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Evaluation of 3D Spheroids for AAV Transduction Studies.

Adeno-associated viruses (AAVs) are potent vectors used for gene delivery in gene therapy products. Their development requires in vitro systems that can reliably detect differences in vector design, serotype performance, regulatory element strength, and expression kinetics. These systems must also support applications such as potency assessment and vector optimization. Here, we describe a streamlined three-dimensional spheroid platform optimized for evaluating AAV potency, transgene expression kinetics, and serotype-specific transduction efficacy across diverse cell lines. Uniform spheroids are generated using ultra-low attachment plates and maintained under conditions that support stable architecture and long-term imaging. Following AAV transduction, fluorescent or luminescent readouts are monitored in real time using live-cell imaging systems. This enables quantitative assessment of reporter signal, dose responsiveness, regulatory element activity, and onset time through continuous kinetic imaging. The platform effectively discriminates between potent and weak vector genome designs and among multiple AAV serotypes. This method demonstrates robust performance across both slowly and rapidly dividing cell lines. These results establish its utility as a scalable and physiologically relevant system for preclinical gene therapy evaluation and development.

Dependovirus↗

Application of cluster analysis for characterization of spatial distribution of particles by stereological methods.

A method for the detection and characterization of clusters of particles observed in section with the electron microscope is presented. Cluster analysis is performed by the division method described by Berthet et al. (1976). Starting from a single cluster, profiles from each electron micrograph are successively classified in sets containing an increasing number of clusters. The decrease in the mean free distance, lambda, between profiles in the clusters, is used for terminating the subdivision procedure. The function relating the mean free distance with the number of clusters is evaluated in each subdivision set. The actual number of clusters is selected on the basis of the slope of that function, at a point where lambda has a value close to the average profile diameter. The method assumes a convex shape for the clusters; the salient feature is that it provides a physical delineation of clusters in the section. Hence, an evaluation of some characteristics of clusters in the three-dimensional sample may be obtained by using standard stereological procedures. Characterization of the volume to which the individual particles of a population are eventually restricted can as a result be performed. Practical problems in the acquisition of the data needed for cluster analysis are discussed and a system using for that purpose a Quantimet 720 image analyser in a basic configuration, connected on line with a PDP 11/10 minicomputer, is presented. Application of the method is illustrated by the analysis of lysosomes in cultured hepatoma (HTC) cells, at the end of mitosis and during the S phase. Cluster analysis shows that in cells actively synthesizing DNA they are grouped in clusters representing 5.7% of the cellular volume. Moreover, the average number of particles per cluster falls from a minimum of thirteen at mitosis to only six at the S phase.

Cells, Cultured↗

Topologically distinct intratumoral heterogeneity scores for predicting high-risk pathological grades in invasive lung adenocarcinoma: A multicenter study across four institutions.

High-risk subtypes of invasive lung adenocarcinoma (IAC), particularly micropapillary- or solid-predominant patterns, are closely associated with poor prognosis. This multicenter retrospective study developed and validated a predictive model for the preoperative identification of these high-risk subtypes using topologically distinct intratumoral heterogeneity (ITH) scores derived from CT images. The study included 1,051 patients with IAC. Two complementary ITH scores were developed: a two-dimensional ITH score, which integrated local radiomics features with global pixel distribution patterns on the largest cross-sectional CT slice, and a three-dimensional ITH score, which extended this quantification across the entire tumor volume. Clinicoradiological features and ITH scores were incorporated as model inputs to construct six base machine learning classifiers and a final stacking ensemble classifier. Model interpretability and robustness were evaluated using SHapley Additive exPlanations (SHAP)-based ablation analyses. An independent dataset from The Cancer Imaging Archive (TCIA) was used for external validation to investigate associations between ITH scores and pathological characteristics, genomic features, recurrence-free survival, and overall survival. The stacking ensemble classifier achieved the best predictive performance, with an area under the receiver operating characteristic curve of 0.875, outperforming models based solely on radiomics features (0.834) or clinicoradiological features (0.792). SHAP analysis identified the 3D ITH score as the most influential contributor to model output, and TCIA validation showed that higher 3D ITH scores were associated with more aggressive tumor biology and poorer survival outcomes. The topologically distinct 3D ITH score may provide a clinically meaningful imaging biomarker for preoperative risk stratification in IAC.

