Evaluation of myocardial properties from image/pressure data: chronic conditions

Since the wall/cavity ratio of a heart chamber is not a biological constant, fractional cavity-surface motion is not a valid performance index and the stresses most commonly used in the myocardial-mechanics literature are not valid expressions of pulling action or contractility. We have developed a system for analyzing and expressing left-ventricular performance and abilities which avoids these problems. It allows one to estimate the following quantities from left-ventricular image data and arterial pressures: "Fractional midwall excursion", the fractional change in a weighted average of inner- and outer-surface dimensions, which is a valid but preload-dependent expression of performance regardless of wall/cavity ratio. "Fractional midwall excursion rate", fractional midwall excursion divided by EKG-normalized ejection time, which is a relatively preload-independent expression of performance regardless of wall/cavity ratio. "Pressure safety factor", systolic pressure-making ability relative to demanded systolic pressure. "Myocardial fiberstress", the intensity of circumferential pulling force in the wall (pulling force per unit cross-sectional area). "Myocardial growth ability", the anabolic responsiveness to habitual systolic fiberstresses, expressed as the reciprocal of long-term-average systolic fiberstresses. (6) "Contractility", the stress-developing ability of the myocardium, specifically the amplitude of the developed stress-stretch function at peak activation. On the average, these quantities are related as follows: Growth ability determines average systolic fiberstresses; contractility and growth ability (or systolic stress) largely determine safety factor; safety factor largely determines fractional midwall excursion and its rate. We have developed a microcomputer program which evaluates these quantities from image/pressure data and displays them digitally and graphically.     

Mathematical model of cardiac mechanogram rhythmicity (based on mollusc heart)

1. The time course of force development by the heart is modelled by Gompertz kinetics from the product of two terms: a cumulative increase in relative number of activated "contractile units", and an exponential decrease in contractile force. 2. For each beat, an "initial condition" is specified by an "intrinsic tension" parameter, and a specific rate of change of tension; cardioactive agents change these specifications. 3. Depending on parameter values, heartbeats are predicted that are constant, or in which the frequency, amplitude and baseline tension are appropriate to inhibited or augmented cardiac activity.     

Coherence, species turnover, and boundary clumping: elements of meta-community structure

Ecologists have identified several kinds of pattern in the distribution of species among sites, including a) nested subsets, b) checkerboards, c) Clementsian gradients, d) Gleasonian gradients, and e) evenly spaced gradients. Most past efforts to diagnose such patterns have focused on only one at a time, often contrasted with a sixth type of pattern, f) "randomness". While there are statistical tests to distinguish each of the first five patterns from randomness, there are currently no established methods for discriminating among these first five patterns in a given data set. Here we propose a method that will identify which of these possibilities is most prevalent in a site-by-species incidence matrix based on three basic aspects of meta-community structure. Our method is based on first ordinating the incidence matrix to identify the dominant axis of variation and identifying three aspects variation along this dominant axis. The first aspect, "coherence", is the degree to which pattern can be collapsed into a single dimension. The second, "species turnover", describes the number of species replacements along this dimension. The third aspect, "boundary clumping", has to do with how the edges of species boundaries are distributed along this dimension. We present methods for analyzing these three aspects of meta-community structure, use them to identify the six different patterns, and illustrate them with a representative set of cases drawn from previously published data.     

Ciliary beating in three dimensions: Steps of a quantitative description

We document a novel approach for quantitative assessment of ciliary activity, exemplified in rapid three-dimensional cyclic motion of the frontal cirri of Stylonychia. Cells held under voltage-clamp control are stimulated by step pulses to elicit reproducible hyperpolarization- or depolarization-induced ciliary motor responses. High-speed video recording at 200 fields per second is used for imaging ciliary organelles of the same cell in two perspectives: the axial view and, following cell rotation by 90 degrees, the lateral view. From video sequences of typically 1 s, the contours of the cirral images are determined and digitized. Computer programs are established to (1) reduce an observed image to a "ciliary axis", (2) sort series of axes by template to generate an averaged ciliary cycle in 2D-projection, and (3) to associate the generalized axial and lateral 2D-images for generation of a sequence of three-dimensional images, which quantitatively represent the cycle in space and time. The method allows us to produce predetermined perspectives of images selected from the ciliary cycle, and to generate stereo views for graphical representation of ciliary motion. The approach includes a potential for extraction of the complete microtubular sliding program of a cilium under reproducible electric stimulation of the ciliary membrane.     

