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PubMed2026

Attribution of PM2.5-Induced Transcriptomic Perturbation to Toxic Components.

Ambient fine particulate matter (PM2.5) is a chemically complex mixture whose health impacts are not fully captured by particle mass. Here, we developed an interpretable chemotranscriptomic framework to attribute PM2.5-induced molecular perturbations to toxicity-relevant components. PM2.5 collected from urban roadside and coastal environments was separated into whole, extractable, and unextractable fractions, characterized by LC/GC × GC-HRMS-based nontarget analysis and inductively coupled plasma mass spectrometry (ICP-MS), and evaluated using cytotoxicity testing and transcriptomic profiling in human bronchial epithelial cells. Urban PM2.5 exhibited greater cytotoxic potency per unit mass than coastal PM2.5, with extractable fractions accounting for most cytotoxic and pathway-level responses. Transcriptomics revealed distinct site-specific modes of action: urban PM2.5 preferentially induced oxidative stress, xenobiotic metabolism, and cell cycle suppression, consistent with acute, nonapoptotic injury, whereas coastal PM2.5 elicited weaker cytotoxicity but stronger interferon-mediated immune and apoptosis-related signaling. Integrating chemical abundance with pathway activity using random forest regression, SHAP interpretation, and mechanistic corroboration reduced 5,033 detected features to 444 pathway-linked candidate drivers. Fewer than 5% of features explained ∼95% of cumulative model contribution. Standard-confirmed contributors included plasticizer-related compounds, aromatic and heteroaromatic combustion products, and copper for urban PM2.5 and secondary/aged organics and nickel for coastal PM2.5. These findings support mechanism-informed prioritization of hazardous PM2.5 components beyond mass-based assessment.

Particulate Matter↗
PubMed1975

An analysis of the binding of the chick oviduct progesterone-receptor to chromatin.

The binding of progesterone-receptor complexes to chromatin from target and nontarget tissues was studied in vitro. Chromatin from both target and nontarget tissues responds in a similar manner to saly and cofactors and has the same K(D) (approx. 3.10(-9) M) for the progesterone-receptor complex. The only observed difference in the binding of the progesterone-receptor complex to target and nontarget chromatins is the difference in total number of acceptor sites. oviduct chromatin has approx. 1300 sites/pg DNA, spleen chromatin has approx. 840 sites/pg DNA, and erythrocyte chromatin has about 330 sites/pg DNA. The K(D) and number of acceptor sites for progesterone-receptor complex binding to oviduct chromatin remains the same even after extensive purification of the progesterone-receptor complex. Activation of cytosol labeled with [3H]progesterone by preincubation at 25 degrees C, analogous to that required for maximal nuclear binding, occurs if the binding studies to chromatin are performed in 0.025 M salt. The absence of an observable temperature effect when the studies are performed at 0.15 M salt is due to the activation of the receptor by salt. The dissociation of the progesterone-receptor complex from chromatin exhibits a single dissociation rate and the initial event is the appearance of free progesterone rather than a progesterone-receptor complex. Lastly, the treatment of chromatin with an antibody prepared against either single-stranded DNA or double-stranded DNA does not alter the extent of binding of the progesterone-receptor complex. Similarly, pretreatment of chromatin with a single-stranded nuclease does not inhibit the capacity of chromatin to bind the hormone-receptor complex.

Animals↗
PubMed1992

PCR-based analysis of the T-cell receptor V beta multigene family: experimental parameters affecting its validity.

