Linoleic acid and linolenic acid elongation products in muscle tissue of Syncerus caffer and other ruminant species

The metabolic elongation products of both linoleic acid and linolenic acid were found in muscle tissues of Syncerus caffer and other ruminants. The acids with four double bonds were predominantly in the linoleic acid series, whereas the higher degrees of unsaturation, mainly five double bonds, were in the linolenic acid series. The total linoleic acid and linolenic acid groups were present in the relative proportions of about 4:1, in contrast with the fish oils, where the acids are mainly in the linolenic acid series. The consistent occurrence of members of both groups of acids in the animals studied here suggests to us that both may be important for structural purposes.     

The assessment of time-dependent changes in human performance.

This paper discribes a series of experiments to illustrate the use of various methods of time series analysis in the delineation of the effects of circadian and ultradian cycles on human performance. These experiments are concerned with measures of both human performance and physiology. They illustrate how the parameters of these time series analytic techniques can be used to postulate physiological mechanisms where time-dependent changes have been shown to be significant. The use of analytic techniques in both the time and frequency domain is illustrated.     

Endurance vs. strength training: comparison of cardiac structures using normal predicted values

The importance of metabolic feedback regulation vs. feedforward regulation of hepatic glucose production (HGP) during exercise was investigated in rats by infusing glucose intravenously from the onset of running. Glucose infusion equaled the average exercise-induced increase from basal to steady state in HGP found in saline-infused control rats. Rats were studied at two work loads, running at 21 (series I) or 18 m/min (series II) for 35 min. Glucose turnover was measured by means of an intravenous [3H]glucose infusion. HGP was suppressed by glucose infusion corresponding to the infused amount of glucose in both series, except for late in exercise in series I, where HGP plus infused glucose tended to exceed HGP in saline-infused rats (P less than 0.10). Muscle glycogenolysis and fat metabolism were similar in both groups in the two series. Plasma glucose was never elevated, whereas insulin was, in glucose- vs. saline-infused rats of both series. Plasma catecholamines were lower in glucose- compared with saline-infused rats in series II. In conclusion, HGP is very sensitive to metabolic feedback inhibition at low exercise intensities. Feedforward control of HGP may play a role at higher work loads (series I). Exogenously supplied glucose, in moderate amounts, may replace HGP specifically without concomitant changes in mobilization of other substrates.     

Effect of rifampicin on development of tolerance to analgesic actions.

Two series of experiments were performed. In the first series the reaction times of mice were determined using the hotplate technique. In the second series of experiments the reactions of rats were determined using the electric footshock technique. In both series of experiments morphine was observed to alter the responses, and chronic morphine administration resulted in tolerance to these actions of morphine. In both series of experiments, tolerance, defined by these same criteria, was inhibited by the concurrent administration of rifampicin.     

An improved surrogate method for detecting the presence of chaos in gait

It has been suggested that the intercycle variability present in the time series of biomechanical gait data is of chaotic nature. However, the proper methodology for the correct determination of whether intercycle fluctuations in the data are deterministic chaos or random noise has not been identified. Our goal was to evaluate the pseudoperiodic surrogation (PPS) [Small et al., 2001. Surrogate test for pseudoperiodic time series data. Physical Review Letters 87(18), 188,101-188,104], and the surrogation algorithms of Theiler et al. [1992. Testing for nonlinearity in time series: the method of surrogate data. Physica D 58(1-4), 77-94] and of Theiler and Rapp [1996. Re-examination of the evidence for low-dimensional, nonlinear structure in the human electroencephalogram. Electroencephalography and Clinical Neurophysiology 98, 213-222], to determine which is the more robust procedure for the verification of the presence of chaos in gait time series. The knee angle kinematic time series from six healthy subjects, generated from a 2-min walk, were processed with both algorithms. The Lyapunov exponent (LyE) and the approximate entropy (ApEn) were calculated from the original data and both surrogates. Paired t-tests that compared the LyE and the ApEn values revealed significant differences between both surrogated time series and the original data, indicating the presence of deterministic chaos in the original data. However, the Theiler algorithm affected the intracycle dynamics of the gait time series by changing their overall shape. This resulted in significantly higher LyE and ApEn values for the Theiler-surrogated data when compared with both the original and the PPS-generated data. Thus, the discovery of significant differences was a false positive because it was not based on differences in the intercycle dynamics but rather on the fact that the time series was of a completely different shape. The PPS algorithm, on the other hand, preserved the intracycle dynamics of the original time series, making it more suitable for the investigation of the intercycle dynamics and the identification of the presence of chaos in the gait time series.     

