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At least 541 records · Page 30Linked to original sources

Mapping structural damage of the optic disk to visual field defect in glaucoma.

PURPOSE: To evaluate the relation between the location of focal visual field defects and optic disk damage in eyes with glaucoma by short-wavelength automated perimetery and confocal scanning laser ophthalmoscopy. METHODS: In 14 patients (14 eyes) with open-angle glaucoma, focal optic disk damage, and focal visual field loss, we obtain visual fields with short-wave-length automated perimetry. The short-wavelength automated perimetry visual field was divided into 21 zones, representing retinal nerve fiber layer arcuate bundles. Test points were compared with a normative database. The optic disk was assessed with a confocal scanning laser ophthalmoscope. Optic disk measurements were calculated in 10-degree sectors and compared with a normative database using a new measure, the rim area ratio, which adjusts for individual differences in disk size. RESULTS: The mean number (+/-SD) of damaged visual field zones was 3.9 (+/-1.9), and the mean number of damaged rim sectors was 5.0 (+/-2.9). Focal defects on the optic disk and on short-wavelength automated perimetry were topographically related with specific damaged visual field zones corresponding to specific damaged rim sectors. CONCLUSIONS: In patients with open-angle glaucoma with focal optic disk damage and focal visual field loss, defects in optic disk and short-wavelength automated perimetry are topographically related. The rim area ratio can be used to identify focal optic nerve defects.

Adult↗

Projections of the basal retrochiasmatic area: a neural site involved in the photic control of pineal metabolism.

It has been shown that the basal retrochiasmatic area (RCHb), situated immediately ventral to the third ventricle behind the suprachiasmatic nucleus and in front of the arcuate nucleus, is implicated in the nocturnal inhibitory process of melatonin production induced by short-term retinal photo-stimulation. In the present study, the projections of the RCHb have been examined using the Phaseolus vulgaris leucoagglutinin (PHA-L) method in the rat. Considering the putative role of the RCHb in contributing to the short-term photo-inhibition of the pineal gland during the night, it is reasonable to suppose that the RCHb may ultimately inhibit the sympathetic outflow of the upper thoracic segments, known to be critically involved in the control of melatonin secretion. Of particular interest, the present anterograde tract-tracing study indicates all possible paths from the RCHb which may conceivably be involved in influencing the sympathetic outflow and, therefore, melatonin production. Thus, apart from a direct projection to the intermediolateral column at thoracic levels of the spinal cord, the RCHb is in a position to control the sympathetic outflow through other potential routes, such as the dorsal parvicellular part of the paraventricular nucleus of the hypothalamus, lateral hypothalamic area, ventromedial nucleus of the hypothalamus, lateral part of the periaqueductal gray and Barrington's nucleus.

Animals↗

Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases.

The diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, and 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two early-stage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, and 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 micromol) than benign cases (mean 67 micromol), and suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent.

Adult↗

Probing specific sequences on single DNA molecules with bioconjugated fluorescent nanoparticles.

Nanometer-sized fluorescent particles (latex nanobeads) have been covalently linked to DNA binding proteins to probe specific sequences on stretched single DNA molecules. In comparison with single organic fluorophores, these nanoparticle probes are brighter, are more stable against photobleaching, and do not suffer from intermittent on/off light emission (blinking). Specifically, we demonstrate that the site-specific restriction enzyme EcoRI can be conjugated to 20-nm fluorescent nanoparticles and that the resulting nanoconjugates display DNA binding and cleavage activities of the native enzyme. In the absence of cofactor magnesium ions, the EcoRI conjugates bind to specific sequences on double-stranded DNA but do not initiate enzymatic cutting. For single DNA molecules that are stretched and immobilized on a solid surface, nanoparticles bound at specific sites can be directly visualized by multicolor fluorescence microscopy. Direct observation of site-specific probes on single DNA molecules opens new possibilities in optical gene mapping and in the fundamental study of DNA-protein interactions.

DNA↗

Spatiotemporal evolution of ventricular fibrillation.