生态设计家具的碳足迹核算与减排效果分析——以木质家具为例

我国的木质家具不仅产量大,而且碳排放强度也相对较高,利用生态设计理念可以降低木质家具的碳足迹。为了定量化生态设计所带来的减排效果,按照减少资源消耗和环境污染、节省住宅空间等木质家具生态设计原则,通过在一款多功能家具的框架内安装不同面板,形成了4种不同材质和结构的设计方案,利用生命周期分析方法核算了4种方案的碳足迹,并进一步量化了改进方案的减排效果。结果表明:4种家具设计的碳足迹从小到大为三聚氰胺板家具、木皮板家具、拼板家具、嵌条板家具,其中,实木类家具原材料碳排放较低,人造板类家具加工过程电力碳排放较低(主要来源于喷涂工段,占电力排放的83%—92%);通过各种减排方案的减排效果分析,发现采用"可拆卸无胶连接方式"改进方案减排效果显为明显;同时发现,合理的"低碳设计"(采用以实木板为基板,以三聚氰胺纸为贴面制作面板),可以避免中纤板喷涂过程的碳排放,从而减少产品整体碳足迹。     

A possible mechanism of participation of neuronal loops cortex - basal ganglia - thalamus - cortex in time perception

A mechanism of time perception is suggested. It is based on a postulate that time when stimulus arrives (parameter "when") is such property of stimulus as its physical properties (parameters "what"), and association "what - when" is perceived in those area of neocortex in which property "what" is processed after its repeated excitation. The time of repeated excitation which determines clock rate of "intrinsic clock", depends on dopamine influence at functioning of the cortico - basal ganglia - thalamocortical loop that promotes contrasted amplification of activity of cortical neurones, firstly activated by stimulus. Accumulation of time counts is performed in the neocortex and coded by the number of neuronal discharges. Duration of current interval is proportional to the number and duration of cycles of repeated neocortical excitation. Time counting can be started involuntary by stimulus, or voluntary due to activation of prefrontal cortex. The mechanism of time perception is similar for stimuli of different modalities owing to resemblance of functioning of topically organised cortico - basal ganglia - thalamocortical loops, it follows from our model that the more (less) concentration of dopamine in the striatumm the higher (low) clock rate, so the real interval will be estimated more (less) precisely and perceived as longer (short). These consequences of the model are in accordance with known experimental data.     

Role of “the frame cycle time” in portal dose imaging using an aS500-II EPID

IntroductionThis paper evaluates the role of an acquisition parameter, the frame cycle time “FCT”, in the performance of an aS500-II EPID.Materials and methodsThe work presented rests on the study of the Varian EPID aS500-II and the image acquisition system 3 (IAS3). We are interested in integrated acquisition using asynchronous mode. For better understanding the image acquisition operation, we investigated the influence of the “frame cycle time” on the speed of acquisition, the pixel value of the averaged gray-scale frame and the noise, using 6 and 15 MV X-ray beams and dose rates of 1–6 Gy/min on 2100 C/D Linacs.ResultsIn the integrated mode not synchronized to beam pulses, only one parameter the frame cycle time “FCT” influences the pixel value. The pixel value of the averaged gray-scale frame is proportional to this parameter. When the FCT <55 ms (speed of acquisition V_f/s > 18 frames/s), the speed of acquisition becomes unstable and leads to a fluctuation of the portal dose response. A timing instability and saturation are detected when the dose per frame exceeds 1.53 MU/frame. Rules were deduced to avoid saturation and to optimize this dosimetric mode.ConclusionThe choice of the acquisition parameter is essential for the accurate portal dose imaging.     

A model of orientational ordering in phosphatidylcholine bilayers based on conformational analysis of the glycerol backbone region.

