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PubMed2026

Comprehensive characterization of MET exon 14 skipping mutations in non-small cell lung cancer.

BACKGROUND: MET exon 14 skipping mutation (METΔex14) is a key driver event in non-small cell lung cancer (NSCLC) and can emerge as an acquired drug resistance mechanism to MET, EGFR or ALK inhibitors. The clinical and genomic features of METΔex14 in NSCLC require further characterization. METHODS: Our study included a total of 585 patients with METΔex14 + NSCLC, comprising 556 baseline samples, 53 samples from patients exhibiting resistance to MET inhibitors, and 16 samples from patients resistant to EGFR/ALK inhibitors. Genomic data from targeted next-generation sequencing (NGS) of tissue and/or plasma samples using GeneseeqPrime™ (a 425 pan-cancer gene panel) were analyzed. RESULTS: Overall, METΔex14 exhibited a prevalence of 1.02% (n = 585) in the screened NSCLC population, with a higher incidence in patients with a sarcomatoid histology. METΔex14 was predominantly detected at the splice donor site, though the non-coding region adjacent to the splice acceptor site contributed considerably to the complexity of METΔex14. Common concurrent alterations identified at baseline included those in TP53 (40.8%), CDK4 (16%) and EGFR (12.4%). Concurrent MET amplification and cell cycle pathway mutations were both associated with worse outcomes in patients treated with crizotinib, with significant co-occurrences observed also among these concurrent genomic variations. In addition, increased chromosomal instability and intra-tumoral heterogeneity correlated with a poorer response to crizotinib. Mechanisms of acquired resistance to MET inhibitors were primarily attributed to on-target MET D1228X/Y1230X mutations or off-target alterations within genes in the RTK/RAS/MAPK and PI3K/AKT/mTOR pathways. Intriguingly, our exploratory analysis also identified the FGFR3::TACC3 fusion as a potential resistance mechanism to savolitinib. Moreover, METΔex14 was identified in 16 patients following progression on EGFR and ALK inhibitors, highlighting the need for developing tailored therapeutic strategies to overcome resistance. CONCLUSIONS: This study provides a comprehensive characterization of METΔex14 in NSCLC, revealing its dual role as a primary driver of oncogenesis and a potential resistance mechanism to EGFR/ALK inhibitors. The identification of concurrent genetic alterations and potential resistance mechanisms enhances our molecular understanding of treatment responses. These findings highlight the need for further investigation into targeted therapies that consider the genomic complexity of METΔex14 to improve treatment efficacy and patient outcomes.

