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PubMed2001

Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6-sulfatoxymelatonin concentration profiles in humans.

Concern about the health effects of extremely low frequency (ELF) magnetic fields (MF) has been raised by epidemiological studies indicating an association between certain cancers and living near power lines or working in high electric field environments. Alterations in pineal function have been proposed as a mechanism through which power-frequency MFs may interact with living organisms. A double blind laboratory study was performed to evaluate daytime exposure effects of 100 microT root mean square (rms) 50 Hz MF. Three head exposure sessions of 30 min each were performed: sham, continuous, and intermittent (15 s on/off cycles) MFs were presented to each subject in early or late afternoon (13:30 or 16:30 hr). Twenty-one healthy male volunteers (20-27 yr old) participated in these 3-weekly experimental conditions. Blood samples were drawn for serum melatonin measurement, hourly at night (from 20:00 to 07:00 hr) under controlled environmental conditions. Urinary excretion of 6-sulfatoxymelatonin (aMT6s), the main melatonin metabolite, was measured for a 17 hr period, by means of urine samples taken at 19:00 hr (14:00-19:00 hr "afternoon period"), 23:00 hr (19:00-23:00 hr "evening period"), and 07:00 hr, day 2 (23:00-07:00 hr day 2 "night-time period"). There were no significant differences in either plasma melatonin or in aMT6s excretion profiles in the three experimental conditions. However, a tendency for a smaller increase of night-time urinary aMT6s after continuous MF exposure was found (P=0.08) particularly in men with the lower excretion rate of aMT6s ("Low Group") (P=0.07). We conclude that this study does not indicate that daytime acute MF exposure influences either melatonin secretion or aMT6s excretion. Inter-individual differences in pineal production of melatonin, however, have to be taken into account in further studies.

Adult↗

PubMed1985

Causal attributions of married couples: when do they search for causes? What do they conclude when they do?

In this study, we examined when and whether married people engage in attributional activity or form causal attributions to explain their partners' behavior. We used an indirect probe to better approximate naturally occurring cognitive activity. We also examined the content of spouses' causal attributions, using both direct and indirect probes. Spouses were asked about frequent as well as infrequent relationship events, and about partner behaviors that had positive or negative impacts on the recipient. Husbands in unsatisfying relationships reported more attributional thoughts than did happily married husbands, whereas wives in the two groups did not differ. Behaviors having negative impacts elicited more attributional activity than did positive behaviors. Behavioral frequency and impact interacted in ways contrary to predictions. Finally, distressed couples were particularly likely to report distress-maintaining attributions and were particularly unlikely to report relationship-enhancing attributions, compared with their nondistressed counterparts.

Adaptation, Psychological↗

PubMed1998

A connectionist multiple-trace memory model for polysyllabic word reading.

A connectionist feedforward network implementing a mapping from orthography to phonology is described. The model develops a view of the reading system that accounts for both irregular word and pseudoword reading without relying on any system of explicit or implicit conversion rules. The model assumes, however, that reading is supported by 2 procedures that work successively: a global procedure using knowledge about entire words and an analytic procedure based on the activation of word syllabic segments. The model provides an account of the basic effects that characterize human skilled reading performance including a frequency by consistency interaction and a position-of-irregularity effect. Furthermore, early in training, the network shows a performance similar to that of less skilled readers. It also offers a plausible account of the patterns of acquired phonological and surface dyslexia when lesioned in different ways.

Humans↗

PubMed2005

Determining the vibrational pattern via overtone cold spectra: C-H methyl stretches of propyne.

Vibrationally mediated photodissociation and photoacoustic (PA) spectroscopy were employed for studying the intramolecular dynamics of propyne initially excited to the first through fourth overtone of methyl C-H stretching modes. Room-temperature PA and jet-cooled action spectra, monitoring the absorption of the parent and the yield of the ensuing H photofragments, respectively, were obtained. The PA spectra exhibit mainly broad features, while the action spectra, due to inhomogeneous structure reduction, expose multiple peaks of recognizable shapes in the differing overtone manifolds. Symmetric rotor simulations of the band contours of the action spectra allowed retrieving of band origins and linewidths. The linewidths of the bands in each manifold enabled estimates for energy redistribution times out of the corresponding states to the bath states, the times ranging from 18+/-6 ps for two quanta of C-H excitation to subpicosecond for five quanta. The data were also analyzed in terms of a normal-mode model and a joint local-/normal-mode model. These models enabled determination of harmonic frequencies, anharmonicities, and interaction parameters reproducing the observed data in all monitored regions and provided spectral assignments. The measured Doppler profiles were well fitted by Gaussians with widths suggesting low average translational energies for the released H photofragments. These low energies and their similarities to those for dissociation of propyne isotopomers preexcited to acetylenic C-H stretches were ascribed to an indirect dissociation process occurring after internal conversion to the ground electronic state and isomerization to allene.

