increase in power ratio at 0.25 THz with a DC biased electric field compared with unbiased NWs.

Best linear unbiased prediction of genomic breeding values using a trait-specific marker-derived relationship matrix.

Directory of Open Access Journals (Sweden)

Zhe Zhang

2010-09-01

Full Text Available With the availability of high density whole-genome single nucleotide polymorphism chips, genomic selection has become a promising method to estimate genetic merit with potentially high accuracy for animal, plant and aquaculture species of economic importance. With markers covering the entire genome, genetic merit of genotyped individuals can be predicted directly within the framework of mixed model equations, by using a matrix of relationships among individuals that is derived from the markers. Here we extend that approach by deriving a marker-based relationship matrix specifically for the trait of interest.In the framework of mixed model equations, a new best linear unbiased prediction (BLUP method including a trait-specific relationship matrix (TA was presented and termed TABLUP. The TA matrix was constructed on the basis of marker genotypes and their weights in relation to the trait of interest. A simulation study with 1,000 individuals as the training population and five successive generations as candidate population was carried out to validate the proposed method. The proposed TABLUP method outperformed the ridge regression BLUP (RRBLUP and BLUP with realized relationship matrix (GBLUP. It performed slightly worse than BayesB with an accuracy of 0.79 in the standard scenario.The proposed TABLUP method is an improvement of the RRBLUP and GBLUP method. It might be equivalent to the BayesB method but it has additional benefits like the calculation of accuracies for individual breeding values. The results also showed that the TA-matrix performs better in predicting ability than the classical numerator relationship matrix and the realized relationship matrix which are derived solely from pedigree or markers without regard to the trait. This is because the TA-matrix not only accounts for the Mendelian sampling term, but also puts the greater emphasis on those markers that explain more of the genetic variance in the trait.

Crop area estimation using high and medium resolution satellite imagery in areas with complex topography

Science.gov (United States)

Husak, G. J.; Marshall, M. T.; Michaelsen, J.; Pedreros, D.; Funk, C.; Galu, G.

2008-07-01

Reliable estimates of cropped area (CA) in developing countries with chronic food shortages are essential for emergency relief and the design of appropriate market-based food security programs. Satellite interpretation of CA is an effective alternative to extensive and costly field surveys, which fail to represent the spatial heterogeneity at the country-level. Bias-corrected, texture based classifications show little deviation from actual crop inventories, when estimates derived from aerial photographs or field measurements are used to remove systematic errors in medium resolution estimates. In this paper, we demonstrate a hybrid high-medium resolution technique for Central Ethiopia that combines spatially limited unbiased estimates from IKONOS images, with spatially extensive Landsat ETM+ interpretations, land-cover, and SRTM-based topography. Logistic regression is used to derive the probability of a location being crop. These individual points are then aggregated to produce regional estimates of CA. District-level analysis of Landsat based estimates showed CA totals which supported the estimates of the Bureau of Agriculture and Rural Development. Continued work will evaluate the technique in other parts of Africa, while segmentation algorithms will be evaluated, in order to automate classification of medium resolution imagery for routine CA estimation in the future.

A Comparison of Alternative Estimators of Linearly Aggregated Macro Models

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Fikri Akdeniz

2012-07-01

Full Text Available Normal 0 false false false TR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif"; mso-ansi-language:TR; mso-fareast-language:TR;} This paper deals with the linear aggregation problem. For the true underlying micro relations, which explain the micro behavior of the individuals, no restrictive rank conditions are assumed. Thus the analysis is presented in a framework utilizing generalized inverses of singular matrices. We investigate several estimators for certain linear transformations of the systematic part of the corresponding macro relations. Homogeneity of micro parameters is discussed. Best linear unbiased estimation for micro parameters is described.

Estimation of coincidence and correlation in non-analogous Monte Carlo particle transport - 159

International Nuclear Information System (INIS)

Szieberth, M.; Leen Kloosterman, J.

2010-01-01

The conventional non-analogous Monte Carlo methods are optimized to preserve the mean value of the distributions and therefore they are not suited for non-Boltzmann problems like the estimation of coincidences or correlations. This paper presents a general method called history splitting for the non-analogous estimation of such quantities. The basic principle of the method is that a non-analogous particle history can be interpreted as a collection of analogous histories with different weights according to the probability of their realization. Calculations with a simple Monte Carlo program for a pulse-height-type estimator prove that the method is feasible and provides unbiased estimation. Different variance reduction techniques have been tried with the method and Russian roulette turned out to be ineffective in high multiplicity systems. An alternative history control method is applied instead. Simulation results of a Feynman-α measurement shows that even the reconstruction of the higher moments is possible with the history splitting method, which makes the simulation of neutron noise measurements feasible. (authors)

Application of single-step genomic best linear unbiased prediction with a multiple-lactation random regression test-day model for Japanese Holsteins.

Science.gov (United States)

Baba, Toshimi; Gotoh, Yusaku; Yamaguchi, Satoshi; Nakagawa, Satoshi; Abe, Hayato; Masuda, Yutaka; Kawahara, Takayoshi

2017-08-01

This study aimed to evaluate a validation reliability of single-step genomic best linear unbiased prediction (ssGBLUP) with a multiple-lactation random regression test-day model and investigate an effect of adding genotyped cows on the reliability. Two data sets for test-day records from the first three lactations were used: full data from February 1975 to December 2015 (60 850 534 records from 2 853 810 cows) and reduced data cut off in 2011 (53 091 066 records from 2 502 307 cows). We used marker genotypes of 4480 bulls and 608 cows. Genomic enhanced breeding values (GEBV) of 305-day milk yield in all the lactations were estimated for at least 535 young bulls using two marker data sets: bull genotypes only and both bulls and cows genotypes. The realized reliability (R 2 ) from linear regression analysis was used as an indicator of validation reliability. Using only genotyped bulls, R 2 was ranged from 0.41 to 0.46 and it was always higher than parent averages. The very similar R 2 were observed when genotyped cows were added. An application of ssGBLUP to a multiple-lactation random regression model is feasible and adding a limited number of genotyped cows has no significant effect on reliability of GEBV for genotyped bulls. © 2016 Japanese Society of Animal Science.

Unaltered Neuronal and Glial Counts in Animal Models of Magnetic Seizure Therapy and Electroconvulsive Therapy

DEFF Research Database (Denmark)

Dwork, A.J.; Christensen, J.R.; Larsen, K.B.

2009-01-01

report on its anatomical effects. We discerned no histological lesions in the brains of higher mammals subjected to electroconvulsive shock (ECS) or MST, under conditions that model closely those used in humans. We sought to extend these findings by determining whether these interventions affected...... the number of neurons or glia in the frontal cortex or hippocampus. Twenty-four animals received 6 weeks of ECS, MST, or anesthesia alone, 4 days per week. After perfusion fixation, numbers of neurons and glia in frontal cortex and hippocampus were determined by unbiased stereological methods. We found...... no effect of either intervention on volumes or total number or numerical density of neurons or glia in hippocampus, frontal cortex, or subregions of these structures. Induction of seizures in a rigorous model of human ECT and MST therapy does not cause a change in the number of neurons or glia...

Stereological Study on the Positive Effect of Running Exercise on the Capillaries in the Hippocampus in a Depression Model

Directory of Open Access Journals (Sweden)

Linmu Chen

2017-11-01

Full Text Available Running exercise is an effective method to improve depressive symptoms when combined with drugs. However, the underlying mechanisms are not fully clear. Cerebral blood flow perfusion in depressed patients is significantly lower in the hippocampus. Physical activity can achieve cerebrovascular benefits. The purpose of this study was to evaluate the impacts of running exercise on capillaries in the hippocampal CA1 and dentate gyrus (DG regions. The chronic unpredictable stress (CUS depression model was used in this study. CUS rats were given 4 weeks of running exercise from the fifth week to the eighth week (20 min every day from Monday to Friday each week. The sucrose consumption test was used to measure anhedonia. Furthermore, stereological methods were used to investigate the capillary changes among the control group, CUS/Standard group and CUS/Running group. Sucrose consumption significantly increased in the CUS/Running group. Running exercise has positive effects on the capillaries parameters in the hippocampal CA1 and DG regions, such as the total volume, total length and total surface area. These results demonstrated that capillaries are protected by running exercise in the hippocampal CA1 and DG might be one of the structural bases for the exercise-induced treatment of depression-like behavior. These results suggest that drugs and behavior influence capillaries and may be considered as a new means for depression treatment in the future.

The rat orbital and agranular insular prefrontal cortical areas: a cytoarchitectonic and chemoarchitectonic study

NARCIS (Netherlands)

van de Werd, H.J.J.M.; Uylings, H.B.M.

2008-01-01

Cytoarchitectonic characterization of borders is necessary for stereological studies (e.g., total cell number estimation), in which particular cortical areas have to be defined. In this study, cytoarchitectonic characteristics are described and illustrated for the rat ventral or orbital frontal

Regularization parameter estimation for underdetermined problems by the χ 2 principle with application to 2D focusing gravity inversion

International Nuclear Information System (INIS)

Vatankhah, Saeed; Ardestani, Vahid E; Renaut, Rosemary A

2014-01-01

The χ 2 principle generalizes the Morozov discrepancy principle to the augmented residual of the Tikhonov regularized least squares problem. For weighting of the data fidelity by a known Gaussian noise distribution on the measured data, when the stabilizing, or regularization, term is considered to be weighted by unknown inverse covariance information on the model parameters, the minimum of the Tikhonov functional becomes a random variable that follows a χ 2 -distribution with m+p−n degrees of freedom for the model matrix G of size m×n, m⩾n, and regularizer L of size p × n. Then, a Newton root-finding algorithm, employing the generalized singular value decomposition, or singular value decomposition when L = I, can be used to find the regularization parameter α. Here the result and algorithm are extended to the underdetermined case, m 2 algorithms when m 2 and unbiased predictive risk estimator of the regularization parameter are used for the first time in this context. For a simulated underdetermined data set with noise, these regularization parameter estimation methods, as well as the generalized cross validation method, are contrasted with the use of the L-curve and the Morozov discrepancy principle. Experiments demonstrate the efficiency and robustness of the χ 2 principle and unbiased predictive risk estimator, moreover showing that the L-curve and Morozov discrepancy principle are outperformed in general by the other three techniques. Furthermore, the minimum support stabilizer is of general use for the χ 2 principle when implemented without the desirable knowledge of the mean value of the model. (paper)

The effect of the timing of prenatal exposure to x-irradiation on Purkinje cell numbers in rat cerebellum

International Nuclear Information System (INIS)

Miki, T.; Satriotomo, I.; Matsumoto, Y.; Kuma, H.; Takeuchi, Y.; Gu

2003-01-01

Full text: Prenatal exposure of the developing brain to X-irradiation is known to cause various deleterious consequences. We have examined the effects of prenatal X-irradiation on the development of the cerebellum. Wistar rats were exposed to 1.5 Gy X-irradiation either on the 14, 15 or 16th day of gestation (E14, E15, E16). Sham-irradiated animals were used as controls. At seven postnatal weeks of age, male rats were deeply anesthetized and killed by intracardiac perfusion with 2.5 % glutaraldehyde in 0.1 M phosphate buffer. The unbiased stereological procedure known as the fractionator method was used to estimate the total number of Purkinje cells in the cerebellum. Body and cerebellar weights from E14 and E15, but not E16 irradiated rats showed significant deficits compared to control animals. Rats irradiated on E16 and control rats had about 285,100 - 304,800 Purkinje cells in the cerebellum. There was no significant difference between these values. However, E14 and E15 irradiated animals had about 117,500 and 196,300 Purkinje cells, respectively. These estimates were significantly different from those observed in both control and E16 irradiated rats. Given that the phase of division of Purkinje cell progenitors is mainly between E14-E15 and the phase of differentiation and migration is between E16-E20, it is concluded that the vulnerable period of the Purkinje cells to X-irradiation closely overlaps the phase of division of progenitors

Galaxy-galaxy lensing estimators and their covariance properties

Science.gov (United States)

Singh, Sukhdeep; Mandelbaum, Rachel; Seljak, Uroš; Slosar, Anže; Vazquez Gonzalez, Jose

2017-11-01

We study the covariance properties of real space correlation function estimators - primarily galaxy-shear correlations, or galaxy-galaxy lensing - using SDSS data for both shear catalogues and lenses (specifically the BOSS LOWZ sample). Using mock catalogues of lenses and sources, we disentangle the various contributions to the covariance matrix and compare them with a simple analytical model. We show that not subtracting the lensing measurement around random points from the measurement around the lens sample is equivalent to performing the measurement using the lens density field instead of the lens overdensity field. While the measurement using the lens density field is unbiased (in the absence of systematics), its error is significantly larger due to an additional term in the covariance. Therefore, this subtraction should be performed regardless of its beneficial effects on systematics. Comparing the error estimates from data and mocks for estimators that involve the overdensity, we find that the errors are dominated by the shape noise and lens clustering, which empirically estimated covariances (jackknife and standard deviation across mocks) that are consistent with theoretical estimates, and that both the connected parts of the four-point function and the supersample covariance can be neglected for the current levels of noise. While the trade-off between different terms in the covariance depends on the survey configuration (area, source number density), the diagnostics that we use in this work should be useful for future works to test their empirically determined covariances.

