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Pregnancy prediction models and eSET criteria for IVF patients--do we need more information?

PURPOSE: The purpose of the present study was to evaluate statistical prediction models and simple allocation criteria, based on predictors for pregnancy, as tools to identify a good prognosis group in a possible eSET setting. METHODS: A pregnancy prediction model based on logistic regression models was generated by analysis of 1675 DET treatment cycles. The model was evaluated and compared to simple eSET allocation criteria. RESULTS: Embryo quality, patient age, and basal FSH were identified as significant predictors (at 5% significance level) of pregnancy. Although comparable to previously generated models, the predictive ability of the present model was relatively poor and practically similar to simple allocation criteria based on age and embryo quality. CONCLUSIONS: Existing prediction models, or simple allocation criteria, are limited in identifying good prognosis patients. Future studies of the applicability of improved pregnancy prediction models will need very comprehensive and detailed patient and embryo information.

Adult↗

[Neuronal septal activity during hippocampal seizure discharges generation in acute model of epilepsy].

The activity of the neurones of the medial septal region (MS) and the hippocampal EEG in control and during the appearance of seizure discharges provoked by electrical stimulation of the perforant path were investigated in the awake rabbit. During afterdischarge generation in the hippocampus the dense neuronal bursts separated by periods of inhibition were recorded in the MS. In one group of neurons the bursts of spikes coincided with the discharges in the hippocampus, in other group-occured during inhibitory periods. When the afterdischarge stopped, in the septal neurons with theta activity the disruption of theta pattern was recorded, which have been correlated with the occurrence of low amplitude high frequency (20-25 Hz) waves in the hippocampal EEG. As a rule, the neuronal activivity of the MS recovered much quickly than EEG of the hippocampus; in some cases the increasing of the theta regularity was observed. The definite accordance of the electrical activity of the hippocampus and MS during seizure discharges suggests that the septohippocampal system operate as integral nervous circuit in these conditions. Diverse in the temporal interrelations between the discharges of MS neurones and ictal discharges in the hippocampus in the different cells possible indicate that various groups of the septal nervous elements have different participation in the seizure development. Appearance of the high frequency bursts in the MS is a possible "precursor" of the seizure onsets.

Acute Disease↗

A simple model of force generation by skeletal muscle during dynamic isometric contractions.

The force that an isometric skeletal muscle will produce in response to time-varying stimulation ("dynamic isometric" force) is important both for understanding muscle function and for designing neuroprostheses. This paper reports a model for predicting the force produced by an isometric skeletal muscle at rest length in response to a wide range of stimulation patterns. The model consists of two linear, first-order systems separated by a static nonlinearity. The rate constant of the second first-order system varies with force level. The model was validated using three cat soleus and three cat plantaris muscles. The following whole-nerve stimulation trains were used: single pulses (twitches), 2-4 pulses, constant rates, triangularly modulated interpulse intervals, and randomly modulated interpulse intervals. The model reproduced most responses accurately. The model shows that a force-dependent rate constant is essential for model validity, and could be used in the control of neuroprostheses.

Analog-Digital Conversion↗

A model of O2.-generation in the complex III of the electron transport chain.

Oxidation of semiquinone by O2 in the Q cycle is known to be one of the sources of superoxide anion (O2.-) in aerobic cells. In this paper, such a phenomenon was analyzed using the chemical kinetics model of electron transfer from succinate to cytochrome c, including coenzyme Q, the complex III non-heme iron protein FeSIII and cytochromes bl, bh and cl. Electron transfers from QH2 to FeSIII and cytochrome bl were assumed to occur according to direct transfer mechanism (dynamic channelling) involving the formation of FeS(red)III-Q.- and Q.--cytochrome bl complexes. For oxidation/reduction reactions involving cytochromes bh and bl, the dependence of the equilibrium and elementary rate constants on the membrane potential (deltapsi) was taken into consideration. The rate of O2.- generation was found to increase dramatically with increase in deltapsi above the values found in State 3. On the other hand, the rate of cytochrome c reduction decreased sharply at the same values of the membrane potential. This explains experimental data that the O2.- generation at State 4 appears to be very much faster than at State 3. A mild uncoupling in State 4 can markedly decrease the superoxide generation due to a decrease in deltapsi below the above mentioned critical level. DeltapH appears to be equally effective as deltapsi in stimulation of superoxide production which depends, in fact, upon the deltamuH+ level.

Benzoquinones↗

Simulation modeling of nuclear steam generator water level process--a case study

Simulation modeling of the nuclear steam generator (SG) water level process in Qinshan Nuclear Power Plant (QNPP) is described in this paper. A practical methodology was adopted so that the model is both simple and accurate for control engineering implementation. The structure of the model is in the form of a transfer function, which was determined based on first-principles analysis and expert experience. The parameters of the model were obtained by taking advantage of the recorded historical response curves under the existing closed-loop control system. The results of process dimensional data verification and experimental tests demonstrate that the simulation model depicts the main dynamic characteristics of the SG water level process and is in accordance with the field recorded response curves. The model has been successfully applied to the design and test of an advanced digital feedwater control system in QNPP.

Journal Article↗

Understanding the role of dietary components on atherosclerosis using genetic engineered mouse models.

The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoking potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.

Alcohol Drinking↗

Phase response characteristics of model neurons determine which patterns are expressed in a ring circuit model of gait generation.