Humans↗

PubMed2025

Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with the tumor microenvironment (TME) playing a pivotal role in its progression and therapeutic resistance. The ubiquitin-proteasome system (UPS), a central regulator of intracellular protein degradation, is increasingly recognized for its involvement in cancer pathogenesis, though its specific role in modulating the CRC TME remains to be fully elucidated. This review aims to systematically summarize current evidence on how the UPS influences the immunosuppressive network within the CRC TME and to evaluate its potential as a therapeutic target. METHODS: We conducted a comprehensive literature search in PubMed, Web of Science, and Scopus databases for original research articles and reviews published between January 2010 and August 2025, using keywords including "ubiquitin-proteasome system," "colorectal cancer," "tumor microenvironment,""immune escape,"and "targeted therapy." Studies were selected based on their relevance to UPS-mediated regulatory mechanisms in CRC TME remodeling, immune cell function, and treatment response. RESULTS: Our analysis of preclinical and clinical evidence reveals that the UPS critically regulates immune evasion in CRC through multiple mechanisms: (1) USP14 stabilizes indoleamine 2,3-dioxygenase 1 (IDO1), enhancing tryptophan catabolism and kynurenine accumulation, which suppresses T-cell activity; (2) E3 ligases including SPOP, C-Cbl, KLHL22, and FBW7 modulate PD-L1/PD-1 protein stability via ubiquitination, thereby influencing immune checkpoint signaling; and (3) ZFP91 facilitates K63-linked ubiquitination of PP2Ac, impairing mTORC1-mediated glycolysis in T cells and reinforcing regulatory T-cell immunosuppression. Additionally, the UPS intersects with key oncogenic pathways such as Wnt/β-catenin, NF-κB, and p53, further shaping the immunosuppressive landscape of CRC. CONCLUSIONS: Targeting the UPS represents a promising strategy to reverse immunosuppression and overcome therapy resistance in CRC. The primary advantage of this approach lies in its ability to simultaneously disrupt multiple immunosuppressive pathways within the TME, offering a potential solution to the limitations of single-target therapies. Current approaches include proteasome inhibitors, E3 ligase modulators, and deubiquitinating enzyme inhibitors, with combination regimens-such as UPS inhibitors with immune checkpoint blockade-showing synergistic efficacy in preclinical models. Future efforts should focus on enhancing the selectivity of UPS-targeting agents, minimizing off-target effects, and integrating genomic profiling to guide personalized treatment. While current evidence strongly supports the therapeutic potential of UPS targeting, its establishment as a reliable alternative therapy in the clinic will depend on overcoming these challenges and validating efficacy in human trials. This review underscores the UPS as a central regulator of the CRC TME and provides a rational basis for novel therapeutic development.

Humans↗

PubMed2025

Multi-omics Mendelian randomization integrating RNA-seq, eQTL and pQTL data revealed CPXM1 as a potential drug target for osteoporosis.

Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mineral density and increased fracture risk, continues to be a major global health concern. Traditional treatments for osteoporosis have limited efficacy and safety profiles, highlighting the need for novel therapeutic targets. This study integrates multi-omics data, including RNA-seq, expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data, through Mendelian randomization (MR) to identify potential drug targets for osteoporosis. By leveraging bidirectional two-sample MR analysis, we identified CPXM1 (Carboxypeptidase X, M14 family member 1) as a novel gene that is causally linked to osteoporosis risk. Through transcriptomic and proteomic validation, we demonstrate that CPXM1 was upregulated in aged bone tissues and osteoporotic conditions in both human and murine models. Gene set enrichment analysis (GSEA) revealed significant dysregulation of bone homeostasis pathways, including increased extracellular matrix degradation and suppression of osteoblast differentiation in aged mice. Furthermore, phenome-wide association studies (PheWAS) confirmed minimal off-target effects of CPXM1, reinforcing its potential as a therapeutic target. Finally, computational drug repurposing predicted several promising drug candidates, including Doxorubicin, 5-Fluorouracil, and 2-Methylcholine, which may target CPXM1 pathways for osteoporosis treatment. These findings highlight CPXM1 as a potential biomarker and therapeutic target, offering new avenues for osteoporosis therapy.

Osteoporosis↗

PubMed2026

[Research Advances on Mechanisms and Interventions of DNA Methylation-Regulated Aging-Related Imbalance in Bone Metabolism].

Aging can induce age-related bone diseases such as osteoporosis. DNA methylation, a core epigenetic regulatory mechanism, participate in the pathological process of aging-induced bone metabolism imbalance by modulating gene expression at the epigenetic level. Using S-adenosylmethionine as a methyl donor, it exhibits characteristics of hypomethylation in genomic repetitive regions and abnormal methylation in CpG islands of promoters of key bone metabolism genes with advancing age. The "epigenetic clock" constructed based on these features can accurately predict an individual's biological age. In bone metabolism, DNA methylation disrupts the osteoblast-osteoclast balance by targeting key factors. Such abnormalities are driven by aging-related inflammation and oxidative stress, while bone loss feedback exacerbates epigenetic disorders, forming a vicious cycle. Targeted intervention strategies have demonstrated significant potential in addressing bone metabolism-related issues. Low-dose DNA methyltransferase inhibitors can improve bone metabolism; nutrients such as folate and cobalamin maintain methylation homeostasis by optimizing one-carbon metabolism pathways; while CRISPR/dCas technology enables precise regulation in the cellular and animal levels, thereby affecting bone metabolism. However, existing strategies still face challenges such as off-target effects and low delivery efficiency. Future research needs to deepen mechanistic studies, optimize intervention methods, and promote their translation into clinical prevention and treatment of osteoporosis.

