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PubMed1985

Comparative theoretical performance for two types of regional hyperthermia systems.

Regional hyperthermia systems have drawn attention because of their potential for depositing power noninvasively in deep-seated tumors. Two such systems that have received clinical attention because of their ability to deposit significant amounts of power in tissue are magnetic induction devices and annular phased array applicators. In this paper, theoretical calculations for the specific absorption rate (SAR) and the resulting temperature distributions for these systems are compared. The finite element method is used in the formulation of both the electromagnetic and thermal boundary value problems. Six detailed patient models based on CT-scan data from the pelvic, visceral, and thoracic regions are generated to simulate a variety of tumor locations. In general, the annular phased array deposited more power within the tumor and produced better temperature distributions than the magnetic induction device. However, the ratio of the maximum power absorbed by the tumor to the maximum power absorbed in normal tissue does not appear to be high enough for either device to heat significant portions of perfused tumors to therapeutic temperatures under a wide range of physiological conditions. The results contained herein should aid the physician in comparative treatment planning with existing regional hyperthermia systems.

Electromagnetic Fields↗

PubMed2026

Sequence optimization targeting mRNA stability enhances monoclonal antibody titers in CHO cells.

This study presents a DNA sequence optimization approach that integrates mRNA stability as a tunable design parameter to enhance monoclonal antibody expression in Chinese hamster ovary (CHO) cells. A comprehensive combinatorial library of synonymous coding-sequence variants of an IgG1 light chain was integrated as single copies at a defined genomic locus in CHO cells with identical regulatory elements. Steady-state mRNA abundance, quantified by deep sequencing of gDNA and mRNA, served as a proxy for mRNA stability. These data were used to train a machine learning model that predicts mRNA abundance from coding sequence using embeddings from a pre-trained nucleotide transformer. This abundance predictor, together with established translational metrics, was incorporated into a genetic algorithm for multi-objective codon optimization. As proof-of-concept, we optimized sequences encoding Trastuzumab to either maximize or minimize the abundance criterion and obtained benchmark sequences from two commercial providers. Using targeted integration, we generated CHO cell lines and measured protein titer and cell-specific productivity. Sequences optimized for high abundance significantly increased intracellular mRNA levels (+41%), protein titer (+59%), and cell-specific productivity (+85%) relative to low-abundance designs, while viable cell densities remained comparable. Compared to commercial benchmarks, high-abundance sequences achieved significantly higher titer (+70%) and cell-specific productivity (+98%). These findings establish mRNA stability as a practical and complementary design parameter for codon optimization in monoclonal antibody production, with potential applicability to other proteins and expression systems.

CHO↗

PubMed1990

Modelling coronary thrombosis from nonanticoagulated human blood in vitro.

The prevalence of ruptured atheromatous plaques underlying the adherent thrombus in the infarct-related coronary arteries, is well documented. In the thrombotic process associated with plaque rupture, hemodynamic forces and the interaction of platelets with exposed collagen fibers play the decisive roles. The shear-induced hemostasis from a nonanticoagulated human blood sample, perfused through polyethylene tubing, was used to simulate rheological changes in the coronary circulation due to plaque disruption. When the hemodynamic conditions of a plaque fissure were mimicked, the sequence of events corresponded to that in vivo: hemostasis (i.e., platelet plug formation in the wall) resulted in the formation of an occlusive thrombus in the lumen of the tubing. Further, the thrombus growth on a collagen fiber, mounted in the lumen of polyethylene tubing through which nonanticoagulated human blood was perfused, was used to mimick the exposure of thrombogenic elements during deep vessel wall injury and the formation of thrombus superimposed on plaque disruption. Morphology of both types of thrombi revealed large numbers of neutrophils and monocytes associated with the platelet mass. The mechanisms of thrombotic reactions were characterized by antagonists and monoclonal antibodies against the platelet activation pathways. Generation of thrombin at an early stage was shown to be the key event and determinant of the final outcome of both thrombotic reactions. It is suggested that the simultaneous measurements of shear-induced hemostasis, clotting, and platelet-collagen interaction from nonanticoagulated human blood provide close experimental approximations to the pathological process of acute coronary syndromes, namely thrombus formation at the site of a disrupted atherosclerotic plaque.

Adolescent↗

PubMed2026

Conditional Diffusion Model-Based Method for Annotation of Antibiotic Resistance Gene Properties.