Life stress on the Roman limes in continental Croatia

The purpose of the paper is to analyze and compare the demographic profiles and disease frequencies between a skeletal series from Zmajevac, a settlement on the Danubian limes, and a composite «non-limes» skeletal series consisting of human osteological remains from three large urban settlements to the west of the limes; roman Mursa (modern Osijek), Cibalae (Vinkovci) and Certissia (Štrbinci). To determine if life stresses were different in settlements on the limes the age and sex distribution in Zmajevac was compared to the composite «non-limes» series. All skeletons were also analyzed for the presence of dental pathology, dental enamel hypoplasia, cribra orbitalia, trauma, and physical stress.

Data collected from the skeletal series show that, with the exception of some indicators of physical stress, no significant differences in quality of life is evident. Both series are characterized by an underrepresentation of subadults from the youngest age category and by similar average adult male and female ages at death. In Zmajevac the average ages at death for adult males and females were 40.0 and 39.0 years respectively, in the composite «non-limes» series 37.4 years for both males and females. The frequencies of dental disease, subadult stress indicators, and trauma are similar in both series. The only consistent difference between the two series is noted in the frequencies of skeletal markers of physical stress, in particular the frequencies of vertebral osteoarthritis and Schmorl's defects. Total male and total female vertebral osteoarthritis frequencies in the two series are significantly different, as is the difference in total male frequencies of Schmorl's defects. Young adult males in the Zmajevac series seem to have been experiencing particularly heavy physical strain on the vertebral column. They exhibit significantly higher frequencies of both vertebral osteoarthritis and Schmorl's defects than young adult males from the composite non-limes series.     

Alamethicin channel kinetics: Studies using fluctuation analysis and multifractal fluctuation analysis

The kinetics of the alamethicine channel incorporated into BLM was studied using detrended fluctuation analysis and multifractal detrended fluctuation analysis. Detrended fluctuation analysis has shown that both the event series formed with dwell times on fixed channel conductivity levels and the event series formed with opened states on all channel conductivity levels are random processes. However, multifractal detrended fluctuation analysis indicated that only dwell times series on fixed channel conductivity levels are random, but the event series formed with opened states on all channel conductivity levels are the correlated multifractal processes.     

Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype

A series of metabotropic glutamate 5 receptor (mGluR5) allosteric ligands with positive, negative or no modulatory efficacy is described. The ability of this series to yield both mGluR5 PAMs and NAMs with single-digit nanomolar potency is unusual, and the underlying SAR is detailed.     

On the sequential packaging of bacteriophage P22 DNA.

Bacteriophage P22 is thought to package daughter chromosomes serially along concatemeric DNA. We present experiments which show that the average DNA packaging series length increases with time after infection, which supports this model. In addition, we have analyzed the effect on average series length of lowering the amount of the various individual proteins involved in DNA packaging. These results support the notion that the protein products of gene 2 and gene 3 are both more stringently required for initiation of sequential DNA packaging series than for their extension, and they are compatible with a model for the control of series length in which that length is determined, at least in part, by a competition between series initiation events and extension events.     