Journal Article↗

Radiographic assessment and orthodontic intervention effects on orthodontically induced root resorption: a systematic review and meta-analysis of clinical trials.

The relative contribution of radiographic methods and characteristics of the orthodontic intervention to orthodontically induced root resorption (OIRR) remains unknown. The aims of this systematic review and meta-analysis were to (1) estimate the pooled OIRR effect across orthodontic intervention versus comparator contrasts, (2) compare pooled estimates by radiographic method (2D [two-dimensional] vs. 3D/CBCT [three-dimensional/cone-beam computed tomography]), and (3) explore whether force mechanics (intrusive versus nonintrusive) modified OIRR magnitude. Seven randomized controlled trials and one prospective study (January 2010-October 2025) were included. Only OIRR was the outcome, reported as correlation coefficients (r). The primary analysis combined within-study intervention-versus-comparator estimates. Subgroup analysis of 2D versus 3D/CBCT imaging was prespecified, whereas post-hoc analysis of intrusive versus nonintrusive mechanics was performed. The pooled analysis for the primary outcome showed a small, nonsignificant OIRR effect (r = 0.07; 95% confidence interval [CI]: -0.12 to 0.27; p = 0.372) with high heterogeneity (I2 = 84.0%). Radiographic method did not change the pooled estimates significantly (p = 0.331). Force-mechanics analysis showed that intrusive mechanics was related to significantly higher root resorption than nonintrusive mechanics (r = 0.40; 95% CI = 0.15 to 0.65 versus r = -0.03; 95% CI = -0.16 to 0.10; p < 0.001). This accounted for 87.1% of the between-study variance. The average orthodontic intervention effect on OIRR was small and not significant; however, the OIRR magnitude was strongly affected by force mechanics, particularly by intrusive forces. There was no significant difference in pooled estimates by radiographic method; however, 3D/CBCT provides superior volumetric quantification and should be used judiciously according ALARA (as low as reasonably achievable) principles.

Root Resorption↗

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface-Condensate Trajectory.

Stem cells exhibit exceptionally prominent transcriptional clusters, which dissolve with progressing differentiation. Although these clusters are assigned central roles in embryonic gene regulation, their formation and loss during differentiation remain poorly understood. This study reveals that these prominent clusters disperse along a conserved trajectory in mouse embryonic stem cells, fruit fly testes, and zebrafish embryos. Imaging and lattice simulations show that these clusters form via surface condensation on H3K27ac-marked super-enhancer regions, which act as genomic scaffolds. Upon differentiation, partial loss of these active epigenetic marks and transcription-driven unfolding lead to dispersal of the prominent clusters. The block copolymer-based lattice simulations explain this process as a conserved trajectory through a three-dimensional state space, governed by surface condensation principles that extend beyond canonical liquid-liquid phase separation. This work marks surface condensation as a biophysical mechanism for the dynamic organization of stem cell-specific transcriptional hubs and demonstrates evolutionary conservation in several organisms. By uncovering a conserved biophysical mechanism for transcriptional organization in development, our work illustrates how polymer properties can contribute to the control of cell identity and&#xa0;fate.

Animals↗

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

A method of relating craniofacial sections to topography in embryos.

The transparent properties of the embedding agent glycol methacrylate facilitate orientation of the complex embryonic craniofacial region. This technique allows for consistent and reproducible section-to-topography orientation. We find it to be a valuable adjunct for envisioning three-dimensional relationships. The contrast of external features of the embryo is enhanced when stained lightly with hematoxylin prior to embedding. The craniofacial region of the embedded embryo is removed with a fine surgical saw and reimbedded. Section-to-topography relationships are readily monitored and documented photographically. Furthermore, it is possible to "preview" sections for symmetry and other considerations of orientation by viewing the cutting face of the block under oblique illumination. A relief image of structures is then visible.

