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Application of silicon improves rhizosheath formation, morpho-physiological and biochemical responses of wheat under drought stress
No full textOsteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous.
No full textOsteosarcoma is the most common primary bone malignancy, often detected in children and adolescents and commonly associated with TP53 alterations along with a high number of chromosomal rearrangements. However, osteosarcoma can affect patients of any age, and some tumors display less genetic complexity. Besides TP53 variants, data on key driving mutations are lacking for many osteosarcomas, particularly those affecting adults. To detect osteosarcoma-specific alterations, we screened transcriptomic and genomic sequencing and copy number data from 150 bone tumors originally diagnosed as osteosarcomas. To increase the precision in gene fusion detection, we developed a bioinformatic tool denoted as NAFuse, which extracts gene fusions that are verified at both the genomic and transcriptomic levels. Apart from the already reported genetic subgroups of osteosarcoma with TP53 structural variants, or MDM2 and/or CDK4 amplification, we did not identify any recurrent genetic driver that signifies the remaining cases. Among the plethora of mutations identified, we found genetic alterations characteristic of, or similar to, those of other bone and soft tissue tumors in 8 cases. These mutations were found in tumors with relatively few other genetic alterations or in adults. Due to the lack of clinical context and available tissue, we can question the diagnosis only on a genetic basis. However, our findings support the notion that osteosarcomas with few chromosomal alterations or adult onset seem genetically distinct from conventional osteosarcomas of children and adolescents
Treatment of gastric cancer and adenocarcinoma of the GEJ-how do AIO clinical studies fit into the treatment landscape?
No full textComprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS.
No full textThe acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2-22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy
The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.
No full textMultiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies. Here we provide a comprehensive multiomics analysis including deep tandem mass tag-based quantitative global (phospho)proteomics, RNA sequencing, and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive MM, plasma cell leukemia and the premalignancy monoclonal gammopathy of undetermined significance, as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells are highly deregulated as compared with healthy plasma cells and is both defined by chromosomal alterations as well as posttranscriptional regulation. A prognostic protein signature was identified that is associated with aggressive disease independent of established risk factors in MM. Integration with functional genetics and single-cell RNA sequencing revealed general and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include potential targets for (immuno)therapies. Our study demonstrates the potential of proteogenomics in cancer and provides an easily accessible resource for investigating protein regulation and new therapeutic approaches in MM
Feasibility Analysis for Active Noise Cancellation Using the Electrical Power Steering Motor
No full textThis paper describes the use of an electric drive as an acoustic actuator for active noise cancellation (ANC). In the presented application, the idea is to improve the noise, vibration, harshness (NVH) characteristics of passenger cars without using additional active or passive damper systems. Many of the already existing electric drives in cars are equipped with the required hardware components to generate noise and vibration, which can be used as compensation signals in an ANC application. To demonstrate the applicability of the idea, the electrical power steering (EPS) motor is stimulated with a control signal, generated by an adaptive feedforward controller, to reduce harmonic disturbances at the driver’s ears. As it turns out, the EPS system generates higher harmonics of the harmonic compensation signal due to nonlinearities in the acoustic transfer path using a harmonic excitation signal. The higher harmonics impair an improvement in the subjective hearing experience, although the airborne noise level of the harmonic disturbance signal can be clearly reduced at the driver’s ears. Therefore, two methods are presented to reduce the amplitude of the higher harmonics. The first method is to limit the filter weights of the algorithm to reduce the amplitude of the harmonic compensation signal. The filter amplitude limitation also leads to a lower amplitude of the higher harmonics, generated by the permanent magnet synchronous machine (PMSM). The second method uses a parallel structure of adaptive filters to actively reduce the amplitude of the higher harmonics. Finally, the effectiveness of the proposed ANC system is demonstrated in two real