The crisis of bacterial antibiotic resistance, which has led to a decline in the effectiveness of antibiotics originally used to combat bacterial infections, has emerged as an urgent challenge for public health. Antibiotic resistance genes (ARGs) are one of the key reasons for bacteria to develop resistance to antibiotics. Therefore, accurately identifying and annotating the critical properties of ARGs is of great importance for addressing the antibiotic resistance emergency. Although existing deep learning models demonstrate remarkable effectiveness in extracting local features from sequence data, they still face limitations in the capacity to further gain the enriched latent representations within the data. To address the critical challenge of extracting higher-quality representations from ARGs sequence data, we propose a novel ARGs properties annotation method based on the conditional diffusion model which is used to learn latent representations through domain-specific knowledge injection. Specifically, during the conditional information integration phase, we systematically incorporate ARGs' domain knowledge to guide the diffusion process in generating high-quality latent representations. To overcome information redundancy caused by direct concatenation of conditional information and intermediate features, we design a cross-attention mechanism that enables feature fusion between heterogeneous information sources, thereby enhancing further the quality of obtained representations. Experimental results on widely used data sets demonstrate the framework's effectiveness in achieving superior prediction performance compared to existing methods.

Anti-Bacterial Agents↗

PubMed1997

Rupture of lens cataract: a novel hereditary recessive cataract model in the mouse.

The RLC is a new mouse model of hereditary cataract. In this mutant, opacity of lens developed spontaneously at 35-60 days of age. The initial histological change was irregular swelling, condensation, degeneration and fragmentation of lens fibers in the deep cortex, leading to rupture of the lens capsule at the posterior pole at 45-100 days of age. Following rupture, the lens nucleus dislocated behind the lens or occasionally in the anterior chamber. Both eyes were affected. Genetic analysis indicated that the mutation was dictated by a single autosomal recessive gene with complete penetrance. Homozygotes of either sex developed cataract with rupture of lens capsule. We named the responsible gene as rupture of lens cataract (rlc) and the mouse strain as RLC. Neither allelism nor linkage was found between rlc and nct, another recessive gene in Nakano cataract mice. The rlc mutation is now fixed in a inbred background since the RLC has been maintained over 20 inbred generations in the laboratory. Although no direct homologous disease of this unusual cataract is found in human, this mutant will provide a valuable tool to investigate the mechanism involved in maintainance of lens.

Animals↗

PubMed1994

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Adult↗

PubMed2000

Numerical simulation of ultrasound-thermotherapy combining nonlinear wave propagation with broadband soft-tissue absorption.

Ultrasound (US) thermotherapy is used to treat tumours, located deep in human tissue, by heat. It features by the application of high intensity focused ultrasound (HIFU), high local temperatures of about 90 degrees C and short treating time of a few seconds. Dosage of the therapy remains a problem. To get it under control, one has to know the heat source, i.e. the amount of absorbed US power, which shows nonlinear influences. Therefore, accurate simulations are essential. In this paper, an improved simulation model is introduced which enables accurate investigations of US thermotherapy. It combines nonlinear US propagation effects, which lead to generation of higher harmonics, with a broadband frequency-power law absorption typical for soft tissue. Only the combination of both provides a reliable calculation of the generated heat. Simulations show the influence of nonlinearities and broadband damping for different source signals on the absorbed US power density distribution.

Computer Simulation↗

PubMed1983

Capillary transport of H2 gas generated locally in renal tissue.

Previous measurements by microspheres have shown a higher blood flow in outer cortex and a lower blood flow in inner cortex than found by diffusible tracers. During vasodilation microspheres have indicated a disproportionate increase in deep cortical blood flow, whereas diffusible tracer distributions remained unchanged. These discrepancies could possibly be explained by a variable net inward transport of diffusible tracers in postglomerular vessels, the transport existing in control, but disappearing during vasodilation. To test this hypothesis H2 gas was produced electrolytically for 1 s at a platinum electrode in midcortex and the resulting gas concentration curve measured polarographically at two electrodes placed above and below the source. Analysis of a mathematical model showed that the ratio of the curve maxima at the two electrodes (Cmo/Cmi) would best reveal a radial net transport. Average Cmo/Cmi at 25 positions in 7 clamped dog kidneys was close to unity, but rose to 1.24 at control flow. During acetylcholine infusion Cmo/Cmi rose to 1.68. Local washout rates at the two electrodes increased equally. Calculations indicated a small outwardly directed net transport in control (3 X 10(-4) cm/s), becoming slightly reinforced during vasodilation (5 X 10(-4) cm/s). Thus the control transport direction is opposite to the hypothesis, and the change during vasodilation was estimated to be too small to explain the disparity between diffusible tracer uptake and microsphere distribution in control. H2 concentration maximum was obtained earlier under control flow than in the clamped kidney, indicating an increase in apparent D of the gas in tissue from 3 X 10(-5) cm2/s to 5 X 10(-5) cm2/s, probably due to mixing of H2 gas in the capillary net work.

