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Rate and frequency interactions in the auditory brainstem response of the adult rat.

Tone pip stimuli were used at different repetition rates to examine influences upon auditory brainstem response components. Rate increases to 80.1/s result in significant latency increases in waves IV and V at all test frequencies. Rate effects occur in rostral brainstem response components which show frequency related latencies different from wave I. Amplitude measures decline at higher repetition rates for waves I and IV at most test frequencies. Rate effects are most pronounced at 8 kHz stimulation which is around the optimal behavioral frequency in rat. At higher rates the second peak of wave I is enhanced at 8 kHz, whereas the third peak of wave I at 40 kHz disappears. These results demonstrate that tone-specific stimuli provide sensitive measures of latency, amplitude and wave morphology of components of the auditory brainstem response as a function of stimulus repetition.

Acoustic Stimulation

Real-time interactive frequency filtering of molecular dynamics trajectories.

Molecular dynamics simulations of atomic motion in protein and nucleic acid molecules must be done on a femtosecond time-scale. Much of this rapid motion is unimportant for the slower changes that are most relevant to biological function (conformational changes, substrate binding, protein folding). The high-frequency motion makes simulations computationally expensive. More importantly, the high frequencies obscure visualization of the relevant dynamics processes. Sessions, Dauber-Osguthorpe and Osguthorpe presented a method for removing high-frequency motions from atomic co-ordinates of trajectories generated by simulation. While that study used fast Fourier methods and emphasized the use of filtering for analysis of trajectories, this communication describes a new method that makes it much easier to use frequency filtering in programs that display trajectories as a sequence of moving images. Tests of the method on systems extending from pure water to proteins and nucleic acid molecules in vacuo and in solution have demonstrated its general utility. Impressed with the power and simplicity of the new method, we wish to present it in sufficient detail to allow others to implement it themselves.

Fourier Analysis

Measurements of edge-induced visual contrast and a spatial-frequency interaction of the Cornsweet illusion.

Measurements were made of the perceived contrast that results from the Cornsweet illusion as a function of the edge contrast and edge width. The physical contrast was varied from 3% to 5%, and the visual extent of the Cornsweet edge varied from 0.1 degrees to 3.0 degrees on each side. Results show that, for low-contrast (less than 20%) and wide edges, the Cornsweet edge yields as much contrast as a real-step lumininance transition with the same edge magnitude. At high contrast (30%-40%) the illusion is reduced relative to a real step, regardless of whether the illusion consists of a conventional Cornsweet edge or an additive combination of a real step and a Cornsweet edge. As a general rule, wide edges yield more contrast than narrow edges. The results are interpreted in terms of the visual describing funtion; a nonlinear model is proposed. The correspondence between the predictions of the model and the perceptual measurements on the Cornsweet edges is good.

Humans

High-frequency ventilation-induced apnea: interaction of frequency, volume, FRC, and CO2.

Apnea is often observed during high-frequency oscillatory ventilation (HFOV). This study on anesthetized dogs varied the oscillator frequency (f) and determined the stroke volume (SV) at which apnea occurred. Relaxation functional residual capacity (FRC) and the eupneic breathing end-tidal CO2 level were held constant. Airway pressure and CO2 were measured from a side port of the tracheostomy cannula. An arterial cannula was inserted for blood gas analysis. Diaphragm electromyogram (EMG) was recorded with bipolar electrodes. Apnea was defined as the absence of phasic diaphragm EMG activity for a minimum of 60 s. During HFOV, SV was increased at each f (5-40 Hz) until apnea occurred. The apnea inducing SV decreased as f increased. SV was minimal at 25-30 Hz. Frequencies greater than 30 Hz required increased SV to produce apnea. The f-SV curve was defined as the apneic threshold. Increased FRC resulted in a downward shift (less SV at the same f) in the apneic threshold. Elevated CO2 caused an upward shift (more SV at the same f) in the apneic threshold. These results demonstrate that the apnea elicited by HFOV is dependent on the interaction of oscillator f and SV, the FRC, and CO2.

Animals

[Familiarity, favorability, and cognitive complexity: integration of frequency of interaction hypothesis and vigilance hypothesis].

Previous studies using Bieri's 'cognitive complexity' score had supported 'vigilance hypothesis' which assumed that impressions of unfavorable persons were more complex than favorable persons. Thus, Bieri's measure seemed to be invalid because the findings were completely contrary to 'frequency of interaction hypothesis', presented in the theoretical framework of 'cognitive complexity', which assumed that impressions of familiar persons were more complex than unfamiliar persons, since people could be supposed to have more intimate acquaintance with favorable persons. The purpose of present study was to indicate the invalidity was caused by the research design where familiarity was dependent on favorability and to show that even Bieri's score could support 'interaction hypothesis', if one variables could be statistically orthogonized to the other. In each of two surveys reported, about two hundred female undergraduates completed a Rep test where they rated favorable and unfavorable persons on the basis of some dimensions which included favorability and familiarity. The results obtained through various regression analyses supported the above predictions. Moreover, it was revealed that, with favorability controlled, Bieri's score showed almost linear increases as familiarity increased, though the score of extremely unfamiliar persons was rather higher than the score the linear function could predict.