Molecular and conformational ordering in aqueous multilamellar suspensions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) have been examined by deuterium nuclear magnetic resonance (2H NMR) in the liquid crystalline (L alpha) phase. Motionally averaged quadrupolar splittings vQ from six sites in the vicinity of the glycerol backbone have been analyzed by a molecular frame and order matrix approach in which the usual assumption of a freely-rotating molecule is not invoked. By assuming a relatively rigid glycerol backbone region, the six vQ values are found to be consistent with a conformation of the glycerol backbone that is almost identical to that of one of the two structures in crystalline DMPC dihydrate (Pearson, R. H., and I. Pascher, 1979, Nature (Lond.) 281: 499-501). The orientation of the most-ordered axis of the DMPC molecule is found to be tilted at an angle of 27 +/- 2 degrees with respect to the long axis of the sn-1 chain in its extended all trans conformation. The ordering of the most ordered molecular axis with respect to the bilayer normal is expressed by an order parameter of Szz approximately equal to 0.6 +/- 0.1, consistent with values in analogous thermotropic liquid crystals.     

Regulation of neurosecretory activity in the freshwater pulmonate Lymnaea stagnalis (L.) with particular reference to the role of the eyes

The process of neurosecretion in the Caudo-Dorsal Cells (CDC) of the freshwater snail Lymnaea stagnalis, which produce an ovulation hormone, shows a diurnal rhythmicity. Synthesis, transport and release of the neurosecretory material (NSM) is high during the evening and the early night and low during the rest of the day, while storage of NSM mainly occurs during the daytime. In the present study the role of the eyes in the regulation of the CDC-rhythm was investigated. During a 24-hr period, at time intervals of 6 hrs, cerebral ganglia, which contain CDC, of blinded and control snails (5 per group) were fixed and the CDC were studied with quantitative electron microscopical methods. The CDC of the controls showed a distinct diurnal thythmicity. Blinding, on the other hand, clearly affected this rhythmicity. The results indicate that after blinding the circadian CDC-rhythms of individual snails are no longer synchronous with each other ("interanimal desynchronization"). It is suggested that the rhythm of CDC neurosecretory activity is synchronized by the natural light/dark cycle via the eyes. The information from the eyes probably reaches the CDC via a nervous pathway. True snyapses and three types of synapse-like structures were found on the CDC. Their role in the regulation of CDC-activity is discussed. The effect of blinding is specific for the CDC; blinding does not influence the diurnal rhythmicity of another type of cerebral neurosecretory cells, the Light Green Cells (LGC). The CDC within a cluster act synchronously. This synchrony does not depend upon the presence of the eyes. Some structures which may be involved in establishing this synchrony, such as subsurface cisterns, desmosome-like structures and "specific release sites", are described.     

The distribution of monoamines in the tel-, di-and mesencephalon of Xenopus laevis tadpoles,with special reference to the hypothalamo-hypophysial system

Summary In an attempt to further our knowledge about the structure and function of the recently identified intrapulmonary Neuro-epithelial Bodies (NEB's) (Lauweryns et al., 1972a, 1972b), lungs of 84 neonatal rabbits and 6 neonatal mice were studied along four different lines of investigation. Several routine and silver staining methods, Falck's fluorescent amine technic and histochemical and electron microscopical techniques were performed.1. In order to test the probable chemoreceptor function of the NEB's, animals were exposed to hypoxia. Under such circumstances, the corpuscular cells of the NEB's secrete their dense-cored, serotonin-containing vesicles at their basal vascular pole. 2. After reserpine pretreatment, the NEB's of otherwise normal animals reveal a distinct amine depletion, the corpuscular cells exhibiting a decreased yellow fluorescence and ultrastructurally a clearing up of their dense-cored vesicles. 3. Studied on serial sections with the electron microscope, various types of morphologically afferent-like and efferent-like nerve endings, making contact as well with the corpuscular cells as amongst themselves have been detailed. 4. Cytochemically the corpuscular cells react positively with alpha-glycerophosphate dehydrogenase, acetylcholinesterase and Solcia's lead hematoxylin stain for endocrine cells producing polypeptides and amines.It is proposed that the NEB's provide an intrapulmonary, hypoxia-sensitive neuro(chemo-) receptor system in addition to the well established central and peripheral (e.g. carotid body) chemoreceptors. They contain and secrete serotonin and probably also related amines or peptides, which could influence the pulmonary vasoconstrictor response. According to classic morphologic criteria, they possess a dual innervation, both afferent and efferent.Various other possible functions of the NEB's in normal and diseased lungs are briefly proposed.This study has been supported by a grant from The Council for Tobacco Research — U.S.A. and the Nationaal Fonds voor Wetenschappelijk Onderzoek — Belgium. We thank P. Theunynck for performing some of the histochemical studies, B. Van Rijkel, B. Emanuel and R. Renwart for technical, G. Pison and St. Ons for photographical and N. Tyberghien for secretarial assistance.     

