Comparison of temperature and doping dependence of elastoresistivity near a putative nematic quantum critical point.

Strong electronic nematic fluctuations have been discovered near optimal doping for several families of Fe-based superconductors, motivating the search for a possible link between these fluctuations, nematic quantum criticality, and high temperature superconductivity. Here we probe a key prediction of quantum criticality, namely power-law dependence of the associated nematic susceptibility as a function of composition and temperature approaching the compositionally tuned putative quantum critical point. To probe the 'bare' quantum critical point requires suppression of the superconducting state, which we achieve by using large magnetic fields, up to 45 T, while performing elastoresistivity measurements to follow the nematic susceptibility. We performed these measurements for the prototypical electron-doped pnictide, Ba(Fe1-xCox)2As2, over a dense comb of dopings. We find that close to the putative quantum critical point, the elastoresistivity appears to obey power-law behavior as a function of composition over almost a decade of variation in composition. Paradoxically, however, we also find that the temperature dependence for compositions close to the critical value cannot be described by a single power law.

Metabolomic profiling by near-infrared spectroscopy as a tool to assess embryo viability: a novel, non-invasive method for embryo selection.

BACKGROUND: The morphology of an embryo has a limited predictive value for assessing viability and ongoing pregnancy, therefore new selection tools are needed to maintain success rates with single-embryo transfer (SET). In this study, we investigated if metabolomic profiling of biomarkers of embryo culture medium by near-infrared (NIR) spectroscopy has a correlation with ongoing pregnancy in SET. METHODS: A total of 333 patients scheduled for in vitro fertilization (IVF) with SET were included in the study. Embryos were selected for transfer by morphological criteria on Days 2 and 3 of in vitro culture, and left over culture media samples were analyzed by NIR spectroscopy. RESULTS: The NIR spectral analysis produced unique metabolomic profiles that correlated to an embryo's reproductive potential. Resulting relative viability scores between positive and negative pregnancy outcomes were statistically significant (P < 0.03). A logistic regression of factors correlated to pregnancy outcomes showed that maternal age, percent fragmentation and relative viability scores all demonstrated a relationship. The extent of the correlation was determined by accuracy computation, where the accuracy of assessing viable embryos on Day 3 by metabolomic profiling was 53.6% and the accuracy of the morphological selection was 38.5%. In addition, the positive predictive value of metabolomic profiling was 0.365 and the negative predictive value was 0.830. CONCLUSIONS: NIR metabolomic profiling of spent embryo culture media was able to distinguish viable embryos from non-viable embryos for reproduction.

An ion-selective electrode for acetate based on a urea-functionalized porphyrin as a hydrogen-bonding ionophore.

An ion-selective electrode for acetate based on (α,α,α,α)-5,10,15,20-tetrakis[2-(4-fluorophenylureylene)phenyl]porphyrin as an ionophore that has no metal center and forms hydrogen bonds to the analyte is described. At pH 7.0 (0.1 M HEPES-NaOH buffer), the electrode based on this ionophore and cationic sites (50 mol % relative to the ionophore) responds to acetate in a linear range from 1.58 × 10(-)(4) to 1.58 × 10(-)(2) M with a slope of -54.8 ± 0.8 mV/decade and a detection limit of (3.06 ± 1.15) × 10(-)(5) M. Selectivity coefficients determined with the separate solution method (SSM) indicate that interferences of hydrophobic inorganic anions are relatively small (log[Formula: see text] (SSM): NO(3)(-), +0.68; SCN(-), +0.60; NO(2)(-), +0.22; I(-), +0.20; ClO(4)(-), +0.12; Br(-), -0.13). Responses to anions that are good hydrogen bond acceptors, i.e., Cl(-), HSO(3)(-), and HCO(3)(-), were Nernstian and were weaker than the response to acetate (log[Formula: see text] (SSM): -0.54, -0.56, and -1.34, respectively). Negligibly small responses were observed for very hydrophilic anions, i.e., F(-), SO(4)(2)(-), and H(2)PO(4)(-)/HPO(4)(2)(-). While aliphatic carboxylates such as formate, propanoate, pyruvate, and lactate gave Nernstian responses similar to acetate, interferences of salicylate and benzoate were considerably decreased in comparison with electrodes based on cationic sites only. Concentrations of acetic acid in vinegar samples were determined by direct potentiometry and agreed with values determined by a standard enzymatic method.

Myoglobin oxygen dissociation by multiwavelength spectroscopy.