Journal Article↗

PubMed2004

A systematic method for identifying small-molecule modulators of protein-protein interactions.

Discovering small-molecule modulators of protein-protein interactions is a challenging task because of both the generally noncontiguous, large protein surfaces that form these interfaces and the shortage of high-throughput approaches capable of identifying such rare inhibitors. We describe here a robust and flexible methodology that couples disruption of protein-protein complexes to host cell survival. The feasibility of this approach was demonstrated through monitoring a small-molecule-mediated protein-protein association (FKBP12-rapamycin-FRAP) and two cases of dissociation (homodimeric HIV-1 protease and heterodimeric ribonucleotide reductase). For ribonucleotide reductase, we identified cyclic peptide inhibitors from genetically encoded libraries that dissociated the enzyme subunits. A solid-phase synthetic strategy and peptide ELISAs were developed to characterize these inhibitors, resulting in the discovery of cyclic peptides that operate in an unprecedented manner, thus highlighting the strengths of a functional approach. The ability of this method to process large libraries, coupled with the benefits of a genetic selection, allowed us to identify rare, uniquely active small-molecule modulators of protein-protein interactions at a frequency of less than one in 10 million.

Carrier Proteins↗

PubMed2001

Kinetics and thermodynamics of T cell receptor- autoantigen interactions in murine experimental autoimmune encephalomyelitis.

In the current study, cellular and molecular approaches have been used to analyze the biophysical nature of T cell receptor (TCR)-peptide MHC (pMHC) interactions for two autoreactive TCRs. These two TCRs recognize the N-terminal epitope of myelin basic protein (MBP1-11) bound to the MHC class II protein, I-A(u), and are associated with murine experimental autoimmune encephalomyelitis. Mice transgenic for the TCRs have been generated and characterized in other laboratories. These analyses indicate that the mice either develop encephalomyelitis spontaneously (172.10 TCR) or only if immunized with autoantigen in adjuvant (1934.4 TCR). Here, we show that the 172.10 TCR binds MBP1-11:I-A(u) with a 4-5-fold higher affinity than the 1934.4 TCR. Consistent with the higher affinity, 172.10 T hybridoma cells are significantly more responsive to autoantigen than 1934.4 cells. The interaction of the 172.10 TCR with cognate ligand is more entropically unfavorable than that of the 1934.4 TCR, indicating that the 172.10 TCR undergoes greater conformational rearrangements upon ligand binding. The studies therefore suggest a correlation between the strength and plasticity of a TCR-pMHC interaction and the frequency of spontaneous disease in the corresponding TCR transgenic mice. The comparative analysis of these two TCRs has implications for understanding autoreactive T cell recognition and activation.

Animals↗

PubMed2002

Ultrasound induced improvement in optical coherence tomography (OCT) resolution.

Optical coherence tomography (OCT) is a rapidly emerging technology for high-resolution biomedical imaging. The axial resolution of this technology is determined by the bandwidth of the source. Commercial sources generally provide resolutions of 10-20 microm whereas laboratory-based solid state lasers have resolutions of approximately 4 microm. The resolution in tissue depends almost exclusively on detecting single scattered events. However, the phenomenon known as multiple scattering results in a deterioration of resolution as a function of depth. In this study, OCT was combined with ultrasound in an attempt to reduce the effect of multiple scattering. The theory is that, with parallel ultrasound and OCT beams, multiply scattered light with a momentum component significantly perpendicular to the OCT beam will be reduced because the light is Doppler shifted outside the bandpass filter of the OCT detection electronics. A 7.5-MHz ultrasound transducer was used to introduce the photon/phonon interaction. A reflecting metal plate was placed within biological tissue, and the point spread function (PSF) was assessed off the reflector. The PSF was determined in the presence of no ultrasound, pulsed ultrasound, and continuous-wave (CW) ultrasound. CW ultrasound resulted in a 17% improvement (P < 0.001) in resolution and pulsed ultrasound resulted in 8% (P < 0.01). Image noise reduction could also be noted. Combining OCT with a parallel ultrasound beam results in an improvement in resolution through a reduced effect of multiple scattering due to photon/phonon interaction. With higher frequencies, better control of the acoustical beam, and tests in media with higher rates of multiple scattering, improved results are anticipated.