In order to assess the relative contributions to pattern-generation of the intrinsic properties of individual neurons and of their connectivity, we examined a ring circuit composed of four complex physiologically based oscillators. This circuit produced patterns that correspond to several quadrupedal gaits, including the walk, the bound, and the gallop. An analysis using the phase response curve (PRC) of an uncoupled oscillator accurately predicted all modes exhibited by this circuit and their phasic relationships--with the caveat that in certain parameter ranges, bistability in the individual oscillators added nongait patterns that were not amenable to PRC analysis, but further enriched the pattern-generating repertoire of the circuit. The key insights in the PRC analysis were that in a gait pattern, since all oscillators are entrained at the same frequency, the phase advance or delay caused by the action of each oscillator on its postsynaptic oscillator must be the same, and the sum of the normalized phase differences around the ring must equal to an integer. As suggested by several previous studies, our analysis showed that the capacity to exhibit a large number of patterns is inherent in the ring circuit configuration. In addition, our analysis revealed that the shape of the PRC for the individual oscillators determines which of the theoretically possible modes can be generated using these oscillators as circuit elements. PRCs that have a complex shape enable a circuit to produce a wider variety of patterns, and since complex neurons tend to have complex PRCs, enriching the repertoire of patterns exhibited by a circuit may be the function of some intrinsic neuronal complexity. Our analysis showed that gait transitions, or more generally, pattern transitions, in a ring circuit do not require rewiring the circuit or any changes in the strength of the connections. Instead, transitions can be achieved by using a control parameter, such as stimulus intensity, to sculpt the PRC so that it has the appropriate shape for the desired pattern(s). A transition can then be achieved simply by changing the value of the control parameter so that the first pattern either ceases to exist or loses stability, while a second pattern either comes into existence or gains stability. Our analysis illustrates the predictive value of PRCs in circuit analysis and can be extended to provide a design method for pattern-generating circuits.

Animals↗

A model for the generation of multiple A to G transitions in the human respiratory syncytial virus genome: predicted RNA secondary structures as substrates for adenosine deaminases that act on RNA.

Human respiratory syncytial virus (HRSV) escape mutants selected with antibodies specific for the attachment (G) protein contain diverse genetic alterations, including point mutations, premature stop codons, frame shift changes and A to G hypermutations. The latter changes have only been found in mutants selected with antibodies directed against the conserved central region of the G protein. This gene segment fulfils substrate requirements for adenosine deaminases that act on RNA (ADARs): i.e. it is an A+U rich region of 137 residues, and 98 or 106 of them--for A/Mon/3/88 or Long HRSV strains, respectively--are predicted to form intramolecular base pairs leading to a stable RNA secondary structure. In addition, when sequences of the G gene from natural isolates are compared in terms of pairwise substitutions, A to G+G to A changes are preferentially observed in regions where stable intramolecular dsRNA secondary structures are predicted to occur. In this study, a model is proposed in which, in addition to nucleotide misincorporations, reiterative A to G changes in HRSV are generated by ADAR activity operating in short segments (100-200 ribonucleotide residues) of the HRSV genome with high tendency for intramolecular base pairing.

Adenine↗

Axon formation: a molecular model for the generation of neuronal polarity.

Neurons have unique structural and functional polarity. In general, information flows from the short dendrites to the long axon, and each neuron has multiple dendrites but only one axon. A detailed description of the cellular events leading to the establishment of axonal-dendritic polarity has been given from an in vitro hippocampal culture model system. Little is known, however, about the nature of the underlying molecular events. New data strongly suggest that actin depolymerization at a growth cone is crucial for axon fate determination. We hypothesize that an autocatalytic positive feedback loop at all growth cones locally regulates actin dynamics and other cellular events required for axon formation. Meanwhile, a negative feedback signal, produced by the positive feedback loop, propagates from all growth cones throughout the neuron and counteracts the positive feedback loops. Such feedback regulation provides a robust mechanism for spontaneous symmetry breaking and the formation of only one axon, even in a symmetric in vitro environment. Based on data from studies of cell migration, axon guidance, vesicle exocytosis, and the regulation of actin and microtubule polymerization, we propose a molecular scheme for the positive feedback loop and discuss possible negative feedback signals. BioEssays 22:172-179, 2000.

Actins↗

Metastatic and nonmetastatic models of retinoblastoma.

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor evolution similar to that seen in human invasive and metastatic disease. Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreal cavity. Tumors progressively invaded the retina, subretinal space, choroid, optic nerve head, and anterior chamber of the eye. Tumors progressed into the subarachnoid space and focally invaded the brain. Metastases were detected in the contralateral optic nerve. Large tumors developed extraocular extensions. The histology of the tumors showed a poorly differentiated pattern with high mitotic rate, foci of necrosis, and calcification. The WERI-Rb model more closely resembled nonmetastatic human retinoblastoma. WERI- Rb tumors were localized in the eye with only anterior choroidal invasion at late stages. To examine potential biological differences in vitro, the retinoblastoma cell lines were cocultured with adherent choroid cells or adherent glioma cells which represent the targets of invasive retinoblastoma in vivo. Consistent with the in vivo observations, Y79 cells but not WERI-Rb cells adhere specifically to both the choroidal and the glioma cell lines.

Animals↗