On the Mahalanobis Distance Classification Criterion for Multidimensional Normal Distributions

Many existing engineering works model the statistical characteristics of the entities under study as normal distributions. These models are eventually used for decision making, requiring in practice the definition of the classification region corresponding to the desired confidence level. Surprisingly enough, however, a great amount of computer vision works using multidimensional normal models leave unspecified or fail to establish correct confidence regions due to misconceptions on the features of Gaussian functions or to wrong analogies with the unidimensional case. The resulting regions incur in deviations that can be unacceptable in high-dimensional models. Here we provide a comprehensive derivation of the optimal confidence regions for multivariate normal distributions of arbitrary dimensionality. To this end, firstly we derive the condition for region optimality of general continuous multidimensional distributions, and then we apply it to the widespread case of the normal probability density function. The obtained results are used to analyze the confidence error incurred by previous works related to vision research, showing that deviations caused by wrong regions may turn into unacceptable as dimensionality increases. To support the theoretical analysis, a quantitative example in the context of moving object detection by means of background modeling is given.

Deriving the full-reducing Krivine machine from the small-step operational semantics of normal order

We derive by program transformation Pierre Crégut s full-reducing Krivine machine KN from the structural operational semantics of the normal order reduction strategy in a closure-converted pure lambda calculus. We thus establish the correspondence between the strategy and the machine, and showcase our technique for deriving full-reducing abstract machines. Actually, the machine we obtain is a slightly optimised version that can work with open terms and may be used in implementations of proof assistants.

Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice

Heart failure is accompanied by severely impaired β-adrenergic receptor (βAR) function, which includes loss of βAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of βAR function is agonist-stimulated receptor phosphorylation by the βAR kinase (βARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in βAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of βARK1 or the β2AR were mated into a genetic model of murine heart failure (MLP−/−). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP−/− and MLP−/−/β2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP−/−/βARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP−/−/βARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP−/− mice but less than controls. Importantly, heightened βAR desensitization in the MLP−/− mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the βARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal βAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit βARK1 as a novel mode of therapy.

Lipotoxic heart disease in obese rats: Implications for human obesity

To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.

A normal β-globin allele as a modifier gene ameliorating the severity of α-thalassemia in mice

Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the α- or the β-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced by unlinked modifying genes. Indeed, by using a mouse model of α-thalassemia, we find that its phenotype is strongly influenced by the genetic background in which the α-thalassemia mutation resides [129sv/ev/129sv/ev (severe) or 129sv/ev/C57BL/6 (mild)]. Linkage mapping indicates that the modifying gene is very tightly linked to the β-globin locus (Lod score = 13.3). Furthermore, the severity of the phenotype correlates with the size of β-chain-containing inclusion bodies that accumulate in red blood cells and likely accelerate their destruction. The β-major globin chains encoded by the two strains differ by three amino acids, one of which is a glycine-to-cysteine substitution at position 13. The Cys-13 should be available for interchain disulfide bridging and consequent aggregation between excess β-chains. This normal polymorphic variation between murine β-globin chains could account for the modifying action of the unlinked β-globin locus. Here, the variation in severity of the phenotype would not depend on a change in the ratio between α- and β-chains but on the chemical nature of the normal β-chain, which is in excess. This work also indicates that modifying genes can be normal variants that—absent an apparent physiologic rationale—may be difficult to identify on the basis of structure alone.

Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice.

Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from transgenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight was comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, and 300 days, respectively, after birth. At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and control mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.

Immunolocalization of estrogen receptor protein in the mouse blastocyst during normal and delayed implantation.

We previously showed that estrogen receptor (ER) mRNA is present in preimplantation mouse embryos. The apparent synthesis of ER mRNA by the blastocyst at the time of implantation when estrogen is required was of special interest. A demonstration of the presence of ER protein would support the idea that estrogen can act directly on the embryo. The mouse embryo at the blastocyst stage is differentiated into two cell types, the trophectoderm and the inner cell mass. To determine whether ER mRNA is translated into ER protein and its cell-specific distribution, immunocytochemical analyses were performed in mouse blastocysts. ER protein was detected in all cell types of the normal, dormant, or activated blastocyst. To trace the fate of ER in these cell types, immunocytochemistry was performed in implanting blastocysts and early egg cylinder stage embryos developed in culture. Again, ER was detected in all cells of the implanting blastocyst. At the early egg cylinder stage, continued expression of ER was observed in cells derived from the inner cell mass or the trophoblast. In trophoblast giant cells, ER was concentrated in small regions of the nucleus, possibly the nucleoli, which was similar to that observed in dormant and activated blastocysts. The embryonic expression of ER at such early stages in a broad array of cells suggests that ER may have a general role during early development.

Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus.

