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A tracking FFT processor for pulsed Doppler analysis beyond the Nyquist limit.

A tracking procedure for processing ultrasound pulsed Doppler signals with instantaneous frequencies beyond the Nyquist limit is discussed. It is based on the observation that the frequency translation required to properly reconstruct an aliased spectrum can be achieved by means of a simple reordering of data provided by a digital fast Fourier transform (FFT) unit. The amount of reordering is automatically derived by the computed value of a spectral parameter, e.g., the mean frequency. The procedure has been tested by introducing some modifications at the output of an FFT unit included in a conventional pulsed Doppler system. As a result, the dynamic evolution of the full Doppler spectrum and related mean frequency can be followed in real time over an extended range. In vitro and in vivo experiments, as well as quantitative measurements carried on with test signals are presented.

Fourier Analysis

Application of molecular dynamics with interproton distance restraints to three-dimensional protein structure determination. A model study of crambin.

The applicability of restrained molecular dynamics for the determination of three-dimensional protein structures on the basis of short interproton distances (less than 4 A) that can be realistically determined from nuclear magnetic resonance measurements in solution is assessed. The model system used is the 1.2 A resolution crystal structure of the 46 residue protein crambin, from which a set of 240 approximate distance restraints, divided into three ranges (2.5 +/- 0.5, 3.0+0.5(-1.0) and 4 +/- 1 A), is derived. This interproton distance set comprises 159 short-range ([i-j] less than or equal to 5) and 56 ([i-j] greater than 5) long-range inter-residue distances and 25 intra-residue distances. Restrained molecular dynamics are carried out using a number of different protocols starting from two initial structures: a completely extended beta-strand; and an extended structure with two alpha-helices in the same positions as in the crystal structure (residues 7 to 19, and 23 to 30) and all other residues in the form of extended beta-strands. The root-mean-square (r.m.s.) atomic differences between these two initial structures and the crystal structure are 43 A and 23 A, respectively. It is shown that, provided protocols are used that permit the secondary structure elements to form at least partially prior to folding into a tertiary structure, convergence to the correct final structure, both globally and locally, is achieved. The r.m.s. atomic differences between the converged restrained dynamics structures and the crystal structure range from 1.5 to 2.2 A for the backbone atoms and from 2.0 to 2.8 A for all atoms. The r.m.s. atomic difference between the X-ray structure and the structure obtained by first averaging the co-ordinates of the converged restrained dynamics structures is even smaller: 1.0 A for the backbone atoms and 1.6 A for all atoms. These results provide a measure with which to judge future experimental results on proteins whose crystal structures are unknown. In addition, from an examination of the dynamics trajectories, it is shown that the convergence pathways followed by the various simulations are different.

Hydrogen Bonding

A sex-chromosome hybrid zone in the grasshopper Podisma pedestris (Orthoptera: Acrididae).

Podisma pedestris exists as both an XO and neoXY form in the Southern French Alps. These chromosome types are shown to be contiguously allopatric and hybrid populations have been located in several places. Hybridisation appears to be occurring freely, but the hybrid zones are quite narrow. In several places the two distributions are separated by geographic barriers such as high mountain ridges and lowlands. The history of this XY chromosomal race is discussed in the light of the genetic dynamics of hybrid zones and the biogeography of this situation. Its origin is probably post-glacial, and it may be extending its range as a salient in one region. A comparison of the porperties of similar cases indicates that the formation of such chromosomal races may be a frequent event in relatively immobile species that are subjected to isolation and expansion by major climatic and ecological changes.

France

Characteristics of spinoreticular and spinothalamic neurons with renal input.