Galaxy–galaxy lensing estimators and their covariance properties

International Nuclear Information System (INIS)

Singh, Sukhdeep; Mandelbaum, Rachel; Seljak, Uros; Slosar, Anze; Gonzalez, Jose Vazquez

2017-01-01

Here, we study the covariance properties of real space correlation function estimators – primarily galaxy–shear correlations, or galaxy–galaxy lensing – using SDSS data for both shear catalogues and lenses (specifically the BOSS LOWZ sample). Using mock catalogues of lenses and sources, we disentangle the various contributions to the covariance matrix and compare them with a simple analytical model. We show that not subtracting the lensing measurement around random points from the measurement around the lens sample is equivalent to performing the measurement using the lens density field instead of the lens overdensity field. While the measurement using the lens density field is unbiased (in the absence of systematics), its error is significantly larger due to an additional term in the covariance. Therefore, this subtraction should be performed regardless of its beneficial effects on systematics. Comparing the error estimates from data and mocks for estimators that involve the overdensity, we find that the errors are dominated by the shape noise and lens clustering, which empirically estimated covariances (jackknife and standard deviation across mocks) that are consistent with theoretical estimates, and that both the connected parts of the four-point function and the supersample covariance can be neglected for the current levels of noise. While the trade-off between different terms in the covariance depends on the survey configuration (area, source number density), the diagnostics that we use in this work should be useful for future works to test their empirically determined covariances.

Unbiased roughness measurements: the key to better etch performance

Science.gov (United States)

Liang, Andrew; Mack, Chris; Sirard, Stephen; Liang, Chen-wei; Yang, Liu; Jiang, Justin; Shamma, Nader; Wise, Rich; Yu, Jengyi; Hymes, Diane

2018-03-01

Edge placement error (EPE) has become an increasingly critical metric to enable Moore's Law scaling. Stochastic variations, as characterized for lines by line width roughness (LWR) and line edge roughness (LER), are dominant factors in EPE and known to increase with the introduction of EUV lithography. However, despite recommendations from ITRS, NIST, and SEMI standards, the industry has not agreed upon a methodology to quantify these properties. Thus, differing methodologies applied to the same image often result in different roughness measurements and conclusions. To standardize LWR and LER measurements, Fractilia has developed an unbiased measurement that uses a raw unfiltered line scan to subtract out image noise and distortions. By using Fractilia's inverse linescan model (FILM) to guide development, we will highlight the key influences of roughness metrology on plasma-based resist smoothing processes. Test wafers were deposited to represent a 5 nm node EUV logic stack. The patterning stack consists of a core Si target layer with spin-on carbon (SOC) as the hardmask and spin-on glass (SOG) as the cap. Next, these wafers were exposed through an ASML NXE 3350B EUV scanner with an advanced chemically amplified resist (CAR). Afterwards, these wafers were etched through a variety of plasma-based resist smoothing techniques using a Lam Kiyo conductor etch system. Dense line and space patterns on the etched samples were imaged through advanced Hitachi CDSEMs and the LER and LWR were measured through both Fractilia and an industry standard roughness measurement software. By employing Fractilia to guide plasma-based etch development, we demonstrate that Fractilia produces accurate roughness measurements on resist in contrast to an industry standard measurement software. These results highlight the importance of subtracting out SEM image noise to obtain quicker developmental cycle times and lower target layer roughness.

Estimating tag loss of the Atlantic Horseshoe crab, Limulus polyphemus, using a multi-state model

Science.gov (United States)

Butler, Catherine Alyssa; McGowan, Conor P.; Grand, James B.; Smith, David

2012-01-01

The Atlantic Horseshoe crab, Limulus polyphemus, is a valuable resource along the Mid-Atlantic coast which has, in recent years, experienced new management paradigms due to increased concern about this species role in the environment. While current management actions are underway, many acknowledge the need for improved and updated parameter estimates to reduce the uncertainty within the management models. Specifically, updated and improved estimates of demographic parameters such as adult crab survival in the regional population of interest, Delaware Bay, could greatly enhance these models and improve management decisions. There is however, some concern that difficulties in tag resighting or complete loss of tags could be occurring. As apparent from the assumptions of a Jolly-Seber model, loss of tags can result in a biased estimate and underestimate a survival rate. Given that uncertainty, as a first step towards estimating an unbiased estimate of adult survival, we first took steps to estimate the rate of tag loss. Using data from a double tag mark-resight study conducted in Delaware Bay and Program MARK, we designed a multi-state model to allow for the estimation of mortality of each tag separately and simultaneously.

Small sample GEE estimation of regression parameters for longitudinal data.

Science.gov (United States)

Paul, Sudhir; Zhang, Xuemao

2014-09-28

Longitudinal (clustered) response data arise in many bio-statistical applications which, in general, cannot be assumed to be independent. Generalized estimating equation (GEE) is a widely used method to estimate marginal regression parameters for correlated responses. The advantage of the GEE is that the estimates of the regression parameters are asymptotically unbiased even if the correlation structure is misspecified, although their small sample properties are not known. In this paper, two bias adjusted GEE estimators of the regression parameters in longitudinal data are obtained when the number of subjects is small. One is based on a bias correction, and the other is based on a bias reduction. Simulations show that the performances of both the bias-corrected methods are similar in terms of bias, efficiency, coverage probability, average coverage length, impact of misspecification of correlation structure, and impact of cluster size on bias correction. Both these methods show superior properties over the GEE estimates for small samples. Further, analysis of data involving a small number of subjects also shows improvement in bias, MSE, standard error, and length of the confidence interval of the estimates by the two bias adjusted methods over the GEE estimates. For small to moderate sample sizes (N ≤50), either of the bias-corrected methods GEEBc and GEEBr can be used. However, the method GEEBc should be preferred over GEEBr, as the former is computationally easier. For large sample sizes, the GEE method can be used. Copyright © 2014 John Wiley & Sons, Ltd.

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

Science.gov (United States)

Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

2010-04-06

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and

Particle sizes from sectional data

DEFF Research Database (Denmark)

Pawlas, Zbynek; Nyengaard, Jens Randel; Jensen, Eva Bjørn Vedel

2009-01-01

We propose a new statistical method for obtaining information about particle size distributions from sectional data without specific assumptions about particle shape. The method utilizes recent advances in local stereology. We show how to estimate separately from sectional data the variance due t...

Kinetic parameter estimation from SPECT cone-beam projection measurements

International Nuclear Information System (INIS)

Huesman, Ronald H.; Reutter, Bryan W.; Zeng, G. Larry; Gullberg, Grant T.

1998-01-01

Kinetic parameters are commonly estimated from dynamically acquired nuclear medicine data by first reconstructing a dynamic sequence of images and subsequently fitting the parameters to time-activity curves generated from regions of interest overlaid upon the image sequence. Biased estimates can result from images reconstructed using inconsistent projections of a time-varying distribution of radiopharmaceutical acquired by a rotating SPECT system. If the SPECT data are acquired using cone-beam collimators wherein the gantry rotates so that the focal point of the collimators always remains in a plane, additional biases can arise from images reconstructed using insufficient, as well as truncated, projection samples. To overcome these problems we have investigated the estimation of kinetic parameters directly from SPECT cone-beam projection data by modelling the data acquisition process. To accomplish this it was necessary to parametrize the spatial and temporal distribution of the radiopharmaceutical within the SPECT field of view. In a simulated chest image volume, kinetic parameters were estimated for simple one-compartment models for four myocardial regions of interest. Myocardial uptake and washout parameters estimated by conventional analysis of noiseless simulated cone-beam data had biases ranging between 3-26% and 0-28%, respectively. Parameters estimated directly from the noiseless projection data were unbiased as expected, since the model used for fitting was faithful to the simulation. Statistical uncertainties of parameter estimates for 10 000 000 events ranged between 0.2-9% for the uptake parameters and between 0.3-6% for the washout parameters. (author)

ERROR BOUNDS FOR SURFACE AREA ESTIMATORS BASED ON CROFTON’S FORMULA

Directory of Open Access Journals (Sweden)

Markus Kiderlen

2011-05-01

Full Text Available According to Crofton's formula, the surface area S(A of a sufficiently regular compact set A in Rd is proportional to the mean of all total projections pA (u on a linear hyperplane with normal u, uniformly averaged over all unit vectors u. In applications, pA (u is only measured in k directions and the mean is approximated by a finite weighted sum bS(A of the total projections in these directions. The choice of the weights depends on the selected quadrature rule. We define an associated zonotope Z (depending only on the projection directions and the quadrature rule, and show that the relative error bS (A/S (A is bounded from below by the inradius of Z and from above by the circumradius of Z. Applying a strengthened isoperimetric inequality due to Bonnesen, we show that the rectangular quadrature rule does not give the best possible error bounds for d =2. In addition, we derive asymptotic behavior of the error (with increasing k in the planar case. The paper concludes with applications to surface area estimation in design-based digital stereology where we show that the weights due to Bonnesen's inequality are better than the usual weights based on the rectangular rule and almost optimal in the sense that the relative error of the surface area estimator is very close to the minimal error.

Estimation of river and stream temperature trends under haphazard sampling

Science.gov (United States)

Gray, Brian R.; Lyubchich, Vyacheslav; Gel, Yulia R.; Rogala, James T.; Robertson, Dale M.; Wei, Xiaoqiao

2015-01-01

Long-term temporal trends in water temperature in rivers and streams are typically estimated under the assumption of evenly-spaced space-time measurements. However, sampling times and dates associated with historical water temperature datasets and some sampling designs may be haphazard. As a result, trends in temperature may be confounded with trends in time or space of sampling which, in turn, may yield biased trend estimators and thus unreliable conclusions. We address this concern using multilevel (hierarchical) linear models, where time effects are allowed to vary randomly by day and date effects by year. We evaluate the proposed approach by Monte Carlo simulations with imbalance, sparse data and confounding by trend in time and date of sampling. Simulation results indicate unbiased trend estimators while results from a case study of temperature data from the Illinois River, USA conform to river thermal assumptions. We also propose a new nonparametric bootstrap inference on multilevel models that allows for a relatively flexible and distribution-free quantification of uncertainties. The proposed multilevel modeling approach may be elaborated to accommodate nonlinearities within days and years when sampling times or dates typically span temperature extremes.

Should total landings be used to correct estimated catch in numbers or mean-weight-at-age?

DEFF Research Database (Denmark)

Lewy, Peter; Lassen, H.

1997-01-01

Many ICES fish stock assessment working groups have practised Sum Of Products, SOP, correction. This correction stems from a comparison of total weights of the known landings and the SOP over age of catch in number and mean weight-at-age, which ideally should be identical. In case of SOP...... discrepancies some countries correct catch in numbers while others correct mean weight-at-age by a common factor, the ratio between landing and SOP. The paper shows that for three sampling schemes the SOP corrections are statistically incorrect and should not be made since the SOP is an unbiased estimate...... of the total landings. Calculation of the bias of estimated catch in numbers and mean weight-at-age shows that SOP corrections of either of these estimates may increase the bias. Furthermore, for five demersal and one pelagic North Sea species it is shown that SOP discrepancies greater than 2% from...

Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

Science.gov (United States)

Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

2013-12-01

The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function). Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers.

Science.gov (United States)

Linhoff, Michael W; Laurén, Juha; Cassidy, Robert M; Dobie, Frederick A; Takahashi, Hideto; Nygaard, Haakon B; Airaksinen, Matti S; Strittmatter, Stephen M; Craig, Ann Marie

2009-03-12

Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2 accounts for a minority of positive clones, indicating that current understanding of mammalian synaptogenic proteins is incomplete. We identify LRRTM1 as a transmembrane protein that induces presynaptic differentiation in contacting axons. All four LRRTM family members exhibit synaptogenic activity, LRRTMs localize to excitatory synapses, and artificially induced clustering of LRRTMs mediates postsynaptic differentiation. We generate LRRTM1(-/-) mice and reveal altered distribution of the vesicular glutamate transporter VGLUT1, confirming an in vivo synaptic function. These results suggest a prevalence of LRR domain proteins in trans-synaptic signaling and provide a cellular basis for the reported linkage of LRRTM1 to handedness and schizophrenia.

Mutually orthogonal Latin squares from the inner products of vectors in mutually unbiased bases

International Nuclear Information System (INIS)

Hall, Joanne L; Rao, Asha

2010-01-01

Mutually unbiased bases (MUBs) are important in quantum information theory. While constructions of complete sets of d + 1 MUBs in C d are known when d is a prime power, it is unknown if such complete sets exist in non-prime power dimensions. It has been conjectured that complete sets of MUBs only exist in C d if a maximal set of mutually orthogonal Latin squares (MOLS) of side length d also exists. There are several constructions (Roy and Scott 2007 J. Math. Phys. 48 072110; Paterek, Dakic and Brukner 2009 Phys. Rev. A 79 012109) of complete sets of MUBs from specific types of MOLS, which use Galois fields to construct the vectors of the MUBs. In this paper, two known constructions of MUBs (Alltop 1980 IEEE Trans. Inf. Theory 26 350-354; Wootters and Fields 1989 Ann. Phys. 191 363-381), both of which use polynomials over a Galois field, are used to construct complete sets of MOLS in the odd prime case. The MOLS come from the inner products of pairs of vectors in the MUBs.

Proliferation of germ cells and somatic cells in first trimester human embryonic gonads as indicated by S and S+G2+M phase fractions

DEFF Research Database (Denmark)

Sørensen, Kristina Pilekær; Lutterodt, Melissa Catherine R; Mamsen, Linn S

2011-01-01

The number of germ cells and somatic cells in human embryonic and foetal gonads has previously been estimated by stereological methods, which are time- and labour-consuming with little information concerning cell proliferation. Here, we studied whether flow cytometry could be applied as an easier...

Wireless Power Transfer for Distributed Estimation in Sensor Networks

Science.gov (United States)

Mai, Vien V.; Shin, Won-Yong; Ishibashi, Koji

2017-04-01

This paper studies power allocation for distributed estimation of an unknown scalar random source in sensor networks with a multiple-antenna fusion center (FC), where wireless sensors are equipped with radio-frequency based energy harvesting technology. The sensors' observation is locally processed by using an uncoded amplify-and-forward scheme. The processed signals are then sent to the FC, and are coherently combined at the FC, at which the best linear unbiased estimator (BLUE) is adopted for reliable estimation. We aim to solve the following two power allocation problems: 1) minimizing distortion under various power constraints; and 2) minimizing total transmit power under distortion constraints, where the distortion is measured in terms of mean-squared error of the BLUE. Two iterative algorithms are developed to solve the non-convex problems, which converge at least to a local optimum. In particular, the above algorithms are designed to jointly optimize the amplification coefficients, energy beamforming, and receive filtering. For each problem, a suboptimal design, a single-antenna FC scenario, and a common harvester deployment for colocated sensors, are also studied. Using the powerful semidefinite relaxation framework, our result is shown to be valid for any number of sensors, each with different noise power, and for an arbitrarily number of antennas at the FC.

Incompletely resolved phylogenetic trees inflate estimates of phylogenetic conservatism.

Science.gov (United States)

Davies, T Jonathan; Kraft, Nathan J B; Salamin, Nicolas; Wolkovich, Elizabeth M

2012-02-01

The tendency for more closely related species to share similar traits and ecological strategies can be explained by their longer shared evolutionary histories and represents phylogenetic conservatism. How strongly species traits co-vary with phylogeny can significantly impact how we analyze cross-species data and can influence our interpretation of assembly rules in the rapidly expanding field of community phylogenetics. Phylogenetic conservatism is typically quantified by analyzing the distribution of species values on the phylogenetic tree that connects them. Many phylogenetic approaches, however, assume a completely sampled phylogeny: while we have good estimates of deeper phylogenetic relationships for many species-rich groups, such as birds and flowering plants, we often lack information on more recent interspecific relationships (i.e., within a genus). A common solution has been to represent these relationships as polytomies on trees using taxonomy as a guide. Here we show that such trees can dramatically inflate estimates of phylogenetic conservatism quantified using S. P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly generated traits can appear to be phylogenetically conserved on poorly resolved trees. We provide a simple rarefaction-based solution that can reliably retrieve unbiased estimates of K, and we illustrate our method using data on first flowering times from Thoreau's woods (Concord, Massachusetts, USA).

Parameter Estimation for Thurstone Choice Models

Energy Technology Data Exchange (ETDEWEB)

Vojnovic, Milan [London School of Economics (United Kingdom); Yun, Seyoung [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-04-24

We consider the estimation accuracy of individual strength parameters of a Thurstone choice model when each input observation consists of a choice of one item from a set of two or more items (so called top-1 lists). This model accommodates the well-known choice models such as the Luce choice model for comparison sets of two or more items and the Bradley-Terry model for pair comparisons. We provide a tight characterization of the mean squared error of the maximum likelihood parameter estimator. We also provide similar characterizations for parameter estimators defined by a rank-breaking method, which amounts to deducing one or more pair comparisons from a comparison of two or more items, assuming independence of these pair comparisons, and maximizing a likelihood function derived under these assumptions. We also consider a related binary classification problem where each individual parameter takes value from a set of two possible values and the goal is to correctly classify all items within a prescribed classification error. The results of this paper shed light on how the parameter estimation accuracy depends on given Thurstone choice model and the structure of comparison sets. In particular, we found that for unbiased input comparison sets of a given cardinality, when in expectation each comparison set of given cardinality occurs the same number of times, for a broad class of Thurstone choice models, the mean squared error decreases with the cardinality of comparison sets, but only marginally according to a diminishing returns relation. On the other hand, we found that there exist Thurstone choice models for which the mean squared error of the maximum likelihood parameter estimator can decrease much faster with the cardinality of comparison sets. We report empirical evaluation of some claims and key parameters revealed by theory using both synthetic and real-world input data from some popular sport competitions and online labor platforms.

A method for estimating abundance of mobile populations using telemetry and counts of unmarked animals

Science.gov (United States)

Clement, Matthew; O'Keefe, Joy M; Walters, Brianne

2015-01-01

While numerous methods exist for estimating abundance when detection is imperfect, these methods may not be appropriate due to logistical difficulties or unrealistic assumptions. In particular, if highly mobile taxa are frequently absent from survey locations, methods that estimate a probability of detection conditional on presence will generate biased abundance estimates. Here, we propose a new estimator for estimating abundance of mobile populations using telemetry and counts of unmarked animals. The estimator assumes that the target population conforms to a fission-fusion grouping pattern, in which the population is divided into groups that frequently change in size and composition. If assumptions are met, it is not necessary to locate all groups in the population to estimate abundance. We derive an estimator, perform a simulation study, conduct a power analysis, and apply the method to field data. The simulation study confirmed that our estimator is asymptotically unbiased with low bias, narrow confidence intervals, and good coverage, given a modest survey effort. The power analysis provided initial guidance on survey effort. When applied to small data sets obtained by radio-tracking Indiana bats, abundance estimates were reasonable, although imprecise. The proposed method has the potential to improve abundance estimates for mobile species that have a fission-fusion social structure, such as Indiana bats, because it does not condition detection on presence at survey locations and because it avoids certain restrictive assumptions.

Intrauterine bisphenol A exposure leads to stimulatory effects on Sertoli cell number in rats

International Nuclear Information System (INIS)

Wistuba, Joachim; Brinkworth, Martin H.; Schlatt, Stefan; Chahoud Ibrahim; Nieschlag, Eberhard

2003-01-01

Using the optical disector for quantifying cell numbers, we investigated whether oral treatment of rats on days 6-21 of gestation with the weakly estrogenic bisphenol A (BPA, 0.1 or 50 mg/kg) or the highly estrogenic ethinyl estradiol (EE, 0.02 mg/kg) alters testicular histology, in those offspring 9-12 month of age. Since production of male germ cells depends on Sertoli cell number, possible changes in that parameter were investigated using unbiased stereology. Spermatogenesis was qualitatively normal in all groups. BPA increases Sertoli cell number per organ but not when expressed as per gram testis. EE did not affect cell number per organ but did affect numbers on a per gram testis basis due to a lowered testis weight. I contrast to the lowering of Sertoli cell numbers that might have been expected according to the estrogen hypothesis, intrauterine administration of these xenoestrogens in fact resulted in minor increases in Sertoli cell numbers and had no qualitative effect on spermatogenesis

Accurate Frequency Estimation Based On Three-Parameter Sine-Fitting With Three FFT Samples

Directory of Open Access Journals (Sweden)

Liu Xin

2015-09-01

Full Text Available This paper presents a simple DFT-based golden section searching algorithm (DGSSA for the single tone frequency estimation. Because of truncation and discreteness in signal samples, Fast Fourier Transform (FFT and Discrete Fourier Transform (DFT are inevitable to cause the spectrum leakage and fence effect which lead to a low estimation accuracy. This method can improve the estimation accuracy under conditions of a low signal-to-noise ratio (SNR and a low resolution. This method firstly uses three FFT samples to determine the frequency searching scope, then – besides the frequency – the estimated values of amplitude, phase and dc component are obtained by minimizing the least square (LS fitting error of three-parameter sine fitting. By setting reasonable stop conditions or the number of iterations, the accurate frequency estimation can be realized. The accuracy of this method, when applied to observed single-tone sinusoid samples corrupted by white Gaussian noise, is investigated by different methods with respect to the unbiased Cramer-Rao Low Bound (CRLB. The simulation results show that the root mean square error (RMSE of the frequency estimation curve is consistent with the tendency of CRLB as SNR increases, even in the case of a small number of samples. The average RMSE of the frequency estimation is less than 1.5 times the CRLB with SNR = 20 dB and N = 512.

Mixed model approaches for diallel analysis based on a bio-model.

Science.gov (United States)

Zhu, J; Weir, B S

1996-12-01

A MINQUE(1) procedure, which is minimum norm quadratic unbiased estimation (MINQUE) method with 1 for all the prior values, is suggested for estimating variance and covariance components in a bio-model for diallel crosses. Unbiasedness and efficiency of estimation were compared for MINQUE(1), restricted maximum likelihood (REML) and MINQUE theta which has parameter values for the prior values. MINQUE(1) is almost as efficient as MINQUE theta for unbiased estimation of genetic variance and covariance components. The bio-model is efficient and robust for estimating variance and covariance components for maternal and paternal effects as well as for nuclear effects. A procedure of adjusted unbiased prediction (AUP) is proposed for predicting random genetic effects in the bio-model. The jack-knife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects. Worked examples are given for estimation of variance and covariance components and for prediction of genetic merits.

Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculation.