Acetylcholine↗

PubMed1997

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Adolescent↗

PubMed1998

Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models.

OBJECTIVE: To evaluate the safety profile of endometrial ablation performed with a thermal balloon as defined by serosal temperature elevation and depth of injury. DESIGN: Observational study with histopathologic correlation conducted in ex vivo and in vivo phases. SETTING: Academic medical center. PATIENT(S): Twenty patients undergoing total abdominal hysterectomy. INTERVENTION(S): Endometrial ablation with a thermal balloon. MAIN OUTCOME MEASURE(S): Serosal temperature elevation and histologic depth of injury. RESULT(S): Ex vivo phase results revealed serosal temperatures remained within a safe physiologic range (<45 degrees C). Greatest depth of myometrial injury in the premenopausal uteri was 5.8 mm over the anterior lower uterine segment. In postmenopausal uterus. the greatest depth of myometrial injury was 3.8 mm in the anterior midline. In vivo phase results revealed mean (+/- SD) peak serosal temperatures of 36.1 +/- 1.6 degrees C. As with the ex vivo phase. histologic examination revealed deep endometrial and superficial myometrial damage to all areas. The greatest depth of myometrial injury occurred in the midfundus at 3.4 mm. CONCLUSION(S): No patients experienced complications or adverse events secondary to treatment. Results showed that transuterine thermal injury is a highly unlikely scenario. In both phases of this study, histologic examination revealed that temperatures exposed to the endometrial layer were sufficient to cause tissue damage.

Adult↗

PubMed2025

Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pretrained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Selection, Genetic↗

PubMed1988

Extraction of "deep" components from scalp EEG.

In an attempt to delineate the relative contribution of surface versus deep components in the EEG of patients with 3 per second generalized spike-wave discharges and clinical petit mal seizures, a mathematical method was devised which allows the splitting of the EEG into two major subsystems. It is based on the observation that broad electrical fields tend to represent activity at deeper structures while discrete narrow fields centered at one electrode position tend to be of more superficial origin. Since source derivation intentionally suppresses broad potential fields, a differentiation between superficial and deep activity can be achieved by subtracting the source density values from the corresponding electrode potential values. This will provide those aspects of the EEG which are contributed mainly by deep generators. The resultant data can then be subjected to eigenfunction analysis which yields few uncorrelated components. The percentage of contribution of each electrode to the total component thus derived can then be displayed as a topographic map. When this methodology was applied to ictal EEGs of three patients consistent results were obtained. The "deep" data yielded mainly two components with mutually perpendicular directions.

Cerebral Cortex↗

PubMed1993

[Photoablation of the cornea with pulsed 2790 nm ErCr:YSGG laser irradiation. Basic studies].

The potential of 3 microns solid-state lasers as an alternative to excimer lasers for photoablative corneal surgery was investigated. A Q-switched ErCr:YSGG laser (2790 nm, 200 ns) was used for irradiation of porcine corneas and agar-agar samples. Mechanical tissue effects (stroma, endothelium) were documented by micromorphology. Laser-induced shock-waves were analyzed by piezo-electric transducers. No sharp ablation threshold, as in excimer laser photoablation, could be determined. Energy fluences < 2 J/cm2 led to dehydration of the irradiated samples. Higher fluences are necessary for the evaporation of tissue water to be so vigorous that the tissue matrix is expelled along with the organic matrix. At high fluences, the ablation rate exceeds the absorption depth of the laser radiation (up to 25 microns/pulse). At fluences between 2.5 and 28 J/cm2 the thermal necrosis zone adjacent to the crater was 7 +/- 3 microns. The intensity of the laser-induced acoustic shock waves can peak to some hundred bar. Small gas bubbles up to 1 mm were found in the surrounding area of the ablation crater. Apparently, they were pressed between the collagen lamellas by the explosive force of the ablative process. In deep excisions (> 75%) endothelial defects underneath the beam axis could be documented. Large-area tissue ablation, with a resolution in the range of 1 micron, as necessary in myopia correction, will not be possible with the present generation of ErCr:YSGG lasers. Its high ablation rate makes this laser suitable as a cutting (astigmatism, keratoplasty, vitreous surgery) and drilling (glaucoma) device.

Animals↗

PubMed2025

Efficient detection and characterization of targets of natural selection using transfer learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pre-trained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Journal Article↗

PubMed1993

Laboratory evaluation of a low prime closed-circuit cardiopulmonary bypass system.

