The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies.

Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria. The aim of the present review was to consider the current body of evidence for potential beneficial effects of dietary nitrate on blood pressure and endothelial function, with emphasis on evidence from acute and chronic human intervention studies. The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans. An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction, with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function. In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation. In conclusion, the evidence for beneficial effects of dietary nitrate on blood pressure and endothelial function is promising. Further long-term randomised controlled human intervention studies assessing the potential effects of dietary nitrate on blood pressure and endothelial function are needed, particularly in individuals with hypertension and at risk of CVD.

Mismatch Negativity (MMN) reveals inefficient auditory ventral stream function in chronic auditory comprehension impairments

Background: Auditory discrimination is significantly impaired in Wernicke’s aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. Methods: Behavioural auditory discrimination thresholds of CVC syllables and pure tones were measured in WA (n=7) and control (n=7) participants. Threshold results were used to develop multiple-deviant mismatch negativity (MMN) oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). Results: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. Conclusions: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.

The exponentiated generalized inverse Gaussian distribution

The modeling and analysis of lifetime data is an important aspect of statistical work in a wide variety of scientific and technological fields. Good (1953) introduced a probability distribution which is commonly used in the analysis of lifetime data. For the first time, based on this distribution, we propose the so-called exponentiated generalized inverse Gaussian distribution, which extends the exponentiated standard gamma distribution (Nadarajah and Kotz, 2006). Various structural properties of the new distribution are derived, including expansions for its moments, moment generating function, moments of the order statistics, and so forth. We discuss maximum likelihood estimation of the model parameters. The usefulness of the new model is illustrated by means of a real data set. (c) 2010 Elsevier B.V. All rights reserved.

Pion structure function within the instanton model

The leading-twist valence-quark distribution function in the pion is obtained at a low normalization scale of an order of the inverse average size of an instanton pc. The momentum dependent quark mass and the quark-pion vertex are constructed in the framework of the instanton liquid model, using a gauge invariant approach. The parameters of instanton vacuum, the effective instanton radius and quark mass, are related to the vacuum expectation values of the lowest dimension quark-gluon operators and to the pion low energy observables. An analytic expression for the quark distribution function in the pion for a general vertex function is derived. The results are QCD evolved to higher momentum-transfer values, and reasonable agreement with phenomenological analyses of the data on parton distributions for the pion is found. ©2000 The American Physical Society.

Optimal trajectory and solution of the inverse kinematics of a robotic manipulator by genetic algorithms

This paper presents the generation of optimal trajectories by genetic algorithms (GA) for a planar robotic manipulator. The implemented GA considers a multi-objective function that minimizes the end-effector positioning error together with the joints angular displacement and it solves the inverse kinematics problem for the trajectory. Computer simulations results are presented to illustrate this implementation and show the efficiency of the used methodology producing soft trajectories with low computing cost. © 2011 Springer-Verlag Berlin Heidelberg.

An inverse method to estimate the moving heat source in machining process

The present work propounds an inverse method to estimate the heat sources in the transient two-dimensional heat conduction problem in a rectangular domain with convective bounders. The non homogeneous partial differential equation (PDE) is solved using the Integral Transform Method. The test function for the heat generation term is obtained by the chip geometry and thermomechanical cutting. Then the heat generation term is estimated by the conjugated gradient method (CGM) with adjoint problem for parameter estimation. The experimental trials were organized to perform six different conditions to provide heat sources of different intensities. This method was compared with others in the literature and advantages are discussed. (C) 2012 Elsevier Ltd. All rights reserved.

Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity

Background Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. Objectives To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. Results A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Conclusion Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.

