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Alpha-2 adrenoreceptor-mediated decrease in gamma-aminobutyric acid outflow in cortical slices and synaptosomes during morphine tolerance.

Morphine tolerance has proven to be accompanied by alterations in the efficiency of many neuronal signals, as well as by an inversion of the noradrenergic signal response of cortical acetylcholine terminals and gamma-aminobutyric acid (GABA) neurons in vivo (decreased acetylcholine and increased GABA release in normal animals, vice versa in tolerant). The latter observation may be relevant in interpreting morphine withdrawal, because the noradrenergic neuron firing rate increases dramatically during its course. This study was designed as an attempt to anatomically localize the inversion of the GABA response to norepinephrine. Because this phenomenon is observed in cortical slices and synaptosomes, it can be postulated that it occurs in the neocortex at the level of the intracortical GABA nerve terminals. Pharmacological analysis demonstrates that although the stimulation observed in controls is alpha-1 adrenoreceptor-mediated, the inhibition in tolerant animals is exerted via alpha-2 adrenoreceptors. Therefore, an increase in number or an improved coupling to the transduction system of alpha-2 adrenoreceptors is hypothesized. This observation gives a clue to a molecular interpretation of the inversion of GABA response to norepinephrine in tolerant animals, which may be of heuristic value in terms of biological interpretation of morphine tolerance.

Animals↗

The effects of spatting and ankle taping on inversion before and after exercise.

OBJECTIVE: To compare the effects of spatting, taping and spatting, taping, and not taping on the amount and rate of inversion of the ankle before and after exercise. DESIGN AND SETTING: We filmed subjects at 60 Hz while they stood on a platform that suddenly inverted the right ankle. Five trials were measured before and after a 30-minute period of drills. SUBJECTS: We tested 15 male rugby players with no history of lower-leg injury within the previous 6 months limiting activity for more than 2 days. MEASUREMENTS: The amount and rate of inversion in the four conditions were digitized and analyzed. RESULTS: The combination of spatting and taping was the most effective in reducing inversion rate and range of motion before and after exercise. CONCLUSIONS: All three taping treatments were effective in reducing the amount and rate of inversion. Exercise loosened the tape, but there may be a functional restriction of the amount and rate of inversion after exercise.

Journal Article↗

Measurement of small one-bond proton-carbon residual dipolar coupling constants in partially oriented (13)C natural abundance oligosaccharide samples: analysis of heteronuclear (1)J(CH)-modulated spectra with the BIRD inversion pulse.

Two 2D J-modulated HSQC-based experiments were designed for precise determination of small residual dipolar one-bond carbon-proton coupling constants in (13)C natural abundance carbohydrates. Crucial to the precision of a few hundredths of Hz achieved by these methods was the use of long modulation intervals and BIRD pulses, which acted as semiselective inversion pulses. The BIRD pulses eliminated effective evolution of all but (1)J(CH) couplings, resulting in signal modulation that can be described by simple modulation functions. A thorough analysis of such modulation functions for a typical four-spin carbohydrate spin system was performed for both experiments. The results showed that the evolution of the (1)H-(1)H and long-range (1)H-(13)C couplings during the BIRD pulses did not necessitate the introduction of more complicated modulation functions. The effects of pulse imperfections were also inspected. While weakly coupled spin systems can be analyzed by simple fitting of cross peak intensities, in strongly coupled spin systems the evolution of the density matrix needs to be considered in order to analyse data accurately. However, if strong coupling effects are modest the errors in coupling constants determined by the "weak coupling" analysis are of similar magnitudes in oriented and isotropic samples and are partially cancelled during dipolar coupling calculation. Simple criteria have been established as to when the strong coupling treatment needs to be invoked.

Carbon↗

Does birth weight predict childhood diet in the Avon longitudinal study of parents and children?

