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Perceived speech rate: the effects of articulation rate and speaking style in spontaneous speech.

In this study, the effect of articulation rate and speaking style on the perceived speech rate is investigated. The articulation rate is measured both in terms of the intended phones, i.e., phones present in the assumed canonical form, and as the number of actual, realized phones per second. The combination of these measures reflects the deletion of phones, which is related to speaking style. The effect of the two rate measures on the perceived speech rate is compared in two listening experiments on the basis of a set of intonation phrases with carefully balanced intended and realized phone rates, selected from a German database of spontaneous speech. Because the balance between input-oriented (effort) and output-oriented (communicative) constraints may be different at fast versus slow speech rates, the effect of articulation rate is compared both for fast and for slow phrases from the database. The effect of the listeners' own speaking habits is also investigated to evaluate if listeners' perception is based on a projection of their own behavior as a speaker. It is shown that listener judgments reflect both the intended and realized phone rates, and that their judgments are independent of the constraint balance and their own speaking habits.

Acoustic Stimulation↗

Is p53 polymorphism maintained by natural selection?

We present here a new interesting feature of the human tumor suppressor gene p53: a very pronounced ethnic and clinal variation of polymorphic codon 72 alleles. The frequency of the A1 (Pro) allele showed a north-south cline from 17% in Swedish Saamis to 63% in African Blacks (Nigerians), and there was a significant (p < 0.001) correlation (r = 0.95) between the A2 frequency and latitude. In the Finnish and Swedish populations no significant differences were found with respect to the genotype and allele distributions in spontaneously aborted fetuses and liveborn children, which makes differential intrauterine selection unlikely. However, the ethnic and clinal variations suggest that the codon 72 polymorphism is balanced and maintained by natural selection.

Alleles↗

HDAC7 regulates apoptosis in developing thymocytes.

Central immune tolerance is established in the thymus for T cells via a complex selection process that involves interactions between CD4+CD8+ double-positive thymocytes and antigen-presenting cells. Cells that express antigen receptors interacting strongly with self peptide MHC complexes are deleted from the repertoire via activation-induced apoptosis, a process termed negative selection. Cells that express an appropriate signal are positively selected and mature into single positive naïve T cells, either CD4 or CD8 positive. The balance between positive and negative selection is thought to play a critical role in the elimination of self-reactive clones and in the establishment of central immune tolerance. We have recently reported that HDAC7, a class II histone deacetylase, is highly expressed in CD4+CD8+ double positive thymocytes. HDAC7 inhibits Nur77 expression, an orphan receptor involved in antigen-induced cell death and in negative selection. The inhibitory effect of HDAC7 on the Nur77 promoter is mediated via the transcription factor MEF2D. During T cell receptor activation, HDAC7 is exported from the nucleus leading to the derepression of Nur77 expression and the induction of apoptosis. These observations define HDAC7 as a regulator of Nur77 and apoptosis in developing thymocytes and indicate that HDAC7 is likely to play an important role in the control of central immune tolerance.

Animals↗

Insecticide resistance genes in mosquitoes: their mutations, migration, and selection in field populations.

Insecticides have been used intensively to control insect populations over the last 50 years and many species of insects have developed resistance to several families of insecticides. These resistances are mainly due to two mechanisms: mutation of the insecticide target protein (leading to a decrease in its affinity for the concerned insecticide family), and increased detoxification. Recent molecular studies suggest that the mutations conferring resistance are rare and sometimes unique events in any given species. The wide geographic distribution of some of these genes can then only be explained by the balance between migration and selection at the population level.

Acetylcholinesterase↗

Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens.

Lineage trees of mutated rearranged Ig V region sequences in B lymphocyte clones often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation. In this study, we use a novel method for analyzing lineage tree shapes, using terms from graph theory to quantify the differences between primary and secondary diversification in rabbits and chickens. In these species, Ig gene diversification starts with rearrangement of a single (in chicken) or a few (in rabbit) V(H) genes. Somatic hypermutation and gene conversion contribute to primary diversification in appendix of young rabbits or in bursa of Fabricius of embryonic and young chickens and to secondary diversification during immune responses in germinal centers (GCs). We find that, at least in rabbits, primary diversification appears to occur at a constant rate in the appendix, and the type of Ag-specific selection seen in splenic GCs is absent. This supports the view that a primary repertoire is being generated within the expanding clonally related B cells in appendix of young rabbits and emphasizes the important role that gut-associated lymphoid tissues may play in early development of mammalian immune repertoires. Additionally, the data indicate a higher rate of hypermutation in rabbit and chicken GCs, such that the balance between hypermutation and selection tends more toward mutation and less toward selection in rabbit and chicken compared with murine GCs.

