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PubMed1999

A 0.5-million-year record of millennial-scale climate variability in the north atlantic

Long, continuous, marine sediment records from the subpolar North Atlantic document the glacial modulation of regional climate instability throughout the past 0.5 million years. Whenever ice sheet size surpasses a critical threshold indicated by the benthic oxygen isotope (delta18O) value of 3.5 per mil during each of the past five glaciation cycles, indicators of iceberg discharge and sea-surface temperature display dramatically larger amplitudes of millennial-scale variability than when ice sheets are small. Sea-surface temperature oscillations of 1 degrees to 2 degreesC increase in size to approximately 4 degrees to 6 degreesC, and catastrophic iceberg discharges begin alternating repeatedly with brief quiescent intervals. The glacial growth associated with this amplification threshold represents a relatively small departure from the modern ice sheet configuration and sea level. Instability characterizes nearly all observed climate states, with the exception of a limited range of baseline conditions that includes the current Holocene interglacial.

Journal Article↗
PubMed2002

Current perception threshold increases during pregnancy but does not change across menstrual cycle.

It is well known that pregnancy reduces anesthetic requirements in response to various noxious stimuli. However, there have been no detailed reports concerning functional changes in nerve fibers during pregnancy. Using a Neurometer, a recently available commercial quantitative sensory monitor, we measured current perception threshold (CPT) values for three frequencies corresponding to the stimulation of A-beta, A-delta and C fibers on the median nerve in women at several stages: late pregnancy, the follicular phase and the luteal phase. A significant difference in CPT values on A fibers was noted between the gravid and the nongravid women, but, no significant difference in CPT values was noted in any of the nongravid women in the follicular or luteal phases. Our results support the current theory that pregnancy changes nerve fiber conduction, as indicated by an increase in CPT values especially on myelinated fibers, but does not cause changes in CPT values across the menstrual cycle.

Adult↗
PubMed1984

Limit cycle oscillations of the human eye.

The altered feedback technique is very suited to display nonlinearities of the human smooth pursuit system. In fact, when the gain of the retinal feedback path is raised, for the horizontal channel, above its normal unitary negative value, a threshold is met beyond which sustained horizontal self-excited smooth oscillations of the eye can be observed, which point out the existence of a stable limit cycle. Furthermore, the characterizing features of both the transient and steady state show a well defined dependence on the total feedback factor K. In particular, the analytical dependence on K of the amplitude and frequency of limit cycle oscillations can be derived. Implications of the experiment with respect to the mathematical modelling of the system are discussed.

Eye Movements↗
PubMed2005

Preferred pedal rate: an index of cycling performance.

The purpose of this study was to determine whether preferred pedal rate (PPR) could be used as an index of cycling performance. Thirteen competitive cyclists cycled at PPR during a graded test and a supra-threshold constant power test (CPT). The results showed that PPR values reported in CPT were correlated to both peak power determined from the graded test and exhaustion time assessed in CPT. Furthermore, multiple regression revealed that PPR values and P (peak) were two predictors of exhaustion time in CPT. Hence, this study suggests that coaches and sports scientists have to take into account PPR values complementary to P (peak) in order to evaluate the capacity of cycling performance.

Adult↗
PubMed1998

Dynamics of the cell cycle engine: Cdk2-kinase and the transition into mitosis.

The autonomous cell divisions during the early development of Xenopus laevis believed to comprise a universal cell cycle engine. Recent experimental data indicates that the Cdk2-cyclin E kinase is required for the rapid divisions during Xenopus embryogenesis and that the complex is crucial for the transition into mitosis. In the present paper, the activity of Cdk2-cyclin E is incorporated into an existing comprehensive model of the cell cycle engine as an activity operating in parallel with the mitosis promotion factor (MPF) on the phosphatase Cdc25. This introduces interesting regulatory and dynamic properties for the transition into mitosis that reveals new insight into the mechanisms of the cell division process. It is shown that the Cdk2-cyclin E complex can act as an effective modulator of the threshold MPF activity needed to initiate mitosis. When the Cdk2-cyclin E activity is below a critical value, the cell cycle arrests in a well-defined state of low MPF activity corresponding to G2 arrest. In agreement with experiments a single mitotic event occurs following injection of free cyclin B. Above a critical activity, the presence of Cdk2-cyclin E allows for sustained oscillations corresponding to repeated cell divisions and the Cdk2-cyclin E may be the cause for the suppressed G2 checkpoint in the early embryonic cell cycles. A detailed bifurcation analysis reveals that the transition from steady to oscillatory behavior involves a homoclinic orbit of infinite period through an omega explosion. The general properties of the omega explosion explain the bifurcation as a dynamic mechanism well-suited for the G2 checkpoint and suggest a plausible explanation for the elongation of the cell cycle as observed at the mid-blastula transition. The proposed mechanism also suggests a plausible explanation of G2 checkpoint failure following DNA damage in human cells overexpressing Cdk2 and we suggest that the onset of mitosis in the mammalian cell occurs as the result of a slow passage through a critical point.