Adult

Frequencies and interactions of regulatory T cells. I. The balance between help and suppression regulates the primary immune response to keyhole limpet hemocyanin in vitro.

Frequencies and efficiencies of regulatory T cells from non-immunized mice were estimated in several assay systems differing from each other in cellular composition and antigen dose (NIP-KLH). The NIP-specific and total IgM responses were quantified. Using 10(4) syngeneic B cells and 50 micrograms/ml NIP-KLH, helper (Th) cells from 5 day immune donors were detected in frequencies of 1:3000-1:4000 in lymphnode and spleen T cells, with an efficiency of 70-90 ng IgM/Th cell in C57B1/6 mice. In non-immune spleen T cells, Th cells were observed in frequencies of 1:16,000-1:38,000, with comparable efficiency, but these Th cells appeared suppressed at increased T cell doses. Polyclonal activation led to the appearance of multiple independently regulated populations of Th cells with similar efficiencies. In the presence of 10(5) syngeneic spleen cells, treated once with anti-Thy-1 antibody and complement and 50 micrograms/ml NIP-KLH, suppressor activity was observed in the same T cell population. Similar to help, suppression fluctuated with increasing T cell numbers. Using 1 x 10(6) spleen cells and 50 micrograms/ml NIP-KLH as assay system, T cells enhanced the responses. Again, several independently regulated populations were observed, with efficiencies slightly higher than those of the above-described Th cells. By maintaining the cellular components of the assay system constant (10(4) B cells) and titrating the antigen, Th cell frequencies showed little variation up to 100 micrograms/ml NIP-KLH and were always suppressed at higher T cell numbers. At 200 micrograms/ml NIP-KLH, the frequency was increased to approximately 1:2000, and not suppressed, i.e., was identical to the frequency observed in mice immunized 5 days previously. Efficiencies increased with increasing doses of antigen. The results strongly indicate that regulatory T cell function shows "plasticity", in the sense that the appearance and the frequencies of helping and suppressing T cell populations highly depend on the micro-environment present in culture.

Animals

Frequency-dependent interactions of mexiletine and quinidine on depolarization and repolarization in canine Purkinje fibers.

The use of the antiarrhythmic agents mexiletine and quinidine in combination can be clinically beneficial when single agent therapy is ineffective in ventricular tachyarrhythmias. We therefore compared the effects of mexiletine (10 microM), quinidine (10 microM) and a series of their combinations (total concentration 10 microM) in canine cardiac Purkinje fibers driven at a wide range of stimulation frequencies. All treatments depressed Vmax in tissues driven rapidly (cycle length 300 msec), but only with greater than or equal to 5 microM quinidine was Vmax depressed at longer cycle lengths. Moreover, the time constants for development of and recovery from frequency-dependent block were different: short (200-500 msec) for mexiletine, long (3-5 sec) for quinidine and intermediate or biexponential for the combination. Although both drugs depressed Vmax (albeit with different time dependencies), action potential duration at all cycle lengths from 300 to 8000 msec was shortened by mexiletine, lengthened by quinidine and largely unaltered by combinations. Fibers treated with quinidine in low Ko and driven at slow rates developed marked action potential prolongation and abnormal automaticity in the form of early afterdepolarizations; the addition of mexiletine was sufficient to reverse this effect. In summary, mexiletine and quinidine produced different and frequency-dependent effects on depolarization and repolarization. The effects of their combinations reflected these actions, with opposing actions on repolarization at any stimulation rate but additive frequency-dependent depression of Vmax. We conclude that the clinically beneficial effects of this combination may reflect additive frequency-dependent effects on cardiac sodium channels in the face of unaltered repolarization time.

Action Potentials

Selecting a cost-effective screening measure for the assessment of preschool social withdrawal.

The utility of teacher judgment (rankings, ratings) and peer judgment (sociometric ratings) were studied as screening variables for preschool social withdrawal/responsiveness. Observational measures of preschoolers' interaction were used as the validation criterion based upon theoretical, empirical, and practical considerations related to development of a multipurpose behavioral assessment system. Results indicated that teacher rankings of students' verbal interaction frequencies (1) were most highly correlated to interaction rate in two preschool settings, (2) had test-retest reliability consistently above Rho = .80, and (3) were useful in that 77% of teachers using this procedure could identify their least socially responsive student within five rankings. The peer nomination sociometric rating was the least reliable measure at retest (Rho = .35) and showed consistently the lowest correlation with observational indices of interaction partner preferences, e.g., reciprocal rate (Rho = .29 to .39). The tendency for relationships among screening measures and the criterion to increase at retest suggested a training effect on screening accuracy. The use of teacher rankings in combination with observational measures to confirm selection accuracy and for monitoring treatment progress is discussed as a cost-effective behavioral assessment procedure for preschool social withdrawal/responsiveness.