Algorithms↗

[Serum anion gap in the umbilical cord blood of healthy newborn infants].

This paper presents the results of the determination of serum anion gap in arterial and venous umbilical cord blood obtained from a carefully selected group of 47 healthy term newborns. In the arterial blood, the following concentrations of particular anions were found: chloride - 102.85 +/- 4.35 mmol/l, bicarbonate - 22.26 +/- 2.67 mmol/l, protein anions - 11.89 +/- 1.00 mmol/l, and residual anions - 14.26 +/- 4.35 mmol/l, while in the venous blood these values were: chloride - 104.28 +/- 4.14 mmol/l, bicarbonate - 20.79 +/- 2.70 mmol/l, protein anions - 12.48 +/- 1.23 mmol/l, and residual anions - 13.03 +/- 3.06 mmol/l. Provided strict clinical and biochemical (acid-base balance and blood gases) selections criteria are applied, these data are likely to represent normal values for term newborns and can be the basis for comparison of umbilical serum anion gap in newborns under depressed conditions, like asphyxia. As discussed, the role of serum anion gap studies in the diagnosis of the type of metabolic acidosis, as well as in the monitoring of neonatal therapy is most important.

Acid-Base Equilibrium↗

Nutritional assessment of hospitalized patients with head and neck cancer.

Nutritional assessment is an important part of the oncologic management of the cancer patient. Although it may be easy to identify weight loss, the criteria for negative energy balance are difficult to display in an ordinary clinical setting. In the present study we assessed the nutritional status and calculated the energy balance in 10 randomly selected cancer patients who were hospitalized at our ENT department. Loss greater than 10% of habitual weight was apparent in 5 patients, while only 2 of these had subnormal serum albumin levels. Another 1 of these patients with weight loss demonstrated reduced arm muscle circumference. Weight index, total body potassium and other anthropometric data did not significantly correlate with weight loss. Although supplementary nutrition was administered to most patients during hospitalization, only 4 patients were in positive energy balance as calculated from food tables. Only 2 out of 5 patients with a history of weight loss were in a positive energy balance. A questionnaire disclosed that insufficient considerations for the patients' food availability were shown. We conclude that malnutrition is a common and often an occult phenomenon in hospitalized patients. This may have an unfavorable influence on oncologic treatment and clinical outcome.

Aged↗

"Routine" preoperative studies. Which studies in which patients?

The utility of mass screening of preoperative patients has never been demonstrated for the majority of tests. Although screening patients to uncover occult disease appears logical, in reality it has resulted in excessive expenditure of our health care dollars with limited benefit. More than $30 billion is spent annually on preoperative examinations, 60% of which are unnecessary. In addition, iatrogenic injury has resulted from the further evaluation and treatment of false-positive results. A selective utilization of routine examinations can accurately supplement the clinician's evaluation, providing the patient with a complete preoperative assessment. The benefits of selective testing must be balanced against the possible omission of warranted examinations, highlighting the need for a more reliable system for test ordering.

Adult↗

A general model for the evolution of recombination.

A general representation of multilocus selection is extended to allow recombination to depend on genotype. The equations simplify if modifier alleles have small effects on recombination. The evolution of such modifiers only depends on how they alter recombination between the selected loci, and does not involve dominance in modifier effects. The net selection on modifiers can be found explicitly if epistasis is weak relative to recombination. This analysis shows that recombination can be favoured in two ways: because it impedes the response to epistasis which fluctuates in sign, or because it facilitates the response to directional selection. The first mechanism is implausible, because epistasis must change sign over periods of a few generations: faster or slower fluctuations favour reduced recombination. The second mechanism requires weak negative epistasis between favourable alleles, which may either be increasing, or held in check by mutation. The selection (si) on recombination modifiers depends on the reduction in additive variance of log(fitness) due to linkage disequilibria (v1 < O), and on non-additive variance in log(fitness) (V'2, V'3.. for epistasis between 2, 3.. loci). For unlinked loci and pairwise epistasis, si = --(v1 +4V2/3)deltar, where deltar is the average increase in recombination caused by the modifier. The approximations are checked against exact calculations for three loci, and against Charlesworth's analyses of mutation/selection balance (1990), and directional selection (1993). The analysis demonstrates a general relation between selection on recombination and observable components of fitness variation, which is open to experimental test.