Sudden cardiac death is the leading cause of death in the industrialized world, with the majority of such tragedies being due to ventricular fibrillation. Ventricular fibrillation is a frenzied and irregular disturbance of the heart rhythm that quickly renders the heart incapable of sustaining life. Rotors, electrophysiological structures that emit rotating spiral waves, occur in several systems that all share with the heart the functional properties of excitability and refractoriness. These re-entrant waves, seen in numerical solutions of simplified models of cardiac tissue, may occur during ventricular tachycardias. It has been difficult to detect such forms of re-entry in fibrillating mammalian ventricles. Here we show that, in isolated perfused dog hearts, high spatial and temporal resolution mapping of optical transmembrane potentials can easily detect transiently erupting rotors during the early phase of ventricular fibrillation. This activity is characterized by a relatively high spatiotemporal cross-correlation. During this early fibrillatory interval, frequent wavefront collisions and wavebreak generation are also dominant features. Interestingly, this spatiotemporal pattern undergoes an evolution to a less highly spatially correlated mechanism that lacks the epicardial manifestations of rotors despite continued myocardial perfusion.

Electric Stimulation↗

A Novel Complete F8 Tandem Duplication Causing Elevated Factor VIII Activity and Associated with Venous Thromboembolism.

Background Coagulation factor VIII (FVIII) is a critical component of the intrinsic coagulation pathway. While elevated FVIII levels are an established risk factor for venous thromboembolism (VTE), genetic variants in the F8 gene directly causing such elevations remain scarce. Here, we report a novel complete F8 tandem duplication identified in a female patient with splanchnic venous thrombosis (SVT). Methods We performed genetic testing using a thrombophilia panel targeting 35 genes involved in thrombosis and haemostasis to detect both point variants and copy number variations (CNVs). Family co-segregation analysis and phenotypic assays for FVIII and von Willebrand factor (VWF) were conducted. The structural basis of the identified F8 copy number gain was elucidated using optical genome mapping (OGM). Full-length F8 mRNA amplification, quantitative PCR, plasma FVIII Western blotting, and X-chromosome inactivation analysis were performed to assess the functional consequences of the duplication. Thrombin generation test (TGT) was employed to assess the hypercoagulable state. Results Genetic testing identified three copies of all 26 exons of the F8 gene in the proband, which was also detected in her mother (CNVs = 3) and son (CNVs = 2). One-stage clotting and chromogenic assays confirmed persistently elevated FVIII activity in the proband and her mother, accompanied by increased FVIII antigen levels. The OGM analysis confirmed a 229 kb tandem duplication including the F8 gene on one of the proband's X chromosomes. The junction regions exhibited high sequence homology and were rich in repetitive sequences, which precluded precise breakpoint mapping. Full-length F8 mRNA amplification revealed no aberrant transcripts, whereas quantitative PCR showed increased F8 mRNA expression in all carriers. Plasma FVIII Western blotting indicated FVIII heavy and light chains of expected molecular weights with increased band intensity in carriers. X-chromosome inactivation analysis in female carriers showed no significant skewing. TGT in two available carriers showed increased thrombin generation compared with a normal control at both low (1 pM) and high (5 pM) tissue factor concentrations. Conclusion We identified a novel complete F8 tandem duplication associated with increased FVIII expression and a hypercoagulable phenotype in a female patient with SVT. These findings support F8 gene dosage gain as a rare gain-of-function mechanism contributing to elevated FVIII levels and thrombophilia, while variation in VWF levels and acquired risk factors may modify thrombotic penetrance.

coagulation factor VIII↗

Matchline dosimetry in step and shoot IMRT fields: a film study.