DNA Methylation↗

PubMed2024

Diagnosis with Metagenomic Next-Generation Sequencing (mNGS) technology and real-time PCR for SARS-CoV-2 Omicron detection using various nasopharyngeal swabs in SARS-CoV-2 Omicron.

BACKGROUND: The SARS-CoV-2 Omicron variant, with the main subtypes BA.5.2 and BF.7 in China, led to off-target effects on the S and N genes from December 1, 2022, to January 31, 2023. The kits used for studying and developing these agents were not adequately and independently evaluated. It is important to verify the performance of commercial Real-Time quantitative PCR (RT-qPCR) tests. OBJECTIVE: We conducted a clinical evaluation of two Real Time SARS-CoV-2 Omicron assays to verify their performance using various detection reagents and clinical specimens. METHODS: We performed clinical evaluations of two existing Chinese SARS-CoV-2 Omicron RT-qPCR kits 2019-nCoV nucleic acid diagnostic kits (Fosun Biotechnology, National instrument registration 20203400299, Shanghai, China) and COVID-19 nucleic acid detection kits (eDiagnosis Biomedicine, National instrument registration 20203400212, Wuhan, China) and using BSD (Bondson) (Guangzhou Bondson Biotechnology Co. Ltd, batch number 2022101), quality controls provided by the inspection center and a large number of clinically confirmed specimens. RESULTS: The concordance rates for the Fosun and eDiagnosis kits were 95% and 100%, respectively. The detection limit for the Fosun and eDiagnosis kits was verified to be 300 copies/mL and 500 copies/mL. The Fosun assay exhibited the largest coefficient of variation (CV) for ORF1ab and N gene at the detection limit concentration (4.80%, 3.49%), whereas eDiagnosis showed a smaller CV (0.93%, 1.10%). In the reference product from the Hangzhou Clinical Laboratory Center test, it was found that Fosun had the lowest sensitivity of 93.47% and a specificity of 100%, while eDiagnosis exhibited 100% for both sensitivity and specificity. The lowest single target gene detection rate of Fosun reagents was 68.7% for the ORF1ab gene and 87.5% for the N gene, while eDiagnosis detection rate was 100%. Among the clinical group S specimens, the missed detection rate of the Fosun reagent was 10.9%, which was higher than the 3.9% of eDiagnosis. However, there was no significant difference in the clinical diagnostic efficiency of the two reagents. CONCLUSIONS: The ORF1ab and N assays of SARS-CoV-2 Omicron on the eDiagnosis platform yielded higher values compared to those on the Fosun platform. Consequently, the eDiagnosis kit has also been used as standard detection reagents. Considering that the Fosun reagent has a relatively low detection limit and targets three single genes, it is more advantageous as a confirmatory reagent for the new museum.

Humans↗

PubMed2001

92nd Annual Meeting of the American Association for Cancer Research. 24-28 March, 2001, New Orleans, Louisiana, USA.

The 92nd Annual Meeting of the AACR comprised over 5000 abstracts, 12 plenary and award lectures and numerous talks in educational sessions, symposia and mini-symposia. Given the wealth of information presented, we narrowed our coverage to the area of prenyltransferase and protein kinase inhibitors. Many rationally designed drugs are now in clinical trials and exciting results were presented for the Bcr-Abl inhibitor STI-571. The cancer community is beginning to envision new ways to evaluate and administer these well-tolerated drugs which do not fit the traditional anticancer drug profile. There is an emphasis in developing surrogate markers for evaluating the mechanism-based effectiveness as well as identifying off-target toxicities. In addition, there is a large effort in investigating effective drug combinations and the use of these new agents as radiosensitisers. Here we present specific examples of these issues as applied to prenylation and protein kinase inhibitors.