Child

Hemispheric differences are found in the identification, but not the detection, of low versus high spatial frequencies.

The processing of sine-wave gratings presented to the left and right visual fields was examined in four experiments. Subjects were required either to detect the presence of a grating (Experiments 1 and 2) or to identify the spatial frequency of a grating (Experiments 3 and 4). Orthogonally to this, the stimuli were presented either at threshold levels of contrast (Experiments 1 and 3) or at suprathreshold levels (Experiments 2 and 4). Visual field and spatial frequency interacted when the task required identification of spatial frequency, but not when it required only stimulus detection. Regardless of contrast level (threshold, suprathreshold), high-frequency gratings were identified more readily in the right visual field (left hemisphere), whereas low-frequency gratings showed no visual field difference (Experiment 3) or were identified more readily in the left visual field (right hemisphere) (Experiment 4). Thus, hemispheric asymmetries in the processing of spatial frequencies depend on the task. These results support Sergent's (1982) spatial frequency hypothesis, but only when the computational demands of the task exceed those required for the simple detection of the stimuli.

Adult

Mechanisms of electromagnetic interaction with cellular systems.

The question of how electromagnetic fields--static or low to high frequency--interact with biological systems is of great interest. The current discussion among biologists, chemists, and physicists emphasizes aspects of experimental verification and of defining microscopic and macroscopic mechanisms. Both aspects are reviewed here. We emphasize that in certain situations nonthermal interactions of electromagnetic fields occur with cellular systems.

Animals

Elucidation of the nifedipine-quinidine interaction.

Four case reports have been published that document a clinically significant drug interaction between nifedipine and quinidine in patients with left ventricular dysfunction. To define the population at risk and the mechanisms involved in manifestations of this interaction, 12 patients currently treated with quinidine for either ventricular or supraventricular arrhythmias were stratified into two groups based on left ventricular ejection fraction (EF) measurements (group A greater than 35%; group B less than 35%). The interaction was conducted through two phases: oral quinidine (Q) and oral quinidine plus nifedipine (N + Q). Pharmacokinetic modeling of total body clearance (CL) and AUC were assessed for each phase. One patient (group A, 70% EF) exhibited the interaction with a 41% decrease in steady-state serum quinidine concentrations. The patient's AUC and CL were 48.2 micrograms/ml.hr (Q) versus 28.6 micrograms/ml.hr (N + Q) and 94.4 ml/min (Q) versus 159.1 ml/min (N + Q), respectively. There was no difference in AUC or CL between the Q and N + Q phases or between groups A and B for the entire population. The N + Q interaction is not hemodynamically mediated. Clinical consideration of the possibility of this low-frequency interaction should be noted.

Adult

AQuA Tools: clear and reliable BEDPE operations for 3D genomics.

MOTIVATION: The genome interacts with itself within the volume of the cell nucleus to process information. These interactions mediate signal integration, gene regulation, and cell identity. The identification of new therapeutic targets from non-coding disease-associated variants relies critically on correctly assigning variants to genes through 3D interactions. Experimental techniques in 3D genomics, such as HiC and HiChIP, allow the mapping of interactions through sequencing. Bioinformatics for 3D genomics contends primarily with contact matrices that contain interaction frequencies for all possible element pairs, and BEDPE files that store element pairs that interact. Whereas the tools available for processing linear genomic data are mature, operating on contact matrices and BEDPE files remains cumbersome, opaque, and error-prone, as researchers have had to shoehorn tools originally designed for linear data. A genome arithmetic designed from the ground up for 3D genomics does not yet exist. RESULTS: We present AQuA Tools, a suite of shell- and R-based command-line tools that provide a set of core operations on contact matrices and BEDPE files motivated by key questions in population genetics, cancer research, and precision medicine. We have designed our core operations to be clear, reliable, intuitive and versatile. Core operations can be chained together along with standard UNIX commands. Our goal is to make AQuA Tools easy for the novice to learn and the go-to choice for power users. We hope our tools will motivate more researchers to use 3D genomic data in their projects. AVAILABILITY AND IMPLEMENTATION: We provide and maintain AQuA Tools at https://github.com/axiotl/aqua-tools.

Genomics

[Development of a method of screening for hemoglobin S for the purpose of genetic consultation in Cuba. Results of an analysis of 24,000 blood samples].

