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How many maps are there in visual cortex?

In addition to a topographic map of the retina, mammalian visual cortex contains superimposed, orderly periodic maps of features such as orientation, eye dominance, direction of motion and spatial frequency. There is evidence that these maps are overlaid so as to ensure that all combinations of the different parameters are represented as uniformly as possible across visual space. However, it is unknown to what extent geometrical factors limit the number of periodic maps which might simultaneously be present, given this constraint. This paper attempts to investigate the question by using a dimension reduction model to generate maps of simple, many- dimensional feature spaces onto a model two-dimensional cortex. The feature space included a model retina, plus N binary variables, corresponding to parameters such as ocular dominance or spatial frequency. The results suggest that geometrical factors do not sharply limit the ability of the cortex to represent combinations of parameters in spatially superimposed maps of similar periodicity. Considerations of uniform coverage suggest an upper limit of six or seven maps. A higher limit, of about nine or ten, may be imposed by the numbers of neurons (or minicolumns) available to represent each of 2(N) features within a given small region of cortex.

Algorithms↗

Therapeutic levels of aspirin and salicylate directly inhibit a model of angiogenesis through a Cox-independent mechanism.

A range of antineoplastic properties is attributed to aspirin, thought to be due to inhibition of cyclooxygenase (Cox) enzymes in tumor cells. One important outcome is that by reducing angiogenic factor secretion by cancer cells, aspirin also inhibits angiogenesis, thereby restricting tumor growth. However, aspirin may also have direct effects on endothelial cells to regulate angiogenesis. Our aim was to quantitate these effects and determine whether they occurred through inhibiting Cox enzymes. The effects of aspirin, salicylate (the natural deacetylated form of aspirin), and the selective Cox inhibitors SC560 and Celecoxib on endothelial cell proliferation, viability, and angiogenesis were compared. Therapeutic aspirin concentrations (0.5 mM) had no detectable effect on endothelial cell viability or proliferation but caused a striking reduction in tubule formation in a three-dimensional collagen angiogenesis assay. This was also seen with equimolar concentrations of salicylate, while selective Cox inhibitors did not inhibit angiogenesis in this assay either alone or in combination. Furthermore, high doses of aspirin or salicylate (5 mM), well above therapeutic plasma concentrations, lead to endothelial cell apoptosis. We conclude that aspirin, at therapeutic concentrations, directly inhibits angiogenesis via a Cox-independent mechanism, which may significantly contribute to its neoplastic protective effects.

Antineoplastic Agents↗

Chemonucleolysis with human stromelysin-1.

STUDY DESIGN: Immunohistologic analysis was performed on surgically removed samples of herniated nucleus pulposus to examine the expression of stromelysin-1. We performed in vitro and in vivo experiments to determine whether recombinant human (rh) stromelysin-1 is capable of degrading nucleus pulposus. OBJECTIVE: To analyze the production of stromelysin-1 in various types of herniated nucleus pulposus, and to examine the effects of this recombinant protein on nucleus pulposus tissues. SUMMARY OF BACKGROUND DATA: The authors previously demonstrated a progressive decrease in herniated nucleus pulposus size in some of the transligamentous and sequestration types of herniated nucleus pulposus using magnetic resonance imaging. An increased production of stromelysin-1, a cartilage proteoglycan degrading enzyme, in herniated nucleus pulposus was reported recently. The authors speculated that if stromelysin-1 is involved in the degradation of herniated nucleus pulposus, stromelysin-1 itself may be used as a chemonucleolytic agent. METHODS: Immunohistologic analysis using streptoavidin-biotin method was performed on 20 herniated nucleus pulposus samples to investigate the expression of stromelysin-1. Five herniated nucleus pulposus samples were incubated in a tissue culture medium in the presence or absence of rh stromelysin-1. After 24 hours of incubation, their weight changes were measured, and the loss of proteoglycan was assessed by Safranin O staining. Rat nucleus pulposus tissues were obtained from coccygeal intervertebral discs, and autologous subcutaneous transplantation was performed. Rh stromelysin-1 was injected into the grafted materials, and the reduction in size was followed by two-dimensional measurements from the skin surface, using engineer's calipers. RESULTS: Immunohistologic analysis demonstrated the production of stromelysin-1 in the granulation tissues of herniated nucleus pulposus. When stromelysin-1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than the control group. In addition, human herniated nucleus pulposus materials obtained at surgery showed significant weight loss when treated with stromelysin-1 in an organ culture system. Safranin O staining revealed extensive depletion of proteoglycan in these herniated nucleus pulposus samples. CONCLUSIONS: Stromelysin-1 is a possible key enzyme in herniated nucleus pulposus resorption, and stromelysin-1 may be a good candidate for use in chemonucleolysis. Administration of human stromelysin-1 may physiologically facilitate the resorption process of herniated nucleus pulposus, increase the healing rate and decrease complications after chemonucleolysis.