The validity of semiquantitative, PCR-based analysis of gene expression within a multigene family, the human T-cell receptor (TCR) beta chain variable region family, was investigated. Primer comparability was addressed by grouping hybridization temperatures and limiting the size range of amplified fragments. Primers selected satisfied criteria for comprehensiveness, match to targets and discrimination of nontargets. Specificity was enhanced by maximizing mismatches with nontargets and using an elevated hybridization temperature. Reaction conditions are described that ensure specificity while maintaining sensitivity. Several results confirmed primer specificity. Limits on precision were documented: probable error was 3%-7% of mean value for target prevalences (% of all TCR mRNA represented by a particular V beta) in the 5%-40% range. Accuracy was limited by the nonlinear relationship between target prevalence and signal obtained. Because of this relationship, the effect of the observed limits of precision varied. Valid distinctions were possible between sufficiently separated prevalences, i.e., 0%-1%, 3%-5%, 10%, 30%, greater than 50%. Additional concerns addressed include: standardization of signals, coamplifiation and effects of primer artifacts, and the nature of the mRNA pool. Only when theoretical and practical limits in precision and accuracy are acknowledged can semiquantitative, PCR-based analysis be used with confidence to assess gene usage within a large, multigene family.

Base Sequence↗
PubMed2026

GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.

Chimeric antigen receptor (CAR) T cell therapy for solid tumors is constrained by the scarcity of safe, uniformly expressed cell-surface targets. Here we identify glycoprotein NMB (GPNMB)-an MiT/TFE-family fusion-driven protein-as being highly, homogeneously and stably expressed in primary and relapsed alveolar soft-part sarcoma (ASPS) and translocation renal cell carcinoma. We develop a GPNMB-directed CAR T cell product, GCAR1, which demonstrates potent activity against patient-matched cells, organoids and xenograft models. Post hoc interim analysis of a first-in-human open-label, individual-participant trial ( NCT07104682 ) for a participant with relapsed/refractory, metastatic ASPS showed that GCAR1 induces stable disease for up to 3 months, accompanied by resolution of many nontarget lesions (primary endpoint), and is well tolerated. GCAR1 T cells expand in peripheral blood as a polyclonal population and remain detectable for 1 month. Spatial transcriptomics identified immunosuppressive niches in a treatment-resistant lesion and immune checkpoint blockade synergized with GCAR1 in a xenograft model. Altogether, our data provide a proof of concept for treating GPNMB-expressing solid tumors with GCAR1 and more broadly targeting surface antigens driven by oncogenic gene fusions with CAR T cell therapies.

Animals↗
PubMed2025

Optical Genome Mapping Is a Powerful Diagnostic Tool in Non-Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) is a diverse and heterogeneous group of hematological malignancies. These lymphomas arise from the clonal proliferation of either B/T or natural killer lymphocytes, and their correct classification relies partly on identifying characteristic structural variants and copy number alterations. Current standard-of-care technologies for detecting these genomic features, chromosome banding analysis (CBA) and fluorescent in situ hybridization (FISH), are labor intensive and have specific limitations. CBA has low resolution and relies on viable cell culture, whereas the targeted approach of FISH does not provide the whole genome view required for comprehensive disease characterization. This highlights the need for higher-resolution nontargeted genomic methods. Previous studies have evaluated optical genome mapping (OGM) as a whole genome alternative for cytogenomic characterization in NHL diagnostics but were restricted in number and to cases with peripheral blood and/or bone marrow invasion. Here, we selected a comprehensive cohort of 110 NHL cases (79 B-NHL and 31 T-NHL/natural killer-NHL) derived from different types of tissue biopsies, all with established histopathological diagnoses. Seventy-eight samples were genomically well characterized at diagnosis by CBA and FISH. The remaining 32 cases were included because of previous CBA failure, although FISH data were available for 20 cases. OGM provided informative results in 94% of the cohort, with a high concordance rate of 97.6% compared with CBA/FISH in detecting clinically relevant aberrations. The 2 variants that were missed were both present at the detection threshold of OGM. In contrast, OGM successfully resolved 26 samples with previous CBA failure and detected 3 additional disease-defining events, resulting in diagnostic reclassification of 1 patient. Finally, OGM identified novel recurrent aberrations that warrant further investigation into their pathogenetic implications. To conclude, OGM robustly detects clinically relevant structural variants and copy number alterations and presents a promising alternative to CBA and FISH in routine diagnostic evaluation of NHL.

Humans↗
PubMed1992

Detection of amplified HPV 6 and 11 DNA in vulvar lesions by hot start PCR in situ hybridization.