Science.gov (United States)

Ding, Xinqiang; Vilseck, Jonah Z; Hayes, Ryan L; Brooks, Charles L

2017-06-13

λ-dynamics is a generalized ensemble method for alchemical free energy calculations. In traditional λ-dynamics, the alchemical switch variable λ is treated as a continuous variable ranging from 0 to 1 and an empirical estimator is utilized to approximate the free energy. In the present article, we describe an alternative formulation of λ-dynamics that utilizes the Gibbs sampler framework, which we call Gibbs sampler-based λ-dynamics (GSLD). GSLD, like traditional λ-dynamics, can be readily extended to calculate free energy differences between multiple ligands in one simulation. We also introduce a new free energy estimator, the Rao-Blackwell estimator (RBE), for use in conjunction with GSLD. Compared with the current empirical estimator, the advantage of RBE is that RBE is an unbiased estimator and its variance is usually smaller than the current empirical estimator. We also show that the multistate Bennett acceptance ratio equation or the unbinned weighted histogram analysis method equation can be derived using the RBE. We illustrate the use and performance of this new free energy computational framework by application to a simple harmonic system as well as relevant calculations of small molecule relative free energies of solvation and binding to a protein receptor. Our findings demonstrate consistent and improved performance compared with conventional alchemical free energy methods.

Design unbiased estimation in line intersect sampling using segmented transects

Science.gov (United States)

David L.R. Affleck; Timothy G. Gregoire; Harry T. Valentine; Harry T. Valentine

2005-01-01

In many applications of line intersect sampling. transects consist of multiple, connected segments in a prescribed configuration. The relationship between the transect configuration and the selection probability of a population element is illustrated and a consistent sampling protocol, applicable to populations composed of arbitrarily shaped elements, is proposed. It...

Improved estimation of the variance in Monte Carlo criticality calculations

International Nuclear Information System (INIS)

Hoogenboom, J. Eduard

2008-01-01

Results for the effective multiplication factor in a Monte Carlo criticality calculations are often obtained from averages over a number of cycles or batches after convergence of the fission source distribution to the fundamental mode. Then the standard deviation of the effective multiplication factor is also obtained from the k eff results over these cycles. As the number of cycles will be rather small, the estimate of the variance or standard deviation in k eff will not be very reliable, certainly not for the first few cycles after source convergence. In this paper the statistics for k eff are based on the generation of new fission neutron weights during each history in a cycle. It is shown that this gives much more reliable results for the standard deviation even after a small number of cycles. Also attention is paid to the variance of the variance (VoV) and the standard deviation of the standard deviation. A derivation is given how to obtain an unbiased estimate for the VoV, even for a small number of samples. (authors)

Improved estimation of the variance in Monte Carlo criticality calculations

Energy Technology Data Exchange (ETDEWEB)

Hoogenboom, J. Eduard [Delft University of Technology, Delft (Netherlands)

2008-07-01

Results for the effective multiplication factor in a Monte Carlo criticality calculations are often obtained from averages over a number of cycles or batches after convergence of the fission source distribution to the fundamental mode. Then the standard deviation of the effective multiplication factor is also obtained from the k{sub eff} results over these cycles. As the number of cycles will be rather small, the estimate of the variance or standard deviation in k{sub eff} will not be very reliable, certainly not for the first few cycles after source convergence. In this paper the statistics for k{sub eff} are based on the generation of new fission neutron weights during each history in a cycle. It is shown that this gives much more reliable results for the standard deviation even after a small number of cycles. Also attention is paid to the variance of the variance (VoV) and the standard deviation of the standard deviation. A derivation is given how to obtain an unbiased estimate for the VoV, even for a small number of samples. (authors)

Multi-level restricted maximum likelihood covariance estimation and kriging for large non-gridded spatial datasets

KAUST Repository

Castrillon, Julio

2015-11-10

We develop a multi-level restricted Gaussian maximum likelihood method for estimating the covariance function parameters and computing the best unbiased predictor. Our approach produces a new set of multi-level contrasts where the deterministic parameters of the model are filtered out thus enabling the estimation of the covariance parameters to be decoupled from the deterministic component. Moreover, the multi-level covariance matrix of the contrasts exhibit fast decay that is dependent on the smoothness of the covariance function. Due to the fast decay of the multi-level covariance matrix coefficients only a small set is computed with a level dependent criterion. We demonstrate our approach on problems of up to 512,000 observations with a Matérn covariance function and highly irregular placements of the observations. In addition, these problems are numerically unstable and hard to solve with traditional methods.

Estimating fluvial wood discharge from timelapse photography with varying sampling intervals

Science.gov (United States)

Anderson, N. K.

2013-12-01

There is recent focus on calculating wood budgets for streams and rivers to help inform management decisions, ecological studies and carbon/nutrient cycling models. Most work has measured in situ wood in temporary storage along stream banks or estimated wood inputs from banks. Little effort has been employed monitoring and quantifying wood in transport during high flows. This paper outlines a procedure for estimating total seasonal wood loads using non-continuous coarse interval sampling and examines differences in estimation between sampling at 1, 5, 10 and 15 minutes. Analysis is performed on wood transport for the Slave River in Northwest Territories, Canada. Relative to the 1 minute dataset, precision decreased by 23%, 46% and 60% for the 5, 10 and 15 minute datasets, respectively. Five and 10 minute sampling intervals provided unbiased equal variance estimates of 1 minute sampling, whereas 15 minute intervals were biased towards underestimation by 6%. Stratifying estimates by day and by discharge increased precision over non-stratification by 4% and 3%, respectively. Not including wood transported during ice break-up, the total minimum wood load estimated at this site is 3300 × 800$ m3 for the 2012 runoff season. The vast majority of the imprecision in total wood volumes came from variance in estimating average volume per log. Comparison of proportions and variance across sample intervals using bootstrap sampling to achieve equal n. Each trial was sampled for n=100, 10,000 times and averaged. All trials were then averaged to obtain an estimate for each sample interval. Dashed lines represent values from the one minute dataset.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects

Directory of Open Access Journals (Sweden)

Nyengaard Jens R

2009-02-01

Full Text Available Abstract Background Temporomandibular joint (TMJ arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-α has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented. Methods Forty-two rabbits (10 weeks old pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14, an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14 and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14. Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator were used to assess and estimate the inflammation in the joints. Results The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and

Unbiased and non-supervised learning methods for disruption prediction at JET

International Nuclear Information System (INIS)

Murari, A.; Vega, J.; Ratta, G.A.; Vagliasindi, G.; Johnson, M.F.; Hong, S.H.

2009-01-01

The importance of predicting the occurrence of disruptions is going to increase significantly in the next generation of tokamak devices. The expected energy content of ITER plasmas, for example, is such that disruptions could have a significant detrimental impact on various parts of the device, ranging from erosion of plasma facing components to structural damage. Early detection of disruptions is therefore needed with evermore increasing urgency. In this paper, the results of a series of methods to predict disruptions at JET are reported. The main objective of the investigation consists of trying to determine how early before a disruption it is possible to perform acceptable predictions on the basis of the raw data, keeping to a minimum the number of 'ad hoc' hypotheses. Therefore, the chosen learning techniques have the common characteristic of requiring a minimum number of assumptions. Classification and Regression Trees (CART) is a supervised but, on the other hand, a completely unbiased and nonlinear method, since it simply constructs the best classification tree by working directly on the input data. A series of unsupervised techniques, mainly K-means and hierarchical, have also been tested, to investigate to what extent they can autonomously distinguish between disruptive and non-disruptive groups of discharges. All these independent methods indicate that, in general, prediction with a success rate above 80% can be achieved not earlier than 180 ms before the disruption. The agreement between various completely independent methods increases the confidence in the results, which are also confirmed by a visual inspection of the data performed with pseudo Grand Tour algorithms.

Diallel analysis for sex-linked and maternal effects.

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Zhu, J; Weir, B S

1996-01-01

Genetic models including sex-linked and maternal effects as well as autosomal gene effects are described. Monte Carlo simulations were conducted to compare efficiencies of estimation by minimum norm quadratic unbiased estimation (MINQUE) and restricted maximum likelihood (REML) methods. MINQUE(1), which has 1 for all prior values, has a similar efficiency to MINQUE(θ), which requires prior estimates of parameter values. MINQUE(1) has the advantage over REML of unbiased estimation and convenient computation. An adjusted unbiased prediction (AUP) method is developed for predicting random genetic effects. AUP is desirable for its easy computation and unbiasedness of both mean and variance of predictors. The jackknife procedure is appropriate for estimating the sampling variances of estimated variances (or covariances) and of predicted genetic effects. A t-test based on jackknife variances is applicable for detecting significance of variation. Worked examples from mice and silkworm data are given in order to demonstrate variance and covariance estimation and genetic effect prediction.

Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density

DEFF Research Database (Denmark)

Hansen, S; Grabau, D A; Rose, C

1998-01-01

included Chalkley counting, estimation of intratumoral microvessel density (MVD) by one hot-spot, MVD by the mean value of three hot-spots, and the highest value of MVD in three hot-spots. In addition, we applied stereology in the quantification of angiogenesis in the whole tumor section by random...

Unraveling cognitive traits using the Morris water maze unbiased strategy classification (MUST-C) algorithm.

Science.gov (United States)

Illouz, Tomer; Madar, Ravit; Louzon, Yoram; Griffioen, Kathleen J; Okun, Eitan

2016-02-01

The assessment of spatial cognitive learning in rodents is a central approach in neuroscience, as it enables one to assess and quantify the effects of treatments and genetic manipulations from a broad perspective. Although the Morris water maze (MWM) is a well-validated paradigm for testing spatial learning abilities, manual categorization of performance in the MWM into behavioral strategies is subject to individual interpretation, and thus to biases. Here we offer a support vector machine (SVM) - based, automated, MWM unbiased strategy classification (MUST-C) algorithm, as well as a cognitive score scale. This model was examined and validated by analyzing data obtained from five MWM experiments with changing platform sizes, revealing a limitation in the spatial capacity of the hippocampus. We have further employed this algorithm to extract novel mechanistic insights on the impact of members of the Toll-like receptor pathway on cognitive spatial learning and memory. The MUST-C algorithm can greatly benefit MWM users as it provides a standardized method of strategy classification as well as a cognitive scoring scale, which cannot be derived from typical analysis of MWM data. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Robust k-mer frequency estimation using gapped k-mers.

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Ghandi, Mahmoud; Mohammad-Noori, Morteza; Beer, Michael A

2014-08-01

Oligomers of fixed length, k, commonly known as k-mers, are often used as fundamental elements in the description of DNA sequence features of diverse biological function, or as intermediate elements in the constuction of more complex descriptors of sequence features such as position weight matrices. k-mers are very useful as general sequence features because they constitute a complete and unbiased feature set, and do not require parameterization based on incomplete knowledge of biological mechanisms. However, a fundamental limitation in the use of k-mers as sequence features is that as k is increased, larger spatial correlations in DNA sequence elements can be described, but the frequency of observing any specific k-mer becomes very small, and rapidly approaches a sparse matrix of binary counts. Thus any statistical learning approach using k-mers will be susceptible to noisy estimation of k-mer frequencies once k becomes large. Because all molecular DNA interactions have limited spatial extent, gapped k-mers often carry the relevant biological signal. Here we use gapped k-mer counts to more robustly estimate the ungapped k-mer frequencies, by deriving an equation for the minimum norm estimate of k-mer frequencies given an observed set of gapped k-mer frequencies. We demonstrate that this approach provides a more accurate estimate of the k-mer frequencies in real biological sequences using a sample of CTCF binding sites in the human genome.

Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary

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Malek Soleimani Mehranjani

2016-06-01

Full Text Available Background: Bisphenol A (BPA, an environmental pollutant, can generate free radicals which damages the reproductive system. Vitamin C is an antioxidant which may prevent the adverse effects of free radicals. Objective: The aim was to investigate the effect of vitamin C on the ovary tissue in rats treated with BPA. Materials and Methods: In this experimental study, 24 female Wistar rats (200±20 gr were randomly divided into 4 groups (n=6: control, BPA (60 μg/Kg/day, vitamin C (150 mg/Kg/day and BPA + vitamin C and orally treated for 20 days. The left ovaries were taken out, fixed for tissue processing and studied using stereological methods. Data were analyzed with SPSS using one-way ANOVA, and the means were considered significantly different at (p<0.05. Results: The total volume of ovary and cortex (p<0.01, medulla (p<0.05, the volume of corpus luteum (p<0.001 and the mean number of antral follicles (p<0.001 significantly reduced in BPA group compared with control, while the number of atretic follicles increased (p<0.05. The volume of oocyte (p<0.01 and its nucleus (p<0.001 in the antral follicles and the thickness of zona pellucida (ZP in the secondary (p<0.05 and antral (p<0.001 follicles significantly decreased in BPA group compared with controls. The above parameters in the BPA + vitamin C group were compensated to control level. Conclusion: Vitamin C can be used as a potential antioxidant in the case of BPA toxication

Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.