Adult↗

Confining barriers for surface state electrons tailored by monatomic Fe rows on vicinal Au111 surfaces.

We fabricated monatomic Fe wires on vicinal Au(111) surfaces and found that decoration of step edges with Fe adatoms has a significant influence on the behavior of surface state electrons confined between regularly arranged steps. On a surface with Fe monatomic rows, angle-resolved photoemission spectra measured in the direction perpendicular to the steps shows parabolic dispersion, in contrast to one-dimensional quantum-well levels observed on a clean surface. Simple analysis using a one-dimensional Kronig-Penney model reveals potential barrier reduction from 20 to 4.6 eV A, suggesting an attractive nature of the Fe adatoms as scatterers.

Journal Article↗

Programmable ultrasound imaging using multimedia technologies: a next-generation ultrasound machine.

High computational and throughput requirements in modern ultrasound machines have restricted their internal design to algorithm-specific hardware with limited programmability. We have architected a programmable ultrasound processing system, Programmable Ultrasound Image Processor (PUIP), to facilitate engineering and clinical ultrasound innovations. Multiple high-performance multimedia processors were used to provide a computing power of 4 billion operations per second. Flexibility was achieved by making our system programmable and multimodal, e.g., B-mode, color flow, cine and Doppler data can be processed. We have successfully designed and implemented the PUIP to fit within an ultrasound machine. It provides a platform for rapid testing of new concepts in ultrasound processing and enables software upgrades for future technologies. Current and future clinical applications include extended fields of view, quantitative measurements, three-dimensional ultrasound reconstruction and visualization, adaptive persistence, speckle reduction, edge enhancement, image segmentation, and motion analysis. The PUIP is a significant step in the evolution of ultrasound machines toward more flexible and generalized systems bridging the gap between many innovative ideas and their clinical use in ultrasound machines.

Algorithms↗

Studies on the specificity of the cholesterol-binding pancreatic proteinase and identification as human pancreatic elastase 1.

The proteolytic attack of the cholesterol-binding pancreatic proteinase (CBPP) on the oxidized insulin A and B chains as well as on glucagon was investigated by kinetic studies. The reaction products were isolated by high-pressure liquid chromatography and identified by amino acid analysis. The combined results reveal a pronounced selectivity of CBPP for the peptide bonds at the carboxy ends of Ala, Val, Leu, Ser, His and Thr residues with Ala, Val and Leu most favoured, indicating a close catalytic relationship to porcine pancreatic elastase [Narayanan, A. S. & Anwar, R. A. (1969) Biochem. J. 114, 11-17] and the anionic porcine pancreatic protease E [Kobayashi R., Kobayashi, Y. & Hirs, C. H. W. (1981) J. Biol. Chem. 256, 2460-2465] which resembles human pancreatic elastase 1. The immunological comparison indeed disclosed the identity of CBPP with human pancreatic elastase 1.

Animals↗

Protein synthesis during transition and stationary phases under glucose limitation in Saccharomyces cerevisiae.