We analyzed the distribution pattern of human papillomavirus (HPV) 6 and 11 DNA in vulvar lesions by in situ hybridization after amplification by the "hot start" polymerase chain reaction (PCR). HPV DNA was routinely detected in granular layer cells showing perinuclear halos and nuclear atypia by in situ hybridization with or without PCR. Cells that lack these changes rarely exhibited HPV DNA with standard in situ hybridization. After amplification, in situ analysis showed that many of the cells that lacked halos and atypia did contain HPV DNA and that the hybridization signal often localized to areas where there was a thickened granular layer. HPV DNA was not noted in the basal cells. The one copy of HPV 16 in SiHa cells was detectable after PCR with a single primer pair by in situ analysis only if the hot start modification was employed. Prior reports describing the PCR in situ methodology noted the need for from five to seven primer pairs. The hot start technique, which may be done by withholding the DNA polymerase until the temperature is sufficiently high to disfavor nontarget specific pathways, allowed the use of a single primer pair and showed that the degree of target-specific amplification, and not the size of the amplified product, determines the success of the PCR in situ technique.

Condylomata Acuminata↗
PubMed2026

Proteome-level evidence that tebuconazole, both alone and in interaction with thiacloprid, affects epigenetic events in bumblebee heads.

Tebuconazole, a widely used ergosterol biosynthesis-inhibiting fungicide, can affect nontargets, especially when combined with insecticides. We employed label-free quantitative proteomics to investigate the effects of long-term exposure to sublethal concentrations (100 μg/L) of tebuconazole, either by itself or alongside the neonicotinoid thiacloprid (100 μg/L), on the heads of Bombus terrestris workers. A Bayesian factor power analysis revealed that the experiment produced conclusive proteomic results. Tebuconazole treatment revealed eleven differentially abundant proteins, which increased elevenfold with thiacloprid. The proteins that changed in the same direction in both treatments suggest the occurrence of epigenetic events because they are involved in histone trimethylation (H3K4me3), pre-mRNA processing, and folate (vitamin B9) metabolism. Following co-exposure, the abundance of histone H2A.V and its associated proteins was affected. Two important detoxification-related proteins, CYP6BE1 and CYP6AQ1 (honey bee homologs), were identified, as well as proteins that suggest hormonal and neurotoxic effects. Overall, this study suggests that tebuconazole affects key epigenetic processes in bumblebee heads at the proteome level, though this was not confirmed at the biological level or through orthogonal methods. The tested chemicals were previously found to affect trimethylations, but not H3K4me3. We suggest analyzing the different trimethylations, their interplay, and associated hallmarks, such as folate levels. SIGNIFICANCE: The effects of pesticides and their combinations on organisms can be unexpected until they are examined using modern, complex methods. High-throughput proteomics can provide data on important biochemical processes affected by pesticides, offering a different perspective to that at the expression level. Despite their low acute toxicity, a group of fungicides that inhibit (ergo)sterol biosynthesis (EBI or SBI) are considered dangerous to pollinators, including bumblebees. This is due to the increasing toxicity of insecticides through the inhibition of cytochrome P450 detoxification enzymes. We found that tebuconazole had a similar effect on epigenetic events when used alone or in combination with the insecticide thiacloprid. Key proteins suggest that H3K4 histone trimethylation (H3K4me3) was impacted. To our knowledge, this expands the existing evidence suggesting that tebuconazole/triazole fungicides affect histone trimethylation H3K27me3. Since literature shows that thiacloprid affects H3K9me3, it is possible that thiacloprid and tebuconazole interact in these epigenetic events that affect each other. Overall, our results suggest that tebuconazole affects proteins involved in histone trimethylation, pre-mRNA processing, and folate metabolism. These are all hallmarks of epigenetic processes and were further extended by the co-exposure of tebuconazole and thiacloprid to more differently abundant proteins. Additionally, the results provide data on cytochrome P450s of the CYP6 family, which act as detoxifying proteins, as well as proteins that indicate hormonal and neurotoxic effects in bumblebee heads. Finally, the results of the Bayesian power analysis confirmed the meaningfulness of the proteomic data analyzed in this study. If the new findings obtained at the proteome level are verified by different methods, the full extent of the side effects of tebuconazole can be revealed.