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Gao, Shuai; Hou, Xinfeng; Jiang, Yonghua; Xu, Zijian; Cai, Tao; Chen, Jiajie; Chang, Gang

2017-01-23

Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable. Herein, we evaluate the hematopoietic differentiation capacity and somatic memory state of hematopoietic progenitor and stem cell (HPC/HSC)-derived-iPSCs (HPC/HSC-iPSCs) using a previously established sequential reprogramming system. We found that HPC/HSCs are amenable to being reprogrammed into iPSCs with unbiased differentiation capacity to hematopoietic progenitors and mature hematopoietic cells. Genome-wide analyses revealed that no global epigenetic memory was detectable in HPC/HSC-iPSCs, but only a minor transcriptional memory of HPC/HSCs existed in a specific tetraploid complementation (4 N)-incompetent HPC/HSC-iPSC line. However, the observed minor transcriptional memory had no influence on the hematopoietic differentiation capacity, indicating the reprogramming of the HPC/HSCs was nearly complete. Further analysis revealed the correlation of minor transcriptional memory with the aberrant distribution of H3K27me3. This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.

SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

Science.gov (United States)

Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

2015-02-10

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

Potential for Bias When Estimating Critical Windows for Air Pollution in Children's Health.

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Wilson, Ander; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Wright, Robert O; Wright, Rosalind J; Coull, Brent A

2017-12-01

Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PREMIM and EMIM: tools for estimation of maternal, imprinting and interaction effects using multinomial modelling

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Howey Richard

2012-06-01

Full Text Available Abstract Background Here we present two new computer tools, PREMIM and EMIM, for the estimation of parental and child genetic effects, based on genotype data from a variety of different child-parent configurations. PREMIM allows the extraction of child-parent genotype data from standard-format pedigree data files, while EMIM uses the extracted genotype data to perform subsequent statistical analysis. The use of genotype data from the parents as well as from the child in question allows the estimation of complex genetic effects such as maternal genotype effects, maternal-foetal interactions and parent-of-origin (imprinting effects. These effects are estimated by EMIM, incorporating chosen assumptions such as Hardy-Weinberg equilibrium or exchangeability of parental matings as required. Results In application to simulated data, we show that the inference provided by EMIM is essentially equivalent to that provided by alternative (competing software packages such as MENDEL and LEM. However, PREMIM and EMIM (used in combination considerably outperform MENDEL and LEM in terms of speed and ease of execution. Conclusions Together, EMIM and PREMIM provide easy-to-use command-line tools for the analysis of pedigree data, giving unbiased estimates of parental and child genotype relative risks.

Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

Energy Technology Data Exchange (ETDEWEB)

Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

2007-06-21

Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

A new method to estimate parameters of linear compartmental models using artificial neural networks

International Nuclear Information System (INIS)

Gambhir, Sanjiv S.; Keppenne, Christian L.; Phelps, Michael E.; Banerjee, Pranab K.

1998-01-01

At present, the preferred tool for parameter estimation in compartmental analysis is an iterative procedure; weighted nonlinear regression. For a large number of applications, observed data can be fitted to sums of exponentials whose parameters are directly related to the rate constants/coefficients of the compartmental models. Since weighted nonlinear regression often has to be repeated for many different data sets, the process of fitting data from compartmental systems can be very time consuming. Furthermore the minimization routine often converges to a local (as opposed to global) minimum. In this paper, we examine the possibility of using artificial neural networks instead of weighted nonlinear regression in order to estimate model parameters. We train simple feed-forward neural networks to produce as outputs the parameter values of a given model when kinetic data are fed to the networks' input layer. The artificial neural networks produce unbiased estimates and are orders of magnitude faster than regression algorithms. At noise levels typical of many real applications, the neural networks are found to produce lower variance estimates than weighted nonlinear regression in the estimation of parameters from mono- and biexponential models. These results are primarily due to the inability of weighted nonlinear regression to converge. These results establish that artificial neural networks are powerful tools for estimating parameters for simple compartmental models. (author)

Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model.

Directory of Open Access Journals (Sweden)

Gerhard Moser

2015-04-01

Full Text Available Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96% had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches.

Estimating the Mass of the Milky Way Using the Ensemble of Classical Satellite Galaxies

Science.gov (United States)

Patel, Ekta; Besla, Gurtina; Sohn, Sangmo Tony; Mandel, Kaisey

2018-06-01

High precision proper motions are currently available for approximately 20% of the Milky Way's known satellite galaxies. Often, the 6D phase space information of each satellite is used separately to constrain the mass of the MW. In this talk, I will discuss the Bayesian framework outlined in Patel et al. 2017b to make inferences of the MW's mass using satellite properties such as specific orbital angular momentum, rather than just position and velocity. By extending this framework from one satellite to a population of satellites, we can now form simultaneous MW mass estimates using the Illustris-Dark cosmological simulation that are unbiased by high speed satellites such as Leo I (Patel et al., submitted). Our resulting MW mass estimates reduce the current factor of two uncertainty in the mass range of the MW and show promising signs for improvement as upcoming ground- and space-based observatories obtain proper motions for additional MW satellite galaxies.

HOW MANY LOBSTERS ARE IN THE SEA?

Directory of Open Access Journals (Sweden)

Ernest Enns

2011-05-01

Full Text Available A lobster fishery must have a reasonable estimate of the number of lobsters within the fishery in order to regulate the annual harvest. Stereological sampling procedures are used to estimate the number of lobsters in a defined region of the sea. From a given point in the fishery, a selective sample in a random direction to the boundary of the fishery is taken. This is repeated to generate a systematic sample from which the total population is estimated.

Targeted estimation of nuisance parameters to obtain valid statistical inference.

Science.gov (United States)

van der Laan, Mark J

2014-01-01

In order to obtain concrete results, we focus on estimation of the treatment specific mean, controlling for all measured baseline covariates, based on observing independent and identically distributed copies of a random variable consisting of baseline covariates, a subsequently assigned binary treatment, and a final outcome. The statistical model only assumes possible restrictions on the conditional distribution of treatment, given the covariates, the so-called propensity score. Estimators of the treatment specific mean involve estimation of the propensity score and/or estimation of the conditional mean of the outcome, given the treatment and covariates. In order to make these estimators asymptotically unbiased at any data distribution in the statistical model, it is essential to use data-adaptive estimators of these nuisance parameters such as ensemble learning, and specifically super-learning. Because such estimators involve optimal trade-off of bias and variance w.r.t. the infinite dimensional nuisance parameter itself, they result in a sub-optimal bias/variance trade-off for the resulting real-valued estimator of the estimand. We demonstrate that additional targeting of the estimators of these nuisance parameters guarantees that this bias for the estimand is second order and thereby allows us to prove theorems that establish asymptotic linearity of the estimator of the treatment specific mean under regularity conditions. These insights result in novel targeted minimum loss-based estimators (TMLEs) that use ensemble learning with additional targeted bias reduction to construct estimators of the nuisance parameters. In particular, we construct collaborative TMLEs (C-TMLEs) with known influence curve allowing for statistical inference, even though these C-TMLEs involve variable selection for the propensity score based on a criterion that measures how effective the resulting fit of the propensity score is in removing bias for the estimand. As a particular special

PRESIDENT’S ADDRESS

Directory of Open Access Journals (Sweden)

Lucie Kubínová

2016-03-01

Full Text Available Dear colleagues, Let me wish you and our Image Analysis & Stereology Journal all the best in 2016. It is great honour for me to be in charge of the International Society for Stereology (ISS. I would like to thank Eric Pirard for all his tremendous work and effort he has put into ISS activities in past years, together with all members of the ISS Board. I am glad Eric is willing to help me with ISS as „Immediate Past President“. I also rely on close collaboration with Ida Eržen and Marko Kreft, the Editors-in-Chief of Image Analysis & Stereology (IAS, IAS Editorial Board and future ISS Board. I appreciate long-term cooperation between the Image Analysis & Stereology Journal and the International Society for Stereology and I am looking forward to broaden our relationships in the future. As a President of ISS I plan to evoke new activities which would help to make ISS vivid and useful to scientific community. We are planning new courses on stereology, image analysis and related topics run in cooperation with ISS with reduced fee for ISS members, competion for the best PhD thesis using stereology and/or image analysis, ISS history mapping, etc. I welcome your further suggestions and comments. I would like to cordially invite you to become members of the International Society for Stereology (http://stereologysociety.org/membership.html and to take part in new activities organized by ISS, such as:Special Session „3D Image Analysis and Stereology in Fluorescence Microscopy“ at ISBI 2016 (in Prague, see http://biomedicalimaging.org/2016/?page_id=768.Round table discussion on „Stereology and 3D image analysis in microscopy“ to be held at the 16th European Microscopy Congress in Lyon (EMC 2016, see http://www.emc2016.fr/en/scientific-programme/special/stereology.It is my intention to involve young people and fresh ideas in the activities of ISS and in further improvement of IAS. Please contact me at lucie

Methodology for uranium resource estimates and reliability

International Nuclear Information System (INIS)

Blanchfield, D.M.

1980-01-01

The NURE uranium assessment method has evolved from a small group of geologists estimating resources on a few lease blocks, to a national survey involving an interdisciplinary system consisting of the following: (1) geology and geologic analogs; (2) engineering and cost modeling; (3) mathematics and probability theory, psychology and elicitation of subjective judgments; and (4) computerized calculations, computer graphics, and data base management. The evolution has been spurred primarily by two objectives; (1) quantification of uncertainty, and (2) elimination of simplifying assumptions. This has resulted in a tremendous data-gathering effort and the involvement of hundreds of technical experts, many in uranium geology, but many from other fields as well. The rationality of the methods is still largely based on the concept of an analog and the observation that the results are reasonable. The reliability, or repeatability, of the assessments is reasonably guaranteed by the series of peer and superior technical reviews which has been formalized under the current methodology. The optimism or pessimism of individual geologists who make the initial assessments is tempered by the review process, resulting in a series of assessments which are a consistent, unbiased reflection of the facts. Despite the many improvements over past methods, several objectives for future development remain, primarily to reduce subjectively in utilizing factual information in the estimation of endowment, and to improve the recognition of cost uncertainties in the assessment of economic potential. The 1980 NURE assessment methodology will undoubtly be improved, but the reader is reminded that resource estimates are and always will be a forecast for the future

Estimating temporary emigration and breeding proportions using capture-recapture data with Pollock's robust design

Science.gov (United States)

Kendall, W.L.; Nichols, J.D.; Hines, J.E.

1997-01-01

Statistical inference for capture-recapture studies of open animal populations typically relies on the assumption that all emigration from the studied population is permanent. However, there are many instances in which this assumption is unlikely to be met. We define two general models for the process of temporary emigration, completely random and Markovian. We then consider effects of these two types of temporary emigration on Jolly-Seber (Seber 1982) estimators and on estimators arising from the full-likelihood approach of Kendall et al. (1995) to robust design data. Capture-recapture data arising from Pollock's (1982) robust design provide the basis for obtaining unbiased estimates of demographic parameters in the presence of temporary emigration and for estimating the probability of temporary emigration. We present a likelihood-based approach to dealing with temporary emigration that permits estimation under different models of temporary emigration and yields tests for completely random and Markovian emigration. In addition, we use the relationship between capture probability estimates based on closed and open models under completely random temporary emigration to derive three ad hoc estimators for the probability of temporary emigration, two of which should be especially useful in situations where capture probabilities are heterogeneous among individual animals. Ad hoc and full-likelihood estimators are illustrated for small mammal capture-recapture data sets. We believe that these models and estimators will be useful for testing hypotheses about the process of temporary emigration, for estimating demographic parameters in the presence of temporary emigration, and for estimating probabilities of temporary emigration. These latter estimates are frequently of ecological interest as indicators of animal movement and, in some sampling situations, as direct estimates of breeding probabilities and proportions.