Metabolic changes have been investigated during continuous growth of yeast cells inoculated in glucose-containing medium until the cells entered the stationary phase in response to glucose exhaustion. Well in advance of glucose exhaustion, a transition phase was observed, characterized by a decrease in the growth rate and a progressive reduction of protein and RNA accumulation. Two-dimensional gel analysis of the proteins synthesized during this stage showed that the pattern of proteins remained similar to that of log-phase cells. When the cells entered the stationary phase, protein accumulation was 10% of that in log-phase cells, and incorporation of labeled RNA precursor was undetectable. Analysis of protein synthesis gave evidence that the synthesis of 95% of the proteins present in log-phase cells was arrested in stationary-phase cells. Among the 20 proteins whose synthesis continues throughout the stationary phase were identified actin, aldehyde dehydrogenase, enolase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and five heat shock proteins. In addition, the synthesis of six new proteins was observed. The occurrence of these new proteins in stationary-phase cells is presumed to result from the release of carbon catabolite repression due to glucose exhaustion.

Carbon↗

Effects of spontaneous respiration on left ventricular function assessed by echocardiography.

The effects of quiet respiration on assessment of left ventricular function by two-dimensional echocardiography were investigated in 12 healthy men. End-diastolic area in the parasternal short-axis view decreased with inspiration (from 17.3 +/- 2.1 [mean +/- SD] to 16.0 +/- 2.1 cm2, p less than .01), while end-systolic area did not change (from 7.6 +/- 1.4 to 7.7 +/- 1.5 cm2; NS). A fixed cursor that was located through the center of the left ventricular area at end-expiration made a tangential cut of the area at end-inspiration were smaller along the cursor than through the center of the short-axis area both at end-diastole (1.9 +/- 1.7 mm; p less than .01) and end-systole (3.8 +/- 4.0 mm; p less than .01). Our results suggest a need for standardization with regard to respiratory phases in assessment of left ventricular function by two-dimensional echocardiography and indicate the occurrence of inspiratory reduction of left ventricular stroke volume associated with decreased diastolic filling. Motion of the heart relative to the echo beam may play a part in the respiratory variations in left ventricular dimensions assessed by M mode echocardiography.

Adult↗

On-line pork carcass grading with the Autofom ultrasound system.

On-line pork carcass grading with the Autofom ultrasound system is described. The system consists of 16 ultrasound transducers positioned in a frame. The carcass is measured fully automatically at 3,200 positions to a depth of approximately 12 cm with a depth resolution of .19 mm. The ultrasound data form a three-dimensional ultrasound image, which is processed for noise reduction, orientation detection, and extraction of 127 features describing the carcass composition. The image features are used in a multivariate regression model, that is used for on-line predictions. On-line tests performed at line speeds up to 1,150 carcasses/h provide predictions of the meat percentage with an accuracy of 1.58 to 1.95%. Good predictions of the fat thickness and primal meat cuts have also been made.

Abattoirs↗

A subfraction of human fibrinogen with high sialic acid content and elongated gamma chains.

Fibrinogen isolated from normal human single donor or pool plasma was fractionated by DEAE-cellulose chromatography. Three different fibrinogen subfractions were obtained. The most acidic fraction comprising 22% of the whole fibrinogen pool was prominent by two special features: 1) its sialic acid content was significantly higher than that of bulk fibrinogen, namely 8 mol of sialic acid/mol of fibrinogen versus 6 mol in bulk fibrinogen. 2) Two-dimensional electrophoresis of the polypeptide chains obtained after reduction revealed a preferential accumulation in this subfraction of the elongated gamma chains previously described as gamma chain heterogeneity of whole human fibrinogen.

Chromatography, DEAE-Cellulose↗

Platelet protein organization: analysis by treatment with membrane-permeable cross-linking reagents.

We have examined platelet protein organization by treatment of intact resting or thrombin-activated platelets with two cross-linking reagents, diamide or dithiobis(succinimidyl propionate) (DTSP). Cross-linked complexes were separated by polyacrylamide gel electrophoresis in the absence of reducing agent and their composition determined after reductive cleavage and analysis in a second-dimensional gel. The most prominent cross-linked species produced by diamide treatment of of resting platelets are (A) cytoskeletal protein homopolymers, such as myosin heavy chain dimer and actin oligomers, and (B) high molecular weight material consisting of homo- or heteropolymers of cytoskeletal proteins and 230,000, 170,000, 100,000, 55,000, and 52,000 dalton proteins. DTSP treatment forms similar complexes and also cross-links membrane glycoproteins IIb and III into high molecular weight material. Thrombin activation of platelets before treatment with diamide or DTSP results in increased cross-linking of myosin and increased incorporation of several proteins, particularly myosin and glycoproteins IIb and III, into high molecular weight material. The results provide evidence for reorganization of cytoskeletal and membrane proteins during platelet function.