Topics in geometry, analysis and inverse problems

The thesis consists of three independent parts. Part I: Polynomial amoebas We study the amoeba of a polynomial, as de ned by Gelfand, Kapranov and Zelevinsky. A central role in the treatment is played by a certain convex function which is linear in each complement component of the amoeba, which we call the Ronkin function. This function is used in two di erent ways. First, we use it to construct a polyhedral complex, which we call a spine, approximating the amoeba. Second, the Monge-Ampere measure of the Ronkin function has interesting properties which we explore. This measure can be used to derive an upper bound on the area of an amoeba in two dimensions. We also obtain results on the number of complement components of an amoeba, and consider possible extensions of the theory to varieties of codimension higher than 1. Part II: Differential equations in the complex plane We consider polynomials in one complex variable arising as eigenfunctions of certain differential operators, and obtain results on the distribution of their zeros. We show that in the limit when the degree of the polynomial approaches innity, its zeros are distributed according to a certain probability measure. This measure has its support on the union of nitely many curve segments, and can be characterized by a simple condition on its Cauchy transform. Part III: Radon transforms and tomography This part is concerned with different weighted Radon transforms in two dimensions, in particular the problem of inverting such transforms. We obtain stability results of this inverse problem for rather general classes of weights, including weights of attenuation type with data acquisition limited to a 180 degrees range of angles. We also derive an inversion formula for the exponential Radon transform, with the same restriction on the angle.

Bayesian Analysis of Linear Inverse Problems with Applications in Economics and Finance

In my PhD thesis I propose a Bayesian nonparametric estimation method for structural econometric models where the functional parameter of interest describes the economic agent's behavior. The structural parameter is characterized as the solution of a functional equation, or by using more technical words, as the solution of an inverse problem that can be either ill-posed or well-posed. From a Bayesian point of view, the parameter of interest is a random function and the solution to the inference problem is the posterior distribution of this parameter. A regular version of the posterior distribution in functional spaces is characterized. However, the infinite dimension of the considered spaces causes a problem of non continuity of the solution and then a problem of inconsistency, from a frequentist point of view, of the posterior distribution (i.e. problem of ill-posedness). The contribution of this essay is to propose new methods to deal with this problem of ill-posedness. The first one consists in adopting a Tikhonov regularization scheme in the construction of the posterior distribution so that I end up with a new object that I call regularized posterior distribution and that I guess it is solution of the inverse problem. The second approach consists in specifying a prior distribution on the parameter of interest of the g-prior type. Then, I detect a class of models for which the prior distribution is able to correct for the ill-posedness also in infinite dimensional problems. I study asymptotic properties of these proposed solutions and I prove that, under some regularity condition satisfied by the true value of the parameter of interest, they are consistent in a "frequentist" sense. Once I have set the general theory, I apply my bayesian nonparametric methodology to different estimation problems. First, I apply this estimator to deconvolution and to hazard rate, density and regression estimation. Then, I consider the estimation of an Instrumental Regression that is useful in micro-econometrics when we have to deal with problems of endogeneity. Finally, I develop an application in finance: I get the bayesian estimator for the equilibrium asset pricing functional by using the Euler equation defined in the Lucas'(1978) tree-type models.

Inverse problems in classical and quantum physics

The subject of this thesis is in the area of Applied Mathematics known as Inverse Problems. Inverse problems are those where a set of measured data is analysed in order to get as much information as possible on a model which is assumed to represent a system in the real world. We study two inverse problems in the fields of classical and quantum physics: QCD condensates from tau-decay data and the inverse conductivity problem. Despite a concentrated effort by physicists extending over many years, an understanding of QCD from first principles continues to be elusive. Fortunately, data continues to appear which provide a rather direct probe of the inner workings of the strong interactions. We use a functional method which allows us to extract within rather general assumptions phenomenological parameters of QCD (the condensates) from a comparison of the time-like experimental data with asymptotic space-like results from theory. The price to be paid for the generality of assumptions is relatively large errors in the values of the extracted parameters. Although we do not claim that our method is superior to other approaches, we hope that our results lend additional confidence to the numerical results obtained with the help of methods based on QCD sum rules. EIT is a technology developed to image the electrical conductivity distribution of a conductive medium. The technique works by performing simultaneous measurements of direct or alternating electric currents and voltages on the boundary of an object. These are the data used by an image reconstruction algorithm to determine the electrical conductivity distribution within the object. In this thesis, two approaches of EIT image reconstruction are proposed. The first is based on reformulating the inverse problem in terms of integral equations. This method uses only a single set of measurements for the reconstruction. The second approach is an algorithm based on linearisation which uses more then one set of measurements. A promising result is that one can qualitatively reconstruct the conductivity inside the cross-section of a human chest. Even though the human volunteer is neither two-dimensional nor circular, such reconstructions can be useful in medical applications: monitoring for lung problems such as accumulating fluid or a collapsed lung and noninvasive monitoring of heart function and blood flow.