Animals↗
PubMed1981

Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise.

Analysis of plasma luteinizing hormone (LH) assays (4 assays per day) permits the discernment of the onset of the physiologic effects of ovulatory release. This threshold value of LH plasma concentration (LH surge-initiating rise, LH SIR) is determined for each cycle in terms of the average baseline level of the previous day. The chronology of follicle and oocyte maturation after LH SIR is similar to that which follows chorionic gonadotropin (hCG) administration: none of the 20 patients, compared with 2 out of 10, had ovulated when laparoscopy was performed 30 to 35 hours and 36 to 38 hours after LH SIR time, respectively; 1 out of 3, 9 out of 14, and 5 out of 5 patients had an in vitro fertilized egg when oocytes were collected 30 to 32, 33 to 35, and 36 to 38 hours after LH SIR time, respectively. Thus the oocyte can be collected 34 to 35 hours after the LH SIR; at this point ovulation has not occurred and the oocyte is capable of being fertilized.

Adult↗
PubMed2003

Laboratory experiments to predict changes in radiocaesium root uptake after flooding events.

Changes in soil solution composition after a flooding event were hypothesised to be one of the key factors in explaining changes in radiocaesium incorporation in the food chain in the areas affected by the Chernobyl accident. A laboratory methodology was set up to monitor changes in the soil solution composition after a sequence of flooding cycles. Experiments were performed using column and batch approaches on test soils with contrasting initial soil solution composition (high and low initial concentrations of K+). Results from column experiments indicated a potential increase in NH(4)(+) concentrations, a parameter which could lead to an increase in the radiocaesium root uptake. Batch results in the soil with high initial K+ concentration showed that after a number of flooding cycles, especially for high ratios of flooding solution/mass of soil, K+ concentration decreased sometimes below a threshold value (around 0.5-1 mmol l(-1)), a fact that could lead to an increase in radiocaesium transfer. For the soils with a low initial K+ concentration, the flooding solution increased K+ and NH(4)(+) values in the soil solution. The comparison of test soils with soils from Ukraine areas affected by flooding showed that the final stage in soil solution composition was similar in both cases, regardless of the initial composition of the soil solution. Moreover, the comparison with unflooded soils from the same area showed that potential changes in other soil parameters, such as (137)Cs activity concentration, clay content, and radiocaesium interception potential, RIP (a parameter that estimates the radiocaesium specific sorption capacity of a soil), should also be monitored for additional effects due to the flooding event. Therefore, the changes in the root uptake would depend on the resulting situation from changes in RIP, K+ and NH(4)(+) values in the soil solution.

Adsorption↗
PubMed2006

Quantify single nucleotide polymorphism (SNP) ratio in pooled DNA based on normalized fluorescence real-time PCR.

BACKGROUND: Conventional real-time PCR to quantify the allele ratio in pooled DNA mainly depends on PCR amplification efficiency determination and Ct value, which is defined as the PCR cycle number at which the fluorescence emission exceeds the fixed threshold. Because of the nature of exponential calculation, slight errors are multiplied and the variations of the results seem too large. We have developed a new PCR data point analysis strategy for allele ratio quantification based on normalized fluorescence ratio. RESULTS: In our method, initial reaction background fluorescence was determined based upon fitting of raw fluorescence data to four-parametric sigmoid function. After that, each fluorescence data point was first subtracted by respective background fluorescence and then each subtracted fluorescence data point was divided by the specific background fluorescence to get normalized fluorescence. By relating the normalized fluorescence ratio to the premixed known allele ratio of two alleles in standard samples, standard linear regression equation was generated, from which unknown specimens allele ratios were extrapolated using the measured normalized fluorescence ratio. In this article, we have compared the results of the proposed method with those of baseline subtracted fluorescence ratio method and conventional Ct method. CONCLUSION: Results demonstrated that the proposed method could improve the reliability, precision, and repeatability for quantifying allele ratios. At the same time, it has the potential of fully automatic allelic ratio quantification.

Alleles↗
PubMed1998

The use of a fixed value of RPE during a ramp protocol. Comparison with the ventilatory threshold.

