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At least 253 records · Page 14Linked to original sources
PubMed1990

Mechanism of O-antigen distribution in lipopolysaccharide.

O-antigen units are nonuniformly distributed among lipid A-core molecules in lipopolysaccharide (LPS) from gram-negative bacteria, as revealed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the actual distribution patterns are complex, multimodal, and strain specific. Although the basic biochemical steps involved in synthesis and polymerization of O-antigen monomers and their subsequent attachment to lipid A-core are known, the mechanism by which specific multimodal distribution patterns are attained in mature LPS has not been previously considered theoretically or experimentally. We have developed probability equations which completely describe O-antigen distribution among lipid A-core molecules in terms of the probability of finding a nascent polymer (O antigen linked to carrier lipid) of length k (Tk) and the probability that a nascent polymer of length k will be extended to k + 1 by polymerase (pk) or transferred to lipid A-core by ligase (qk). These equations were used to show that multimodal distribution patterns in mature LPS cannot be produced if all pk are equal to p and all qk are equal to q, conditions which indicate a lack of selectivity of polymerase and ligase, respectively, for nascent O-antigen chain lengths. A completely stochastic model (pk = p, qk = q) of O-antigen polymerization and transfer to lipid A-core was also inconsistent with observed effects of mutations which resulted in partial inhibition of O-antigen monomer synthesis, lipid A-core synthesis, or ligase activity. The simplest explanation compatible with experimental observations is that polymerase or ligase, or perhaps both, have specificity for certain O-antigen chain lengths during biosynthesis of LPS. Our mathematical model indicates selectively probably was associated with the polymerase reaction. Although one may argue for a multimodal distribution pattern based on a kinetic mechanism i.e., varying reaction parameters in space or in time during cell growth, such a model requires complex sensory and regulatory mechanisms to explain the mutant data and mechanisms for sequestering specific components of LPS biosynthesis to explain the distribution pattern in normal cells. We favor the simple alternative of enzyme specificity and present generalized equations which should be useful in analysis of other analogous biochemical systems.

Antigens, Bacterial↗
PubMed2006

Combination of multimodal imaging and molecular genetic information to investigate complex psychiatric disorders.

Multimodal imaging, the combination of several brain imaging techniques in one subject, provides a wealth of parameters and favours the interpretation of complex models in schizophrenia research. Moreover, new imaging tools allow the investigation of distinct neurotransmitter systems and their modulation by pharmacological intervention. An important feature of multimodal imaging is the possibility to characterize the activation dependencies of different neurotransmitters and provide the experimental tool to test system models of brain function and dysfunction. The combination of measurement techniques with high temporal resolution (e. g. MEG, EEG) and high spatial resolution (e. g. fMRI) facilitate the understanding of local and global systems as well as time characteristics. Moreover, the association of imaging parameters with genetic variations of neurotransmitter systems allows the investigation of neurotransmitter activity and its role in the pathophysiology of schizophrenia. To overcome the limitations of standard statistical methods, new approaches in machine learning have to be adapted to handle multiple parameters obtained from brain imaging and genetic measurements.

Brain↗
PubMed2026

Integrating histology and spatial transcriptomics via multimodal transformers and contrastive representation learning for accurate gene expression prediction.

Predicting spatial gene expression from Histological images is a fundamental task in understanding tissue organization and molecular phenotypes. However, existing methods often rely on single-model representations or lack effective alignment between image and transcriptomic features. To address these limitations, we propose a unified multimodal learning framework that integrates histological imaging and spatial transcriptomics through a shared latent representation space. Specifically, histological H&E images are encoded by a ResNet50-based convolutional stem and a MobileViT Transformer backbone to extract hierarchical visual representations. Both modalities are projected into a shared latent space via linear-GELU-dropout transformation blocks, enabling cross-modal alignment through a contrastive learning objective that maximizes agreement between the corresponding image and the spot embeddings. Experimental results on the 10x Genomics Visium dataset of human liver tissue demonstrate that MViTGene achieves significantly higher prediction accuracy than existing methods across multiple gene subsets, with improvements of 20%, 33%, and 12% in predicting marker genes, highly expressed genes, and highly variable genes, respectively. The significant improvement in relevance indicates that the model can more accurately capture the true correspondence between tissue morphology and gene expression, therefore enabling more reliable biological interpretation. It provides a computational tool for high-throughput spatial gene expression prediction that balances performance and interpretability.