The Varian millennium 120 multileaf collimator has curved leaf ends. Transmission through the leaf ends generates a small asymmetric penumbral dose effect. This design can lead to hot spots between neighbouring beam segments during step and shoot IMRT dose delivery. We have observed some matchlines with film for clinical beams optimized using the pinnacle radiotherapy treatment planning system; hence we sought to verify the optimum leaf offset required to minimize the matchline effect. An in-house program was created to control the MLC leaf banks in 2 cm steps with a 2 cm gap. The gap was varied by the following offset values from 0.0 to 0.1 cm. Two types of radiographic films (Kodak EDR and XV films) and a radiochromic film (Gafchromic MD-55-2) were used to measure the optical density maps. The films were positioned in a solid water phantom perpendicular to the beam axis and irradiated at d(max) using a 6 MV photon beam. An ion chamber (IC4) was used to measure point doses for normalization in a beam umbral minima position. The relative mean peak to valley dose ratios measured with no leaf offset were 1.31, 1.30 and 1.31 for the XV, EDR2 and Gafchromic films, respectively. For a 0.07 cm gap per leaf and a performance of end leaf repeatability of 0.01 cm, the central matchline was reduced to about 1.0 for all dosimeters, with two mini-peaks measured as 1.05, 1.05 and 1.08 each side of the matchline, for XV, EDR2 and Gafchromic, respectively. The average relative dose across the umbra for this offset was XO-mat V = 1.01, EDR = 1.01 and radiochromic film = 1.02, respectively. While we expected the beam penumbral tails from segment neighbours to cause overprediction of the dose in the central valley regions due to the energy response of radiographic films, by normalizing all dosimeters to an ion chamber reading in the minimum we could not observe any major shape distortion between the radiographic film and radiochromic film results. In conclusion, relative doses measured by radiographic and radiochromic films agree well with IC4 within +/-2%.

Film Dosimetry↗

Fast photoacoustic imaging system based on 320-element linear transducer array.

A fast photoacoustic (PA) imaging system, based on a 320-transducer linear array, was developed and tested on a tissue phantom. To reconstruct a test tomographic image, 64 time-domain PA signals were acquired from a tissue phantom with embedded light-absorption targets. A signal acquisition was accomplished by utilizing 11 phase-controlled sub-arrays, each consisting of four transducers. The results show that the system can rapidly map the optical absorption of a tissue phantom and effectively detect the embedded light-absorbing target. By utilizing the multi-element linear transducer array and phase-controlled imaging algorithm, we thus can acquire PA tomography more efficiently, compared to other existing technology and algorithms. The methodology and equipment thus provide a rapid and reliable approach to PA imaging that may have potential applications in noninvasive imaging and clinic diagnosis.

Acoustics↗

PULPO: pipeline of understanding large-scale patterns of oncogenomic signatures.

SUMMARY: PULPO v1.0 is a novel; fully automated pipeline designed for the preprocess and extraction of mutational signatures from raw Optical Genome Mapping (OGM) data. Built using Snakemake and executed within an isolated, Conda-managed environment, PULPO transforms complex cytogenetic alterations, captured at ultra-high resolution, into Catalogue of somatic mutations in cancer mutational signatures (COSMIC). This innovative approach not only enables researchers to work directly from raw OGM inputs but also streamlines the traditionally complex process of signature extraction, making advanced oncogenomic analyses accessible to users with varying levels of bioinformatics expertise. By facilitating the integration of comprehensive structural variants (SVs) and copy number variants (CNVs) data with established signature catalogues, PULPO paves the way for improved diagnostic accuracy and personalized therapeutic strategies. AVAILABILITY AND IMPLEMENTATION: The pipeline is open source and freely available under the MIT License at https://github.com/OncologyHNJ/PULPO-v.1.0 and DOI in Zenodo: https://zenodo.org/records/17749097.

Software↗

Rapid derivation of cloning-competent cells from peripheral blood advances conservation biobanking.

Establishing viable cell lines from endangered species is essential for conservation, yet traditional fibroblast derivation from skin biopsies faces challenges including contamination risk and extended culture timelines. Here, we demonstrate that endothelial progenitor cells (EPCs) and pericytes isolated from peripheral blood represent robust alternatives to fibroblasts for biobanking. Compared to canid fibroblasts, canid blood-derived cells exhibit 2- to 3-fold faster doubling rates (15 to 20 h vs. ~35 h for fibroblasts) and reduced time to banked cell lines (1.5 to 2 wks vs. 3 to 4 wks for fibroblasts). Proteomic profiling of 32 canonical markers confirmed EPCs and pericytes represent distinct populations with lineage-specific molecular signatures. Optical genome mapping demonstrated equivalent genomic stability across cell types with no detectable structural variants or aneuploidies. Finally, interspecific somatic cell nuclear transfer (iSCNT) experiments confirmed both EPCs and pericytes generate viable canid embryos with efficiency meeting or exceeding fibroblasts. As a proof of concept for conservation cloning, iSCNT embryos made with gray wolf blood-derived cells had a 15% implantation rate following embryo transfer and resulted in six viable fetuses. These findings support integrating blood-derived cell banking into conservation programs, which enables opportunistic genetic preservation during standard management activities and expands options for genetic rescue through assisted reproductive technologies.