Using the Guttman scale to define and estimate measurement error in items over time: the case of cognitive decline and the meaning of "points lost"

We used a Guttman model to represent responses to test items over time as an approximation of what is often referred to as "points lost" in studies of cognitive decline or interventions. To capture this meaning of "point loss", over four successive assessments, we assumed that once an item is incorrect, it cannot be correct at a later visit. If the loss of a point represents actual decline, then failure of an item to fit the Guttman model over time can be considered measurement error. This representation and definition of measurement error also permits testing the hypotheses that measurement error is constant for items in a test, and that error is independent of "true score", which are two key consequences of the definition of "measurement error"--and thereby, reliability--under Classical Test Theory. We tested the hypotheses by fitting our model to, and comparing our results from, four consecutive annual evaluations in three groups of elderly persons: a) cognitively normal (NC, N?=?149); b) diagnosed with possible or probable AD (N?=?78); and c) cognitively normal initially and a later diagnosis of AD (converters, N?=?133). Of 16 items that converged, error-free measurement of "cognitive loss" was observed for 10 items in NC, eight in converters, and two in AD. We found that measurement error, as we defined it, was inconsistent over time and across cognitive functioning levels, violating the theory underlying reliability and other psychometric characteristics, and key regression assumptions.     

Cerebellar cortex: simulation of recurrent collateral inhibition with the aid of a set of neuronal automata. I. Model and global results

In view of a study on the transfer function of the cerebellar cortex a modelization of each of the various subsystems was undertaken. The recurrent collateral inhibition existing between Purkinje cells was mimicked by means of an assembly of neuronal automata (NA) temporally evolving at random through three states ("silent", "tonic" and "phasic" and interacting with simple rules. In such an assembly--by comparison with a control group of independent NA--a drastic modulation of activity appears. First the total of the mean number of state shifts is increased by more than 10%. This increase is clearly hierarchical with a maximal effect for the "silent" state. Second the average duration of each state also varies, although in a contrasted manner. Third, and moreover, a clear spatial cooperativity emerges. Indeed all the individually coupled NA are in the same "silent" state at identical moments for more than 5.5% of the total running time. A cyclic repetition of this spatiotemporal cooperativity is apparent. The emergence of these collective properties--which can not be deduced linearly from the unitary elements--introduces a parameter of order leading to a coherent functioning of the system.     

Rotational diffusion of calcium-dependent adenosine-5'-triphosphatase in sarcoplasmic reticulum: a detailed study

The Ca2+-Mg2+ adenosine-5'-triphosphatase (ATPase) in sarcoplasmic reticulum has been covalently labeled with the phosphorescent triplet probe erythrosinyl 5-isothiocyanate. The rotational diffusion of the protein in the membrane at 25 degrees C was examined by measuring the time dependence of the phosphorescence emission anisotropy. Detailed analysis of both the total emission S(t) = Iv(t) + 2IH(t) and anisotropy R(t) = [Iv(t) - IH(t)]/[Iv(t) + 2IH(t)] curves shows the presence of multiple components. The latter is incompatible with a simple model of protein movement. The experimental data are consistent with a model in which the sum of four exponential components defines the phosphorescence decay. The anisotropy decay corresponds to a model in which the phosphor itself or a small phosphor-bearing segment reorients on a sub-microsecond time scale about an axis attached to a larger segment, which in turn reorients on a time scale of a few microseconds about an axis fixed in the frame of the ATPase. A fraction of the protein molecules rotate on a time scale of 100-200 microseconds about the normal to the bilayer, while the rest are rotationally stationary, at least on a sub-millisecond time scale.     

Cellular signaling: aspects for tumor diagnosis and therapy.