STUDY OBJECTIVE: Low birth weight predicts cardiovascular disease in adulthood, and one possible explanation is that children with lower birth weight consume more fat than those born heavier. Therefore, the objective of this study was to investigate associations between birth weight and childhood diet, and in particular, to test the hypothesis that birth weight is inversely related to total and saturated fat intake. DESIGN: Prospective cohort study. SETTING: South west England. PARTICIPANTS: A subgroup of children enrolled in the Avon longitudinal study of parents and children, with data on birth weight and also diet at ages 8, 18, 43 months, and 7 years (1152, 998, 848, and 771 children respectively). MAIN RESULTS: Associations between birth weight and diet increased in strength from age 8 to 43 months, but had diminished by age 7 years. Fat, saturated fat, and protein intakes were inversely, and carbohydrate intake was positively associated with birth weight at 43 months of age, after adjusting for age, sex, and energy intake. After adjustment for other confounders, all associations were weakened, although there was still a suggestion of a relation with saturated fat (-0.48 (95% CI -0.97, 0.02) g/day per 500 g increase in birth weight. Similar patterns were seen in boys and girls separately, and when the sample was restricted to those with complete data at all ages. CONCLUSIONS: A small inverse association was found between birth weight and saturated fat intake in children at 43 months of age but this was not present at 7 years of age. This study therefore provides little evidence that birth weight modifies subsequent childhood diet.

Birth Weight↗

Computer control of pH and DO in a laboratory fermenter using a neural network technique.

In this contribution, the advantages of the artificial neural network approach to the identification and control of a laboratory-scale biochemical reactor are demonstrated. It is very important to be able to maintain the levels of two process variables, pH and dissolved oxygen (DO) concentration, over the course of fermentation in biosystems control. A PC-supported, fully automated, multi-task control system has been designed and built by the authors. Forward and inverse neural process models are used to identify and control both the pH and the DO concentration in a fermenter containing a Saccharomyces cerevisiae based-culture. The models are trained off-line, using a modified back-propagation algorithm based on conjugate gradients. The inverse neural controller is augmented by a new adaptive term that results in a system with robust performance. Experimental results have confirmed that the regulatory and tracking performances of the control system proposed are good.

Algorithms↗

A study of dipole localization accuracy for MEG and EEG using a human skull phantom.

OBJECTIVE: To investigate the accuracy of forward and inverse techniques for EEG and MEG dipole localization. DESIGN AND METHODS: A human skull phantom was constructed with brain, skull and scalp layers and realistic relative conductivities. Thirty two independent current dipoles were distributed within the 'brain' region and EEG and MEG data collected separately for each dipole. The true dipole locations and orientations and the morphology of the brain, skull and scalp layers were extracted from X-ray CT data. The location of each dipole was estimated from the EEG and MEG data using the R-MUSIC inverse method and forward models based on spherical and realistic head geometries. Additional computer simulations were performed to investigate the factors affecting localization accuracy. RESULTS: Localization errors using the relatively simpler locally fitted sphere approach are only slightly greater than those using a BEM approach. The average localization error over the 32 dipoles was 7-8 mm for EEG and 3 mm for MEG. CONCLUSION: The superior performance of MEG over EEG appears to be because the latter is more sensitive to errors in the forward model arising from simplifying assumptions concerning the conductivity of the skull, scalp and brain.

Computer Simulation↗

Identification of complex stiffness tensor from waveform reconstruction.

An inverse method is proposed in order to determine the viscoelastic properties of composite-material plates from the plane-wave transmitted acoustic field. Analytical formulations of both the plate transmission coefficient and its first and second derivatives are established, and included in a two-step inversion scheme. Two objective functions to be minimized are then designed by considering the well-known maximum-likelihood principle and by using an analytic signal formulation. Through these innovative objective functions, the robustness of the inversion process against high level of noise in waveforms is improved and the method can be applied to a very thin specimen. The suitability of the inversion process for viscoelastic property identification is demonstrated using simulated data for composite materials with different anisotropy and damping degrees. A study of the effect of the rheologic model choice on the elastic property identification emphasizes the relevance of using a phenomenological description considering viscosity. Experimental characterizations show then the good reliability of the proposed approach. Difficulties arise experimentally for particular anisotropic media.

Journal Article↗

A novel workflow for the inverse QSPR problem using multiobjective optimization.

A workflow for the inverse quantitative structure-property relationship (QSPR) problem is reported in this paper for the de novo design of novel chemical entities (NCE) in silico through the application of existing QSPR models to calculate multiple objectives, including prediction confidence measures, to be optimized during the de novo design process. Two physical property datasets are applied as case studies of the inverse QSPR workflow (IQW): mean molecular polarizability and aqueous solubility. The case studies demonstrate the optimization of molecular structures to within a property range of interest; the optimized structures are then validated against QSPR models that are generated from sets of alternative descriptors to those used in the IQW. The paper concludes with a discussion of the results from the case studies.

Least-Squares Analysis↗

Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1.

BACKGROUND: Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. OBJECTIVES: To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. DESIGN: Wechsler Intelligence Scale for Children-Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. RESULTS: Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. CONCLUSIONS: Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1.