Multiwavelength optical spectroscopy was used to determine the oxygen-binding characteristics for equine myoglobin. Oxygen-binding relationships as a function of oxygen tension were determined for temperatures of 10, 25, 35, 37, and 40 degrees C, at pH 7.0. In addition, dissociation curves were determined at 37 degrees C for pH 6.5, 7.0, and 7.5. Equilibration was achieved with a myoglobin solution, at the desired temperature and pH, and 16 oxygen-nitrogen gas mixtures of known oxygen fraction. Correction for the inevitable presence of metmyoglobin was made by using a three-component least squares analysis and by correcting the end point oxymyoglobin spectra for the presence of metmyoglobin. The PO2 at which myoglobin is half-saturated with O2 (P50) was determined to be 2.39 Torr at pH 7.0 and 37 degrees C. The myoglobin dissociation curve was well fit by the Hill equation [saturation = PO2/(PO2 + P50)].

A new method for studying plaque morphology.

A histologic method was developed for three-dimensional (3-D) analysis of atherosclerotic plaques removed from the carotid bifurcation during endarterectomy. By sectioning the plaque at frequent intervals (0.5 to 1.0 mm), it is possible to obtain important information on plaque constituents with regard to their volume and distribution within the lesion. These data from each section are combined with those from other sections and displayed in a 3-D format for the entire length of the lesion. The tissues making up each of the 10 carotid plaques were outlined and digitized for each histologic section by position along the lesion. From the areas outlined a 3-D model was created by a computer-aided design program. Quantitative information on tissue distribution within the plaque was measured. Fibrous tissue constituted between 35% and 70% of plaque volume; loose necrosis from 0.5% to 30% of the plaque and thrombus occupied, at a maximum, 10% even though if was present in six of the 10 plaques. To investigate the distribution of constituents about the long axis, measurements were also made from each of the four quadrants of each section. The reproducibility of the measurements of three sets of sections at 10-mm separation showed that estimates of the amount of some constituents were very reproducible whereas others had considerable variation related to the small volume they occupied within the lesion. By generating a complete 3-D reproduction of the contents of atherosclerotic plaques, it may be possible to identify those features of the plaque that are most responsible for the development of ischemic events.

Characteristics of visual display units that may cause visual difficulties.

The physical characteristics of a visual display unit (VDU) are compared to those of paperwork, through a review of the literature. Certain display characteristics are shown to enhance visual performance using a VDU whilst others significantly decrease it when compared to using hard copy. Overall, display characteristics do not necessarily render VDU use more difficult than if doing similar visual tasks without using a VDU.

3D ultrasonic image feature localization based on magnetic scanhead tracking: in vitro calibration and validation.

The basis of a three-dimensional (3D) ultrasound imaging system was constructed from a commercially available magnetometer-based position and orientation measurement (POM) device, a standard B-Mode ultrasound instrument and a personal computer. To evaluate the system's performance, a novel method was devised using an iterative, least-squares technique to simultaneously determine the system's calibration parameters and measure its precision in locating points in three-dimensional space. When tested separately, the POM system located single points with a root mean squared (RMS) uncertainty of from 1.4 mm to 3.2 mm over the 610 mm working radius of the system. When combined with the ultrasound instrument, the RMS uncertainty in locating point targets varied from 2.1 mm to 3.5 mm. These results establish the lower limits of variability to be expected from this system when locating fiducial anatomical landmarks for repeated examinations of the same region of the body, and when making numerical 3D reconstructions from multiple planar images.

Ultrasonic three-dimensional reconstruction: in vitro and in vivo volume and area measurement.

This study validates the use of an ultrasound three-dimensional reconstruction system to measure phantom and blood conduit geometry. Independently determined uniform and stenotic phantom dimensions are compared with reconstruction-based measurements. Lower extremity saphenous vein bypass graft reconstructions were performed to demonstrate clinical application. Uniform phantom independent and reconstructed volume correlation was high (r = 0.989), the average volume difference was 4.68 mm3 and the average area difference was 0.4 mm2. An in vitro 28% diameter reduction was detected. Stenotic bypass graft segment volume was 795 mm3; following successful angioplasty the volume increased to 1419 mm3. Advantages of this technique are its accuracy, the luminal information it provides and the absence of mechanical arm or acoustic transmitter limitations. We are exploring the possibility that measurement of luminal change over time may allow stenosis detection prior to hemodynamic disturbance, in an ongoing clinical saphenous vein bypass graft surveillance study.