BACKGROUND: The purpose of our investigation was to assess the use of a fixed value (12-13) of the Rating of Perceived Exertion (RPE) scale (6-20) as a valid method for the determination of the workload corresponding to the ventilatory threshold (VT) during a ramp protocol on a cycle ergometer. METHODS: Eleven trained cyclists (22 +/- 3 years of age; VO2max: 65.2 +/- 12.4 ml.kg-1.min-1) were selected as subjects. DESIGN: Each of the subjects performed a ramp protocol on a cycle ergometer (starting at 25 W, with increases of 25 W.min-1 until exhaustion). Gas exchange data were analysed continually during the test to detect the ventilatory threshold (VT) of the subjects. In addition values of RPE were obtained from each subject in the last 15 sec of each 2-minute-interval during the tests, and immediately after exhaustion. The RPE threshold (RPET) was defined as a constant value of 12-13. Mean values of VT and RPET were expressed as VO2 (ml.kg-1.min-1), %VO2max, heart rate (bpm) and power output (W), and were compared using a paired "t"-test. RESULTS: No significant difference (p < 0.05) was found between mean values of VT and RPET, when both parameters where expressed either as VO2, %VO2max, heart rate, or power output. CONCLUSIONS: In conclusion, a fixed value (12-13) of the RPE scale might be used to detect the exercise intensity corresponding to VT. Such parameter may therefore be used for exercise prescription in substitution to more sophisticated methodologies.

Adult↗
PubMed2001

Preferential arterial imaging using gated thick-slice gadolinium-enhanced phase-contrast acquisition in peripheral MRA.

PURPOSE: To investigate the feasibility of preferential arterial imaging using gadolinium-enhanced thick-slice phase-contrast imaging. METHODS: Six healthy volunteers were studied using a peripheral-gated segmented k-space CINE phase-contrast pulse sequence using four views per RR interval with flow encoding in the superior-inferior direction. Images at the level of the popiteal trifurcation were acquired postcontrast with different section thicknesses (4-8 cm) and VENC values (20-150 cm/sec), and phase-difference processing. RESULTS: The post-gadolinium contrast-enhanced thick-slice phase-contrast acquisitions demonstrated the ability to visualize the tibio-peroneal (trifurcation) arteries, especially in systole. With MR contrast agents, the signal from blood is raised significantly above that of stationary tissue from T(1) shortening such that the partial volume artifact is reduced in thick-slice acquisitions. Furthermore, by selecting the VENC value as a function of the cardiac cycle, the noise floor can be raised to selectively suppress flow values less than that of the noise threshold, allowing better accentuation of arterial structures at systole. CONCLUSIONS: Thick-slice phase-contrast acquisition with phase-difference processing has been observed to reduce partial volume artifacts when an MR contrast agent substantially increases signal in the vasculature over that of normal background tissue. Preferential arterial images can be obtained by either increasing the VENC value to selectively suppress signal from slow flow in the veins or by subtracting the diastolic phase image from the peak systolic phase image. J. Magn. Reson. Imaging 2001;13:714-721.

Adult↗
PubMed2006

Loss of parasympathetic innervation leads to sustained expression of pro-inflammatory genes in the rat lacrimal gland.

It has been shown that removal of parasympathetic innervation to the lacrimal gland (LG) leads to rapid reduction in tear flow. Additionally, removal of the neural input resulted in disorganization of LG structure and changes in the expression of genes associated with the secretory pathway and inflammation. The goal of this study was to investigate the change in pro-inflammatory and pro-apoptotic gene expression in the rat LG following parasympathetic denervation. Male Long-Evans rats underwent unilateral sectioning of the greater superficial petrosal nerve and were sacrificed 7 days or 2.5 months later. cDNA was synthesized from LG RNA from the contralateral control (Ctla) and parasympathectomized (Px) glands and comparative real-time PCR was performed. Mean threshold cycles (MC(T)) for the Ctla and Px LG genes were normalized to 18S rRNA MC(T) values, and the relative fold change was calculated for each gene using the 2(-DeltaDeltaC)(T) method. The expression of nuclear factor kappa B1, caspase 1, eotaxin, leukocyte antigen MRC-OX44, allograft inflammatory factor-1, MHC class II molecules RT.1B and RT.1D, IgG receptor FcRn, and macrophage metalloelastase was increased and remained elevated in the Px LG, compared with the Ctla LG. Increased expression of the initiator of apoptosis gene, caspase 2, was confirmed, but expression of the executor gene, caspase 6, was not elevated in the Px LG. Reduced expression of genes associated with post-translational protein processing-furin convertase, protein disulfide isomerase, and UDP-gal transporter isozyme 1-was noted in the Px LG. No significant changes in the expression of genes associated with lysosomal and non-lysosomal-mediated protein degradation were found. Removal of parasympathetic input may lead to decreased capacity for protein synthesis and elevated immune responses in the Px LG. These changes occur without increases in expression of the muscarinic acetylcholine receptor subtype 3, and may suggest the early changes in LG acinar cells and the pathophysiology of autoimmune responses.