Cells are organic microsystems with functional compartments interconnected by complex signal chains. Intracellular signaling routes and signal reception from the extracellular environment are characterized by redundancy, i.e., parallel pathways exist. If a cell is exposed to an external "signal input", the signal processing elements within the cell provide a response that will be a pattern of reactions manifest as a metabolic, morphologic or electric "signal output". Cell-chip hybrid structures are miniaturized analytical systems with the capability to monitor such cell responses in real time and under continuous control of the environmental conditions. A system analysis approach gives an idea of how the biological component of these hybrid structures works. This is exemplified by the putative role of the microenvironmental pH as a parameter of the utmost importance for the malignant "mode" of tumor cells, which can be monitored and modeled on such hybrid structures.     

The ontogeny and maintenance of adult symmetry properties in the ctenophore, Mnemiopsis mccradyi

Ctenophores are biradially symmetrical animals. The body is composed of four identical quadrants which are organized along an oral-aboral axis. Most species have eight comb rows, two tentacles, and an apical organ (located on the aboral surface). During embryogenesis there is a fixed pattern of cleavage, a precocious specification of blastomere developmental potential, and an inability to regulate for portions of the embryo that have been removed. When blastomeres are separated at the two-cell stage each blastomere develops into a "half-animal" with four comb rows, one tentacle, and half an apical organ. In contrast, adult ctenophores regenerate readily. When an adult ctenophore is cut in half to produce "half-animals," in most cases each half regenerates the missing half. In some cases, however, bisected animals remain as "half-animals" which repair the wound site but do not replace all of the missing structures. When animals are cut in half along the tentacular or esophageal axis at different stages of embryogenesis a transition period is detected when the capacity for adult regeneration begins. This transition occurs at the time when the formation of the apical organ is complete and comb row function becomes coordinated. Embryos bisected prior to this time remain as "half-animals" even after growing to large reproductive sizes, while animals bisected after the transition period usually regenerate the missing structures within 2-3 days. When adult "half-animals" (produced by bisection either before or after the transition period) are cut into "quarter-pieces," the pieces regenerate to form either "half-animals" or whole animals. Thus, "half-animals" produced prior to the transition period--although they failed to undergo embryonic regulation--have not irreversibly lost the capacity to form whole animals if challenged to regenerate during adult stages. When aboral blastomeres destined to form the apical organ, tentacles, and comb rows are removed from early cleavage stages (prior to the transition period), the embryo does not form these structures at the appropriate time. However, the resulting deficient adults spontaneously form these structures from remaining blastomere lineages soon after hatching. These experiments suggest that as long as some quadrant-specific cells of the oral pole are present at the time of the transition period, the structures of that quadrant will be spontaneously replaced during the adult period.(ABSTRACT TRUNCATED AT 400 WORDS)     

A heuristic solution of the identifiability problem of the age-period-cohort analysis of cancer occurrence: lung cancer example

Background

The Age–Period–Cohort (APC) analysis is aimed at estimating the following effects on disease incidence: (i) the age of the subject at the time of disease diagnosis; (ii) the time period, when the disease occurred; and (iii) the date of birth of the subject. These effects can help in evaluating the biological events leading to the disease, in estimating the influence of distinct risk factors on disease occurrence, and in the development of new strategies for disease prevention and treatment.

Methodology/Principal Findings

We developed a novel approach for estimating the APC effects on disease incidence rates in the frame of the Log-Linear Age-Period-Cohort (LLAPC) model. Since the APC effects are linearly interdependent and cannot be uniquely estimated, solving this identifiability problem requires setting four redundant parameters within a set of unknown parameters. By setting three parameters (one of the time-period and the birth-cohort effects and the corresponding age effect) to zero, we reduced this problem to the problem of determining one redundant parameter and, used as such, the effect of the time-period adjacent to the anchored time period. By varying this identification parameter, a family of estimates of the APC effects can be obtained. Using a heuristic assumption that the differences between the adjacent birth-cohort effects are small, we developed a numerical method for determining the optimal value of the identification parameter, by which a unique set of all APC effects is determined and the identifiability problem is solved.

Conclusions/Significance

We tested this approach while estimating the APC effects on lung cancer occurrence in white men and women using the SEER data, collected during 1975–2004. We showed that the LLAPC models with the corresponding unique sets of the APC effects estimated by the proposed approach fit very well with the observational data.     