Echolucent regions in carotid plaque: preliminary analysis comparing three-dimensional histologic reconstructions to sonographic findings.

This study compares sonographic and histologic findings within defined spatial regions in carotid artery plaque, using computer generated three-dimensional reconstructions. Twenty-four patients (14 asymptomatic, 10 symptomatic) with angiographically documented 70% to 99% carotid artery stenosis were examined with ultrasonic B-mode imaging prior to endarterectomy. Using a standardized protocol for instrument set-up and scanning technique, echolucent regions in the plaque were identified. After endarterectomy, each plaque was sectioned at 0.5 to 1.0 millimeter increments throughout its length. Sites containing intraplaque hemorrhage, cholesterol clefts, foam cells, necrotic cores, dense calcification and speckled calcification were identified. These areas were outlined on a template, digitized and imported into a computer program that created three-dimensional reconstructions of the histologic findings. Each carotid plaque was divided into quadrants for analysis: (1) lateral wall proximal to the common carotid bifurcation (flow divider); (2) medial wall proximal to the flow divider; (3) lateral wall distal to the flow divider; and (4) medial wall distal to the flow divider. The odds of finding intraplaque hemorrhage, foam cells, necrotic cores and speckled calcification were significantly higher in quadrants with an echolucent region identified by ultrasonography (odds ratio (95% confidence interval) for intraplaque hemorrhage = 3.5 (1.4-8.6); foam cells = 4.0 (1.6-9.9); necrotic cores = 3.2 (1.2-8.4); speckled calcification = 4.0 (1.6-9.8). This preliminary analysis demonstrates the potential of these newly developed techniques for comparing ultrasonic imaging to histology.

Diffusion-based model of pulse oximetry: in vitro and in vivo comparisons.

A model of pulse oximetry is developed based on the three-dimensional photon diffusion theory. To test the applicability of the model, an in vitro assay was developed. Three different scattering levels and six different relative dye concentrations were analyzed. Average percent errors of 13.9% were obtained over the full range of the study. An in vivo clinical study of two pulse oximeter probes with different spectral characteristics was compared with results estimated by the model. The model correctly predicted the changes in pulse oximeter response resulting from the wavelength changes. A x(2) test gave a probability of 20% that the model fit the data. These results demonstrated the utility of the photon diffusion theory for the modeling of tissue optics.

Orthogonal-plane fluorescence optical sectioning: three-dimensional imaging of macroscopic biological specimens.

An imaging technique called orthogonal-plane fluorescence optical sectioning (OPFOS) was developed to image the internal architecture of the cochlea. Expressions for the three-dimensional point spread function and the axial and lateral resolution are derived. Methodologies for tissue preparation and for construction, alignment, calibration and characterization of an OPFOS apparatus are presented. The instrument described produced focused, high-resolution images of optical sections of an intact, excised guinea-pig cochlea. The lateral and axial resolutions of the images were 10 and 26 microns, respectively, within a 1.5-mm field of view.

Carotid artery intraplaque hemorrhage and stenotic velocity.

BACKGROUND AND PURPOSE: One of the proposed mechanisms for sudden expansion of a carotid bifurcation plaque is hemorrhage within the lesion. It has been postulated that the sudden increase in plaque size will acutely reduce blood flow to the ipsilateral hemisphere and induce either a transient ischemic attack or a stroke. In this study, the relation between peak systolic velocity at the site of narrowing and its potential role in the development of intraplaque hemorrhage were investigated. METHODS: Ten patients who had carotid endarterectomy were examined by duplex Doppler sonography before surgery to determine the peak systolic velocity at the site of maximal narrowing. The excised carotid plaques were sectioned at 1-mm intervals and examined for histological evidence of intraplaque hemorrhage. The recorded peak systolic velocities in patients with intraplaque hemorrhage were compared with the velocities in cases in which no hemorrhage was identified. RESULTS: Five of the ten patients had intraplaque hemorrhage. Four of the five patients with intraplaque hemorrhage had a peak systolic velocity of > 420 cm/sec and diastolic velocities of > 160 cm/sec; none of the patients without intraplaque hemorrhage had such high values. CONCLUSIONS: Peak systolic velocity is significantly higher in patients with intraplaque hemorrhage. The specificity and sensitivity of a peak systolic velocity of > 420 cm/sec in predicting intraplaque hemorrhage remains to be determined.

Computed tomography from optical projections for three-dimensional reconstruction of thick objects.