Estimation of Areal Mean Rainfall in Remote Areas Using B-SHADE Model

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Tao Zhang

2016-01-01

Full Text Available This study presented a method to estimate areal mean rainfall (AMR using a Biased Sentinel Hospital Based Area Disease Estimation (B-SHADE model, together with biased rain gauge observations and Tropical Rainfall Measuring Mission (TRMM data, for remote areas with a sparse and uneven distribution of rain gauges. Based on the B-SHADE model, the best linear unbiased estimation of AMR could be obtained. A case study was conducted for the Three-River Headwaters region in the Tibetan Plateau of China, and its performance was compared with traditional methods. The results indicated that B-SHADE obtained the least estimation biases, with a mean error and root mean square error of −0.63 and 3.48 mm, respectively. For the traditional methods including arithmetic average, Thiessen polygon, and ordinary kriging, the mean errors were 7.11, −1.43, and 2.89 mm, which were up to 1027.1%, 127.0%, and 358.3%, respectively, greater than for the B-SHADE model. The root mean square errors were 10.31, 4.02, and 6.27 mm, which were up to 196.1%, 15.5%, and 80.0%, respectively, higher than for the B-SHADE model. The proposed technique can be used to extend the AMR record to the presatellite observation period, when only the gauge data are available.

Limitations to estimating bacterial cross-speciestransmission using genetic and genomic markers: inferencesfrom simulation modeling

Science.gov (United States)

Julio Andre, Benavides; Cross, Paul C.; Luikart, Gordon; Scott, Creel

2014-01-01

Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced.

Multi-population Genomic Relationships for Estimating Current Genetic Variances Within and Genetic Correlations Between Populations.

Science.gov (United States)

Wientjes, Yvonne C J; Bijma, Piter; Vandenplas, Jérémie; Calus, Mario P L

2017-10-01

Different methods are available to calculate multi-population genomic relationship matrices. Since those matrices differ in base population, it is anticipated that the method used to calculate genomic relationships affects the estimate of genetic variances, covariances, and correlations. The aim of this article is to define the multi-population genomic relationship matrix to estimate current genetic variances within and genetic correlations between populations. The genomic relationship matrix containing two populations consists of four blocks, one block for population 1, one block for population 2, and two blocks for relationships between the populations. It is known, based on literature, that by using current allele frequencies to calculate genomic relationships within a population, current genetic variances are estimated. In this article, we theoretically derived the properties of the genomic relationship matrix to estimate genetic correlations between populations and validated it using simulations. When the scaling factor of across-population genomic relationships is equal to the product of the square roots of the scaling factors for within-population genomic relationships, the genetic correlation is estimated unbiasedly even though estimated genetic variances do not necessarily refer to the current population. When this property is not met, the correlation based on estimated variances should be multiplied by a correction factor based on the scaling factors. In this study, we present a genomic relationship matrix which directly estimates current genetic variances as well as genetic correlations between populations. Copyright © 2017 by the Genetics Society of America.

Evaluation of sampling strategies to estimate crown biomass

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Krishna P Poudel

2015-01-01

Full Text Available Background Depending on tree and site characteristics crown biomass accounts for a significant portion of the total aboveground biomass in the tree. Crown biomass estimation is useful for different purposes including evaluating the economic feasibility of crown utilization for energy production or forest products, fuel load assessments and fire management strategies, and wildfire modeling. However, crown biomass is difficult to predict because of the variability within and among species and sites. Thus the allometric equations used for predicting crown biomass should be based on data collected with precise and unbiased sampling strategies. In this study, we evaluate the performance different sampling strategies to estimate crown biomass and to evaluate the effect of sample size in estimating crown biomass. Methods Using data collected from 20 destructively sampled trees, we evaluated 11 different sampling strategies using six evaluation statistics: bias, relative bias, root mean square error (RMSE, relative RMSE, amount of biomass sampled, and relative biomass sampled. We also evaluated the performance of the selected sampling strategies when different numbers of branches (3, 6, 9, and 12 are selected from each tree. Tree specific log linear model with branch diameter and branch length as covariates was used to obtain individual branch biomass. Results Compared to all other methods stratified sampling with probability proportional to size estimation technique produced better results when three or six branches per tree were sampled. However, the systematic sampling with ratio estimation technique was the best when at least nine branches per tree were sampled. Under the stratified sampling strategy, selecting unequal number of branches per stratum produced approximately similar results to simple random sampling, but it further decreased RMSE when information on branch diameter is used in the design and estimation phases. Conclusions Use of

Enhancing Groundwater Cost Estimation with the Interpolation of Water Tables across the United States

Science.gov (United States)

Rosli, A. U. M.; Lall, U.; Josset, L.; Rising, J. A.; Russo, T. A.; Eisenhart, T.

2017-12-01

Analyzing the trends in water use and supply across the United States is fundamental to efforts in ensuring water sustainability. As part of this, estimating the costs of producing or obtaining water (water extraction) and the correlation with water use is an important aspect in understanding the underlying trends. This study estimates groundwater costs by interpolating the depth to water level across the US in each county. We use Ordinary and Universal Kriging, accounting for the differences between aquifers. Kriging generates a best linear unbiased estimate at each location and has been widely used to map ground-water surfaces (Alley, 1993).The spatial covariates included in the universal Kriging were land-surface elevation as well as aquifer information. The average water table is computed for each county using block kriging to obtain a national map of groundwater cost, which we compare with survey estimates of depth to the water table performed by the USDA. Groundwater extraction costs were then assumed to be proportional to water table depth. Beyond estimating the water cost, the approach can provide an indication of groundwater-stress by exploring the historical evolution of depth to the water table using time series information between 1960 and 2015. Despite data limitations, we hope to enable a more compelling and meaningful national-level analysis through the quantification of cost and stress for more economically efficient water management.

Estimating the relationship between abundance and distribution

DEFF Research Database (Denmark)

Rindorf, Anna; Lewy, Peter

2012-01-01

based on Euclidean distance to the centre of gravity of the spatial distribution. Only the proportion of structurally empty areas, Lloyds index, and indices of the distance to the centre of gravity of the spatial distribution are unbiased at all levels of abundance. The remaining indices generate...

A TOA-AOA-Based NLOS Error Mitigation Method for Location Estimation

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Tianshuang Qiu

2007-12-01

Full Text Available This paper proposes a geometric method to locate a mobile station (MS in a mobile cellular network when both the range and angle measurements are corrupted by non-line-of-sight (NLOS errors. The MS location is restricted to an enclosed region by geometric constraints from the temporal-spatial characteristics of the radio propagation channel. A closed-form equation of the MS position, time of arrival (TOA, angle of arrival (AOA, and angle spread is provided. The solution space of the equation is very large because the angle spreads are random variables in nature. A constrained objective function is constructed to further limit the MS position. A Lagrange multiplier-based solution and a numerical solution are proposed to resolve the MS position. The estimation quality of the estimator in term of “biased” or “unbiased” is discussed. The scale factors, which may be used to evaluate NLOS propagation level, can be estimated by the proposed method. AOA seen at base stations may be corrected to some degree. The performance comparisons among the proposed method and other hybrid location methods are investigated on different NLOS error models and with two scenarios of cell layout. It is found that the proposed method can deal with NLOS error effectively, and it is attractive for location estimation in cellular networks.

Photoconductivity of Selenium and Sulphur Doped a-Si:H thin Films

OpenAIRE

SHARMA, Sanjeev Kumar; GUPTA, Himanshu

2014-01-01

The accurate estimation of tree biomass is crucial for the efficient management of forest resources. In this study, we used a subsampling method for unbiased estimates of above-ground tree biomass. The method consists of 2 stages: the first stage consists of randomized branch sampling (RBS) and the second stage uses importance sampling (IS). RBS is used to select a path from the butt of an object branch to a terminal segment. IS is used for selecting a disk that produces unbiased estimates of...

Implant surface preparation in the surgical treatment of experimental peri-implantitis with autogenous bone graft and ePTFE membrane in cynomolgus monkeys

DEFF Research Database (Denmark)

Schou, Søren; Holmstrup, Palle; Jørgensen, Torben

2003-01-01

peri-implantitis; treatment; implant surface preparation; nonhuman primates; histology; stereology......peri-implantitis; treatment; implant surface preparation; nonhuman primates; histology; stereology...

Renal and Myocardial Histopathology and Morphometry in Rats with Adenine - Induced Chronic Renal Failure: Influence of Gum Acacia

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Badreldin H. Ali

2014-08-01

Full Text Available Background/Aim: Chronic kidney disease (CKD is associated with increased occurrence of cardiovascular system dysfunction. Previous studies have revealed a number of alterations in the kidneys and heart during CKD. However, unbiased quantitative studies on these structures in this disease have so far not been addressed. Materials and Methods: We induced CKD in rats by feeding adenine (0.75% w/w, four weeks and using unbiased stereological methods, investigated the effect of the ensuing CKD on the kidneys and left ventricular structure. Since gum acacia (GA has previously been shown to ameliorate the severity of CKD in humans and rodents, we investigated the effect of giving GA (15% w/v in the drinking water concomitantly with adenine on the kidneys and left ventricular structure using the above model. Results: The CKD was confirmed by standard biochemical indices in plasma and urine and by accumulation of the uremic toxin indoxyl sulfate. Additionally, it increased blood pressure. In rats with CKD absolute volume of left ventricle was significantly increased, and the volume density and absolute volume of myocardial capillaries were decreased, whilst the same parameters of myocardium and interstitial tissue were increased. Renal morphometry demonstrated significant increase in kidney volume and interstitial tissue in adenine- treated rats. Similarly, glomerular Bowman's capsule was significantly thickened. The myocardial and renal changes were significantly mitigated by GA treatment. Conclusions: These results add to our existing knowledge of the pathophysiology of adenine - CKD and provides plausible histopathological and morphometric evidence for the usefulness of GA in CKD.

Intramolecular Hydroamination of Unbiased and Functionalized Primary Aminoalkenes Catalyzed by a Rhodium Aminophosphine Complex

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Julian, Lisa D.; Hartwig, John F.

2010-01-01

We report a rhodium catalyst that exhibits high reactivity for the hydroamination of primary aminoalkenes that are unbiased toward cyclization and that possess functional groups that would not be tolerated in hydroaminations catalyzed by more electrophilic systems. This catalyst contains an unusual diaminophosphine ligand that binds to rhodium in a κ3-P,O,P mode. The reactions catalyzed by this complex typically proceed at mild temperatures (room temperature to 70 °C), occur with primary aminoalkenes lacking substituents on the alkyl chain that bias the system toward cyclization, occur with primary aminoalkenes containing chloride, ester, ether, enolizable ketone, nitrile, and unprotected alcohol functionality, and occur with primary aminoalkenes containing internal olefins. Mechanistic data imply that these reactions occur with a turnover-limiting step that is different from that of reactions catalyzed by late transition metal complexes of Pd, Pt, and Ir. This change in the turnover-limiting step and resulting high activity of the catalyst stem from favorable relative rates for protonolysis of the M-C bond to release the hydroamination product vs reversion of the aminoalkyl intermediate to regenerate the acyclic precursor. Probes for the origin of the reactivity of the rhodium complex of L1 imply that the aminophosphine groups lead to these favorable rates by effects beyond steric demands and simple electron donation to the metal center. PMID:20839807

Age estimation in the living: Transition analysis on developing third molars.