Animals↗

Soft-x-ray laser interferometry of a pinch discharge using a tabletop laser.

We have used a tabletop soft-x-ray laser and a wave-front division interferometer to probe the plasma of a pinch discharge. A very compact capillary discharge-pumped Ne-like Ar laser emitting at 46.9 nm was combined with a wave division interferometer based on Lloyd's mirror and Sc-Si multilayer-coated optics to map the electron density in the cathode region of the discharge. This demonstration of the use of tabletop soft-x-ray laser in plasma interferometry could lead to the widespread use of these lasers in the diagnostics of dense plasmas.

Journal Article↗

Perceived structure from optic flow: consistent versus variable mapping of 3-D Euclidean structure.

In an earlier study (Börjesson & Lind, 1996), the perception of Euclidean structure from polar projected two-frame apparent motion sequences was studied. The results showed that Euclidean structure is not perceived. However, at larger visual angles a certain consistency in the mapping between distal and perceived structure exists. The aim of the present study was to more precisely examine how this degree of consistency varies as a function of visual angle. In Experiments 1 and 2, slant judgments of simulated and real planes indicated that the degree of consistency is a positive function of visual angle. No definite sign of a Euclidean mapping could, however, be found even in the full view condition. Experiment 3 examined texture gradients and the response method used. The results showed that texture gradients did not influence the degree of consistency of the mapping between distal and judged depth and that the response method was both reliable and valid. However, texture gradients did influence the absolute values of the slant judgments. The role of Euclidean and affine mappings of distal structure is discussed and it is proposed that the perceptually important distinction is not between affine and Euclidean mapping, but rather between two types of affine mappings--consistent and variable.

Analysis of Variance↗

Vitrectomy for non-ischaemic macular oedema in retinal vein occlusion.

PURPOSE: To evaluate the effect of vitrectomy in eyes with non-ischaemic macular oedema secondary to hemi and central retinal vein occlusion. METHODS: This retrospective study analysed the outcome of eight patients with non-ischaemic macular oedema without posterior vitreous detachment. Six patients had a central retinal vein occlusion and two had a hemi retinal vein occlusion. A standard three-port vitrectomy was performed in all patients. Retinal mapping by optical coherence tomography and visual acuity (VA) testing were performed before vitrectomy and at 1, 2 and 12 months postoperatively. RESULTS: At the 1-month follow-up there was a statistically significant reduction in retinal thickness (Wilcoxon; p = 0.04) that persisted at 2 months (Wilcoxon; p = 0.04). However, at 12 months there was no difference compared with baseline. LogMAR VA was significantly improved at 1 month (Wilcoxon p = 0.04), but at 2 and 12 months there was no difference compared with baseline. CONCLUSIONS: Vitrectomy in hemi and central retinal vein occlusion has the potential to reduce macular oedema and improve VA in the early postoperative phase but does not seem to improve the longterm outcome of the disease.

Adult↗

The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and metabolism.

Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.

Adaptation, Physiological↗

Measurement of abdominal wall compliance in normal subjects and tetraplegic patients.

On inspiration descent of the diaphragm is opposed by the passive properties of the abdominal wall, the tone of its muscles, and the inertia of the abdominal contents. As a result, intra-abdominal pressure rises and promotes rib cage expansion. In patients with high spinal injury the diaphragm is the most important muscle of inspiration and abdominal wall displacement is more evident than in normal subjects. Abdominal wall compliance has been measured by relating gastric pressure to abdominal wall displacement, which was determined by means of an optical contour mapping system. Six normal subjects and six tetraplegic patients were studied in the supine posture, during passive expiration from total lung capacity to functional residual capacity. Over this lung volume range the normal subjects partitioned an average of 31% of expired volume to the abdominal compartment, while the corresponding average figure in the patients was 77% of expired volume. Since the range of gastric pressure was similar in the two groups, it is concluded that abdominal wall compliance is greater in tetraplegic patients. This high compliance could have a detrimental effect on lower rib cage expansion.