Animals↗
PubMed1977

Nonindependence of feature processing in initial consonants.

Mutual dependence in the processing of manner and place of articulation was investigated in two experiments. The first study assessed the location of the voiced-voiceless boundary as a function of place of articulation, and the second investigated the location of the labial-alveolar boundary as a function of manner class. In both experiments, the location of the phonetic boundary systematically varied as a function of the nontarget feature value. These results indicate that the processing of phonetic feature information occurs in parallel, with decisions about one feature influencing the particular value assigned to another feature.

Acoustic Stimulation↗
PubMed1976

Levels of feature analysis in processing visual patterns.

In this paper, a revised Pandemonium-like model of visual-feature processing is formulated and a preliminary test of its feasibility is reported. The model differentiates visual-feature processing into a series of hierarchical stages organized by increasing complexity, with the output of each stage going both to the next higher stage, and directly to a more central processor. In the experiment, subjects sorted decks of cards into piles according to the presence or absence of a target stimulus which differed from nontargets in a variety of different features; detection of a feature was sufficient for detection of a target. The data generally supported the revised Pandemonium model, in that targets which differed from nontargets in features thought to be low in the hierarchy were processed faster than targets whose difference was in a high level feature. An extension of the revised model did somewhat less well in predicting the results of sorting for targets in which detection of any one of several features was sufficient for target detection.

Adult↗
PubMed1992

Event-related potentials and the identification of deviant visual stimuli.

The effects of deviant visual stimuli on event-related potentials were investigated in a counting task (Experiment 1) and in a reaction time task (Experiment 2). In Experiment 2 the interstimulus interval was either short or long (340 vs. 1020 ms). The stimuli (two angles within a frame) were frequent (Standard) or deviant (differing from the Standard either in the orientation of the two angles, or in the thickness of the frame, or in both of these features). In various conditions the target stimuli were defined by one of the deviant features or by the conjunction of these features. Subjects were more accurate in the counting task, and the reaction time was shortest when the target feature was the deviant angle orientation. Performance was lowest for the conjunction of the deviant features. The deviant angle orientation elicited a posterior negative wave in the 140-180 ms range. As the interstimulus interval increased, the magnitude of this component decreased. All stimuli with relevant (attended) deviant features elicited another posterior negative wave in the 180-260 ms range, as well as an anterior positivity with similar latency. When the interstimulus interval was short, and the only target was the Conjunction Deviant, the summed occipital activity to the relevant features of deviant nontarget stimuli was larger than the negativity to the Conjunction Deviant. Target stimuli elicited late positive waves, which were sometimes preceded by central negativity.

Adolescent↗
PubMed1992

Mismatch detection and the latency of temporal judgements.

Event-related potentials were recorded in two auditory tasks involving the discrimination of pitch or duration of binaurally presented tones. Frequently-presented nontarget tones, when compared to the same tones in a simple reaction time task, elicited two negative peaks, NA1 and NA2, followed by a positive peak, nontarget positivity. Infrequently-presented target tones, when compared to the nontargets, elicited mismatch negativity (MMN), followed by N2 and P3b. The peak latencies of NA1 and NA2 did not differ between the pitch and duration tasks, but the duration of NA1 and the peak latencies of mismatch negativity, N2, and P3b, as well as reaction time, increased in parallel for the duration task. It is proposed that the NA1-nontarget positivity sequence reflects the initiation, maintenance, and termination of an attention-modulated process, which is required for the performance of an auditory discrimination task, and that the MMN-N2-P3b sequence reflects a process elicited by infrequently-presented targets, which is the main determinant of reaction time under these testing conditions.

Adult↗
PubMed2026

A Parallel Accumulation-Mobility Aligned Fragmentation Strategy Utilizing High-Resolution Ion Mobility for High-Performance Proteomics Analysis.