Animals↗
PubMed2005

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression.

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.

Adult↗
PubMed1988

Termination of sustained ventricular tachycardia by ultrarapid subthreshold stimulation in humans.

Our purpose was to investigate the efficacy, safety, and electrophysiological mechanism of ultrarapid subthreshold electrical stimulation in terminating sustained ventricular tachycardia (VT) in humans. Fifteen patients with inducible sustained hemodynamically stable VT and whose VT cycle length ranged between 295 and 440 msec (337 +/- 60 msec) were included in this study. The stimulation threshold and ventricular myocardial effective refractory period were determined during VT, and the values ranged between 0.4 and 1.2 mA (mean, 0.7 +/- 0.3 mA) and between 185 and 245 msec (mean, 225 +/- 20 msec), respectively. Trains of ultrarapid subthreshold stimulation were delivered with cycle lengths of 100 to 10 msec in decremental steps of 10 msec. A 5-second pause was allowed between each step (decrement). A 2-msec pulse width was used in all patients, and a 4-msec pulse width was also tested in eight patients. Any apparent captured beat was disregarded. In eight (53%) patients, ultrarapid subthreshold stimulation terminated VT, and in the remaining seven (47%) patients, it did not. The lowest subthreshold stimulation that effectively terminated VT was 0.05 mA. In 10 patients, the site of early activity during VT was determined by endocardial catheter mapping, and subthreshold stimulation more effectively terminated VT in eight patients when it was applied close to the site of early activity. In seven patients who underwent mapping-guided arrhythmia surgery, subthreshold stimulation was applied close to the site of early activity and successfully terminated VT. In no patient did subthreshold stimulation produce acceleration of VT or induce ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

The effect of stage duration on the calculation of peak VO2 during cycle ergometry.

This study investigated the influence of stage duration on the calculation of peak oxygen consumption (peak VO2 to determine whether both the lactate threshold (LT) and peak VO2 could be measured during the same test without compromising the peak VO2 value obtained. Eight moderately-active females (mean age +/- SD = 19.6 +/- 2.5 years) performed three peak VO2 tests on an electrically-braked cycle ergometer. Power output was increased every minute for the short peak VO2 test (S) and every three minutes for the long peak VO2 tests (L). Testing took place over two weeks with all tests separated by at least 48 hours. The first peak VO2 test was a long test (L1) and served as familiarisation. The subjects then performed a short (S) and a long (L2) peak VO2 test in random, counterbalanced order. For each subject, all three tests were performed at the same time of day in controlled environmental conditions. There was no significant difference between the two exercise protocols for peak VO2 when expressed in ml x kg(-1) x min(-1) (F[1,7]=3.47, P=0.105) or in L x min(-1) (F[1,7]=3.39. P=0.108). However, the maximum heart rate (HRmax) achieved in S was significantly less than the HRmax achieved in L2 (F[1,7]=33.4, P<0.001). The power output at exhaustion (Wpeak) was significantly greater in S than in L2 (F[1,7]=56.5, P<0.001). The data from this study therefore showed that in moderately-active females, a three-minute incremental protocol, allowing for the simultaneous calculation of the LT, could be used without compromising peak VO2, but that HRmax and Wpeak were affected.

Adolescent↗
PubMed1987

Prolongation of cell cycle transit time and the presence of non-cycling cells in human lymphoblastoid cells cultured under adverse conditions.

The growth characteristics of B lymphocytes infected with Epstein-Barr virus (lymphoblastoid cells) have been investigated by flow cytometric analysis of DNA content and by estimation of cell culture doubling times. It was found that the manipulative procedures involved in the cell cycle analysis resulted in a slowing of the growth rate. This slowing of growth was brought about by the prolongation of cell cycle transit times and by the entry of cells into a short-lived non-cycling pool. The entry of a proportion of the cells into the non-cycling pool may be the normal response of lymphoblastoid cells to non-optimal conditions. The non-cycling cells survived in culture with a T 1/2 of approximately 30-60 hr and continued to secrete immunoglobulin. Their surface transferrin receptors were considerably reduced, which suggests that the failure to divide may have resulted from a failure of growth factor receptors to reach a threshold value following mitosis.