Animals↗

Experimental infarct sizing using computer processing and a three-dimensional model.

A method for noninvasive sizing of myocardial infarction, in which data from technetium-99m stannous pyrophosphate scintigrams and a three-dimensional model were used, was tested on experimental, acute anterior infarcts in dogs. The results indicate that the method does size experimental anterior infarcts accurately, but further testing will be necessary to assess the capabilities of the technique for sizing other types of infarcts.

Animals↗

Zea mays Meiotic Spindle Ultrastructure Reveals Kinetochore-Microtubule Interface and Embedded Membrane Components.

UNLABELLED: Introduction: Spindles are microtubules-based machines whose primary function is to accurately segregate chromosomes in both mitotic and meiotic cell division. The structure of spindles is critical for their function; errors in morphology or attachment to chromosomes lead to aneuploidy, potentially resulting in disease, infertility, and lethality. Electron microscopy studies have yielded fine-detail spindle ultrastructures in many plant and animal species, but no studies have investigated the spindle of Zea mays, a critical crop, and cytogenetic model system. METHODS: Here we use electron tomography (ET), reconstruction, and modeling to obtain three-dimensional, nanometer-resolution of the Z. mays meiotic spindle. Structures such as microtubules, kinetochores, vesicles, membrane channels, and nuclear envelope were modeled through a partial spindle reconstruction, and confirmed using immunostaining and live fluorescence microscopy. RESULTS: ET revealed that maize spindles contain 8-18 kinetochore microtubules (kMTs) per kinetochore, which are approximately 776 nm in diameter and 316 nm in depth. Small &#x223c;37 nm vesicles were identified, as well as larger (&#x223c;5 &#xb5;m long, 800 nm wide) membrane structures with channels that allow spindle microtubules to pass through. These membrane channels stain positively for the ER-marker protein disulfide isomerase. Imaging of prophase meiotic cells revealed a cross-hatch microtubule arrangement in the perinuclear ring on the external surface of the nuclear envelope, which also contained type II nuclear grooves with transnuclear microtubules passing from the nucleus to the cytoplasm. CONCLUSIONS: Z. mays meiotic spindles are similar to animal counterparts with a comparable number of kMTs and pre-spindle transnuclear microtubules but also plant-specific features such as Golgi-derived vesicles to assist cell plate formation, internal ER membrane channels, and a perinuclear microtubule ring that aids spindle assembly. Maize kinetochores have an electron-diffuse ball in cup morphology that is comparable in size to Drosophila kinetochores and larger than mammalian kinetochores. .

Zea mays↗

Ten quick tips for spatial transcriptomics analysis.

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while retaining spatial context within tissue sections. Since the foundational work by St&#xe5;hl et al. in 2016, the field has expanded rapidly, with diverse platforms now spanning sequencing-based (e.g., Visium, Visium HD, Slide-seq, Stereo-seq, and Seq-Scope) and imaging-based (e.g., MERFISH, Xenium, and CosMx SMI) approaches. The breadth of platforms, data structures, and computational tools, however, can be daunting for newcomers. Here, we present ten quick tips spanning the entire ST research workflow: whether ST suits a given biological question, how to select a platform aligned with study objectives, how to understand and process ST data, and which software tools to employ for analysis and visualization. We further discuss interpreting spatial patterns in biological context, integrating complementary modalities such as single-cell RNA sequencing and spatial proteomics, and leveraging public datasets and sharing results. Finally, we highlight current limitations of ST, particularly the challenge of reconstructing three-dimensional tissue architecture from serial tissue sections. This review provides biologists, bioinformaticians, and clinician-scientists with a concise, platform-neutral roadmap for incorporating ST into research, from experimental design to biological discovery.

Spatial Transcriptomics↗

Mega-Enhancer Bodies Organize Neuronal Long Genes in the Cerebellum.