We recorded in the CA1 region from hippocampal slices of prion protein (PrP) gene knockout mice to investigate whether the loss of the normal form of prion protein (PrPC) affects neuronal excitability as well as synaptic transmission in the central nervous system. No deficit in synaptic inhibition was found using field potential recordings because (i) responses induced by stimulation in stratum radiatum consisted of a single population spike in PrP gene knockout mice similar to that recorded from control mice and (ii) the plot of field excitatory postsynaptic potential slope versus the population spike amplitude showed no difference between the two groups of mice. Intracellular recordings also failed to detect any difference in cell excitability and the reversal potential for inhibitory postsynaptic potentials. Analysis of the kinetics of inhibitory postsynaptic current revealed no modification. Finally, we examined whether synaptic plasticity was altered and found no difference in long-term potentiation between control and PrP gene knockout mice. On the basis of our findings, we propose that the loss of the normal form of prion protein does not alter the physiology of the CA1 region of the hippocampus.

Nonlinear control of heart rate variability in human infants.

Nonlinear analyses of infant heart rhythms reveal a marked rise in the complexity of the electrocardiogram with maturation. We find that normal mature infants (gestation greater than or equal to 35 weeks) have complex and distinctly nonlinear heart rhythms (consistent with recent reports for healthy adults) but that such nonlinearity is lacking in preterm infants (gestation > or = to 27 weeks) where parasympathetic-sympathetic interaction and function are presumed to be less well developed. Our study further shows that infants with clinical brain death and those treated with atropine exhibit a similar lack of nonlinear feedback control. These three lines of evidence support the hypothesis championed by Goldberger et al. [Goldberger, A.L., Rigney, D.R. & West, B.J. (1990) Sci. Am. 262, 43-49] that autonomic nervous system control underlies the nonlinearity and possible chaos of normal heart rhythms. This report demonstrates the acquisition of nonlinear heart rate dynamics and possible chaos in developing human infants and its loss in brain death and with the administration of atropine. It parallels earlier work documenting changes in the variability of heart rhythms in each of these cases and suggests that nonlinearity may provide additional power in characterizing physiological states.

Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells.

In the present study, we define a group of natural killer (NK) clones (group 0) that fails to lyse all of the normal allogeneic target cells analyzed. Their specificity for HLA class I molecules was suggested by their ability to lyse class I-negative target cells and by the fact that they could lyse resistant target cells in the presence of selected anti-class I monoclonal antibodies. The use of appropriate target cells represented by either HLA-homozygous cell lines or cell transfectants revealed that these clones recognized all the HLA-C alleles. By the use of monoclonal antibodies directed to either GL183 or EB6 molecules, we showed that the EB6 molecules were responsible for the recognition of Cw4 and related alleles, while the GL183 molecules recognized Cw3 (and related C alleles). These data suggest that the GL183 and the EB6 molecules can function, in individual NK clones, as independent receptors for two different groups of HLA-C alleles, (which include all known alleles for locus C), thus resulting in their inability to lyse all normal HLA-C+ target cells. Indirect immunofluorescence and fluorescence-activated cell sorting analysis revealed that the presently defined GL183+EB6+ group 0 NK clones brightly express EB6 molecules (EB6bright) while the GL183+EB6+ group 2 clones (unable to recognize Cw4) express an EB6dull phenotype. These data also imply that the density of EB6 receptors may be critical for the generation of an optimal negative signal upon interaction with appropriate HLA-C alleles.

An extended Herschel drop-out source in the center of AS1063: a normal dusty galaxy at z=6.1 or SZ substructures?

In the course of our 870 μm APEX/LABOCA follow-up of the Herschel Lensing Survey we have detected a source in AS1063 (RXC J2248.7-4431) that has no counterparts in any of the Herschel PACS/SPIRE bands, it is a Herschel “drop-out” with S_870/S_500 ≥ 0.5. The 870 μm emission is extended and centered on the brightest cluster galaxy, suggesting either a multiply imaged background source or substructure in the Sunyaev-Zel’dovich increment due to inhomogeneities in the hot cluster gas of this merging cluster. We discuss both interpretations with emphasis on the putative lensed source. Based on the observed properties and on our lens model we find that this source may be the first submillimeter galaxy (SMG) with a moderate far-infrared (FIR) luminosity (L_FIR < 10^12 L_⊙) detected so far at z > 4. In deep HST observations we identified a multiply imaged z ~ 6 source and measured its spectroscopic redshift to be z = 6.107 with VLT/FORS. This source may be associated with the putative SMG, but it is most likely offset spatially by 10−30 kpc and they may be interacting galaxies. With a FIR luminosity in the range [5−15] × 10^11 L_⊙ corresponding to a star formation rate in the range [80−260] M_⊙ yr^-1, this SMG would be more representative of the z > 4 dusty galaxies than the extreme starbursts detected so far. With a total magnification of ~25 it would open a unique window to the normal dusty galaxies at the end of the epoch of reionization.