Biological Evolution↗

Controlling inbreeding by constraining the average relationship between parents of young bulls entering AI progeny test programs.

In breeding is known to impair the health, fertility, and productivity of dairy cattle and other livestock species. Mating programs can address inbreeding concerns on the farm, at least in the short term, but long-term control of inbreeding in a dairy population requires consideration of relationships between young bulls entering AI progeny test programs. The present study discusses an application of optimal contribution methodology to selection of young AI bulls in the five major US dairy breeds. Elite cows and active AI sires from the Ayrshire, Brown Swiss, Guernsey, Holstein, and Jersey breeds were considered as potential bull parents. Genetic merit of selected sires and dams was maximized subject to various constraints on the mean additive genetic relationship within the selected group. Relationships between selected parents can be reduced substantially relative to current levels, but the corresponding reduction in genetic merit may be large. This loss in genetic merit occurs due to lower selection intensity, although it is mainly a reflection of a larger number of bull parents (with progeny more evenly distributed among these parents), rather than selection of genetically inferior "outcross" parents that wouldn't otherwise have been considered. Selected parents were generally older and slightly less inbred than those that would have been chosen had inbreeding been ignored. Although severe restrictions on relationships can be costly, in terms of lost genetic progress, it appears that moderate constraints can keep relationships at a manageable level without a significant loss in genetic merit. Cooperation between breed associations and several competing AI companies may be required to facilitate implementation of this methodology in dispersed populations, but if this can be accomplished, prospects for achieving a balance between inbreeding and selection seem positive.

Animals↗

Prediction of dry matter intake throughout lactation in a dynamic model of dairy cow performance.

In the dynamic modeling of dairy cow performance over a full lactation, the difference between net energy intake and net energy used for maintenance, growth, and output in milk accumulates in body reserves. A simple dynamic model of net energy balance was constructed to select, out of some common dry matter intake (DMI) prediction equations, the one that resulted in a minimum cumulative bias in body energy deposition. Dry matter intake was predicted using the Cornell Net Carbohydrate and Protein System, Agricultural Research Council, or National Research Council (NRC) DMI equations from body weight (BW) and predicted fat-corrected milk yield. The instantaneous BW of cows at progressive weeks of lactation was simulated as the numerical integral of the BW change obtained from the predicted net energy balance. Predicted DMI and BW from each DMI equation, using either of 2 equations to describe maintenance energy expenditures, were compared statistically against observed data from 21 herd average published full lactation data sets. All DMI equations underpredicted BW and DMI, but the NRC DMI equation resulted in the minimum cumulative error in predicted BW and DMI. As a general solution to prevent predicted BW from deviating substantially over time from the observed BW, a lipostatic feedback mechanism was integrated into the NRC DMI equation as a 2-parameter linear function of the relative size of simulated body reserves and week of lactation. Residual sum of squares was reduced on average by 52% for BW predictions and by 41% for DMI predictions by inclusion of the negative feedback with parameters taken from the average of all 21 least squares fits. Similarly, root mean square prediction error (%) was reduced by 30% on average for BW predictions and by 23% for DMI predictions. Inclusion of a feedback of energy reserves onto predicted DMI, simulating lipostatic regulation of BW, solved the problem of final BW deviation within a dynamic model and improved its DMI prediction to a satisfactory level.

Adipose Tissue↗

Multisensory training of standing balance in older adults: I. Postural stability and one-leg stance balance.