Humans↗
PubMed2002

Model for variation of laser power with M2.

A functional relationship between M2 of a multimode laser and its extraction efficiency from a uniformly pumped cylindrical laser medium is derived from numerical calculations by use of helicoid modes.

Journal Article↗
PubMed2000

Sensory evoked potentials in SIV-infected monkeys with rapidly and slowly progressing disease.

Human immunodeficiency virus (HIV-1) infects the central nervous system (CNS) early in the course of disease progression and leads to some form of neurological disease in 40-60% of cases. Both symptomatic and asymptomatic HIV-infected subjects also show abnormalities in evoked potentials. As part of an effort to further validate an animal model of the neurological disease associated with lentiviral infection, we recorded multimodal sensory evoked potentials (EPs) from nine rhesus macaques infected with passaged strains of SIVmac (R71/E17), prior to and at 1 month intervals following inoculation. The latencies of forelimb and hindlimb somatosensory evoked potentials (SEP) and flash visual evoked potentials (VEP) were measured. Within 14 weeks of inoculation, all but two animals had progressed to end-stage disease (rapid progressors). The two animals with slowly progressing disease (AQ15 and AQ94) had postinoculation life spans of 109 and 87 weeks, respectively. No significant changes were observed in evoked potentials recorded during the control period or at any time in the animals with slowly progressing disease. However, all of the monkeys with rapidly progressing disease exhibited increases in latency for at least one evoked potential type. The overall mean increases in somatosensory and visual evoked potential peak latencies for the rapid progressors were 22.4 and 25.3%, respectively. For comparison, the changes in slow progressors were not significant (1.8 and -1.9%, respectively). These results, coupled with our previous finding of slowed motor evoked potentials in the same cohort of macaques (Raymond et al.: J Neurovirol 1999;5:217-231), demonstrate a broad and somewhat variable pattern of viral injury to both sensory and motor system structures, resembling the findings in HIV-infected humans. These results coupled with our earlier work demonstrating cognitive and motor behavioral impairments in the same monkeys support the use of the SIVmac-infected rhesus macaque as a model of AIDS-related neurological disease.

Animals↗
PubMed2003

A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation.

The determination of brain tumor margins both during the presurgical planning phase and during surgical resection has long been a challenging task in the therapy of brain tumor patients. Using a model of gliosarcoma with stably green fluorescence protein-expressing 9L glioma cells, we explored a multimodal (near-infrared fluorescent and magnetic) nanoparticle as a preoperative magnetic resonance imaging contrast agent and intraoperative optical probe. Key features of nanoparticle metabolism, namely intracellular sequestration by microglia and the combined optical and magnetic properties of the probe, allowed delineation of brain tumors both by preoperative magnetic resonance imaging and by intraoperative optical imaging. This prototypical multimodal nanoparticle has unique properties that may allow radiologists and neurosurgeons to see the same probe in the same cells and may offer a new approach for obtaining tumor margins.

Animals↗
PubMed2026

GBFN: A gated bimodal fusion network leveraging foundation model embeddings for cancer drug sensitivity prediction.