In vitro effects of GSM modulated radiofrequency fields on human immune cells

Despite the important role of the immune system in defending the body against infections and cancer, only few investigations on possible effects of radiofrequency (RF) radiation on function of human immune cells have been undertaken. Aim of the present investigation was therefore to assess whether GSM modulated RF fields have adverse effects on the functional competence of human immune cells. Within the frame of the multidisciplinary project "Biological effects of high frequency electromagnetic fields (EMF)" sponsored by the National Occupation Hazard Insurance Association (AUVA) in vitro investigations were carried out on human blood cells. Exposure was performed at GSM Basic 1950 MHz, an SAR of 1 mW/g in an intermittent mode (5 min "ON", 10 min "OFF") and a maximum Delta T of 0.06 degrees C for the duration of 8 h. The following immune parameters were evaluated: (1) the intracellular production of interleukin-2 (IL-2) and interferon (INF) gamma in lymphocytes, and IL-1 and tumor necrosis factor (TNF)-alpha in monocytes were evaluated with monoclonal antibodies. (2) The activity of immune-relevant genes (IL 1-alpha and beta, IL-2, IL-2-receptor, IL-4, macrophage colony stimulating factor (MCSF)-receptor, TNF-alpha, TNF-alpha-receptor) and housekeeping genes was analyzed with real time PCR. (3) The cytotoxicity of lymphokine activated killer cells (LAK cells) against a tumor cell line was determined in a flow cytometric test. For each parameter, blood samples of at least 15 donors were evaluated. No statistically significant effects of exposure were found and there is no indication that emissions from mobile phones are associated with adverse effects on the human immune system.     

Robustness of post-reconstruction and direct kinetic parameter estimates under rigid head motion in dynamic brain PET imaging

ObjectiveDynamic PET imaging is extensively used in brain imaging to estimate parametric maps. Inter-frame motion can substantially disrupt the voxel-wise time-activity curves (TACs), leading to erroneous maps during kinetic modelling. Therefore, it is important to characterize the robustness of kinetic parameters under various motion and kinetic model related factors.MethodsFully 4D brain simulations ([¹⁵O]H₂O and [¹⁸F]FDG dynamic datasets) were performed using a variety of clinically observed motion patterns. Increasing levels of head motion were investigated as well as varying temporal frames of motion initiation. Kinetic parameter estimation was performed using both post-reconstruction kinetic analysis and direct 4D image reconstruction to assess bias from inter-frame emission blurring and emission/attenuation mismatch.ResultsKinetic parameter bias heavily depends on the time point of motion initiation. Motion initiated towards the end of the scan results in the most biased parameters. For the [¹⁸F]FDG data, k₄ is the more sensitive parameter to positional changes, while K₁ and blood volume were proven to be relatively robust to motion. Direct 4D image reconstruction appeared more sensitive to changes in TACs due to motion, with parameter bias spatially propagating and depending on the level of motion.ConclusionKinetic parameter bias highly depends upon the time frame at which motion occurred, with late frame motion-induced TAC discontinuities resulting in the least accurate parameters. This is of importance during prolonged data acquisition as is often the case in neuro-receptor imaging studies. In the absence of a motion correction, use of TOF information within 4D image reconstruction could limit the error propagation.     

Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules

In virtual microscopy, a sequential process of captures of microscopical fields, allows to construct a virtual slide which is visualized using a specialized software, called the virtual microscopy viewer. This tool allows useful exploration of images, composed of thousands of microscopical fields of view at different levels of magnification, emulating an actual microscopical examination. The aim of this study was to establish the main pathologist's navigation patterns when exploring virtual microscopy slides, using a graphical user interface, adapted to the pathologist's workflow. Four pathologists with a similar level of experience, graduated from the same pathology program, navigated six virtual slides. Different issues were evaluated, namely, the percentage of common visited image regions, the time spent at each and its coincidence level, that is to say, the region of interest location. In addition, navigation patterns were also assessed, i.e., mouse movement velocities and linearity of the diagnostic paths. Results suggest that regions of interest are determined by a complex combination of the visited area, the time spent at each visit and the coincidence level among pathologists. Additionally, linear trajectories and particular velocity patterns were found for the registered diagnostic paths.