BACKGROUND: The effects of standing balance training on the ability to maintain stability in both static two-leg and one-leg stance were tested in healthy older adults. METHODS: Subjects (age range 65-90 years) were randomly assigned to a training (n = 12) or control group (n = 12). Training subjects received a 10-hour balance training program which selectively manipulated sensory inputs from the visual, vestibular, and somatosensory systems. RESULTS: Training subjects showed significantly improved stability (root-mean-square values of anteroposterior platform torque) after training in five of the eight training conditions (when somatosensory inputs were changed or when two or more sensory systems were simultaneously manipulated) (p < .006). When tested 4 weeks after completion of training, subjects (a) fell less frequently when the ankle/foot somatosensory inputs were minimized and (b) stood longer on one leg than the control group (p < .001). CONCLUSIONS: Balance training designed to improve intersensory interaction could effectively improve balance performance in healthy older adults.

Accidental Falls↗

A beta-lactamase-dependent Gal4-estrogen receptor beta transactivation assay for the ultra-high throughput screening of estrogen receptor beta agonists in a 3456-well format.

Estrogen action is mediated via two estrogen receptor (ER) subtypes, ERalpha and ERbeta. Selective ER modulators with balanced high affinity for ERalpha and ERbeta have been developed as therapeutics for the treatment of a variety of diseases, including hormone-responsive breast cancer and osteoporosis. Recent data based primarily on the evaluation of ER-knockout mice have revealed that ERalpha and ERbeta may regulate separate and distinct biological processes. The identification of ERbeta specific ligands could further enhance our understanding of ERbeta biology. In addition, compounds targeting ERbeta may prove useful as therapeutic agents with activity profiles distinguishable from that of estradiol. To discover novel selective ligands for ERbeta, we developed and characterized a cell-based Gal4-ERbeta beta-lactamase reporter gene assay (GERTA) in CHO cells for the ligand-induced activation of the human ERbeta. The sensitivity and selectivity of this assay were found to be comparable to those of an ER ligand-binding assay. The assay was optimized for screening in an ultra high throughput 3456-well nanoplate format and was successfully used to screen a large compound collection for ERbeta agonists. Compounds identified in a primary screen were tested in an in vitro ligand-binding assay to characterize further the selectivity and potency for ERbeta.

Animals↗

EMERGY-based environmental systems assessment of a multi-purpose temperate mixed-forest watershed of the southern Appalachian Mountains, USA.

Emergy (with an 'm') synthesis was used to assess the balance between nature and humanity and the equity among forest outcomes of a US Forest Service ecosystem management demonstration project on the Wine Spring Creek watershed, a high-elevation (1600 m), temperate forest located in the southern Appalachian mountains of North Carolina, USA. EM embraces a holistic perspective, accounting for the multiple temporal and spatial scales of forest processes and public interactions, to balance the ecological, economic, and social demands placed on land resources. Emergy synthesis is a modeling tool that allows the structure and function of forest ecosystems to be quantified in common units (solar emergy-joules, sej) for easy and meaningful comparison, determining 'system-value' for forcing factors, components, and processes based on the amount of resources required to develop and sustain them, whether they are money, material, energy, or information. The Environmental Loading Ratio (ELR), the units of solar emergy imported into the watershed via human control per unit of indigenous, natural solar emergy, was determined to be 0.42, indicating that the load on the natural environment was not ecologically damaging and that excess ecological capacity existed for increasing non-ecological activities (e.g. timbering, recreation) to achieve an ELR of 1.0 (perfect ecological-economic balance). Three forest outcomes selected to represent the three categories of desired sustainability (ecological, economic, and social) were evaluated in terms of their solar emergy flow to measure outcome equity. Direct economic contribution was an order of magnitude less (224 x 10(12)solar emergy-joules (sej) ha(-1)) than the ecological and social contributions, which were provided at annual rates of 3083 and 2102 x 10(12)sejha(-1), respectively. Emergy synthesis was demonstrated to holistically integrate and quantify the interconnections of a coupled nature-human system allowing the goals of ecological balance and outcome equity to be measured quantitatively.

Appalachian Region↗

Waiting list for kidney transplant. Some patients wait too long.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.

Algorithms↗

Prognostic importance of cardiac arrhythmias in systemic sclerosis.