Brain↗

An analytical model of multilayer ultrasonic transducers with an inversion layer.

Inversion layer ultrasonic transducers have been investigated recently as an interesting approach in wideband transducer design. In this paper we present an analytical model of multilayer ultrasonic transducers with an inversion layer. Our analysis of the wave propagation problem of an inversion layer transducer includes a functional decomposition of the electrical input impedance. It becomes clear from this decomposition that an inversion layer transducer can be modeled as three elements in series connection, i.e., a clamped capacitance, a classical motional impedance, and a coupled motional impedance. The first two elements make up the classical model of a single element transducer. The coupled motional impedance describes the coupled interaction between the regular and the inverted piezoelectric sublayers, and thus reflects the effect of an inversion layer. We present examples which show that inversion layer transducers are advantageous in achieving such useful features as dual-frequency operation mode as used in harmonic imaging or broadband performance desired in most ultrasonic applications.

Journal Article↗

Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature.

OBJECTIVE: To assess the strength of evidence for an inverse relationship between blood pressure and birth weight. DESIGN: A systematic review of the published literature. SETTING: Published studies describing the relationship between blood pressure and birth weight since 1956. SUBJECTS: More than 66,000 subjects aged 0-71 years. RESULTS: Thirty-four studies described the relationship of blood pressure with birth weight. The majority of the studies of children and adults showed that blood pressure fell with increasing birth weight. Studies of adolescents were inconsistent. In neonates there was a positive relationship between blood pressure and birth weight. The pattern with age was supported by the limited number of studies with repeated measures and was dependent neither on the method of analysis nor on work from a single academic group or country. CONCLUSIONS: Blood pressure is inversely related to birth weight in children and in adults. The positive results in neonates and the inconsistency in adolescence may be related to the unusual growth dynamics during these phases of growth. Further studies should concentrate on the mechanisms which underlie the relationship.

Adolescent↗

Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma.

Xiphophorus interspecies hybrids provide several well-characterized genetic models of melanoma susceptibility. The Xiphophorus CDKN2A/B gene, homologous to mammalian CDKN2A/B cyclin-dependent kinase inhibitors (p16 and p15), is a candidate tumor susceptibility gene in these models. Using real-time PCR and Western blot analysis, we analyzed expression of CDKN2A/B in spontaneous and UV-induced primary melanomas from individual backcross hybrid fish. We found that CDKN2A/B mRNA is highly expressed in melanomas (18-fold), relative to other fish tissues. Expression is also elevated, to a lesser extent (9.5-fold), in melanized skin from tumor-bearing fish. However, quantitative levels of CDKN2A/B mRNA in tumors varied considerably and positively correlated with expression of the Xmrk oncogene, suggesting possible functional interaction between Xmrk and CDKN2A/B expression. As a homolog corresponding to members of the mammalian CDKN2 family which regulate cell cycle progression at the G1 checkpoint, the CDKN2A/B p13 protein is a putative regulator of the G1 checkpoint apparatus in Xiphophorus. Since CDKN2A is often observed to be inversely regulated compared to RB in some human tumors, and is capable of transcriptionally regulating RB in human ovarian tumors, we cloned the Xiphophorus maculatus RB cDNA and analyzed RB expression by real-time PCR and Western blot analysis in the fish melanomas. These experiments were designed to ascertain whether CDKN2A/B and RB expression were inversely correlated. Our results indicate that RB mRNA was consistently expressed at only a 2-fold higher level in both tumors and melanized skin than in muscle. Qualitatively similar results were obtained for protein expression. These results collectively suggest that (i) Xmrk and CDKN2A/B may be co-regulated at the transcriptional level, and (ii) there is little, if any, alteration of RB expression in Xiphophorus melanomas.

Amino Acid Sequence↗

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities.

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 - e(-beta t)), with A representing the blood volume and beta the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter beta and flow (r = 0.994) as well as A * beta and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation.

Blood Flow Velocity↗

Paracentric inversion of chromosome 7(q22-31) associated with nonobstructive azoospermia.