Despite recent progress in deep learning for cancer drug sensitivity prediction, many existing models still rely on task-specific representation learning or relatively simple multimodal fusion, which may limit their ability to capture complex drug-cell interactions. To address this issue, we developed GBFN, a gated bimodal fusion network for continuous IC50 prediction that integrates pretrained drug and cell-line representations. Specifically, drug embeddings were obtained from SMI-TED, whereas cell-line embeddings were derived from transcriptomic profiles using BulkFormer. These two modalities were then combined through a dimension-wise gated fusion module and used to predict IC50 values in matched drug-cell line pairs. On the CCLE-based benchmark, GBFN outperformed representative neural baselines, including GraphDRP, TGSA, and TransEDRP, and achieved the best overall performance, with an R² of 0.8714 and an RMSE of 0.8938. Moreover, ablation analysis showed that the model using drug features and cell-line expression data with gated fusion performed better than the corresponding model using direct concatenation, indicating that the improvement was associated with the fusion strategy rather than with the input modalities alone. In addition, cell-line expression data were more informative than mutation data in the present setting, and adding mutation data to the model using drug features and expression data did not further improve performance. Across major cancer types, GBFN maintained generally high cell-line-level predictive performance, and perturbation-based attribution identified biologically relevant transcriptomic programs in selected drug-cell line settings. Together, these findings support GBFN as a compact and effective framework for continuous drug response prediction.

Humans↗
PubMed2000

Action of locally administered NMDA and AMPA/kainate receptor antagonists in spinal cord injury.

NMDA or AMPA/kainate receptor antagonists have been shown to provide neuroprotection following in vitro spinal cord injury, but the mechanisms by which these agents improve behavioral recovery and protect axonal function remains unclear. We hypothesized that treatment of spinal cord injury with these drugs would attenuate glutamate excitatory transmission by blocking the effects of glutamate receptors at the injury site or would improve spinal cord blood flow. To test these hypotheses, we observed the effects of locally administered MK-801 (30 nmol) or NBQX (5 or 15 nmol) into the injured spinal cord on axonal conduction and post-traumatic ischemia of the cord. The outcome measures were multimodality evoked potentials and blood flow in an acute compression injury model in rats. We found that locally administered MK-801 or NBQX 15 min after spinal cord injury attenuated the amplitude, delayed the latency of sensory evoked potentials and increased the sensory conduction time across the injury site, but did not improve blood flow during the 4-h period of observation. These results demonstrate that the NMDA and non-NMDA receptor antagonists produced a blockade of glutamate excitatory transmission in the afferent pathways at the injury site. It is suggested that the neuroprotection provided by these agents following spinal cord injury is mediated through blockade of glutamate ionotropic receptors in the injured spinal cord, but is not related to improvement of SCBF.

Animals↗
PubMed2007

Practice parameter for the assessment and treatment of children and adolescents with oppositional defiant disorder.

Oppositional defiant disorder (ODD) is a common clinical problem in children and adolescents. Oppositionality and associated types of aggressive behavior are among the most common referral problems in child psychiatry. Grouped among the disruptive behavior disorders, ODD is frequently comorbid with other psychiatric conditions and often precedes the development of conduct disorder (CD), substance abuse, and severely delinquent behavior. Youth with ODD may also have specific CD behaviors, such as aggression. Although compared with CD there exists a smaller and less sophisticated empirical database for ODD, this parameter draws upon the existing ODD and CD literature to make recommendations regarding diagnosis and treatment of ODD. The etiology of ODD is complex and its development is based on a cumulative risk/protective factor model that combines biological, psychological, and social factors. Recommended treatment is multimodal and extensive, involving individual and family psychotherapeutic approaches, medication, and sociotherapy. Methodologically sound controlled clinical trials are lacking.

Adolescent↗
PubMed2005

Tunable waveguides via photo-oxidation of plasma-polymerized organosilicon films.

Plasma-enhanced chemical vapor deposition (PECVD) of dimethylsilane and hexamethyldisilane produced thin films with a refractive index of 1.56 +/- 0.01 at 633 nm. A decrease in the refractive index of approximately 3% was observed after irradiation with UV light from an ArF laser operating at 193 nm. Lower-intensity UV light from a Hg arc lamp induced a slower and controllable decrease in the refractive index. Top-side prism coupling showed the as-deposited organosilicon films to be multimode at 633 nm and single mode at 1550 nm. A model predicted that 30 s of UV irradiation with the Hg arc lamp would decrease the refractive index of the light-guiding film by approximately 0.01, converting the waveguide into single-mode operation across the spectrum of essential wavelengths for microphotonics. Irradiation followed by further coupling experiments confirmed this tunability. Trimming the refractive index of patternable organosilicon polymeric films presents a method of optimizing the coupling performance of PECVD microphotonic interconnect layers postdeposition.