Comparative analysis of the relationship between anterior and posterior corneal shape analyzed by Scheimpflug photography in normal and keratoconus eyes

Background To analyze and compare the relationship between anterior and posterior corneal shape evaluated by a tomographic system combining the Scheimpflug photography and Placido-disc in keratoconus and normal healthy eyes, as well as to evaluate its potential diagnostic value. Methods Comparative case series including a sample of 161 eyes of 161 subjects with ages ranging from 7 to 66 years and divided into two groups: normal group including 100 healthy eyes of 100 subjects, and keratoconus group including 61 keratoconus eyes of 61 patients. All eyes received a comprehensive ophthalmologic examination including an anterior segment analysis with the Sirius system (CSO). Antero-posterior ratios for corneal curvature (k ratio) and shape factor (p ratio) were calculated. Logistic regression analysis was used to evaluate if some antero–posterior ratios combined with other clinical parameters were predictors of the presence of keratoconus. Results No statistically significant differences between groups were found in the antero–posterior k ratios for 3-, 5- and 7-mm diameter corneal areas (p ≥ 0.09). The antero–posterior p ratio for 4.5- and 8-mm diameter corneal areas was significantly higher in the normal group than in the keratoconus group (p < 0.01). The k ratio for 3, 5, and 7 mm was significantly higher in the keratoconus grade IV subgroup than in the normal group (p < 0.01). Furthermore, significant differences were found in the p ratio between the normal group and the keratoconus grade II subgroup (p ≤ 0.01). Finally, the logistic regression analysis identified as significant independent predictors of the presence of keratoconus (p < 0.01) the 8-mm anterior shape factor, the anterior chamber depth, and the minimal corneal thickness. Conclusions The antero-posterior k and p ratios are parameters with poor prediction ability for keratoconus, in spite of the trend to the presence of more prolate posterior corneal surfaces compared to the anterior in keratoconus eyes.

Electrodynamic heart model construction and ECG simulation

Objectives: In this paper, we present a unified electrodynamic heart model that permits simulations of the body surface potentials generated by the heart in motion. The inclusion of motion in the heart model significantly improves the accuracy of the simulated body surface potentials and therefore also the 12-lead ECG. Methods: The key step is to construct an electromechanical heart model. The cardiac excitation propagation is simulated by an electrical heart model, and the resulting cardiac active forces are used to calculate the ventricular wall motion based on a mechanical model. The source-field point relative position changes during heart systole and diastole. These can be obtained, and then used to calculate body surface ECG based on the electrical heart-torso model. Results: An electromechanical biventricular heart model is constructed and a standard 12-lead ECG is simulated. Compared with a simulated ECG based on the static electrical heart model, the simulated ECG based on the dynamic heart model is more accordant with a clinically recorded ECG, especially for the ST segment and T wave of a V1-V6 lead ECG. For slight-degree myocardial ischemia ECG simulation, the ST segment and T wave changes can be observed from the simulated ECG based on a dynamic heart model, while the ST segment and T wave of simulated ECG based on a static heart model is almost unchanged when compared with a normal ECG. Conclusions: This study confirms the importance of the mechanical factor in the ECG simulation. The dynamic heart model could provide more accurate ECG simulation, especially for myocardial ischemia or infarction simulation, since the main ECG changes occur at the ST segment and T wave, which correspond with cardiac systole and diastole phases.

Mapping the emergence of heart disease in a black, urban population in Africa: The Heart of Soweto Study

Background: There is increasing evidence that many populations in the developing world are in epidemiologic transition with the subsequent emergence of more affluent disease states. The Heart of Soweto Study will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of I million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 prevalent cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 incident cases. Sub-studies of the relationship between HIV status and H D and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a developing world community in epidemiologic transition. Initially documented Population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Heart rate variability characterization using a time-frequency based instantaneous frequency estimation technique

In this paper, a new method for characterizing the newborn heart rate variability (HRV) is proposed. The central of the method is the newly proposed technique for instantaneous frequency (IF) estimation specifically designed for nonstationary multicomponen signals such as HRV. The new method attempts to characterize the newborn HRV using features extracted from the time–frequency (TF) domain of the signal. These features comprise the IF, the instantaneous bandwidth (IB) and instantaneous energy (IE) of the different TF components of the HRV. Applied to the HRV of both normal and seizure suffering newborns, this method clearly reveals the locations of the spectral peaks and their time-varying nature. The total energy of HRV components, ET and ratio of energy concentrated in the low-frequency (LF) to that in high frequency (HF) components have been shown to be significant features in identifying the HRV of newborn with seizures.