Animals↗

PubMed2002

Development of the spray drift task force database for aerial applications.

This article is part of a series describing the development of the Spray Drift Task Force (SDTF) database and its application to agricultural chemical exposure risk assessment modeling. The series describes the development of a large generic database (assuming that active ingredient rate is not a factor affecting physical drift) and its use in estimating spray movement immediately following application by aerial methods. The components of the database are described. In agreement with field trials in the open literature, the database shows that the major variables affecting off-target spray deposition are droplet size, spray release position (boom height and length), and wind speed and direction. In addition, secondary parameters that can affect these variables and drift are also discussed.

Aerosols↗

PubMed1992

Perceptual-motor coordination and style in healthy boys and those with minimal brain dysfunction.

Differences in visual-motor tracking by 8- to 9-yr.-old boys diagnosed with Minimal Brain Dysfunction or healthy have been analyzed. The subject's task was to use two computer keys to control a cursor line within a target which moved horizontally in two directions over the display. Target size and speed were the experimental variables. Off-target incidences and durations were measured and evaluated. The latter were longer and the former were more frequent on small targets for boys with brain dysfunction than for healthy boys. The two measures correlated negatively in most situations. The perceptual-motor style expressed by means of the distribution of coincidences of the two measures being over or under a criterion set equal to the corresponding averages of the healthy boys was different in the two groups. Brain-damaged boys were characterized mostly by the combination of high incidence of low duration misses for small and fast targets and by high incidence of high duration misses for large and slow targets, whereas most healthy boys showed a few misses of low duration for large and slow targets and few misses of high duration for small and fast targets.

Attention↗

PubMed2026

Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.

Inherited genodermatoses are a heterogeneous group of rare monogenic disorders. Among these, epidermolysis bullosa (EB) and ichthyoses represent paradigmatic disorders characterized by severe skin fragility and hyperkeratosis, respectively, and impaired barrier function, often with profound effects on quality of life and systemic health. Current management remains largely palliative, underscoring the urgent need for disease-modifying therapies. Over the past 2 decades, advances in epithelial stem cell biology, vector engineering and genome editing technologies have transformed the therapeutic landscape for genodermatoses. Ex vivo gene therapy has provided the first proof that genetically corrected epidermal stem cells can achieve long-term tissue regeneration in EB skin patients, establishing a new paradigm for regenerative medicine. In parallel, the emergence of programmable genome engineering platforms, including CRISPR/Cas nucleases, base editors and prime editors, have enabled increasingly precise strategies for mutation-specific correction in both recessive and dominant disorders. Furthermore, the development of in vivo topical approaches is expanding the possibility of directly targeting the skin. Despite these advances, substantial translational barriers continue to limit broad clinical implementation. Efficient and durable targeting of epidermal stem cells within a highly regenerative tissue, together with safe delivery across the skin barrier, stringent control of off-target activity, scalable manufacturing and demonstration of long-term safety, remain major challenges for the clinical translation of these approaches. In this Review, we discuss the current state of gene therapy for genodermatoses, highlighting key clinical milestones, emerging genome editing technologies and next-generation delivery systems. We further examine the biological and regulatory challenges that need to be overcome to bridge the gap between experimental innovation and clinically accessible therapies for patients with inherited skin diseases.

epidermolysis bullosa (EB)↗

PubMed2026

Integrative cross-tissue transcriptome-wide association and metabolomic analysis reveals novel genetic risk loci for aortic aneurysm.