Dynamic regulation of gene expression plays a key role in establishing the diverse neuronal cell types in the brain. Recent findings in genome biology suggest that three-dimensional (3D) genome organization has important, but mechanistically poorly understood functions in gene transcription. Beyond local genomic interactions between promoters and enhancers, we find that cerebellar granule neurons undergoing differentiation in vivo exhibit striking increases in long-distance genomic interactions between transcriptionally active genomic loci, which are separated by tens of megabases within a chromosome or located on different chromosomes. Among these interactions, we identify a nuclear subcompartment enriched for near-megabase long enhancers and their associated neuronal long genes encoding synaptic or signaling proteins. Neuronal long genes are differentially recruited to this enhancer-dense subcompartment to help shape the transcriptional identities of granule neuron subtypes in the cerebellum. SPRITE analyses of higher-order genomic interactions, together with IGM-based 3D genome modeling and imaging approaches, reveal that the enhancer-dense subcompartment forms prominent nuclear structures, which we term mega-enhancer bodies. These novel nuclear bodies reside in the nuclear periphery, away from other transcriptionally active structures, including nuclear speckles located in the nuclear interior. Together, our findings define additional layers of higher-order 3D genome organization closely linked to neuronal maturation and identity in the brain.

Journal Article↗

Computer-monitored radionuclide tracking of three-dimensional mandibular movements. Part I: theoretical approach.

A new technique for the three-dimensional recording of a person's mandibular movement is described. A small and harmless radioactive source is fixed on the patient's skin at the point of interest or sealed in a tooth cavity. Using the proper collimation, the motion of the point source is recorded via a gamma camera and minicomputer. Long-term storage on a magnetic device offers playback, slow motion facilities, and data analysis through the use of sophisticated computer languages. Simultaneous recordings using two cameras, or postsynchronization of two different views of an experiment, enable the three-dimensional restitution of mandibular movements. Superimposition of a grid of radioactive spots spaced at measured intervals during the recording permits a straightforward calibration of the patient's motion. Multiple sources in a single experiment may be recorded to describe the displacement of several points of interest. This method, derived from nuclear medicine techniques, offers a powerful tool of general interest for the tracking of dynamic events in many fields of dentistry such as temporomandibular joint dysfunction and prosthetic restorative techniques. Further considerations on our experimental settings and results will be published in part II.

Analog-Digital Conversion↗

How advances in chromosome conformation capture (3C) methods are reshaping our understanding of gene regulation in hematopoiesis.

The three-dimensional organization of the DNA within the nucleus plays a key role in regulating gene expression. Over the past two decades, advances in chromosome conformation capture (3C) technologies, in tandem with other methods, have shown that the genome forms a complex structure at multiple scales. Early studies identified large-scale structures such as chromosome territories, compartments and topologically associating domains (TADs). As the resolution of 3C techniques has improved, it has become possible to identify contacts between regulatory elements in detail and more recently, it has become possible to define intricate structures within cis-regulatory elements. In this chapter, we review the development of 3C-based methodologies and discuss the strengths and limitations of the different approaches. We examine how these technologies have refined our understanding of genome organization and gene regulation. Recent high-resolution studies reveal that chromatin architecture extends beyond classical domain structures to include nanoscale organization. Integration of 3C data with super-resolution imaging and molecular dynamics simulations supports a model in which genome folding is governed by the biophysical properties of chromatin.