Diagnostic Imaging↗

PubMed2004

Regulation of immature protein dynamics in the endoplasmic reticulum.

The quality of nascent protein folding in vivo is influenced by the microdynamics of the proteins. Excessive collisions between proteins may lead to terminal misfolding, and the frequency of protein interactions with molecular chaperones determines their folding rates. However, it is unclear how immature protein dynamics are regulated. In this study, we analyzed the diffusion of immature tyrosinase in the endoplasmic reticulum (ER) of non-pigmented cells by taking advantage of the thermal sensitivity of the tyrosinase. The diffusion of tyrosinase tagged with yellow fluorescence protein (YFP) in living cells was directly measured using fluorescent correlation spectroscopy. The diffusion of folded tyrosinase in the ER of cells treated with brefeldin A, as measured by fluorescent correlation spectroscopy, was critically affected by the expression level of tyrosinase-YFP. Under defined conditions in which random diffusional motion of folded protein was allowed, we found that the millisecond-order diffusion rate observed for folded tyrosinase almost disappeared for the misfolded molecules synthesized at a nonpermissive high temperature. This was not because of enhanced aggregation at the high temperature, as terminally misfolded tyrosinase synthesized in the absence of calnexin interactions showed comparable, albeit slightly slower, diffusion. Yet, the thermally misfolded tyrosinase was not immobilized when measured by fluorescence recovery after photobleaching. In contrast, terminally misfolded tyrosinase synthesized in cells in which alpha-glucosidases were inhibited showed extensive immobilization. Hence, we suggest that the ER represses random fluctuations of immature tyrosinase molecules while preventing their immobilization.

Bacterial Proteins↗

PubMed1999

Laying hens in large flocks in a perchery system: influence of stocking density on location, use of resources and behaviour.

1. ISA Brown laying hens (3000) were housed in a perchery in 10 pens, each with 300 birds. The pens varied in size to produce 4 different stocking densities: 9.9 birds/m2 (n = 3), 13.5/m2 (n = 2), 16.0/m2 (n = 2) and 19.0/m2 (n = 3). Observations began at 20 weeks of age and continued until 69 weeks to establish the spatial distribution of the birds, usage of the different resources and the expression of behaviour. 2. Overall, birds spent most time on the perch frame (47%), litter area (23%), slatted floor (17%) and nestbox area (9%). 3. There was no effect of density on the proportion of birds observed on the slatted floor or on the elevated perches but as density increased the proportion on the littered area decreased. 4. Space usage was determined vertically, horizontally and longitudinally. Individual birds were seen to use about 80% of the pen volume available to them. This value was similar for all densities and showed that individuals did not have separate home ranges. 5. Fewer vertical movements were made within the main perch frame at the upper than at the lower levels but movements between the perches of the main frame and the nestbox rails were relatively frequent. This may help birds move up and down through the main frame. 6. Behaviours which decreased in incidence with crowding included moving, foraging and dust-bathing. Behaviours which increased with crowding included standing. Behaviours which were unaffected included resting, preening, prelaying behaviour, comfort behaviour and the minor behaviours. 7. The proportion of birds engaged in feeding and drinking was unaffected by density, except each time the chain feeders (which operated intermittently) ran more hens were seen feeding at the lower densities. This suggests that food delivery stimulated feeding behaviour; there may have been some restriction at the higher densities on birds feeding when and where they wanted. 8. Stocking density had no effect on the frequency of agonistic interactions: threats, lunges, comb/head pecks, chases and fights. 9. The incidence of damaging pecking was low and not density dependent. 10. Increasing density within the range investigated inhibited the expression of a number of behaviours and limited the use of specific resources: bird welfare at 19 birds/m2 may have been very slightly impaired.

Aggression↗

PubMed1979

The weekend workshop for dysfunctional couples: assets and limitations.