Abdominal Muscles↗

Specificity of color connectivity between primate V1 and V2.

To examine the functional interactions between the color and form pathways in the primate visual cortex, we have examined the functional connectivity between pairs of color oriented and nonoriented V1 and V2 neurons in Macaque monkeys. Optical imaging maps for color selectivity, orientation preference, and ocular dominance were used to identify specific functional compartments within V1 and V2 (blobs and thin stripes). These sites then were targeted with multiple electrodes, single neurons isolated, and their receptive fields characterized for orientation selectivity and color selectivity. Functional interactions between pairs of V1 and V2 neurons were inferred by cross-correlation analysis of spike firing. Three types of color interactions were studied: nonoriented V1/nonoriented V2 cell pairs, nonoriented V1/oriented V2 cell pairs, and oriented V1/nonoriented V2 cell pairs. In general, interactions between V1 and V2 neurons are highly dependent on color matching. Different cell pairs exhibited differing dependencies on spatial overlap. Interactions between nonoriented color cells in V1 and V2 are dependent on color matching but not on receptive field overlap, suggesting a role for these interactions in coding of color surfaces. In contrast, interactions between nonoriented V1 and oriented V2 color cells exhibit a strong dependency on receptive field overlap, suggesting a separate pathway for processing of color contour information. Yet another pattern of connectivity was observed between oriented V1 and nonoriented V2 cells; these cells exhibited interactions only when receptive fields were far apart and failed to interact when spatially overlapped. Such interactions may underlie the induction of color and brightness percepts from border contrasts. Our findings thus suggest the presence of separate color pathways between V1 and V2, each with differing patterns of convergence and divergence and distinct roles in color and form vision.

Animals↗

Functional and structural assessment of intercellular communication. Increased conduction velocity and enhanced connexin expression in dibutyryl cAMP-treated cultured cardiac myocytes.

Remodeling of conduction pathways in the hypertrophic response to myocardial injury is a potential mechanism leading to the development of anatomic substrates of lethal arrhythmias. To delineate the responsible mechanisms and to directly relate changes in intercellular coupling at gap junctions with electrophysiological alterations, we studied the effects of cAMP, a mediator of cardiac hypertrophy, on action potential conduction velocity and connexin expression in neonatal rat ventricular myocyte cultures. Conduction velocity was measured with an optical activation mapping technique in cells loaded with the voltage-sensitive dye RH-237. Action potentials were conducted 24% to 29% more rapidly (P < .005) after incubating cultures for 24 hours with the cAMP analogue dibutyryl cAMP (db-cAMP, 1 mmol/L). However, db-cAMP caused no change in the maximum rate of rise of the action potential upstroke, Vmax. Electron and immunofluorescence microscopy revealed a significant increase in the number and size of gap junctions in db-cAMP-treated cells. Immunoblotting showed that the total amounts of the ventricular gap junction proteins connexin43 and connexin45 (Cx43 and Cx45, respectively) increased 2- to 4-fold. Immuno-precipitation of metabolically labeled connexin proteins revealed a dose-dependent increase in the rate of Cx45 protein synthesis in myocytes exposed to db-cAMP ( > 2-fold after a 4-hour exposure) but no change in the Cx43 synthesis rate. Northern blot analysis demonstrated a time-dependent increase in the amount of Cx43 mRNA, with a maximum 3.3-fold increase after 4 hours of exposure to 1 mmol/L db-cAMP; cycloheximide did not block this effect. In contrast, Cx45 mRNA levels were not altered significantly after db-cAMP treatment. Thus, cAMP causes a significant increase in conduction velocity that appears to be attributable largely to enhanced expression of proteins responsible for intercellular communication. Cx43 and Cx45 levels appear to be upregulated by cAMP by disparate molecular mechanisms.

Action Potentials↗