OBJECTIVE: To examine an unusual paracentric inversion of chromosome 7 found in an azoospermic man. DESIGN: Case report. SETTING: Infertility clinic at a private hospital. PATIENT(S): An azoospermic but otherwise apparently healthy man. INTERVENTION(S): Karyotyping with peripheral blood lymphocytes, microdissection testicular sperm extraction (TESE), and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm count and GBG banding. RESULTS: A karyogram revealed paracentric inversion of chromosome 7 with breakpoints at 7q22 and 7q31. Testicular histopathology confirmed the Sertoli cell-only syndrome. Successful pregnancy and delivery were achieved with microdissection TESE and ICSI. CONCLUSION(S): Paracentric inversion of chromosome 7(q22-31) associated with nonobstructive azoospermia is rare. Chromosome 7q22-31 may be responsible for impaired spermatogenesis.

Adult↗

Lipid profiles in adolescent Filipinos: relation to birth weight and maternal energy status during pregnancy.

BACKGROUND: The finding that persons with low birth weight have a higher cardiovascular disease (CVD) risk than do persons with higher birth weight remains poorly understood. OBJECTIVE: We tested the hypothesis that maternal arm fat area (MAFA) in the third trimester of pregnancy and birth weight of offspring are inversely related to the offspring's risk of CVD. DESIGN: In a 1-y birth cohort study (1983-1984), 296 male and 307 female offspring were followed up (1998-1999) to measure their lipid profiles. Participants came from randomly selected communities of Cebu, Philippines. RESULTS: MAFA (log cm2) was positively associated (beta) with HDL cholesterol (0.12 log mg/dL; P < 0.01) and inversely associated with total cholesterol (-10.0 mg/dL; P < 0.10), LDL cholesterol (-13.1 mg/dL; P < 0.01), and the ratios of total to HDL cholesterol and LDL to HDL cholesterol (both P < 0.001) in males. These relations were independent of birth weight, present adiposity, energy and fat intakes, maturity, and income. Birth weight < or = 2.6 kg was associated with elevated LDL cholesterol (9.9 mg/dL; P < 0.01) and an elevated ratio of LDL to HDL cholesterol (0.22; P < 0.10) only in males. In females, MAFA related positively to total (15.5 mg/dL; P < 0.05) and LDL (11.9 mg/dL; P < 0.05) cholesterol. CONCLUSIONS: In this Filipino population, mothers with low energy status during pregnancy gave birth to male offspring who had a high CVD risk in adolescence, as indicated by lipid profiles. The findings in females are less consistent with the fetal origins hypothesis and suggest sex differences in the relation between fetal nutrition and postnatal lipid metabolism.

Adipose Tissue↗

Reciprocal tapping in spastic hemiparesis.

OBJECTIVE: To locate the source of slowness in typing movements in subjects with spastic hemiparesis and to examine whether enlargement of keys would facilitate typing. DESIGN: Experimental within-subjects design. SETTING: Werkenrode, a special school for physically disabled young children. SUBJECTS: Eleven subjects (mean age 17.1 years) diagnosed as having spastic hemiparesis, most as a result of cerebral palsy. INTERVENTIONS: Subjects made fast reciprocal tapping movements with one finger of both hands separately within a 10-second interval. Keys of 12 x 12 mm and 24 x 24 mm were used. MAIN OUTCOME MEASURES: Interkey response interval (IRI), dwell time (interval during which the key is pressed) and forces were measured. Also, the standard deviation and coefficient of variation of the variables were calculated to determine regularity of the movements. RESULTS: The impaired hand tapped slower and more irregularly and exerted less force. In addition, the duration of the dwell phase was lengthened for this hand. However, the percentage dwell time as a function of IRI was not different between hands. Enlargement of the keys shortened flight time (i.e. time in which the finger moves through the air from one key to the next) of the impaired hand, but not dwell time. CONCLUSIONS: The entire movement is slower for the impaired hand. Disturbances are not exclusively located at the inversion of the movement. With respect to keyboard design, enlarged keys and a locked repeat function of the keys may be beneficial for subjects suffering from spasticity.

Adolescent↗

Properties of arabinonucleic acids (ANA & 20'F-ANA): implications for the design of antisense therapeutics that invoke RNase H cleavage of RNA.

Inversion of configuration of the C2' position of RNA leads to a very unique nucleic acid structure: arabinonucleic acid (ANA). ANA, and its 2'-fluoro derivative (2'F-ANA) from hybrids with RNA that are capable of activating RNase H, resulting in cleavage of the RNA strand. In this paper, we review the properties of duplexes formed between ANA (or 2'F-ANA) and its RNA complement. These studies support the notion that RNase H is sensitive to the minor groove dimensions of the hybrid substrate.

Arabinonucleotides↗