Here we present a novel data-independent acquisition (DIA) mass spectrometry (MS) operating mode termed parallel accumulation-mobility aligned fragmentation (PAMAF) that offers enhanced speed and sensitivity of ion fragmentation analysis for discovery workflows such as bottom-up proteomics. This mode of operation leverages high-resolution ion mobility (HRIM) separation capabilities of the structures for lossless ion manipulation technology to achieve HRIM-based precursor isolation in place of traditional quadrupole filtering approaches. PAMAF mode increases the number of features that can be identified per MS1/MS2 acquisition cycle by employing mobility-based time alignment to associate fragment ions with their corresponding precursor ions. By using a high-speed, lossless separation technique for precursor isolation instead of the comparatively slow and wasteful quadrupole filtering, ion losses are avoided while simultaneously increasing the rate at which precursor ions are sequentially fragmented and detected. In addition, by accumulating ions while the previous packet of ions is being analyzed, the PAMAF mode achieves ∼100% ion utilization efficiency. Benchmarking results of LC-PAMAF-MS analysis of a whole cell protein digest showed ∼6× more protein group identifications compared to a standard data-dependent acquisition analysis without HRIM on the same QTOF instrument, and >100 x improvement for low-load workflows. Quantitative evaluations demonstrated that PAMAF mode could quantify low abundance peptides, including those undetectable by data-dependent acquisition. In addition, since precursor isolation in PAMAF mode is size-based rather than m/z-based, coeluting isobars and isomers can be resolved prior to fragmentation, eliminating chimeric spectra that compromise identification accuracy. We also explored the benefits of combining HRIM and quadrupole isolation to achieve improved specificity termed DIA-PAMAF mode, which enabled the detection of over 8000 protein groups from a HeLa digest analysis. PAMAF mode brings a powerful new technique to the field of proteomics with the potential to improve the sensitivity and selectivity of mass spectrometry-based proteomics.

Proteomics↗
PubMed1992

Time effects on event-related brain potentials and vigilance performance.

A review of the literature showed that in vigilance or oddball tasks, changes over time in event-related potentials (ERPs) and performance measures often seem to be unrelated, but a number of studies had some shortcomings. In the present study a visual vigilance experiment was carried out, in which single-trial ERPs and performance data of 40 males were obtained. A relationship between time trends in behavioral and ERP measures was found: an early P3 amplitude and response latency (RT) showed an inversely varying relation over time. Analysis of covariance showed that the two linear trends tap the same aspect of processing: both trends became insignificant when adjusted for common variance. A negative correlation between mean values of P3 amplitude and RT rather than for change scores has been observed in previous studies, but has been ignored in the literature. However, correlations with RT have also been reported for other ERP deflections. Although there were several correlations between mean scores, most time-induced changes in ERP parameters appeared to be unrelated to worsening performance, for which several explanations are advanced. The ERP results do not support the hypothesis that a decrement in performance is caused by increasing difficulty discriminating targets from nontargets. A gradual decline in effort or resources allocated to the task might be an alternative explanation of performance deterioration. However, an effort-hypothesis cannot easily be tested. Effort is often invoked post hoc, and has previously been associated with many ERP components. The relationship between ERPs and the signal detection measures "sensitivity" d' and "response bias" beta is discussed.

Adolescent↗
PubMed2024

Genetic modification of the shikimate pathway to reduce lignin content in switchgrass (Panicum virgatum L.) significantly impacts plant microbiomes.