Spinoreticular (SRT) and spinothalamic (STT) neurons were studied for responses to renal and somatic stimuli in 34 cats that were anesthetized with alpha-chloralose. SRT cells were antidromically activated from the medial medullary reticular formation near the gigantocellular tegmental field contralateral (35 cells), ipsilateral (15 cells), or both contralateral and ipsilateral (11 cells) to the recording site. Collision tests showed that activation from two electrodes resulted from stimulation of separate axonal branches and not from current spread. Twenty STT cells were activated from the spinothalamic tract just medial to the medial geniculate nucleus. SRT cells were located in laminae I, V, VII, and VIII of the T12-L2 segments. Most cells were located in lamina VII. STT cells were found in laminae I, V, and VII. The axons of 12 SRT cells were located in the ventrolateral or ventral quadrants of the upper cervical spinal cord. Antidromic conduction velocities of SRT cells averaged 48.7 +/- 3.7 m/s. No differences in conduction velocity were found between cells projecting to different reticular sites. In addition conduction velocity did not vary with the type of somatic or renal input. Antidromic conduction velocities of STT cells averaged 46.4 +/- 4.7 m/s. Renal nerve stimulation excited 58 and inhibited 3 SRT cells. All 20 STT cells were excited. Thirty SRT cells were excited only by A-delta input, 26 received both A-delta- and C-fiber inputs, and 2 cells received only C-fiber input. Ten STT cells received A-delta input only and 10 received both A-delta- and C-fiber inputs. All cells with renal input also received somatic input. Thirty-six SRT cells (59%) were classified as high threshold, 12 (20%) as wide dynamic range, and 10 (16%) as deep. Ten STT cells were classified as high threshold and 10 as wide dynamic range. Somatic receptive fields of STT cells were usually simple and invariably included the left flank region, although many of the fields extended to the left hindlimb or abdomen. Eighteen of the 20 were restricted to the ipsilateral side. In contrast, somatic receptive fields of SRT cells were primarily bilateral (71%). While all but two receptive fields included the left flank area, most extended to one or both hindlimbs, the abdomen, or the right flank. Inhibitory receptive fields were found for 33% of the SRT cells and 20% of the STT cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways

[Inhibitory effect of prolactin secretion by luteinizing hormone releasing hormone agonist (buserelin)].

The LH RH agonist Buserelin was continuously administered through the nose over an extended period to 5 patients with endometriosis at daily doses ranging between 300 micrograms and 1,200 micrograms. The clinical findings and endocrinological dynamics, with emphasis on PRL secretion function, were investigated and the findings below were obtained. The clinical findings showed Buserelin to be effective against endometriosis. The administration of Buserelin markedly inhibited the secretion of LH and FSH under LH-RH loading. The administration of Buserelin markedly inhibited the secretion of PRL and the degree of inhibition appeared to be dependent on the dose and duration of Buserelin administration. No correlation between E2 and PRL was observed during Buserelin administration. The findings suggest that Buserelin inhibits PRL secretion by direct CNS activity, not indirectly through inhibition of E2 production.

Administration, Intranasal

Response and receptive-field properties of spinomesencephalic tract cells in the cat.

Recordings were made from 90 identified spinomesencephalic tract (SMT) cells in the lumbosacral spinal cord of cats anesthetized with alpha-chloralose and pentobarbital sodium. Recording sites were located in laminae I-VIII. Antidromic stimulation sites were located in different regions of the rostral and caudal midbrain including the periaqueductal gray, midbrain reticular formation, and the deep layers of the superior colliculus. Twelve SMT cells were antidromically activated from more than one midbrain level or from sites in the medial thalamus. The mean conduction velocity for the population of cells sampled was 45.2 +/- 21.4 m/s. Cells were categorized based on their responses to graded intensities of mechanical stimuli and the location of excitatory and/or inhibitory receptive fields. Four major categories of cells were encountered: wide dynamic range (WDR); high threshold (HT); deep/tap; and nonresponsive. WDR and HT cells had excitatory and/or inhibitory receptive fields restricted to the ipsilateral hindlimb or extending to other parts of the body including the tail, forelimbs, and face. Some cells had long afterdischarges following noxious stimulation, whereas others had high rates of background activity that was depressed by nonnoxious and noxious stimuli. Deep/tap cells received convergent input from muscle, joint, or visceral primary afferent fibers. The placement of mechanical lesions at different rostrocaudal levels of the cervical spinal cord provided information related to the spinal trajectory of SMT axons. Six axons were located contralateral to the recording electrode in the ventrolateral/medial or lateral funiculi while two were located in the ventrolateral funiculus of the ipsilateral spinal cord. Stimulation at sites used to antidromically activate SMT cells resulted in the inhibition of background and evoked responses for 22 of 25 cells tested. Inhibitory effects were observed on responses evoked by low/high intensity cutaneous stimuli and by the activation of joint or muscle primary afferent fibers. Based on the response and receptive-field properties of SMT cells it is suggested that the SMT may have an important role in somatosensory mechanisms, particularly those related to nociception.

Animals

Mammographic equipment, technique, and quality control.