Science.gov (United States)

Tangmose, Sara; Thevissen, Patrick; Lynnerup, Niels; Willems, Guy; Boldsen, Jesper

2015-12-01

A radiographic assessment of third molar development is essential for differentiating between juveniles and adolescents in forensic age estimations. As the developmental stages of third molars are highly correlated, age estimates based on a combination of a full set of third molar scores are statistically complicated. Transition analysis (TA) is a statistical method developed for estimating age at death in skeletons, which combines several correlated developmental traits into one age estimate including a 95% prediction interval. The aim of this study was to evaluate the performance of TA in the living on a full set of third molar scores. A cross sectional sample of 854 panoramic radiographs, homogenously distributed by sex and age (15.0-24.0 years), were randomly split in two; a reference sample for obtaining age estimates including a 95% prediction interval according to TA; and a validation sample to test the age estimates against actual age. The mean inaccuracy of the age estimates was 1.82 years (±1.35) in males and 1.81 years (±1.44) in females. The mean bias was 0.55 years (±2.20) in males and 0.31 years (±2.30) in females. Of the actual ages, 93.7% of the males and 95.9% of the females (validation sample) fell within the 95% prediction interval. Moreover, at a sensitivity and specificity of 0.824 and 0.937 in males and 0.814 and 0.827 in females, TA performs well in differentiating between being a minor as opposed to an adult. Although accuracy does not outperform other methods, TA provides unbiased age estimates which minimize the risk of wrongly estimating minors as adults. Furthermore, when corrected ad hoc, TA produces appropriate prediction intervals. As TA allows expansion with additional traits, i.e. stages of development of the left hand-wrist and the clavicle, it has a great potential for future more accurate and reproducible age estimates, including an estimated probability of having attained the legal age limit of 18 years. Copyright © 2015

THE CAPILLARY PATTERN IN HUMAN MASSETER MUSCLE DURING AGEING

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Erika Cvetko

2013-10-01

Full Text Available The effect of ageing on the capillary network in skeletal muscles has produced conflicting results in both, human and animals studies. Some of the inconsistencies are due to non-comparable and biased methods that were applied on thin transversal sections, especially in muscles with complicated morphological structures, such as in human masseter muscle. We present a new immunohistochemical method for staining capillaries and muscle fibres in 100 µm thick sections as well as novel approach to 3D visualization of capillaries and muscle fibres. Applying confocal microscopy and virtual 3D stereological grids, or tracing capillaries in virtual reality, length of capillaries within a muscle volume or length of capillaries adjacent to muscle fibre per fibre length, fibre surface or fibre volume were evaluated in masseter muscle of young and old subjects by an unbiased approach. Our findings show that anatomic capillarity is well maintained in masseter muscle in old subjects; however, vascular remodelling occurs with age, which could be a response to changed muscle function and age-related muscle fibre type transformations.

A punctual flux estimator and reactions rates optimization in neutral particles transport calculus by the Monte Carlo method

International Nuclear Information System (INIS)

Authier, N.

1998-12-01

One of the questions asked in radiation shielding problems is the estimation of the radiation level in particular to determine accessibility of working persons in controlled area (nuclear power plants, nuclear fuel reprocessing plants) or to study the dose gradients encountered in material (iron nuclear vessel, medical therapy, electronics in satellite). The flux and reaction rate estimators used in Monte Carlo codes give average values in volumes or on surfaces of the geometrical description of the system. But in certain configurations, the knowledge of punctual deposited energy and dose estimates are necessary. The Monte Carlo estimate of the flux at a point of interest is a calculus which presents an unbounded variance. The central limit theorem cannot be applied thus no easy confidence level may be calculated. The convergence rate is then very poor. We propose in this study a new solution for the photon flux at a point estimator. The method is based on the 'once more collided flux estimator' developed earlier for neutron calculations. It solves the problem of the unbounded variance and do not add any bias to the estimation. We show however that our new sampling schemes specially developed to treat the anisotropy of the photon coherent scattering is necessary for a good and regular behavior of the estimator. This developments integrated in the TRIPOLI-4 Monte Carlo code add the possibility of an unbiased punctual estimate on media interfaces. (author)

Enhanced online model identification and state of charge estimation for lithium-ion battery with a FBCRLS based observer

International Nuclear Information System (INIS)

Wei, Zhongbao; Meng, Shujuan; Xiong, Binyu; Ji, Dongxu; Tseng, King Jet

2016-01-01

Highlights: • Integrated online model identification and SOC estimate is explored. • Noise variances are online estimated in a data-driven way. • Identification bias caused by noise corruption is attenuated. • SOC is online estimated with high accuracy and fast convergence. • Algorithm comparison shows the superiority of proposed method. - Abstract: State of charge (SOC) estimators with online identified battery model have proven to have high accuracy and better robustness due to the timely adaption of time varying model parameters. In this paper, we show that the common methods for model identification are intrinsically biased if both the current and voltage sensors are corrupted with noises. The uncertainties in battery model further degrade the accuracy and robustness of SOC estimate. To address this problem, this paper proposes a novel technique which integrates the Frisch scheme based bias compensating recursive least squares (FBCRLS) with a SOC observer for enhanced model identification and SOC estimate. The proposed method online estimates the noise statistics and compensates the noise effect so that the model parameters can be extracted without bias. The SOC is further estimated in real time with the online updated and unbiased battery model. Simulation and experimental studies show that the proposed FBCRLS based observer effectively attenuates the bias on model identification caused by noise contamination and as a consequence provides more reliable estimate on SOC. The proposed method is also compared with other existing methods to highlight its superiority in terms of accuracy and convergence speed.

Estimating tree bole volume using artificial neural network models for four species in Turkey.

Science.gov (United States)

Ozçelik, Ramazan; Diamantopoulou, Maria J; Brooks, John R; Wiant, Harry V

2010-01-01

Tree bole volumes of 89 Scots pine (Pinus sylvestris L.), 96 Brutian pine (Pinus brutia Ten.), 107 Cilicica fir (Abies cilicica Carr.) and 67 Cedar of Lebanon (Cedrus libani A. Rich.) trees were estimated using Artificial Neural Network (ANN) models. Neural networks offer a number of advantages including the ability to implicitly detect complex nonlinear relationships between input and output variables, which is very helpful in tree volume modeling. Two different neural network architectures were used and produced the Back propagation (BPANN) and the Cascade Correlation (CCANN) Artificial Neural Network models. In addition, tree bole volume estimates were compared to other established tree bole volume estimation techniques including the centroid method, taper equations, and existing standard volume tables. An overview of the features of ANNs and traditional methods is presented and the advantages and limitations of each one of them are discussed. For validation purposes, actual volumes were determined by aggregating the volumes of measured short sections (average 1 meter) of the tree bole using Smalian's formula. The results reported in this research suggest that the selected cascade correlation artificial neural network (CCANN) models are reliable for estimating the tree bole volume of the four examined tree species since they gave unbiased results and were superior to almost all methods in terms of error (%) expressed as the mean of the percentage errors. 2009 Elsevier Ltd. All rights reserved.

Estimating Daily Reference Evapotranspiration in a Semi-Arid Region Using Remote Sensing Data

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Peshawa M. Najmaddin

2017-07-01

Full Text Available Estimating daily evapotranspiration is challenging when ground observation data are not available or scarce. Remote sensing can be used to estimate the meteorological data necessary for calculating reference evapotranspiration ETₒ. Here, we assessed the accuracy of daily ETₒ estimates derived from remote sensing (ETₒ-RS compared with those derived from four ground-based stations (ETₒ-G in Kurdistan (Iraq over the period 2010–2014. Near surface air temperature, relative humidity and cloud cover fraction were derived from the Atmospheric Infrared Sounder/Advanced Microwave Sounding Unit (AIRS/AMSU, and wind speed at 10 m height from MERRA (Modern-Era Retrospective Analysis for Research and Application. Four methods were used to estimate ETₒ: Hargreaves–Samani (HS, Jensen–Haise (JH, McGuinness–Bordne (MB and the FAO Penman Monteith equation (PM. ETₒ-G (PM was adopted as the main benchmark. HS underestimated ETₒ by 2%–3% (R2 = 0.86 to 0.90; RMSE = 0.95 to 1.2 mm day−1 at different stations. JH and MB overestimated ETₒ by 8% to 40% (R2= 0.85 to 0.92; RMSE from 1.18 to 2.18 mm day−1. The annual average values of ETₒ estimated using RS data and ground-based data were similar to one another reflecting low bias in daily estimates. They ranged between 1153 and 1893 mm year−1 for ETₒ-G and between 1176 and 1859 mm year−1 for ETₒ-RS for the different stations. Our results suggest that ETₒ-RS (HS can yield accurate and unbiased ETₒ estimates for semi-arid regions which can be usefully employed in water resources management.

Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining.

Science.gov (United States)

Røge, Rasmus; Riber-Hansen, Rikke; Nielsen, Søren; Vyberg, Mogens

2016-07-01

Manual estimation of Ki67 Proliferation Index (PI) in breast carcinoma classification is labor intensive and prone to intra- and interobserver variation. Standard Digital Image Analysis (DIA) has limitations due to issues with tumor cell identification. Recently, a computer algorithm, DIA based on Virtual Double Staining (VDS), segmenting Ki67-positive and -negative tumor cells using digitally fused parallel cytokeratin (CK) and Ki67-stained slides has been introduced. In this study, we compare VDS with manual stereological counting of Ki67-positive and -negative cells and examine the impact of the physical distance of the parallel slides on the alignment of slides. TMAs, containing 140 cores of consecutively obtained breast carcinomas, were stained for CK and Ki67 using optimized staining protocols. By means of stereological principles, Ki67-positive and -negative cell profiles were counted in sampled areas and used for the estimation of PIs of the whole tissue core. The VDS principle was applied to both the same sampled areas and the whole tissue core. Additionally, five neighboring slides were stained for CK in order to examine the alignment algorithm. Correlation between manual counting and VDS in both sampled areas and whole core was almost perfect (correlation coefficients above 0.97). Bland-Altman plots did not reveal any skewness in any data ranges. There was a good agreement in alignment (>85 %) in neighboring slides, whereas agreement decreased in non-neighboring slides. VDS gave similar results compared with manual counting using stereological principles. Introduction of this method in clinical and research practice may improve accuracy and reproducibility of Ki67 PI.

11 YEARS OF BIOSTEREOLOGY IN CHINA

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Hong Shen

2011-05-01

Full Text Available Biostereology in China is very active. Here is a brief summary: Organization: The organization of biostereology in China was founded in Nov. 1988. Its name is Chinese Society of Biomedical Stereology (CSBS, and is affiliated to the Chinese Society for Stereology (CSS. The first joint president of CSS/BMC was Prof. Peixuan Tang, the second and now the third, is Prof. Dewen Wang. There are 556 registered members. Academic Congresses: Sessions of the National Biostereological Congress were convened in 1990, 1992, 1996 and 2000. Publications: Four works were written and published in China. One is "Quantitative Histology" (Luji Shi, 1964, another is "Stereological Morphometry For Cell Morphology" (Fusheng Zheng, 1990, the third one is "Practical Biostereological Techniques" (Hong Shen and Yingzhong Shen, 1991 and the fourth one is "Quantitative Cytology and Cytochemistry Techniques" (Genxing Xu, 1994. A Chinese Journal of Stereology and Image Analysis has been published since 1996. Courses: More than ten national training courses on biostereology were held. In some medical universities or colleges, a biostereology course has been set up. Theoretical studies: Some new concepts, parameters and methods for stereology and morphometry were put forward, such as: regular form factor, volume concavity, surface concavity, area concavity, boundary concavity, curve profile area density, positive university for immunohistochemistry stain etc. Application: Stereological methods have been widely applied in biomedical studies. The applied field covered most of the morphological domain of biology. The main applications of biostereology are quantitative pathological diagnosis and prognosis of tumor cells and histostructures. Most studies utilize classical stereological methods. New stereological methods should be popularized and applied in the future. Image Analysis System: Image analysis systems are widely used in biostereological studies. About ten kinds of image

ESTIMATION OF THE NUMBER OF NEURONS IN THE HIPPOCAMPUS OF RATS WITH PENICILLIN INDUCED EPILEPSY

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Ilgaz Akdogan

2011-05-01

Full Text Available Epilepsy is a neurological disease arising from strong and uncontrollable electrical firings of a group of neurons in the central nervous system. Experimental epileptic models have been developed to assess the physiopathology of epileptic seizures. This study was undertaken to estimate the number of neurons in the rat hippocampus with penicillin induced epilepsy, using a stereological method, "the optical fractionator". In the experimental group, 500 IU penicillin-G was injected intra-cortically, and in the control group, the same volume of saline was administered. A week later, the animals were decapitated and their brains were removed by craniatomy. Frozen brains were cut with a thickness of 150 ěm in a cryostat. Sections were collected by systematic random sampling and stained with hematoxylen-eosin. Microscopic images of pyramidal cell layers from hippocampus CA1, CA2 and CA3 subfields were then transferred to a monitor, using a 100x objective (N.A. = 1.25. Using the optical disector method, the neurons were counted in the frames and determined with a fractionator sampling scheme. The total pyramidal neuron number was then estimated using the optical fractionator method. The total pyramidal neuron number was found to be statistically lower in the experimental group (mean = 142,888 ± 11,745 than in the control group (mean = 177,953 ± 10,907 (p < 0.05. The results suggest that a decrease in the hippocampal neuronal number in a penicillin model of epilepsy can be determined objectively and efficiently using the optical fractionator method.