Ambulatory electrocardiography was performed in 183 patients with systemic sclerosis recruited from five centers who were selected to reflect a balanced population with respect to disease extent and duration. Ventricular ectopy occurred in 67 percent of patients and was strongly correlated by both univariate and multivariate analyses with total mortality and with sudden death. By multivariate analysis, ventricular ectopy was strongly associated with increasing patient age and with other evidence of cardiac and pulmonary involvement but not with clinical and laboratory measures of duration and extent of systemic sclerosis. Evidence of myocardial fibrosis thought to be secondary to microvascular alteration is common in systemic sclerosis, but the clinical implications of myocardial involvement are less well appreciated. The present data suggest the need for ambulatory electrocardiography in the clinical assessment of selected patients with systemic sclerosis, especially those with cardiac or pulmonary involvement, as well as for studies of the effects of antiarrhythmic therapy.

Adolescent↗

Signals of Natural Selection Across Regions of Low Recombination in Wild Populations of the Purple Sea Urchin, Strongylocentrotus purpuratus.

Structural variants (SVs) are increasingly recognized as important components of genetic architecture. Yet our understanding of the evolutionary forces maintaining SVs in natural populations is limited. Chromosomal inversions in particular can facilitate local adaptation in populations with high gene flow, including many marine species. The purple sea urchin (Strongylocentrotus purpuratus) is a powerful system to study these dynamics due to its high gene flow, lack of population structure, and broad latitudinal range. We analyzed whole genome sequence data from 137 individuals sampled across seven populations to identify regions of low recombination using scans for elevated linkage disequilibrium and genetic differentiation. Such regions may arise from structural variants, including chromosomal inversions. We identified nine regions showing signatures of reduced recombination, including three way genotype clustering, long range linkage, and hanging bridge patterns frequently associated with inversion polymorphisms. The regions were polymorphic within locations and along the species range with three loci showing concordant signatures of balancing and spatially heterogeneous selection based on enrichment of outliers and distinct patterns of allelic age. Additionally, these loci showed enrichment for genes associated with biomineralization and development. Our results provide the first evidence for regions of low recombination in the purple sea urchin genome, several of which display genomic signatures consistent with structural variants such as chromosomal inversions. These findings add to growing evidence that regions of reduced recombination constitute an important component of standing genetic variation in natural populations and may play a key role in adaptation to heterogeneous environments.

Strongylocentrotus purpuratus↗

The effect of altered sodium balance upon renal vascular reactivity to angiotensin II and norepinephrine in the dog. Mechanism of variation in angiotensin responses.

The mechanism whereby the vasoconstrictor response to angiotensin II (AII) is influenced by sodium balance or disease is unclear. To explore this question, the renal vascular responses (RVR) to intrarenal injections of subpressor doses of AII and norepinephrine were studied in dogs with an electromagnetic flowmeter. Acute and chronic sodium depletion increased plasma renin activity (PRA) and blunted the RVR to AII, while acute sodium repletion and chronic sodium excess plus desoxycorticosterone acetate decreased PRA and enhanced the RVR to AII. The magnitude of the RVR to AII was inversely related to PRA. The RVR to norepinephrine was unaffected by sodium balance and was not related to PRA. Inhibition of the conversion of angiotensin I to AII by SQ 20,881 during sodium depletion lowered mean arterial blood pressure (MABP), increased renal blood flow (RBF), and enhanced the RVR to AII but not to norepinephrine. Administration of bradykinin to chronically sodium-depleted dogs also lowered the MABP and increased RBF but had no effect on the RVR to AII. SQ 20,881 had no effect on MABP, RBF, or the RVR to AII in the dogs with chronic sodium excess and desoxycorticosterone acetate. Administration of indomethacin to chronically sodium-depleted dogs lowered RBF but did not influence the RVR to AII. The results indicate that the RVR to AII is selectively influenced by sodium balance and that the magnitude of the response is inversely related to the availability of endogenous AII. The data did not suggest that the variations in the RVR to AII were because of direct effects of sodium on vascular contraction, changes in the number of vascular AII receptors, or the renal prostaglandins. The results are consistent with the hypothesis that the vasoconstrictor effect of AII in the renal vasculature is primarily dependent upon the degree to which the AII vascular receptors are occupied by endogenous hormone.

Angiotensin II↗