The most important improvements in mammographic technique were the introduction of single- or double-emulsion high-contrast film-screen combinations for mammography, the use of a specially designed low-kilovoltage Bucky grid to reduce scattered radiation, and the introduction of smaller focal spots to improve imaging geometry. Magnification techniques, especially the spot-film technique, yields clearer delineation of high-contrast microcalcifications. Dedicated mammographic equipment with specially designed x-ray tubes is necessary for modern high-quality mammography. However, in many modern mammographic units, the automatic exposure controller still fails to provide appropriate and constant optical film density over a wide range of tissue thickness and absorption. Extended-cycle processing of single-emulsion mammographic films can yield better image contrast and reduce exposure by up to 30%. Exposure times of less than 1 second are recommended to avoid the unnecessary higher doses caused by longer exposure times and reciprocity law failure. The wide dynamic range in mammography can be reduced by a beam equalization filter, and thus be better adapted to the decreased latitude of modern high-contrast mammographic screen-film systems. Mammographic film reading (detection of subtle microcalcifications) can be facilitated by modern computer evaluation of previously digitized mammograms. Standardization and assurance of image quality have been major challenges in the technical development of mammography. Different technical and anthropomorphic phantoms have been designed to measure and compare practical image quality. Detailed quality control measures have been developed. The benefit of a single or annual screening mammography, calculated in gained life expectancy, by far outweighs the relative risk for radiation-induced breast cancer.

Female

A model describing nonlinearities in hearing by active processes with saturation at 40 dB.

Data from literature related to nonlinearities of the peripheral part of the hearing system are collected and extended by results from measurements of acoustical responses, masking, cubic difference tones and Zwicker tones. The data indicate 40 dB as a significant value for the dynamic range in neurophysiology as well as for the sensation level in psychoacoustics dividing the total level range into two areas of different characteristics. A preliminary model assuming that the outer hair cells act as an amplifier which contains saturation (corresponding to 40 dB) and feed back to sensitize the inner hair cells is used to describe the measured effects at least qualitatively.

Auditory Fatigue

White noise analysis of Phycomyces light growth response system. II. Extended intensity ranges.

By means of white gaussian noise stimulation, the Wiener kernels are derived for the Phycomyces light growth response for a variety of intensity conditions. In one experiment the intensity I, rather than log I, is used as the input variable. Under the very limited dynamic range of that experiment, the response is fairly linear. To examine the dependence of the kernels on dynamic range, a series of experiments were performed in which the range of log I was halved and doubled relative to normal. The amplitude of the kernels, but not the time course, is affected strongly by the choice of dynamic range, and the dependence reveals large-scale nonlinearities not evident in the kernels themselves. In addition kernels are evaluated for experiments at a number of absolute intensity levels ranging from 10(-12) to 10(-3) W/cm2. The kernel amplitudes are maximal at about 10(-6) W/cm2. At 10(-12) W/cm2, just above the absolute threshold, the respond is very small. The falloff at high intensity, attributable to inactivation of the photoreceptor, is analyzed in the framework of a first-order pigment kinetics model, yielding estimates for the partial extinction coefficient for inactivation epsilonI455 = (1.5 +/- 0.2) X 10(4) liter/mol-cm and a regeneration time constant of tau = (2.7 +/- 0.6) min. A model is introduced which associates the processes of adaptation and photoreceptor inactivation. The model predicts that the time constants for adaptation and pigment should be identical. This prediction is consistent with values in this and the preceding paper. The effects of pigment inactivation are simulated by a linear electronic analog circuit element, which may be cascaded with the linear simulator circuit in the preceding paper.

Adaptation, Physiological

A versatile and sensitive method for measuring oxygen.

Oxygen dependence of the lifetime of the excited triplet state of phosphorescent molecules can be used to measure the oxygen concentration in aqueous media. These measurements are insensitive to much of the optical interference that limits the usefulness of measurements based on the oxygen dependent quenching of luminescence intensity. The measurements also extend to significantly lower oxygen concentrations than are normally attainable using oxygen electrodes. The phosphorescence lifetimes can be accurately measured from a few microseconds to seconds, permitting a wide dynamic range of oxygen concentration measurements. With currently available probes, for example, it is possible to make continuous measurement of oxygen concentrations from 10(-4) M to 10(-8) M in a single experiment.

Animals

EMG responses to load perturbations of the upper limb: effect of dynamic coupling between shoulder and elbow motion.