Journal Article↗
PubMed2006

Design issues and priorities in team and nonpharmacological arthritis care research.

Nonpharmacologic and team care research present unique design challenges. Nonpharmacologic care by nature is multifaceted and complex. Rarely do patients receive an intervention in isolation. The delivery of a single or group of interventions can be provided by one provider but is frequently provided by teams. Therefore, it is imperative that clinical researchers design studies that evaluate single and multimodal interventions as well as studies that best reproduce the team model of service delivery to accurately examine interventions. While it is well accepted that the research question drives the design, it is imperative to recognize that certain aspects of nonpharmacologic and team care restrict the implementation or effectiveness of specific design components. For example, as patients are required to actively engage in lifestyle changes, double-blinding cannot be employed. In addition, there is no accepted operational definition of team care in arthritis. It is important to keep in mind the characteristics of these interventions in the selection of a research design and develop strategies to best examine these interventions. Combining aspects of randomized controlled trials with qualitative methods is one technique to enrich data collected on these interventions. Certain features of pharmacovigilance studies may also serve as an alternative model. The use of national or regional registries for longterm clinical followup as seen in orthopedic surgery may prove to be applicable in the design of studies for evaluation of team care. Our article will discuss issues related to the design and synthesis of arthritis care research, and the role of patients in the design of clinical trials; describe collaborative international activities furthering team and nonpharmacological arthritis care research; and identify research activities that may influence future practice and the health of people with arthritis.

Arthritis↗
PubMed2006

Factors influencing the accuracy of biomechanical breast models.

Recently it has been suggested that finite element methods could be used to predict breast deformations in a number of applications, including comparison of multimodality images, validation of image registration and image guided interventions. Unfortunately knowledge of the mechanical properties of breast tissues is limited. This study evaluated the accuracy with which biomechanical breast models based on finite element methods can predict the displacements of tissue within the breast in the practical clinical situation where the boundaries of the organ might be known reasonably accurately but there is some uncertainty on the mechanical properties of the tissue. For two datasets, we investigate the influence of tissue elasticity values, Poisson's ratios, boundary conditions, finite element solvers and mesh resolutions. Magnetic resonance images were acquired before and after compressing each volunteer's breast by about 20%. Surface displacement boundary conditions were derived from a three-dimensional nonrigid image registration. Six linear and three nonlinear elastic material models with and without skin were tested. These were compared to hyperelastic models. The accuracy of the models was evaluated by assessing the ability of the model to predict the location of 12 corresponding anatomical landmarks. The accuracy was most sensitive to the Poisson's ratio and the boundary condition. Best results were achieved for accurate boundary conditions, appropriate Poisson's ratios and models where fibroglandular tissue was at most four times stiffer than fatty tissue. These configurations reduced the mean (maximum) distance of the landmarks from 6.6 mm (12.4 mm) to 2.1 mm (3.4 mm) averaged over all experiments.

Algorithms↗
PubMed2004

Solving the neuroimaging puzzle: the multimodal integration of neuroelectromagnetic and functional magnetic resonance recordings.

In this chapter, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are reviewed. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model, and regularized linear inverse source estimates. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) and event-related (coupling of activated voxels) fMRI. As an example, these methods were applied to EEG (128 electrodes) and fMRI data, which were recorded in separate sessions while normal subjects executed voluntary right one-digit movements.

Brain Mapping↗
PubMed2000

Multimodal sensory integration in the strike-feeding behaviour of predatory fishes.