We have explored the potential advantages of a low prime closed-circuit cardiopulmonary bypass (CPB) system using a non-human primate model. Although manufacturers have reduced priming volumes in individual CPB components, the standard circuit volume remains high because of the tubing diameter and length necessary for gravity drainage. By replacing gravity drainage with the negative pressure generated by a centrifugal pump, we can realize significant tubing volume reduction. Closed-circuit bypass was conducted on 13 baboons ranging from 5-15 kg. The circuit consisted of a centrifugal pump, a hollow fiber oxygenator, and 1/4" arterial and venous tubing. The design of the circuit included the capacity to remove a limited amount of venous air. Circulatory arrest during deep hypothermia with volume displacement into a reservoir was also accomplished with this circuit. The potential benefits of this low prime closed-circuit bypass system include blood conservation and reduction in blood surface area contact. The future safe clinical use of this type of closed-circuit bypass for routine open heart surgery will depend upon the incorporation of a device in the venous line to remove air. This is the greatest threat to patient safety in a closed circuit system and its use for open chest surgery must wait until an efficient venous air elimination device is available.

Blood Transfusion, Autologous↗

PubMed1976

Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation.

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight-junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin- A chick-skin system is presented as a responsive model for the controlled study of junction assembly.

Animals↗

PubMedDate not supplied

Estimates of the net excitatory currents evoked by visual stimulation of identified neurons in cat visual cortex.

The action potential discharge response of single neurons to both visual stimulation and injections of current were obtained during intracellular recordings in cat visual cortex in order to estimate the net excitatory current arriving at the soma during visual stimulation. Of 45 neurons recorded intracellularly, 19 pyramidal neurons and one basket cell were labelled with horseradish peroxidase. The discharge of all neurons adapted to constant current. For 40 neurons, a single exponential provided a good fit to the adapting discharge (r2 = 0.73 +/- 0.03) for all current intensities. Superficial layer neurons were significantly faster adapting [P < 0.001, mean (+/- SEM) time constant of adaptation = 11.5 +/- 1.3 ms; n = 20] than deep layer neurons (mean time constant of adaptation = 51.4 +/- 6.4 ms; n = 10). The percentage adaptation of the spike frequency, %(peak - adapted rate)/peak, was determined from the fitted exponential. Superficial layer neurons adapted significantly more strongly (P < 0.01, mean = 67 +/- 3%) than deep layer neurons (mean = 51 +/- 5%). The mean firing frequency in response to a current step of 320 ms duration had a linear relationship to the amplitude of the injected current (slope 66 spikes/s/nA; origin zero, mean r2 = 0.94; n = 33). This relationship provided a means of estimating the net peak excitatory current generated by visual stimuli. The estimated mean peak somatic current during the passage of a bar across the receptive field was 1.1 nA and the average current for the duration of the visually evoked discharge was 0.64 nA (n = 17). The transfer response of real and model neurons was obtained by differentiating the discharge response to a step input current and was then used to predict the output of the neuron following an arbitrary input. When these transfer responses were convolved with known input signals in model neurons, the predicted output was close to the simulated response of the model neuron to the same input waveforms. The transfer response was calculated for eight real neurons. Estimates of the net excitatory current arriving at the soma during visual stimulation was obtained by deconvolution. The mean peak somatic current for these neurons was 0.62 nA.

Action Potentials↗

PubMed1991

Neuroblastoma grafts are noninvasively removed within mouse neocortex by selective laser activation of intracellular photolytic chromophore.

Studies of neural cell transplantation would be aided by the ability to damage or destroy, noninvasively and extremely selectively, grafted cells at defined times following their initial implantation. Mechanisms of graft integration and performance could be investigated, also providing insight into natural injury and repair mechanisms. At long wavelengths between 650 and 850 nm, laser energy can penetrate several millimeters of brain tissue without absorption or damage to the unpigmented tissue. However, targeted cells are selectively damaged by illumination at these long wavelengths if they contain latex nanospheres with incorporated cytolytic chromophores (e.g., chlorin e6). Light penetration allows many thousands of cells to be lesioned simultaneously, noninvasively, and deep within a surrounding matrix of other tissue. Such laser-activated damage has been termed laser photolysis (PL). We studied damage to C1300 neuroblastoma (NB) cells grafted into mouse neocortex in vivo by this process of PL. NB cells provided a simple and reproducible model of neural grafting, allowing direct histologic assessment of cellular growth and viability by distinct morphologic and mitotic criteria. Cells were cultured by standard methods, labeled in vitro by brief exposure to nanospheres containing chlorin e6, and grafted to sites within deep layers of mouse neocortex. Mice were exposed to transcranial, fractionated, unfocused pulses of 670-nm-wavelength energy totaling 90-120 J/cm2. We histologically assessed graft growth and cellular viability over a period from 2 d to 4 weeks, measured graft volumes quantitatively during the period of early rapid growth in controls (2 and 7 d), and generated 3-D reconstructions from serial sections to assist in visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