Load perturbations were applied to the arm of human subjects under conditions where both limb segments (upper arm and forearm) were free to move. The perturbations consisted of pulses of torque 50 ms in duration and of pseudo-random sequences of such pulses. They were applied to either the forearm or the upper arm. Under all conditions, the perturbations resulted in angular motion at the shoulder and elbow joints and evoked consistent responses in muscles acting about these joints (biceps, triceps, anterior and posterior deltoid). Activity in biceps and triceps was not related simply to angular motion at the elbow joint. For example, activation of biceps could be evoked during elbow flexion (by applying a torque perturbation at the shoulder) as well as during elbow extension (by applying a torque perturbation at the elbow). The effect of varying degrees of dynamic coupling between upper arm and forearm on EMG responses was investigated by applying torque perturbations to the upper arm over a wide range of elbow angles. When the forearm is extended, such a perturbation induces a greater amount of elbow flexion than when the forearm is in a flexed position. The results of these experiments showed that the larger was the amount of flexion of the forearm induced by the perturbation, the larger was the activation of biceps. The results are incompatible with the notion of a negative feedback of total muscle length as being responsible for the EMG activity following the load perturbations. It is suggested that the EMG responses can best be interpreted functionally in terms of parameters more global than muscle length. Among such global parameters, changes in net torque at a joint resulting from the perturbation gave the best correlation with the pattern of EMG activities observed.

Arm

Solution conformation of thymosin beta 4: a nuclear magnetic resonance and simulated annealing study.

The conformation of the polypeptide thymosin beta 4 in solutions of 60% (v/v) trifluoroethanol-d3 and 50% (v/v) hexafluoroisopropyl-d2 alcohol in water is investigated by nuclear magnetic resonance (NMR) spectroscopy. Under these conditions thymosin beta 4 adopts an ordered structure. By use of a combination of two-dimensional NMR techniques, the 1H NMR spectrum of thymosin beta 4 is assigned. A set of 180 approximate interproton distance constraints is derived from nuclear Overhauser enhancement (NOE) measurements. These, together with 33 phi constraints obtained for JNH alpha coupling data and the 23 psi dihedral angles identified on the basis of the pattern of short-range NOEs, form the basis of a three-dimensional structure determination by dynamical simulated annealing. The calculations are carried out starting from three initial structures, an alpha-helix, an extended beta-strand, and a mixed alpha/beta structure. Ten independent structures are computed from each starting structure by using different random number seeds for the assignments of the initial velocities. All 30 calculated structures satisfy the experimental constraints, display very small deviations from idealized covalent geometry, and possess good nonbonded contacts. Analysis of the 30 converged structures indicates that there are two helical regions extending from residues 4-16 and from residues 30-40, which are well defined both in terms of atomic root mean square differences and backbone torsion angles. For the two helical regions individually the average backbone rms difference between all pairs of structures is approximately 2 A. The two helices exhibit typical amino acid preferences for specific locations at the ends of helices.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Optical plankton analyser: a flow cytometer for plankton analysis, II: Specifications.

An analysing flow cytometer, the optical plankton analyser (OPA), is presented. The instrument is designed for phytoplankton analysis, having a sensitivity comparable with commercially available flow cytometers, but a significantly extended particle size range. Particles of 500 microns in width and over 1,000 microns in length can be analysed. Sample flow rates of up to 55 microliters/s can be used. Also, the dynamic range of the instrument is significantly increased for particles larger than about 5 microns. The optics, hydraulics, and electronics of the instrument are described, including the best form for a low fluid shear cuvette. The new pulse quantification technique we call digital integration is presented. This technique is essential for the instrument to handle both short and very long particles with a large dynamic range. Test measurements demonstrating particle size range and dynamic range are presented. Dynamic ranges of 10,000 and 100,000 were typically observed, measuring field samples with Microcystis aeruginosa colonies, whereas one sample showed a dynamic range of 10(6). A simple method for interpretation of time of flight (TOF) data in terms of particle morphology is presented. The specifications of the instrument are given.

Electronic Data Processing

Quantitative assessment of disparity vergence components.

Earlier evidence suggests qualitatively that at least two control modes may mediate a single vergence response. Thus, in a vergence response to step disparity, the transient component drives the initial fast dynamic portion of the response, while the sustained component maintains the latter slower portion of the response. The authors extended this hypothesis by quantitatively defining the stimulus pattern and dynamics that elicit this dichotomous behavior. The disparity target consisted of vertical lines 2 deg in height presented to each eye. Ramp disparity velocities ranged from 0.7 deg/sec to 36 deg/sec with amplitude of up to 4 deg. Photoelectric recordings of eye movements from both eyes were subtracted to give the vergence response. Fast and slow ramp stimulus velocities were found to elicit transient and sustained component responses respectively. In addition, the finding of staircase-like responses to fast ramp stimuli has strong implications on control mechanisms, indicating a sampling process in the transient component of the disparity vergence system.