UNLABELLED: Switchgrass (Panicum virgatum L.) is considered a sustainable biofuel feedstock, given its fast-impact growth, low input requirements, and high biomass yields. Improvements in bioenergy conversion efficiency of switchgrass could be made by reducing its lignin content. Engineered switchgrass that expresses a bacterial 3-dehydroshikimate dehydratase (QsuB) has reduced lignin content and improved biomass saccharification due to the rerouting of the shikimate pathway towards the simple aromatic protocatechuate at the expense of lignin biosynthesis. However, the impacts of this QsuB trait on switchgrass microbiome structure and function remain unclear. To address this, wild-type and QsuB-engineered switchgrass were grown in switchgrass field soils, and samples were collected from inflorescences, leaves, roots, rhizospheres, and bulk soils for microbiome analysis. We investigated how QsuB expression influenced switchgrass-associated fungal and bacterial communities using high-throughput Illumina MiSeq amplicon sequencing of ITS and 16S rDNA. Compared to wild-type, QsuB-engineered switchgrass hosted different microbial communities in roots, rhizosphere, and leaves. Specifically, QsuB-engineered plants had a lower relative abundance of arbuscular mycorrhizal fungi (AMF). Additionally, QsuB-engineered plants had fewer Actinobacteriota in root and rhizosphere samples. These findings may indicate that changes in the plant metabolism impact both AMF and Actinobacteriota similarly or potential interactions between AMF and the bacterial community. This study enhances understanding of plant-microbiome interactions by providing baseline microbial data for developing beneficial bioengineering strategies and by assessing nontarget impacts of engineered plant traits on the plant microbiome. IMPORTANCE: Bioenergy crops provide an important strategy for mitigating climate change. Reducing the lignin in bioenergy crops could improve fermentable sugar yields for more efficient conversion into bioenergy and bioproducts. In this study, we assessed how switchgrass engineered for low lignin impacted aboveground and belowground switchgrass microbiome. Our results show unexpected reductions in mycorrhizas and actinobacteria in belowground tissues, raising questions on the resilience and function of genetically engineered plants in agricultural systems.

Panicum↗
PubMed1979

Prolactin receptors in the ovary.

The binding of prolactin (PRL) to the plasma membranes of bovine and human ovaries was investigated using both homologous and heterologous 125I-prolactin. Saturation and Scatchard analysis demonstrated that human prolactin binds to human ovarian membranes with a Kd of 2 x 10(-10) M; to bovine ovarian membranes with a Kd of 1.9 x 10(-10) M; and to bovine corpora lutea membranes with a Kd of 1.9 x 10(-10) M. The concentrations of binding sites in bovine and human ovaries were 2.9 x 10(-15) moles/mg of protein and 2.0 x 10(-15) moles/mg of protein, respectively. The number of bindings sites in the bovine corpora lutea was 1.5 x 15(-15) moles/mg of protein. Specificity studies with bovine PRL, ovine PRL, human luteinizing hormone, human follicle-stimulating hormone, and bovine growth hormone showed this binding to be specific. Comparison of binding of PRL to membranes of other target and nontarget tissues suggests that the ovary is one of the primary target tissues. These data suggest that prolactin plays a role in the ovarian cycle.

Animals↗
PubMed1992

Enhancement of continuous performance task reaction time by smoking in non-deprived smokers.

In a test of the withdrawal-deficit hypothesis of the cognitive effects of cigarette smoking, non-deprived smokers participated in two sessions held on consecutive days. In both sessions, subjects performed two 20-min continuous performance tasks (CPTs). The CPT was a relatively "easy" version designed to require minimal practice (digit 0 target response; digits 1-9 nontarget response; 19% of stimuli targets). In one session, subjects smoked a cigarette prior to each CPT; in the other session they did not smoke (session order counterbalanced). Reaction time (RT) was significantly faster in the smoking session than in the non-smoking session with no difference in number of incorrect responses, a finding incompatible with the withdrawal-deficit hypothesis. Further, light inhalers (as assessed by pre-smoking to post-task increase in expired air carbon monoxide) appeared to process nontarget stimuli faster than deep inhalers, especially in the no smoking session. The results also indicated that, at least during the first CPT of each session, the performance of females in the no smoking session was poorer than in the smoking session and poorer than males regardless of session. In the latter part of the first CPT, the performance of males in the smoking session was better than their performance in the no smoking session. No clear pattern emerged for the second CPT.

Adolescent↗
PubMed1992

Proton beams in radiation therapy.

The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation-treated patients was 11,763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eye, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in-field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eye view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology.

Arteriovenous Malformations↗