B-Lymphocytes↗
PubMedDate not supplied

Alternative designs for a genetic switch: analysis of switching times using the piecewise power-law representation.

Some genes are thought to be switched discontinuously ON or OFF in response to environmental or developmental stimuli, whereas other genes are thought to be switched in a continuously variable fashion. We have previously identified criteria that distinguish between discontinuous and continuous genetic switches for an inducible catabolic pathway. These two types of switches exhibit several additional characteristics, beyond their qualitatively distinct behaviors, that influence their natural selection. These characteristics include threshold value, magnitude of the input signal required for switching ('switching effort'), magnitude of the corresponding output signal, duty cycle, switching time, and robustness. In order to characterize the biological design principles governing such switches, we have developed mathematical models of generic gene circuits and analyzed their behavior. Here we report the results of a comparative study designed to identify essential differences in switching time. This study has been greatly facilitated by use of the piecewise power-law representation, which was first developed by systems engineers in the 1940s and adapted for biochemical systems in the early 1970s. With this approach, we have been able to derive analytical expressions for switching time. When the alternative designs are made as nearly equivalent as possible, by the method of mathematically controlled comparison, we find that the switching times for the continuous case are less than that for the corresponding discontinuous case. We also find that ON times are faster than OFF times in all cases. These results are discussed in the specific context of the inducible lactose operon of Escherichia coli.

Escherichia coli↗
PubMed2004

Serum progesterone concentrations on the day of HCG administration cannot predict pregnancy in assisted reproduction cycles.

The effect of subtle rises of progesterone in the late follicular phase of cycles of ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonists on pregnancy outcome is controversial. This study used receiver-operating characteristic (ROC) analysis to gain further insight into the predictive value of serum progesterone concentrations on the day of human chorionic gonadotrophin (HCG) injection in normally responding patients receiving the long protocol of GnRH agonist (group L; n = 218) and in low responders receiving the short ('flare-up') protocol (group S; n = 159). ROC analysis showed that serum progesterone concentration on the HCG day was not indicative of conception and non-conception cycles in the whole population studied, in group L or in group S. To further assess the potential impact of 'high' concentrations of circulating progesterone on the day of HCG administration on pregnancy rates and outcome, the threshold value (<0.9 ng/ml) to discriminate between women with 'high' (group H; n = 197) and 'normal' (group N; n = 180) progesterone was applied. No significant differences were found with respect to pregnancy and miscarriage rates between these two groups. Serum progesterone concentrations on the day of HCG administration therefore cannot predict pregnancy in assisted reproduction cycles using GnRH agonists and gonadotrophins.

Adult↗
PubMed1996

[Shock-induced, but not terminated ventricular tachycardia in a patient with implantable defibrillator].

A 62-year-old male patient with coronary artery disease and drug refractory sustained ventricular tachycardia received an implantable cardioverter defibrillator (PRX III, model 1720, CPI) with a transvenous lead system (Endotak, model 0115, CPI) in combination with a subcutaneous array electrode (SQ array, model 049, CPI). The intraoperative defibrillation threshold was 15 J and was confirmed 1 week later at the hospital discharge test. Three months after discharge from hospital the patient reported 5 shocks during moderate physical exertion followed by a tachycardia associated with dizziness which terminated spontaneously. The print out of the stored electrogram showed a supraventricular tachycardia (probably sinus tachycardia) with a heart rate of 154/min which activated the device. Antitachycardia pacing did not terminate the supraventricular tachycardia, and hence shock therapy was delivered. The first shock (34 J) converted the supraventricular tachycardia to a ventricular tachycardia with a heart rate of 178/min, which was not terminated by four consecutive 34 J DC shocks. There was no hint of a device or lead failure. Determination of the defibrillation threshold reconfirmed the 15 J value for termination of ventricular fibrillation. However, neither a 1 J shock nor a 34 J shock terminated a monomorphic sustained ventricular tachycardia (cycle length 340 ms) induced by noninvasive programmed electrical stimulation. The ventricular tachycardia was, however, reproducibly terminate by antitachycardia pacing. It is concluded that an inappropriate high-energy DC shock might induce a sustained ventricular tachycardia. However, a sufficient defibrillation threshold for the termination of ventricular fibrillation does not necessarily mean that a sustained ventricular tachycardia will be terminated by a high-energy DC shock.

Coronary Disease↗