Natural occurrence of the C series of fumonisins in moldy corn

We analyzed 44 moldy corn samples for the B and C series of fumonisins by high-performance liquid chromatography. Of the 44 samples, 32 (73%) were contaminated with both the B and C series of fumonisins and 6 were contaminated with only the B series of fumonisins. The incidence of fumonisin C1 in moldy corn was 71%; the incidence was 11% for fumonisin C3 and 43% for fumonisin C4. Their mean levels ranged from 500 to 1,900 ng/g. This is the first report on the natural occurrence of the C series of fumonisins and fumonisin B4 in moldy corn.     

5-sulfonyl-benzimidazoles as selective CB2 agonists-part 2

In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis.     

Quantitative structure-activity relationship studies on some anticancerous, antiviral and cytostatic agents

QSAR studies using molecular connectivity and van der Waal volume have been performed on a new series of hydroxyguanidine derivatives and a series of isoindolediones. Regression analysis has shown that anticancer and antiviral activity of hydroxyguanidines as well as cytostatic activity of isoindolediones correlate well with both the structural parameters.     

Assessment of adult skeletons to detect prenatal exposure to trypan blue in mice

A Skeletal Variant Assay System (SVAS) consisting of a group of 88 spontaneously occurring qualitative variations of the adult mouse skeleton was studied in CD-1 mice which had been exposed in utero by way of three daily ip injections of their dams on days 7-9 of gestation with trypan blue. Treatment groups received daily doses of 0.25 cc of 0, .037, .075, .15, or .30% trypan blue dissolved in 0.9% NaCl. Two separate series of experiments were performed, and skeletons were examined at 62 +/- 2 days postnatal. Sixty-six and 58 of the variants occurred in the two series, respectively. Frequencies of occurrence of substantial numbers of variants differed from Untreated (UNTD) and Vehicle-Treated (VEH) values in a dose-related manner for both series. At the high dose 18 and 22 variants occurred with significantly different (P less than .01) frequencies from UNTD in the two series. Contrasting high-dose animals with vehicle controls revealed significant differences in 24 and 17 variants. There were 13 and 14 variants in the two series, respectively, which differed from both UNTD and VEH. If one considers differences at P less than .01 in one comparison and P less than .05 in the other, then 22 and 18 variants qualify as being significantly different from both controls in the two series. Agreement between the two series was excellent regarding which variants were affected. Several differed significantly from both UNTD and VEH in both series of experiments. Among these were a number which appeared more or less specific to trypan blue exposure. They include Dyssymphysis of the Atlas, Carpal Fusions, and Tarsal Fusions. Although increased frequency of an Interfrontal bone is seen with several treatments, the magnitude of the response and the low doses at which it is elicited are unique to trypan blue exposure. Numerous low-dose effects are striking in this set of experiments, making the SVAS a very sensitive indicator of trypan blue exposure. In addition to the variants mentioned, a large cluster of cervical (C) vertebrae variants, including dyssymphyses, fusions, imperfect transverse foramina of C1 and C2, and accessory transverse foramina of C3-C6, as well as vertebral fusions at various levels (especially cervical, sacral, and caudal), appear to be the principal effects of exposure to this compound. In addition, rib malformations at the high dose level, and increased frequency of occurrence of 27-presacral vertebrae at all dose levels, were important effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasticity in canine airway smooth muscle

The large volume changes of some hollow viscera require a greater length range for the smooth muscle of their walls than can be accommodated by a fixed array of sliding filaments. A possible explanation is that smooth muscles adapt to length changes by forming variable numbers of contractile units in series. To test for such plasticity we examined the muscle length dependence of shortening velocity and compliance, both of which will vary directly with the number of thick filaments in series. Dog tracheal smooth muscle was studied because its cells are arrayed in long, straight, parallel bundles that span the length of the preparation. In experiments where muscle length was changed, both compliance and velocity showed a strong dependence on muscle length, varying by 1.7-fold and 2.2-fold, respectively, over a threefold range of length. The variation in isometric force was substantially less, ranging from a 1.2- to 1.3-fold in two series of experiments where length was varied by twofold to an insignificant 4% variation in a third series where a threefold length range was studied. Tetanic force was below its steady level after both stretches and releases, and increased to a steady level with 5-6 tetani at 5 min intervals. These results suggest strongly that the number of contractile units in series varies directly with the adapted muscle length. Temporary force depression after a length change would occur if the change transiently moved the filaments from their optimum overlap. The relative length independence of the adapted force is explained by the reforming of the filament lattice to produce optimum force development, with commensurate changes of velocity and compliance.     

Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors

The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented.     

Box-Jenkins modeling of chronological series of twin births and single births

A time-series analysis by Box-Jenkins modeling of the monthly observations of twin births and singleton births was attempted. The study is population based. The single-birth series has been matched to the twin-birth series for maternal birth cohort, parity of the twin birth, and residence of the parents. Three-hundred forty-one twin pairs and 340 singleton births were grouped into chronological series spanning 72 months of observation. Univariate and bivariate time-series analyses were used. Box-Jenkins modeling shows that both series share the same basic demographic and reproductive risk factors, such as ovulation and conception rates, abortions, sexual intercourse, and the less well-known random events that determine the time of delivery. These factors are randomly related to both birth processes but exert a more important influence on twin births. Beyond these crude features, twin- and single-birth series differ by the frequency of their seasonal cycle. Twin births show low-frequency variations because of a rather limited number of factors that impinge markedly on the twinning process. Single births are subjected to higher frequency variations that can be ascribed to a greater number of structuring factors, the action of which is less pervasive. Only the January peak is common to both types of births. Aside from the common features, the bivariate analysis shows that both series of births are independent, neither being related to the other. It is concluded that the subtle structuring of both processes is largely distinct. The large fraction of the unaccounted variation of each birth process (about 70%) suggests that most of the variation is due to as yet unidentified factors. The search for environmental and geocosmic factors at the origin of conception and confinement should be considered in future undertakings.     

Synthesis and evaluation of efavirenz (Sustiva) analogues as HIV-1 reverse transcriptase inhibitors: replacement of the cyclopropylacetylene side chain

Two series of efavirenz analogues have been developed: one in which the cyclopropane ring has been replaced by small heterocycles and another in which the entire acetylenic side chain has been replaced by alkyloxy groups. Several members of both series show equivalent potency to efavirenz against both wild-type virus and the key K103N mutant.     

Change in cerebral bioelectric activity during whole body hypothermia and regional cooling of the head]

Two series of experiments were conducted on dogs. In the first series of experiments dogs were subjected to deep hypothermia with an external chilling of the organism; in the second series-to the isolated deep hypothermia of the head with the maintenance of normothermia in the organism. Bioelectrical activity of the brain and circulation minute volume were recorded in the animals of both series. As revealed, depression of the bioelectrical activity was more pronounced and a prevalence of slow waves was observed in general hypothermia; at the same time a more even reduction of the electrical activity in all the EEG frequencies under study was seen in the series with local hypothermia. A reduction of the circulation minute volume was also more pronounced in the first series of experiments; in the authors' opinoin this was associated with the difference in the character of the EEG evolution with the same depth of hypothermia of the brain.     

Simultaneous alignment of dual-axis tilt series

We present a strategy for the alignment of dual-axis tomographic series, based on reference points and simultaneous alignment of both series. Each series is first aligned individually, an affine transformation is determined to bring the two series in a unique reference system, and all experimental coordinates are combined in a single system of equations. In case of severe shrinkage, a global and a local refinement of the orientation parameters are performed to correct all minors misalignments.The strategy is illustrated on tomographic experiments performed on sections from plastic-embedded biological samples. The efficiency in correcting the misalignment of gold particles and in improving the quality of the reconstruction is documented both visually and quantitatively.In our approach every region of the tomogram is associated with its own orientation parameters and can be eventually reconstructed with the preferred algorithm. This is convenient in the computation of 3D averages of equivalent structures. A simulation experiment is presented to show that the performances of this approach are superior to those of the method of rotation in direct space.