Animals↗

The Impact of Baseline Negative Emotions on Postoperative Quality of Life in Adolescent Idiopathic Scoliosis Patients: A 2-Year Follow-Up Study.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that develops during puberty without a clear etiology. Beyond physical manifestations, AIS severely impacts adolescents' psychological and social well-being, leading to anxiety, depression, and low self-esteem. While advancements in surgical techniques have enhanced objective outcomes, existing studies on AIS have primarily focused on objective indices, with limited attention to the long-term impact of preoperative negative emotions on patient-reported subjective quality of life. METHODS: This was a retrospective cohort study. A total of 112 eligible AIS patients who underwent posterior spinal correction surgery between April and August 2023 were enrolled. Inclusion criteria included confirmed AIS, completion of 2-year follow-up, and informed consent; exclusion criteria included missing imaging/questionnaire data, comorbid psychiatric/neurological diseases, or prior spinal surgery. Patients were grouped using the Hospital Anxiety and Depression Scale (HADS) administered on admission. Quality of life was assessed preoperatively and 2&#x2009;years postoperatively using the Scoliosis Research Society-22 (SRS-22, evaluating self-image, mental health, pain, function, treatment satisfaction) and Short Form 36 Health Survey (SF-36, assessing 8 physical and mental health dimensions). Statistical analysis was performed via SPSS, using independent t-tests, paired t-tests, Mann-Whitney U test, and chi-square test. p&#x2009;<&#x2009;0.05 was considered significant. RESULTS: There were no significant differences in baseline characteristics (age, gender, BMI, surgical parameters, scoliosis type, preoperative/postoperative Cobb angles) between the two groups (all p&#x2009;>&#x2009;0.05). Preoperatively, SRS-22 and SF-36 scores showed no inter-group differences (all p&#x2009;>&#x2009;0.05). Postoperatively, the Negative Emotion Group had significantly lower scores in SRS-22 mental health (3.9&#x2009;&#xb1;&#x2009;0.3 vs. 4.5&#x2009;&#xb1;&#x2009;0.2) and treatment satisfaction (4.0&#x2009;&#xb1;&#x2009;0.3 vs. 4.6&#x2009;&#xb1;&#x2009;0.7), as well as SF-36 general health (68.6&#x2009;&#xb1;&#x2009;6.4 vs. 79.7&#x2009;&#xb1;&#x2009;13.3), role-emotional (61.3&#x2009;&#xb1;&#x2009;9.3 vs. 70.8&#x2009;&#xb1;&#x2009;9.7), and mental health (61.8&#x2009;&#xb1;&#x2009;14.3 vs. 68.9&#x2009;&#xb1;&#x2009;10.7) (all p&#x2009;<&#x2009;0.05); no inter-group differences were observed in physical function-related dimensions. Both groups showed significant improvements in physical function-related dimensions postoperatively. The Non-Negative Emotion Group also exhibited significant improvements in SRS-22 self-image/pain and SF-36 bodily pain (all p&#x2009;<&#x2009;0.05), while the Negative Emotion Group showed no significant improvements in these dimensions. CONCLUSIONS: Preoperative anxiety and depression do not affect the recovery of physical function in AIS patients after spinal correction surgery but significantly impede improvements in subjective quality of life dimensions, including mental health and treatment satisfaction. These findings highlight the need to integrate psychological assessment and targeted interventions into the perioperative management of AIS. Such a patient-centered approach will help optimize both physical and psychological outcomes, ultimately achieving comprehensive rehabilitation for AIS adolescents.

Humans↗

Computed tomography of the head: clinical experience of the first 3000 scans with EMI scanner.

Computer tomography (CT) findings obtained from the first 3,000 scans on 2,031 patients were analyzed and discussions were made on various kinds of neurological diseases, especially from the neurosurgical point of view. CT showed an excellent resolution for three-dimensional morphological pattern of intracranial lesion with a high percentage of diagnostic accuracy as reported from other institutes, resulting in making much earlier morphological diagnosis of intracranial lesion possible than any other examination. Scan methods consisted of plain CT, contrast enhanced CT, and metrizamide CT cisternography. Sequential delayed enhanced CT offered more useful information for high diagnostic accuracy, particularly for nature of brain tumor. Metrizamide CT cisternography was performed for the evaluation of cerebrospinal fluid dynamics and diagnosis of skull base tumors. CT is a new, epoch-making and non-invasive diagnostic approach in neuroradiology and contributes to obtain the better achievement of neurosurgical results.

Adolescent↗

The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man.