An optical tomography system is developed for generating three-dimensional reconstructions of thick objects from projections. The system is useful for studying transparent structures that are 1-10 mm in diameter. Evaluation of the reconstruction system with a test object demonstrates 98% geometric accuracy, 90% accuracy in the detection of boundaries, and 90% accuracy in the measurement of absorbance. Reconstructions are computed from 96 parallel projections spaced evenly within 180 degrees . Accurate alignment of the projections is achieved with a cross-correlation method following data acquisition. Application of the optical tomography reconstruction technique to an intact cochlea permits measurement of internal structures with 16-microm pixels and a diffraction-limited resolution of 24 microm.

A-band shortening in single fibers of frog skeletal muscle.

The question of whether A-bands shorten during contraction was investigated using two methods: high-resolution polarization microscopy and electron microscopy. During shortening from extended sarcomere lengths in the passive state, sarcomere-length changes were essentially accounted for by I-band shortening. During active shortening under otherwise identical conditions, the sarcomere length change was taken up approximately equally by A- and I-bands. Several potential artifacts that could give rise to apparent A-band shortening were considered and judged unlikely. Results obtained with polarization microscopy were similar to those obtained with electron microscopy. Thus, modest but significant thick filament shortening appears to occur during active sarcomere shortening under physiological conditions.

Sarcomere length dependence of the force-velocity relation in single frog muscle fibers.

The force-velocity relation of single frog fibers was measured at sarcomere lengths of 2.15, 2.65, and 3.15 microns. Sarcomere length was obtained on-line with a system that measures the distance between two markers attached to the surface of the fiber, approximately 800 microns apart. Maximal shortening velocity, determined by extrapolating the Hill equation, was similar at the three sarcomere lengths: 6.5, 6.0, and 5.7 microns/s at sarcomere lengths of 2.15, 2.65, and 3.15 microns, respectively. For loads not close to zero the shortening velocity decreased with increasing sarcomere length. This was the case when force was expressed as a percentage of the maximal force at optimal fiber length or as a percentage of the sarcomere-isometric force at the respective sarcomere lengths. The force-velocity relation was discontinuous around zero velocity: load clamps above the level that kept sarcomeres isometric resulted in stretch that was much slower than when the load was decreased below isometric by a similar amount. We fitted the force-velocity relation for slow shortening (less than 600 nm/s) and for slow stretch (less than 200 nm/s) with linear regression lines. At a sarcomere length of 2.15 microns the slopes of these lines was 8.6 times higher for shortening than for stretch. At 2.65 and 3.15 microns the values were 21.8 and 14.1, respectively. At a sarcomere length of 2.15 microm, the velocity of stretch abruptly increased at loads that were 160-170% of the sarcomere isometric load, i.e., the muscle yielded. However, at a sarcomere length of 2.65 and 3.15 microm yield was absent at such loads. Even the highest loads tested (260%) resulted in only slow stretch. It is concluded that properties of the force generators change with sarcomere length. This is not anticipated by the cross-bridge model of muscle contraction.

A general coupled spectrophotometric assay for decarboxylases.

A rapid, continuous spectrophotometric method has been developed for the assay of decarboxylases. The assay uses a coupled enzyme system in which liberated CO2 is reacted with phosphoenolpyruvate and phosphoenolpyruvate carboxylase to form oxaloacetate, which in turn is reduced by malate dehydrogenase to L-malate concomitantly with the oxidation of NADH to NAD. The resultant decrease in absorbance at 340 nm accurately reflects the activity of the decarboxylase. The method is capable of detecting the liberation of as little as 1 nmol of CO2/min and was tested in assays of lysine decarboxylase, orotidine-5'-phosphate decarboxylase, and 4'-phosphopantothenoyl-L-cysteine decarboxylase.

Pauses, steps, and the mechanism of contraction.

Despite widespread controversy still surrounding the phenomenon, stepwise shortening has now been confirmed by five independent methods in this laboratory, and by several other methods in different laboratories. In this paper we offer preliminary evidence obtained with the most recent method--measurement of 'isotonic muscle length transients'. We find that the muscle length inflections observed after quick release to an isotonic load correspond to pauses and steps at the sarcomere level. Thus, pauses and steps are reflected not only in sarcomere length and segment length signals, but in the muscle length signal as well. We review several of the more illuminating features of stepwise shortening, as well as new ultrastructural observations which, taken together, point to an hypothesis for the generation of steps. The steps may be generated by shortening of one or another of the sarcomere's filaments: connecting filaments in the unactivated myofibril and thick filaments in the activated myofibril. Supporting evidence is considered.