BACKGROUND: Aortic aneurysm (AA) is a life-threatening cardiovascular condition with a strong genetic component, however, its molecular mechanisms remain poorly understood. Although genome-wide association studies (GWAS) have identified numerous risk loci, most prior studies have investigated genetic and metabolic factors separately, leaving the causal pathways from genetic variants to disease largely unexplored. METHODS: We established an integrative framework combining cross-tissue transcriptome-wide association studies (TWAS) with metabolomic mediation analysis. First, we integrated GWAS data from FinnGen R12 with multi-tissue expression quantitative trait loci (eQTL) data from Genotype-Tissue Expression Project (GTEx) V8, then performed cross-tissue TWAS using the Unified Test for MOlecular SignaTures (UTMOST) and single-tissue validation with the Functional Summary-based Imputation (FUSION) to prioritize susceptibility genes. Second, we applied Mendelian randomization (MR), colocalization, and Fine-mapping Of CaUsal gene Sets (FOCUS) to assess causality and identify high-confidence genes. Third, we performed metabolite mediation analysis to uncover metabolic pathways linking genetic variants to disease risk. Finally, we validated key findings in mouse models of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) using Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) and Western blotting. RESULTS: We identified multiple novel susceptibility genes for AA and its subtypes. Key genes included ADH family members (ADH1A, ADH1B, ADH4, ADH6) and ZNF827, which showed cross-subtype associations with strong colocalization evidence in vascular tissues. Metabolite mediation analysis revealed significant pathways involving N-acetylphenylalanine and methionine sulfoxide. Functional enrichment revealed distinct biological mechanisms: AA and AAA were primarily associated with metabolic pathways, whereas TAA-related genes were enriched in developmental and contractile processes. PheWAS indicated no significant off-target associations. Critically, experimental validation in mouse models confirmed significant upregulation of ZNF827 in TAA and ADH6 in AAA at both mRNA and protein levels, corroborating the genetic predictions. CONCLUSION: This integrated cross-omics analysis identifies novel genetic loci and, crucially, uncovers specific nutrient-related metabolic pathways that mediate genetic risk. These findings provide a mechanistic basis for future nutritional and metabolic intervention studies in AA and its subtypes.

MAGMA↗

PubMed2026

CRISPR-Cas technologies for precision genome editing in plants: advances, applications, and future perspectives.

Developing climate-smart crops with enhanced crop productivity, nutritional quality, resistance to biological and environmental stressors is vital for global food security. While hybrid breeding forms the cornerstone of modern crop improvement, conventional breeding approaches are limited by genetic barriers and prolonged breeding cycles. CRISPR-Cas based genome editing has revolutionized plant biology by allowing precise, efficient, and multiplex genetic modifications. This review provides a comprehensive synthesis of a recent advances in CRISPR-Cas technologies and their strategic applications in crop genetics and hybrid breeding. We summarize major genome-editing strategies, including gene knock-out, base editing (BE), knock-in, gene replacement, epigenome editing, and transcriptional regulation. Furthermore, we contrast stable, transient, and DNA-free delivery systems, highlighting ribonucleoprotein (RNP)-mediated delivery for minimizing off-target effects and avoiding transgene integration. We showcase how these technologies accelerate hybrid breeding by engineering male sterility systems, fixing heterosis, and generating high-throughput mutant libraries for trait discovery. Finally, we synthesize major bottlenecks in tissue culture-independent transformation and delivery systems, while outlining how emerging paradigms like de novo domestication and synthetic biology will shape the future of climate-resilient agriculture.

CRISPR/Cas↗

PubMed2026

Genome Editing in Solanaceae: Harnessing CRISPR-Cas Technology for Precision Crop Improvement.