The search for useful model systems for the study of sensory processing in vertebrate nervous systems has resulted in many neuroethological studies investigating the roles played by a single sensory modality in a given behaviour. However, behaviours relying solely upon information from one sensory modality are relatively rare. Animals behaving in a complex, three-dimensional environment receive a large amount of information from external and internal receptor arrays. Clearly, the integration of sensory afference arising from different modalities into a coherent 'gestalt' of the world is essential to the behaviours of most animals. In the last several years our laboratory team has examined the roles played by the visual and lateral line sensory systems in organizing the feeding behaviour of two species of predatory teleost fishes, the largemouth bass, Micropterus salmoides, and the muskellunge, Esox masquinongy. The free-field feeding behaviours of these fishes were studied quantitatively in intact animals and compared to animals in which the lateral line and visual systems had been selectively suppressed. All groups of animals continued to feed successfully, but significant differences were observed between each experimental group, providing strong clues as to the relative role played by each sensory system in the organization of the behaviour. Furthermore, significant differences exist between the two species. The differences in behaviour resulting when an animal is deprived of a given sensory modality reflect the nature of central integrative sensory processes, and these behavioural studies provide a foundation for further neuroanatomical and physiological studies of sensory integration in the vertebrate central nervous system.

Animals↗
PubMed1999

Lessons from large trials: the MTA study as a model for evaluating the treatment of childhood psychiatric disorder.

OBJECTIVE: To review the methodology of the Multimodal Treatment Study of Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA study, and its implications for the design of future child mental health treatment studies. METHOD: The characteristics of large-scale studies envisioned by trialists engaged in cardiovascular and cancer research provide the framework for reviewing key elements of the MTA study--objectives, research questions, measurement, sampling, and exposure to treatment--and discussing important methodological decisions the MTA investigators had to make. RESULTS: The MTA study is a complex, standardized, carefully implemented, randomized control trial. Review of the MTA study indicated that future studies should be aligned clearly with either effectiveness or efficacy objectives but not both. Questions selected for study should be simple, clear, and important. Measurement, sampling, and data collection must adhere to the principle of simplicity to ensure maximum participation. All methodological decisions should be geared to attaining the research objectives: in effectiveness trials, this means evaluating treatments that have a high potential for dissemination if proven successful and recruiting only new referrals from child mental health settings. CONCLUSIONS: The MTA study has raised the standard for technical excellence in child treatment research and will draw attention to some fundamental issues in large-scale child treatment studies, including articulating objectives and questions, setting priorities for measurement and sampling, and identifying treatments for evaluation that have a high probability of dissemination if found effective.

Attention Deficit Disorder with Hyperactivity↗
PubMedDate not supplied

Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene.

PURPOSE: Previous work showed quantitative imaging of T-cell migration into a tumor site by positron emission tomography (PET), using retroviral transduction of mutated thymidine kinase (sr39TK) reporter genes into immunized T-lymphocytes. PROCEDURES AND RESULTS: In order to improve the sensitivity and flexibility of the imaging analysis, lentivirus, that expressed sr39TK, was used to transduce the lymphocytes that migrated to an immunogenic sarcoma site. In comparison to retrovirally transduced lymphocytes, the lentivirally transduced lymphocytes showed enhanced PET signal when equal numbers of transduced lymphocytes were transferred. Furthermore, in order to utilize multimodality in vivo imaging capability, a tri-fusion reporter gene containing sr39TK, synthetic Renilla luciferase (hRluc), and enhanced green fluorescent protein (eGFP) was inserted into a lentiviral transfer vector. Using the adoptive transfer model, tumor-specific lymphocytic migration was detected by both microPET scan and bioluminescence imaging. CONCLUSION: The multimodal imaging strategy coupled with lentiviral reporter construct delivery demonstrated here can facilitate future molecular imaging studies.

Animals↗
PubMed2006

Molecular imaging: a new way to study molecular processes in vivo.

Non-invasive imaging of reporter gene expression using different imaging modalities is increasing its role for the in vivo assessment of molecular processes. Multimodality imaging protocols overcome limitations to a single imaging modality and provide a thorough view of specific processes, often allowing a quantitative measurement and direct visualization of the process in a specific target organ or tissue. The use of the right reporter gene for the development of animal models and the characterization of its expression in different conditions and tissues is fundamental for basic, translational and future pharmacological applications of a given model. This paper summarizes the major steps in the development and evaluation of a specific animal model for in vivo molecular imaging studies and describes the first example of an animal model designed for the in vivo assessment of a specific receptor activity and its possible evolution towards multimodality imaging analysis.

Animals↗