Electrophoretic screening system is worked out, which combines a high resolving power in polyacrylamide gel and a principle of simultaneous treatment of a large number of examples. 24,000 blood examples from inhabitants of Havana province (Cuba) are analysed in order to check the efficiency of the method described, to find the hemoglobin S frequency and to use these results in further genetic consulting. The frequency of hemoglobin S carriers is found to be 3.0%, that of hemoglobin C--0.7%. 15 rare hemoglobin variants are detected, 9 variants of alpha-chain and 3 variants of beta-chain are detected. One case was a result of hemoglobin S and a variant of alpha-chain interaction. Frequencies of S, C and A alleles were 0.016, 0.0038 and 0.98 respectively.

Anemia, Sickle Cell

The effects of a modeling film on social isolation in preschool children: a methodological investigation.

Children in Headstart program (N=113) were assessed on two occasions using a naturalistic observation system and peer sociometric measures. Thirty-two children were selected by O'Connor's (1969, 1972) convergent criteria of teacher rankings and being below 15% peer interaction frequency. Half of the children saw an experimental modeling film designed to teach children how to initiate entry into peer groups and half of the children saw a control film. The present investigation included methodological elements left uncontrolled in previous investigations. Results indicated no significant multivariate F ratios for treatment main effects, sociometric main effects, or treatment by sociometric interactions. This failure to replicate previous results with the O'Connor film raises serious methodological criticisms of previous work with socially withdrawn children.

Behavior Therapy

Integrated single-cell and spatial transcriptomic analyses reveal malignant epithelial glycolytic heterogeneity and spatial niche remodeling during colorectal cancer progression.

Colorectal cancer (CRC) progression is shaped by metabolic reprogramming and complex interactions within the tumor microenvironment. However, the cellular heterogeneity, spatial organization, and clinical relevance of glycolytic activity in CRC remain incompletely understood. In this study, we integrated single-cell RNA sequencing, bulk transcriptomics, and spatial transcriptomics data to systematically characterize glycolytic heterogeneity in CRC. Glycolytic activity was quantified using five independent scoring methods, consistently showing that epithelial cells exhibited the highest glycolytic activity across the two single-cell cohorts. Stratification of CopyKAT-verified aneuploid malignant epithelial cells into high-glycolysis (HG) and low-glycolysis (LG) subgroups by glycolysis scores revealed that HG cells exhibited higher stemness scores and chromosomal copy number variations. Cell-cell communication analysis revealed that, compared with LG cells, HG cells exhibited increased interaction frequency and strength with immune and stromal populations, indicating enhanced malignant epithelial-microenvironment crosstalk. Spatial transcriptomics analyses further revealed that glycolytic activity varied across normal colorectal tissue, primary CRC, and colorectal liver metastases, accompanied by progressive remodeling of epithelial-associated spatial niches and MIF-mediated intercellular communication. Bulk transcriptomic analysis identified a glycolysis-related prognostic signature with robust predictive performance, which served as an independent prognostic factor for overall survival in CRC cohorts. Collectively, these findings indicate that glycolytic heterogeneity is a key feature of CRC malignant epithelial cells and is closely associated with tumor progression, microenvironmental remodeling, and clinical outcomes.

Humans

A peer-mediated social network intervention to enhance the social integration of persons with moderate and severe disabilities.

Increasingly, parents, teachers, and students with disabilities are advocating for interventions that go beyond skill training to provide support for participation in integrated environments and support for friendships. The present research demonstrated a social network intervention for youths with moderate and severe disabilities. Two groups of nondisabled peers were recruited to participate in weekly discussions with an adult integration facilitator to increase opportunities for social interaction for 2 students (1 with autism and 1 who was moderately mentally retarded). The groups met to discuss social interactions that had occurred with the students with disabilities and to talk about strategies to promote greater inclusion of the students into ongoing social interaction. The nondisabled students participated in the design and implementation of social skills interventions during transition times and lunch. The nondisabled students used self-monitoring data sheets to record the quantity and quality of interactions. The frequency of interaction, number of opportunities for interaction, and appropriateness of social interactions were analyzed with a multiple baseline design. Results indicated that the social network intervention was successful in increasing the quantity and quality of interactions and that the network strategy promoted the development of friendships. The results are discussed in terms of the need for additional research showing the relationships between increases in social competence, peer-mediated intervention, and the development and support of friendship.

Adolescent

[The problems of evaluating the automatized and exploratory intellectual actions of man].

On the basis of psychological testing two groups of subjects have been formed: "automatizators" and "searchers". The incompatibility in the individual structure of the ability to automatized and searching actions, according to the data, are connected with the presence of the complex of alternative signs of cognitive styles. The neurophysiological organization of searching and automatized intellectual actions was studied by a method of computer toposcopy of the synchronous electrical processes. It has been shown that there are spatial-frequency interactions of electrical processes of the cerebral cortex, characteristic for each of the two above mentioned individuals groups, which are probably based on the functioning of neuronal networks with different lability levels.

Adult