Estimation of Total Glomerular Number Using an Integrated Disector Method in Embryonic and Postnatal Kidneys

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Michel G Arsenault

2014-06-01

Full Text Available Congenital Anomalies of the Kidney and Urinary Tract (CAKUT are a polymorphic group of clinical disorders comprising the major cause of renal failure in children. Included within CAKUT is a wide spectrum of developmental malformations ranging from renal agenesis, renal hypoplasia and renal dysplasia (maldifferentiation of renal tissue, each characterized by varying deficits in nephron number. First presented in the Brenner Hypothesis, low congenital nephron endowment is becoming recognized as an antecedent cause of adult-onset hypertension, a leading cause of coronary heart disease, stroke, and renal failure in North America. Genetic mouse models of impaired nephrogenesis and nephron endowment provide a critical framework for understanding the origins of human kidney disease. Current methods to quantitate nephron number include (i acid maceration (ii estimation of nephron number from a small number of tissue sections (iii imaging modalities such as MRI and (iv the gold standard physical disector/fractionator method. Despite its accuracy, the physical disector/fractionator method is rarely employed because it is labour-intensive, time-consuming and costly to perform. Consequently, less rigourous methods of nephron estimation are routinely employed by many laboratories. Here we present an updated, digitized version of the physical disector/fractionator method using free open source Fiji software, which we have termed the integrated disector method. This updated version of the gold standard modality accurately, rapidly and cost-effectively quantitates nephron number in embryonic and post-natal mouse kidneys, and can be easily adapted for stereological measurements in other organ systems.

Impact of nonlinearity on changing the a priori of trace gas profile estimates from the Tropospheric Emission Spectrometer (TES

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S. S. Kulawik

2008-06-01

Full Text Available Non-linear maximum a posteriori (MAP estimates of atmospheric profiles from the Tropospheric Emission Spectrometer (TES contains a priori information that may vary geographically, which is a confounding factor in the analysis and physical interpretation of an ensemble of profiles. One mitigation strategy is to transform profile estimates to a common prior using a linear operation thereby facilitating the interpretation of profile variability. However, this operation is dependent on the assumption of not worse than moderate non-linearity near the solution of the non-linear estimate. The robustness of this assumption is tested by comparing atmospheric retrievals from the Tropospheric Emission Spectrometer processed with a uniform prior with those processed with a variable prior and converted to a uniform prior following the non-linear retrieval. Linearly converting the prior following a non-linear retrieval is shown to have a minor effect on the results as compared to a non-linear retrieval using a uniform prior when compared to the expected total error, with less than 10% of the change in the prior ending up as unbiased fluctuations in the profile estimate results.

Large biases in regression-based constituent flux estimates: causes and diagnostic tools

Science.gov (United States)

Hirsch, Robert M.

2014-01-01

It has been documented in the literature that, in some cases, widely used regression-based models can produce severely biased estimates of long-term mean river fluxes of various constituents. These models, estimated using sample values of concentration, discharge, and date, are used to compute estimated fluxes for a multiyear period at a daily time step. This study compares results of the LOADEST seven-parameter model, LOADEST five-parameter model, and the Weighted Regressions on Time, Discharge, and Season (WRTDS) model using subsampling of six very large datasets to better understand this bias problem. This analysis considers sample datasets for dissolved nitrate and total phosphorus. The results show that LOADEST-7 and LOADEST-5, although they often produce very nearly unbiased results, can produce highly biased results. This study identifies three conditions that can give rise to these severe biases: (1) lack of fit of the log of concentration vs. log discharge relationship, (2) substantial differences in the shape of this relationship across seasons, and (3) severely heteroscedastic residuals. The WRTDS model is more resistant to the bias problem than the LOADEST models but is not immune to them. Understanding the causes of the bias problem is crucial to selecting an appropriate method for flux computations. Diagnostic tools for identifying the potential for bias problems are introduced, and strategies for resolving bias problems are described.

Mass estimates from stellar proper motions: the mass of ω Centauri

Science.gov (United States)

D'Souza, Richard; Rix, Hans-Walter

2013-03-01

We lay out and apply methods to use proper motions of individual kinematic tracers for estimating the dynamical mass of star clusters. We first describe a simple projected mass estimator and then develop an approach that evaluates directly the likelihood of the discrete kinematic data given the model predictions. Those predictions may come from any dynamical modelling approach, and we implement an analytic King model, a spherical isotropic Jeans equation model and an axisymmetric, anisotropic Jeans equation model. This maximum likelihood modelling (MLM) provides a framework for a model-data comparison, and a resulting mass estimate, which accounts explicitly for the discrete nature of the data for individual stars, the varying error bars for proper motions of differing signal-to-noise ratio, and for data incompleteness. Both of these two methods are evaluated for their practicality and are shown to provide an unbiased and robust estimate of the cluster mass. We apply these approaches to the enigmatic globular cluster ω Centauri, combining the proper motion from van Leeuwen et al. with improved photometric cluster membership probabilities. We show that all mass estimates based on spherical isotropic models yield (4.55 ± 0.1) × 106 M⊙[D/5.5 ± 0.2 kpc]3, where our modelling allows us to show how the statistical precision of this estimate improves as more proper motion data of lower signal-to-noise ratio are included. MLM predictions, based on an anisotropic axisymmetric Jeans model, indicate for ω Cen that the inclusion of anisotropies is not important for the mass estimates, but that accounting for the flattening is: flattened models imply (4.05 ± 0.1) × 106 M⊙[D/5.5 ± 0.2 kpc]3, 10 per cent lower than when restricting the analysis to a spherical model. The best current distance estimates imply an additional uncertainty in the mass estimate of 12 per cent.

Tapering the sky response for angular power spectrum estimation from low-frequency radio-interferometric data.

Science.gov (United States)

Choudhuri, Samir; Bharadwaj, Somnath; Roy, Nirupam; Ghosh, Abhik; Ali, Sk Saiyad

2016-06-11

It is important to correctly subtract point sources from radio-interferometric data in order to measure the power spectrum of diffuse radiation like the Galactic synchrotron or the Epoch of Reionization 21-cm signal. It is computationally very expensive and challenging to image a very large area and accurately subtract all the point sources from the image. The problem is particularly severe at the sidelobes and the outer parts of the main lobe where the antenna response is highly frequency dependent and the calibration also differs from that of the phase centre. Here, we show that it is possible to overcome this problem by tapering the sky response. Using simulated 150 MHz observations, we demonstrate that it is possible to suppress the contribution due to point sources from the outer parts by using the Tapered Gridded Estimator to measure the angular power spectrum C ℓ of the sky signal. We also show from the simulation that this method can self-consistently compute the noise bias and accurately subtract it to provide an unbiased estimation of C ℓ .

Unbiased total electron content (UTEC), their fluctuations, and correlation with seismic activity over Japan

Science.gov (United States)

Cornely, Pierre-Richard; Hughes, John

2018-02-01

Earthquakes are among the most dangerous events that occur on earth and many scientists have been investigating the underlying processes that take place before earthquakes occur. These investigations are fueling efforts towards developing both single and multiple parameter earthquake forecasting methods based on earthquake precursors. One potential earthquake precursor parameter that has received significant attention within the last few years is the ionospheric total electron content (TEC). Despite its growing popularity as an earthquake precursor, TEC has been under great scrutiny because of the underlying biases associated with the process of acquiring and processing TEC data. Future work in the field will need to demonstrate our ability to acquire TEC data with the least amount of biases possible thereby preserving the integrity of the data. This paper describes a process for removing biases using raw TEC data from the standard Rinex files obtained from any global positioning satellites system. The process is based on developing an unbiased TEC (UTEC) data and model that can be more adaptable to serving as a precursor signal for earthquake forecasting. The model was used during the days and hours leading to the earthquake off the coast of Tohoku, Japan on March 11, 2011 with interesting results. The model takes advantage of the large amount of data available from the GPS Earth Observation Network of Japan to display near real-time UTEC data as the earthquake approaches and for a period of time after the earthquake occurred.

Precise estimates of mutation rate and spectrum in yeast

Science.gov (United States)

Zhu, Yuan O.; Siegal, Mark L.; Hall, David W.; Petrov, Dmitri A.

2014-01-01

Mutation is the ultimate source of genetic variation. The most direct and unbiased method of studying spontaneous mutations is via mutation accumulation (MA) lines. Until recently, MA experiments were limited by the cost of sequencing and thus provided us with small numbers of mutational events and therefore imprecise estimates of rates and patterns of mutation. We used whole-genome sequencing to identify nearly 1,000 spontaneous mutation events accumulated over ∼311,000 generations in 145 diploid MA lines of the budding yeast Saccharomyces cerevisiae. MA experiments are usually assumed to have negligible levels of selection, but even mild selection will remove strongly deleterious events. We take advantage of such patterns of selection and show that mutation classes such as indels and aneuploidies (especially monosomies) are proportionately much more likely to contribute mutations of large effect. We also provide conservative estimates of indel, aneuploidy, environment-dependent dominant lethal, and recessive lethal mutation rates. To our knowledge, for the first time in yeast MA data, we identified a sufficiently large number of single-nucleotide mutations to measure context-dependent mutation rates and were able to (i) confirm strong AT bias of mutation in yeast driven by high rate of mutations from C/G to T/A and (ii) detect a higher rate of mutation at C/G nucleotides in two specific contexts consistent with cytosine methylation in S. cerevisiae. PMID:24847077

Regression estimators for generic health-related quality of life and quality-adjusted life years.

Science.gov (United States)

Basu, Anirban; Manca, Andrea

2012-01-01

To develop regression models for outcomes with truncated supports, such as health-related quality of life (HRQoL) data, and account for features typical of such data such as a skewed distribution, spikes at 1 or 0, and heteroskedasticity. Regression estimators based on features of the Beta distribution. First, both a single equation and a 2-part model are presented, along with estimation algorithms based on maximum-likelihood, quasi-likelihood, and Bayesian Markov-chain Monte Carlo methods. A novel Bayesian quasi-likelihood estimator is proposed. Second, a simulation exercise is presented to assess the performance of the proposed estimators against ordinary least squares (OLS) regression for a variety of HRQoL distributions that are encountered in practice. Finally, the performance of the proposed estimators is assessed by using them to quantify the treatment effect on QALYs in the EVALUATE hysterectomy trial. Overall model fit is studied using several goodness-of-fit tests such as Pearson's correlation test, link and reset tests, and a modified Hosmer-Lemeshow test. The simulation results indicate that the proposed methods are more robust in estimating covariate effects than OLS, especially when the effects are large or the HRQoL distribution has a large spike at 1. Quasi-likelihood techniques are more robust than maximum likelihood estimators. When applied to the EVALUATE trial, all but the maximum likelihood estimators produce unbiased estimates of the treatment effect. One and 2-part Beta regression models provide flexible approaches to regress the outcomes with truncated supports, such as HRQoL, on covariates, after accounting for many idiosyncratic features of the outcomes distribution. This work will provide applied researchers with a practical set of tools to model outcomes in cost-effectiveness analysis.