Malnutrition and climate-induced stress remain major constraints to global food and nutritional security despite the yield gains of the Green Revolution. Solanaceae crops such as tomato, potato, brinjal, and pepper are key sources of vitamins, minerals, and bioactive compounds. Yet, their genetic improvement has been limited by narrow diversity and complex polygenic traits. The advent of CRISPR/Cas-mediated genome editing provides a transformative platform for precision crop improvement by enabling targeted modification of genes controlling stress tolerance, yield, and nutritional quality. In Solanaceae, CRISPR/Cas applications have successfully enhanced resistance against major pathogens (SlMlo1, SlPelo, SlDCL2), improved abiotic stress tolerance through editing of SlMAPK3, SlCBF1, and SlBZR1, and optimized fruit quality traits via modulation of Psy1, CrtR-b2, and fiAD2/3. Emerging innovations, such as base and prime editing, and RNP-mediated transgene-free delivery, are expanding the precision and scope of editing. However, challenges persist, including genotype-dependent transformation, low HDR efficiency, and incomplete understanding of off-target and epigenetic effects. Integrating CRISPR with omics-guided gene discovery, efficient transformation systems, and regulatory harmonization can accelerate the development of nutritionally enriched, stress-resilient, and sustainable Solanaceae varieties. This review synthesizes recent advances, identifies critical limitations, and outlines future opportunities for deploying CRISPR/Cas technology to achieve next-generation breeding and food system resilience.

CRISPR/Cas↗

PubMed2020

Battling Neurodegenerative Diseases with Adeno-Associated Virus-Based Approaches.

Neurodegenerative diseases (NDDs) are most commonly found in adults and remain essentially incurable. Gene therapy using AAV vectors is a rapidly-growing field of experimental medicine that holds promise for the treatment of NDDs. To date, the delivery of a therapeutic gene into target cells via AAV represents a major obstacle in the field. Ideally, transgenes should be delivered into the target cells specifically and efficiently, while promiscuous or off-target gene delivery should be minimized to avoid toxicity. In the pursuit of an ideal vehicle for NDD gene therapy, a broad variety of vector systems have been explored. Here we specifically outline the advantages of adeno-associated virus (AAV)-based vector systems for NDD therapy application. In contrast to many reviews on NDDs that can be found in the literature, this review is rather focused on AAV vector selection and their preclinical testing in experimental and preclinical NDD models. Preclinical and in vitro data reveal the strong potential of AAV for NDD-related diagnostics and therapeutic strategies.

Animals↗

PubMed2026

CRISPR/Cas9-Mediated Site-Directed Mutagenesis of Genes in Klebsiella pneumoniae.

Constructing target-gene mutants with a common genetic background is crucial for elucidating gene function in antimicrobial resistance (AMR) research. Taking advantage of the single-guide RNA (sgRNA) and protospacer adjacent motif (PAM) sequence (3'-NGG) specificity of the Cas9 protein in the CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system and codon degeneracy, the authors design a repair template that incorporates the desired point mutation while excluding the PAM sequence disrupted by a synonymous substitution, thereby preventing re-cleavage by CRISPR/Cas9. This method employs two available plasmids, pCasKP-apr and pSGKP-spe, offering straightforward operation and high screening specificity. As a result, the approach enables efficient generation of genetically defined mutant strains of Klebsiella pneumoniae (K. pneumoniae) and is readily adaptable to routine laboratory settings. Furthermore, the protocol minimizes off-target editing, shortens experimental timelines, reduces screening workload, and provides a reliable platform for investigating resistance mechanisms, validating candidate genes, and supporting functional genomics studies in clinically relevant bacterial pathogens.

Klebsiella pneumoniae↗

PubMed1999

Contrast enhancement in microplanar beam radiography.

In x-ray radiography, the target produces a useful shadow from absorption of the primary beam, while the scattered radiation into the off-target region decreases the contrast of the target image. A bundle of closely spaced microplanar beams can reduce the scattered radiation and give superior image contrast compared with a single macrobeam of the same dimensions. To further reduce the scattered radiation and increase the image contrast, we place an air gap between the tissue phantom and the detector. The primary and scattered photon flux of a single microplanar beam is measured as a function of thickness inside the phantom and in the air gap. Results show that a bundle of closely spaced, microplanar beams increase the image contrast by 22% and a 2 cm air gap decreases the scattered photon flux by about half, improving the contrast by an additional 16%. Thus an overall improvement of 41% in contrast can be achieved with microplanar beam radiography.