Two major new trends are emerging in the field of sexual counseling: the use of self-help programs and the increasing reliance on group therapy to overcome specific sexual complaints. The weekend sexual enhancement workshop represents a synthesis of both trends, but efficacy regarding outcome has not been well documented. In order to investigate specific changes in sexual and marital adjustment, two intensive weekend programs were conducted. Pre- and postmeasures were obtained for both groups. Based on the results of 15 couples who displayed a diversity of sexual dysfunctions, several conclusions can be drawn. The weekend workshop format appears effective in achieving three of its four major goals: (1) Couple communication improves via the stimulus of new information, group discussion, and permission to talk sexually. Marital satisfaction increases, particularly where the history of marital conflict is not chronic. (2) Attitude change occurs, and erroneous beliefs are relinquished in the face of new input. (3) The frequency of sexual interaction increases. (4) Long-standing sexual dysfunctions are not resolved as a result of group participation and information on self-help methods alone. Finally, the role of such weekend programs in sexual counseling in discussed.

Adult↗

PubMed2002

A qualitative investigation of the temporal patterning of the precompetitive anxiety response.

The aim of this study was to examine retrospective perceptions and causal beliefs about temporal experiences of competitive anxiety and related symptoms in the lead up to competition. Qualitative interviews were conducted with 9 elite performers to examine the interaction of intensity, frequency and direction of symptoms associated with competitive anxiety before competition. Data analysis identified six causal networks that supported theoretical predictions suggesting that intensity of cognitive anxiety symptoms remained relatively stable in the lead up to competition, whereas somatic anxiety peaked sharply at the onset of performance. Frequency of anxiety symptoms increased as the competition approached and changes in interpretation of anxiety symptoms were also reported, with self-confidence identified as a moderating variable. The findings highlight the dynamic properties of the stress response and emphasize the need to consider the idiosyncratic nature of the level, frequency and interpretation of performers' precompetitive experiences.

Adult↗

PubMed2006

Social context of needle selling in Baltimore, Maryland.

Although much of the debate surrounding the distribution of sterile syringes to injection drug users (IDUs) has focused on needle exchange programs (NEPs), IDUs acquire their syringes from three major sources: NEPs, pharmacies, and secondary exchangers or needle sellers. The purpose of the present study is to examine types and frequencies of social interactions among drug injectors who sell needles, most of which come from NEPs, compared with individuals who do not sell needles. Specifically, we compared engagement in drug-related behaviors, roles in the drug economy, and social network membership. Data were collected as part of the SHIELD study, an HIV prevention intervention targeted at drug users and their social networks (n=910) from February 2001 through September 2003 in Baltimore, Maryland (USA). In this sample, 56 participants reported selling needles. Needle sellers had higher levels of engagement in drug-related social interactions, including using drugs with others, giving or receiving drugs from others, and buying drugs with other users. Participants who sold needles had a significantly higher number of roles in the drug economy. Also, they had more social network members who were injectors, with whom they talked about risky drug behaviors, gave needles to, and shared cookers and bleach with. Compared with nonselling injectors, needle sellers engage in HIV risk-related behaviors, such as injecting daily and sharing injection equipment, more frequently. The study's findings may be useful to determine whether secondary exchangers should be targeted for HIV prevention activities both to reduce their own risk and to diffuse risk reduction information throughout the drug using community.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Hemispheric asymmetry for word naming: effects of frequency and regularity of pronunciation.

Observers named visually presented words as quickly as possible when the words were presented to the centre of a viewing screen (Experiments 1, 5, and 6) or were flashed to either the left visual field/right hemisphere (LVF/RH) or right visual field/left hemisphere (RVF/LH) on each trial (Experiments, 2, 3, and 4). Words varied in frequency of occurrence in the language and in regularity of pronunciation. On lateralised trials, there was a RVF/LH advantage for both error rate and reaction time, with this hemispheric asymmetry for word naming being independent of both frequency and regularity. The RVF/LH advantage was also independent of whether the letters within a word were arranged horizontally or vertically. Error rates and reaction times were lower for high-than for low-frequency words and lower for words with a regular pronunciation than for exception words. In addition, on centre trials the effects of regularity were larger for low-frequency words than for high-frequency words. However, when words were presented in the visual periphery, the effects of regularity were of the same magnitude for high-and low-frequency words. In view of the theoretical importance of the Frequency by Regularity interaction, this latter result suggests that word processing is qualitatively different in the visual periphery than in the centre of vision; indicating that perceptual asymmetries in a typical visual half-field experiment may be limited in what they can tell us about the relative contributions of the two hemispheres to processing words in the centre of vision.

Journal Article↗

PubMed2004

Flower color microevolution in wild radish: evolutionary response to pollinator-mediated selection.