Eye Movements

Psychophysical evaluation of cochlear prostheses in a monkey model.

Functional aspects of cochlear prostheses implanted in the scala tympani were tested in monkeys trained to perform a simple reaction-time task. Thresholds for detection of electrical stimulation and dynamic ranges were tested for a wide range of frequencies of sinusoidal stimulation and for biphasic rectangular pulses of various durations and repetition rates. The results are comparable with available data from implanted human patients and extend these findings, exploring various aspects of electrical stimulation in greater detail.

Acoustic Stimulation

EnsMart: a generic system for fast and flexible access to biological data.

The EnsMart system (www.ensembl.org/EnsMart) provides a generic data warehousing solution for fast and flexible querying of large biological data sets and integration with third-party data and tools. The system consists of a query-optimized database and interactive, user-friendly interfaces. EnsMart has been applied to Ensembl, where it extends its genomic browser capabilities, facilitating rapid retrieval of customized data sets. A wide variety of complex queries, on various types of annotations, for numerous species are supported. These can be applied to many research problems, ranging from SNP selection for candidate gene screening, through cross-species evolutionary comparisons, to microarray annotation. Users can group and refine biological data according to many criteria, including cross-species analyses, disease links, sequence variations, and expression patterns. Both tabulated list data and biological sequence output can be generated dynamically, in HTML, text, Microsoft Excel, and compressed formats. A wide range of sequence types, such as cDNA, peptides, coding regions, UTRs, and exons, with additional upstream and downstream regions, can be retrieved. The EnsMart database can be accessed via a public Web site, or through a Java application suite. Both implementations and the database are freely available for local installation, and can be extended or adapted to 'non-Ensembl' data sets.

Animals

Ribosome dynamics at the conserved PGP motif governs 2A peptide-bond-skipping efficiency.

Viral 2A oligopeptides drive an unusual ribosome recoding event in which peptide-bond formation fails at a conserved PG↓P motif, producing two discrete proteins without canonical termination. Despite decades of study, the molecular basis of 2A-mediated peptide-bond skipping remains poorly understood. Here, we combine quantitative 2A reporters with high-resolution ribosome profiling to interrogate ribosome dynamics at the core 2A sequences. We identify a pausing event at the terminal proline codon of the PGP motif that functions as a kinetic decision point: ribosome dwell time at this site inversely correlates with skipping efficiency. Increasing nascent chain flexibility by inserting linkers immediately upstream of the 2A sequence reduces ribosome occupancy at the terminal proline codon and enhances peptide-bond skipping. Strikingly, amino acid repeats positioned distally upstream also modulate 2A activity, indicating long-range coupling between nascent chain properties outside of the ribosome and the peptidyl transferase center inside the ribosome. In particular, hydrophobic residues potently suppress skipping, an effect that can be rescued by extending flexible segments within the peptide exit tunnel. Together, our findings support a model in which nascent chain features-beyond the core 2A motif-dynamically tune ribosomal recoding efficiency through co-translational feedback into the catalytic center.

Ribosomes

Studies on protein folding, unfolding and fluctuations by computer simulation. III. Effect of short-range interactions.

The theoretical model of proteins on the two-dimensional square lattice, introduced previously, is extended to include the specific short-range interactions. Attractive long-range interactions with various specificities and non-specific repulsive long-range interactions in the form of self-avoidance of the polymer chain are also operative in the model. Dynamics of the model protein is studied by a Monte Carlo method. The short-range interactions are found to accelerate the folding and unfolding transitions. Non-specific part of the attractive long-range interactions have a competing effect of decelerating the transitions. When the short-range interactions are weighted beyond a certain extent over the attractive long-range interactions are weighted beyond a certain extent over the attractive long-range interactions, the all-or-none character of the folding and unfolding transitions is destroyed. How the destruction proceeds is quantitatively expressed in terms of the S-H curves. The limiting case of dominance of the specific short-range interactions over the attractive long-range interactions is studied in detail. The lattice polymer in this limit does not behave like a globular protein at all. This observation leads to a reexamination of the currently popular notion of the dominance of the short-range interactions. A new concept of consistency is proposed to replace it. Possible mechanisms of the acceleration of the transitions by the specific short-range interactions are discussed.

Computers