Cadmium Radioisotopes↗

PubMed2000

Monte Carlo calculation for microplanar beam radiography.

In radiography the scattered radiation from the off-target region decreases the contrast of the target image. We propose that a bundle of collimated, closely spaced, microplanar beams can reduce the scattered radiation and eliminate the effect of secondary electron dose, thus increasing the image dose contrast in the detector. The lateral and depth dose distributions of 20-200 keV microplanar beams are investigated using the EGS4 Monte Carlo code to calculate the depth doses and dose profiles in a 6 cm x 6 cm x 6 cm tissue phantom. The maximum dose on the primary beam axis (peak) and the minimum inter-beam scattered dose (valley) are compared at different photon energies and the optimum energy range for microbeam radiography is found. Results show that a bundle of closely spaced microplanar beams can give superior contrast imaging to a single macrobeam of the same overall area.

Humans↗

PubMed2002

Eye-tracking measures and human performance in a vigilance task.

BACKGROUND: Visual scanning is necessary for aviation safety and similar vigilance tasks, but little is known about its characteristics in such tasks, including possible changes with alertness and fatigue. We explored concurrent eye movements and human performance during a vigilance task designed to require frequent visual scanning. Effects of time and auditory stimuli were examined. METHOD: A corneal-reflectance, PC-based system (Eyegaze Development System, LC Technologies) provided eye movement measures. Stimuli were four digits in a rectangular array, changed at an event rate of 4 s for a task duration of 30 min. There were 20 subjects who were asked to respond to specific, infrequent signal arrays by bar press, under both 50 dBA white noise and 90 dBA intermittent and unpredictable sound-burst conditions, counterbalanced for order. RESULTS: With time-on-task, subjective fatigue ratings increased, dwell time defined as the total duration of fixations on target digits decreased, number of fixations decreased, and fixations were further from target digits in both conditions. Fixation durations [mean (M) = 258 ms; standard deviation (SD) = 54 ms] did not change significantly with time or condition. Off-target visual scan-paths were less frequently followed by hits than were on-target scan-paths in both conditions. With the sound-burst condition, fixations were closer to target digits and hit rates increased. CONCLUSIONS: Dwell time, number, and accuracy of fixations on target objects decreased with time on task, and inaccurate scan-paths were often associated with performance errors. Sound bursts increased fixation accuracy and hit rate. The results provide a basis for visual scan analyses during vigilance tasks, with applications to alertness monitoring and prediction.

Adult↗

PubMed2002

The agricultural dispersal-valley drift spray drift modeling system compared with pesticide drift data.

The coupling of the valley drift (VALDRIFT) atmospheric dispersion/deposition model with the agricultural dispersal (AGDISP) aircraft wake model generates a modeling system for predicting the off-target drift of pesticides sprayed in a mountain valley. The approach uses the AGDISP near-field spray model to estimate the mass fraction of pesticide remaining airborne after initial application, then the VALDRIFT complex terrain model to estimate the drift of pesticide from the target area. The modeling system inputs include detailed spray information, a measure (or estimate) of winds in the valley, and the valley topographic characteristics; the results are pesticide concentrations throughout the valley atmosphere and pesticide deposition to the valley surface. The AGDISP and VALDRIFT models are operated independently, with the results from AGDISP being used as input to VALDRIFT through user-created data files. The modeling system was evaluated using pesticide drift data from spray trials conducted in the Mill Creek Canyon of Utah's Wasatch Mountains, USA, during the late spring of 1993. The predicted deposition compared within a factor of three of the observations (70% of the time) at all sampling locations extending several kilometers down-valley from the spray treatment block. The overall average ratio of predicted-to-observed deposition was 0.9.

Agriculture↗