Investigation of the nuclear matter density distributions of the exotic 12 Be, 14 Be and 8 B nuclei by elastic proton scattering in inverse kinematics

The proton-nucleus elastic scattering at intermediate energies is a well-established method for the investigation of the nuclear matter distribution in stable nuclei and was recently applied also for the investigation of radioactive nuclei using the method of inverse kinematics. In the current experiment, the differential cross sections for proton elastic scattering on the isotopes $^{7,9,10,11,12,14}$Be and $^8$B were measured. The experiment was performed using the fragment separator at GSI, Darmstadt to produce the radioactive beams. The main part of the experimental setup was the time projection ionization chamber IKAR which was simultaneously used as hydrogen target and a detector for the recoil protons. Auxiliary detectors for projectile tracking and isotope identification were also installed. As results from the experiment, the absolute differential cross sections d$sigma$/d$t$ as a function of the four momentum transfer $t$ were obtained. In this work the differential cross sections for elastic p-$^{12}$Be, p-$^{14}$Be and p-$^{8}$B scattering at low $t$ ($t leq$~0.05~(GeV/c)$^2$) are presented. The measured cross sections were analyzed within the Glauber multiple-scattering theory using different density parameterizations, and the nuclear matter density distributions and radii of the investigated isotopes were determined. The analysis of the differential cross section for the isotope $^{14}$Be shows that a good description of the experimental data is obtained when density distributions consisting of separate core and halo components are used. The determined {it rms} matter radius is $3.11 pm 0.04 pm 0.13$~fm. In the case of the $^{12}$Be nucleus the results showed an extended matter distribution as well. For this nucleus a matter radius of $2.82 pm 0.03 pm 0.12$~fm was determined. An interesting result is that the free $^{12}$Be nucleus behaves differently from the core of $^{14}$Be and is much more extended than it. The data were also compared with theoretical densities calculated within the FMD and the few-body models. In the case of $^{14}$Be, the calculated cross sections describe the experimental data well while, in the case of $^{12}$Be there are discrepancies in the region of high momentum transfer. Preliminary experimental results for the isotope $^8$B are also presented. An extended matter distribution was obtained (though much more compact as compared to the neutron halos). A proton halo structure was observed for the first time with the proton elastic scattering method. The deduced matter radius is $2.60pm 0.02pm 0.26$~fm. The data were compared with microscopic calculations in the frame of the FMD model and reasonable agreement was observed. The results obtained in the present analysis are in most cases consistent with the previous experimental studies of the same isotopes with different experimental methods (total interaction and reaction cross section measurements, momentum distribution measurements). For future investigation of the structure of exotic nuclei a universal detector system EXL is being developed. It will be installed at the NESR at the future FAIR facility where higher intensity beams of radioactive ions are expected. The usage of storage ring techniques provides high luminosity and low background experimental conditions. Results from the feasibility studies of the EXL detector setup, performed at the present ESR storage ring, are presented.

Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists

The cannabinoid CB(2) receptor is known to modulate osteoclast function by poorly understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O-methylhonokiol (MH) is a CB(2) receptor-selective antiosteoclastogenic lead structure (K(i) < 50 nM). Intriguingly, MH triggers a simultaneous G(i) inverse agonist response and a strong CB(2) receptor-dependent increase in intracellular calcium. The most active inverse agonists from a library of MH derivatives inhibited osteoclastogenesis in RANK ligand-stimulated RAW264.7 cells and primary human macrophages. Moreover, these ligands potently inhibited the osteoclastogenic action of endocannabinoids. Our data show that CB(2) receptor-mediated cAMP formation, but not intracellular calcium, is crucially involved in the regulation of osteoclastogenesis, primarily by inhibiting macrophage chemotaxis and TNF-α expression. MH is an easily accessible CB(2) receptor-selective scaffold that exhibits a novel type of functional heterogeneity.

Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function

BACKGROUND: Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR. METHODS: The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant. CONCLUSIONS: There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

OBJECTIVES: We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. BACKGROUND: We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. METHODS: Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 +/- 1 years, n = 20) and older (61 +/- 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR(+)/CD34(+) and KDR(+)/CD133(+)) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. RESULTS: We observed thicker IMT in older as compared to younger subjects (0.68 +/- 0.03 mm Vs. 0.48 +/- 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = -0.466 P < 0.05; r = -0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R (2 )= 0.58). CONCLUSION: Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.