Evolutionary ecologists are fundamentally interested in how species interactions affect evolutionary change. We tested the degree to which plant-pollinator interactions affect the frequency of flower color morphs of Raphanus sativus. Petal color in R. sativus is determined by two independently assorting loci, producing four petal colors (yellow, white, pink, and bronze). We assessed the impact of pollinator discrimination on changes in flower color variation by comparing the frequency of colors produced in the presence (open pollination) versus absence (null pollination) of pollinator discrimination. We also assessed the impact of postpollination and developmental effects on progeny colors using equal pollinations with all four color morphs. Our results from open pollinations found an overrepresentation of yellow progeny in the next generation, when compared with both null pollinations and cumulative ratios based on Hardy-Weinberg and linkage equilibria assumptions. When these results were combined with those from equal pollinations, the overrepresentation of yellow could be attributed to selection from pollinators. Yet, surveys in the field the following year found no flower color frequency changes in the next generation. These results illustrate that flower color microevolution can be driven by both pollinator discrimination and other nonpollinator selective forces acting during the seed-to-adult transition, countering selection imposed by pollinators.

Animals↗

PubMed1989

Energy deposition in small cylindrical targets by ultrasoft x-rays.

A Monte Carlo technique has been employed to calculate the energy deposition events in small cylindrical targets (less than or equal to 100 nm), including sizes which represent the DNA duplex, nucleosome and chromatin fibre, by simulated electron tracks from C (278 eV), A1 (1487 eV) and Ti (4509 eV) characteristic ultrasoft x-rays in water. Detailed examples of input data tables for the generation of electron tracks produced from the x-ray photon interactions are presented. Frequencies of energy deposition events per gray for target sizes from 1 to 100 nm are given and comparisons have been made with radiations of different qualities.

Chromatin↗

PubMed1984

Contrasts in marital satisfaction throughout old age: an exchange theory analysis.

In aggregate, older spouses report moderate to high levels of marital satisfaction; however, it is not clear whether these evaluations continue throughout the duration of the marital career or if there are declines at different age stages of late life. Mean factor scores on frequency of positive interaction and negative sentiment with spouse were computed from questionnaire responses of 318 married persons aged 55 to 90 years in a quasilongitudinal design. Contrasts in levels of interaction and sentiment were apparent between three successive age groups, with greatest marital satisfaction found in 63- to 69-year-old group. Multiple regression analyses demonstrated continuity in social and personal predictors of marital satisfaction across all three old age groups, with greatest predictivity for 55- to 62-year-old group. Fewest predictors and least predictivity emerged for oldest group, aged 70 to 90 years. Results suggest greater potential for happiness as well as vulnerability than has heretofore been attributed to older marriages.

Aged↗

PubMed1994

Physical, psychological, and social resources as moderators of the relationship of stress to mental health of the very old.

The purpose of this pilot study was to assess the attenuating effects of physical, psychological, and social resources on the relationship between stress and mental health among the oldest old. Physical resources include perceived health and independence in functional and instrumental activities of daily living, while psychological resources include mastery, self-esteem, and coping. Social resources are measured by frequency of social interaction and size of the social network. Among the 124 women and 31 men (M = 89 years), greater independence in IADLs and greater perceived control of events significantly attenuated the adverse effects of strain on psychological well-being.

Activities of Daily Living↗

PubMed1995

Modelling thymic functions in a cellular automaton.

Along the lines developed by Celada and Seiden, for simulating an immune system by means of cellular automata, we have constructed a 'thymus' where T cells undergo positive and negative selection. The populations thus 'matured' have been analyzed and their performance has been tested in machina. The key feature of this thymus is to allow chance meeting and possible interaction between newly born T cells and antigen presenting cells. The latter represent both the epithelial and the dendritic cells of the biological organ and are equipped with MHC molecules that can accommodate selected self peptides. All possible specificities are represented among the virgin T cells entering the thymus, but this diversity is drastically reduced by the time they exit as mature elements. In the model organ the fate of T cells, i.e. whether they will undergo proliferation or apoptosis, is governed by their capacity to recognize MHCs and the affinity of this interaction. Crucial parameters turn out to be the concentration of presenting cells, the number of types of MHC per cell, the 'size of self' in terms of the number of different peptides and their prevalence. According to the results, events in the automaton can realize unforeseen cooperations and competitions among receptors, depending upon the interaction order and frequency, and ultimately determine the rescue or the killing of thymocytes. Thus the making of the mature T repertoire has a random component and cannot be completely predicted.

Antigen Presentation↗