Actins↗

[Usefulness of 3-D dynamic pulmonary xenon-133 SPECT for thoracoscopic lung volume reduction surgery in patients with pulmonary emphysema].

Six patients with pulmonary emphysema scheduled to undergo thoracoscopic lung volume reduction surgery (TLVRS) were evaluated by three-dimensional (3-D) dynamic pulmonary xenon-133 SPECT. Serial 30-second dynamic SPECT data for equilibrium and washout (for 5 min) were acquired using a continuous repetitive rotating acquisition mode with a triple-detector SPECT system. SPECT data were reconstructed to 3-D images with a color, surface-rendering technique, and a 3-D fusion image of the 3-min washout image over the equilibrium image was obtained. Regional ventilation was visually assessed on the fusion 3-D images and quantified by xenon-133 half-washout time (T1/2) and mean transit time (MTT). The 3-D fusion image localized and lateralized the worst diseased sites with xenon-133 retention. Xenon-133 retention, T1/2 and MTT were reduced on these images in five patients with improved pulmonary function tests following TLVRS. However, xenon-133 retention was greater in one with asynchronous diaphragm movement after TLVRS. This modality will assist TLVRS in determining the lung resection target and in evaluating the treatment effect.

Endoscopy↗

Automated interpretation of myocardial SPECT perfusion images using artificial neural networks.

UNLABELLED: The purpose of this study was to develop a computer-based method for automatic detection and localization of coronary artery disease (CAD) in myocardial bull's-eye scintigrams. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest-stress scintigraphy and coronary angiography within 3 mo was studied. Different image data reduction methods, including pixel averaging and two-dimensional Fourier transform, were applied to the bull's-eye scintigrams. After a quantitative and qualitative evaluation of these methods, 30 Fourier components were chosen as inputs to multilayer perceptron artificial neural networks. The networks were trained to detect CAD in two vascular territories, using coronary angiography as gold standard. A "leave one out" procedure was used for training and evaluation. The performance of the networks was compared to those of two human experts. RESULTS: One of the human experts detected CAD in one of two vascular territories, with a sensitivity of 54.4% at a specificity of 70.5%. The sensitivity of the networks was significantly higher at that level of specificity (77.2%, p = 0.0022). The other expert had a sensitivity of 63.2% at a specificity of 61.5%. The networks had a sensitivity of 77.2% (p = 0.038) at this specificity level as well. The differences in sensitivity between human experts and networks for the other vascular territory were all less than 6% and were not statistically significant. CONCLUSION: Artificial neural networks can detect CAD in myocardial bull's-eye scintigrams with such a high accuracy that the application of neural networks as clinical decision support tools appears to have significant potential.

Coronary Angiography↗

Daily ultrasound-based image-guided targeting for radiotherapy of upper abdominal malignancies.

PURPOSE: Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. METHODS AND MATERIALS: A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. RESULTS: A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly because of limited visibility due to daily variations in colonic and gastric air. US imaging was facilitated in intrahepatic tumors and asthenic patients. The mean +/- SD shift from the skin mark position was 4.9 +/- 4.35, 6.0 +/- 5.31, and 6.0 +/- 6.7 mm in the x, y, and z direction, respectively. The mean magnitude vector of three-dimensional alignment correction was 11.4 +/- 7.6 mm. The proportion of daily alignments corrected by a magnitude of >10, >15, and >20 mm was 48.9%, 25.1%, and 12.7%, respectively. The magnitude of shifts in the principal directions, as well as the three-dimensional vector of displacement, was statistically significant (test against the zero hypothesis) at p <0.0001. The guidance structures that were the most valuable for identification of the TV position were the branches of the portal vein, hepatic artery, and dilated bile ducts in intrahepatic lesions and the aorta, celiac trunk, superior mesenteric artery, and extrahepatic aspects of the portal vein system in retroperitoneal and extrahepatic lesions. The mean total setup time was 4.6 min. The correlation of BAT targeting with target setup error assessment in the control CT scans in 15 patients revealed setup error reduction in 14 of 15 alignments. The average setup error reduction, assessed as a reduction in the length of setup error three-dimensional magnitude vector, was 54.4% +/- 26.9%, with an observed mean magnitude of residual setup error of 4.6 +/- 3.4 mm. The sole worsening of an initial setup was by a magnitude of <2 mm. US targeting resulted in statistically significant improvements in patient setup (p = 0.03). CONCLUSION: Daily US-guided BAT targeting for patients with upper abdominal tumors was feasible in the vast majority of attempted setups. This method of US-based image-guided tumor targeting has been successfully implemented in clinical routine. The observed improved daily repositioning accuracy might allow for individualized reduction of safety margins and optional dose escalation. Compared with the established application of the BAT device for prostate radiotherapy, in which the target can be directly visualized, the TV in the present study was predominantly positioned relative to guidance vascular structures in close anatomic relation. We perceived an enormous potential in improved and individualized patient positioning for fractionated radiotherapy and also for stereotactic extracranial radiotherapy and radiosurgery, especially for tumors of the liver and pancreas.