A method has been developed to measure local glucose consumption in the various structures of the brain in man with three-dimensional resolution. [18F]-2-deoxy-2-fluoro-D-glucose is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissue. A mathematical model and derived operational equation are used which enable local cerebral glucose consumption to be calculated in terms of the following measurable variables. An intravenous bolus of [18F]-2-deoxy-2-fluoro-D-glucose is given and the arterial specific activity monitored for a predetermined period of from 30 to 120 minutes. Starting at 30 minutes, the activity in a series of sections through the brain is determined with three-dimensional resolution by an emission tomographic scanner. The method was used to measure local cerebral glucose consumption in two normal volunteers. The values in gray matter structures range from 5.79 mg/100 g per minute in the cerebellar cortex to 10.27 in the visual cortex, whereas, in white matter structures, the values range from 3.64 mg/100 g per minute in the corpus callosum to 4.22 in the occipital lobe. Average values for gray matter, white matter, and whole brain metabolic rates, calculated as a weighted average based on the approximate volume of each structure, are 8.05, 3.80, and 5.90 mg/100 g per minute, respectively. The value of 5.9 mg/100 g per minute compares favorably with values previously reported.

Adult↗

The use of 3-dimensional (3D) printing in teaching musculoskeletal oncology for medical undergraduates.

INTRODUCTION: The approach to integrating relevant anatomy in the medical curriculum has been debated for many years. Current literature has explored the broad impact of 3D printing in medical education. However, there is little evidence on 3D printing for the teaching of musculoskeletal oncology (MSO). This is a self-controlled case series (SCCS) study that aims to analyse the effectiveness of 3D printed models in MSO in enhancing the learning experience, engagement and understanding of clinical and surgical anatomy for medical students. METHOD: A cross-sectional cohort study involving 75 clinical year medical students across 3 years from 2 medical schools that rotated through a single teaching hospital's orthopaedic department. Participants first viewed a set of computed-tomography (CT) images of a large pelvic osteosarcoma from a free open-source database, the Cancer Genome Atlas Sarcoma Collection (TCGA-SARC). A standardised 10-minute pre-intervention questionnaire which comprised 15 questions categorised by: 4 questions in 'anatomical knowledge', 7 questions in 'spatial awareness', 4 questions in 'surgical planning and complications', was administered to assess the baseline knowledge in their interpretation of the pathology via CT images only. Next, a 3D-printed model of the pelvic osteosarcoma, which included colour-coded adjacent structures, was provided as an adjunct to answer the same questionnaire. This concluded with a 5-point Likert scale feedback survey to gauge their perspectives and experience. RESULTS: The mean scores comparing their pre- and post-intervention assessment questionnaire increased by +1.34 from 8.15 (SD = 1.85) to 9.49 (SD = 1.7) (p < 0.001). The final year students had the greatest improvement of +1.54 from 8.00 (SD = 1.89) to 9.54 (SD = 1.59) (p = 0.004). There was no significant difference between the scores amongst the 2 medical schools. 91% of students agreed that the 3D model had helped them further their understanding of the anatomy of the sarcoma and 87% would want 3D printing models to augment their learning in anatomy. Baseline weaker students demonstrated significantly greater improvement in scores compared with baseline stronger students (mean difference +2.04 vs +0.30, p < 0.001). CONCLUSION: 3D printing is an effective teaching adjunct for musculoskeletal oncology surgical anatomy for medical undergraduates and could be used to enhance their understanding and learning experience. 3D models could be integrated in the teaching curriculum of surgical anatomy for undergraduate students.

Humans↗

A system for the three-dimensional construction, manipulation and display of microbiological models.

A system is described for building up serial sections into a three dimensional structure, incorporating density, that can be displayed and then further manipulated by rotation about three orthogonal axes. The initial application was to produce a computer model of a protein structure and to compare the diverse images obtained from rotation with the two dimensional images observed in related electron micrographs. To obtain sufficient contrast in the electron microscope images of protein structures, the specimens need to be stained and since this can cause some deformation of the observed images, it is also necessary to simulate ths possible effects of stain on the protein model. Because of the need to compare numerous orientations of the combined model, techniques are available either for speeding up the comparison or for obtaining better accuracy. The methods have been applied to the interpretation of electron micrograph images of microbiological specimens, where the three dimensional structure of the specimen is an important aid in understanding its biological function, but the techniques are also applicable to more general serial reconstruction requirements.

Adenoviridae↗