Abdominal Neoplasms↗

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction.

OBJECTIVES: This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping. BACKGROUND: The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue. METHODS: Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data. RESULTS: From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.

Animals↗

Measurement of cerebral microvessel diameters after embolic stroke in rat using quantitative laser scanning confocal microscopy.

Perfusion of the microcirculation after stroke is central to preserving neuronal function and improving functional outcome. Using laser scanning confocal microscopy (LSCM) and a novel computer software program, MIRAGE, we measured a reduction in cerebral microvessel diameter after 1 and 4 h of embolic middle cerebral artery (MCA) occlusion. The methodology used by MIRAGE for measurement of blood vessel diameter involves a linearly applied spherical inflation technique. Three-dimensional quantitative analysis revealed a significant (P<0.05) mean 10-12% reduction in vessel diameter in the ipsilateral cortex when compared to the homologous region in the contralateral hemisphere. This reduction was seen only in the cortex and not the striatum. A larger reduction in mean vessel diameter in the ipsilateral cortex, 16-30% (P<0.05) was observed when compared to sham control rats. These results are in strong agreement with other studies using different stroke models and imaging techniques. Our work represents a novel application of LSCM technology to the three dimensional investigation of microvessel diameter changes in acute stroke and identifies its potential as an important tool for investigation of cerebral pathology.

Animals↗

A simplified procedure for the reduction and alkylation of cysteine residues in proteins prior to proteolytic digestion and mass spectral analysis.

A procedure for reduction and alkylation of cysteine residues in proteins was developed using the volatile reagents triethylphosphine and iodoethanol. These reagents may be used to modify proteins in solution, as well as proteins in gel slices, prior to proteolytic digestion and mass spectral analysis. The procedure eliminates several steps with both types of samples. Samples in solution do not need to be desalted following reduction and alkylation, with excess reagent being removed under vacuum. For gel slices, the procedure combines washing, destaining, reduction and alkylation into a single step. The procedure was applied successfully to samples as complex as serum, and we demonstrated alkylation of cysteines to be quantitative in purified proteins. We also were able to reduce and alkylate proteins with these reagents during the gas phase. Elimination of the need for desalting of samples after reaction raised the possibility of automation of the procedure for liquid samples, which is difficult with conventional reduction and alkylation chemistries.

Alkylating Agents↗

Remediation of DNAPL pools using dense brine barrier strategies.

Although dense nonaqueous phase liquid (DNAPL) pools are an important source of groundwater contamination, little experimental data have been generated to develop a mature level of understanding of the problem, and few strategies specifically aimed at remediation have been advanced. We discuss the dominant importance of these features in subsurface systems, present novel two- and three-dimensional heterogeneous experimental systems, and show results from two evolving strategies for remediating DNAPL pools. These strategies involve the joint use of a dense brine barrier and controlled mobilization of trapped DNAPL using small-volume surfactant flushes. These experiments demonstrate a controlled, substantial reduction of entrapped DNAPL in both two- and three-dimensional heterogeneous domains, using less than a single pore volume of flushing solution in some cases.

Porosity↗