Characterization of a glow discharge ion source for the mass spectrometric analysis of organic compounds

AbstractA glow discharge ion source has been constructed for the mass spectrometric analysis of organic compounds. Characterization of the source has been made by studying the effect of pressure and discharge current on ionic distributions by anodic ion sampling along the discharge axis. Ion and electron densities and electronic temperatures have been calculated by using the single Langmuir probe technique to correlate the extraction efficiency with measured ion distributions and gain some insight into the ionization of organic molecules. The spectra obtained for several classes of organic compounds show that formation of parent-molecular ions by proton transfer, resulting partly from the background water molecules, is a major low energy process while charge transfer, Penning ionization, and electron ionization are probably responsible for the fragmentation observed. The spectra result from the simultaneous occurrence of high and low energy reactions, and their structural information content is very high, yielding both molecular and extensive fragment ion information. The glow discharge ion source has proved to be essentially maintenance-free, easy to operate, stable, and can be used at reasonable mass resolution (up to 7000). The source also provides picogram range detection limits and has a linear response range of about six orders of magnitude, which makes it an interesting ion source for routine analysis. Preliminary work conducted with chromatographic interfaces indicates that its use can be easily extended to both gas and liquid chromatography

Isokinetic assessment of the flexor-extensor balance of the knee in athletes with total rupture of the anterior cruciate ligament Avaliação isocinética do equilíbrio flexo-extensor do joelho nos atletas com ruptura total do ligamento cruzado anterior

The purpose of this study was to assess the flexor-extensor group of muscles of the knee in young athletes diagnosed with a total rupture of the anterior cruciate ligament (ACL). Eighteen knees of 18 athletes (14 men and 4 women) with an average age of 21.6 years (range 16-32 years) were assessed with a Cybex 6000 model isokinetic apparatus. The average interval between occurrence of the injury and assessment was 10.2 months (range 2 - 48 months). There was an associated meniscal injury in eight of the knees. Athletes with any other kind of associated injury, limitation, or blockage of the movement of the joint, significant pain during the exam, or interval between injury and exam of less than two months were excluded from the study. The parameters studied were the peak torque-velocity and flexor-extensor relationships at the constant angular velocities of 60°/sec and 240°/sec. Previous warming-up was done by means of an ergometric bicycle and adaptation with 3 submaximal repetitions. The contra-lateral side, which presented no injury, was used as control. Peak torque (PT) at the constant velocity of 60°/sec was greater than that at 240°/sec for knees with and without injuries. However, there was no significant difference between the injured and uninjured sides at 60°/sec or at 240°/sec. The average value for the flexor-extensor relationship at 60°/sec on the injured was 60% (( 6), compared to 57% (( 10) on the contra-lateral side. At 240°/sec, the average value was 75% ((10) on the injured side, and 65% ((12) on the contra-lateral side. In conclusion, despite the complete rupture of the ACL of one knee, the average values for the flexor-extensor relationship were similar on the injured and uninjured sides at the velocity of 60°/sec. As the velocity increased, an increase in the values for the flexor-extensor relationship of the knee also occurred, indicating a tendency of the performance of the flexor muscle group to approach that of the extensor muscle group, and this tendency was more pronounced on the side of the injury.<br>O objetivo desse estudo foi avaliar o grupo muscular flexo-extensor do joelho de esportistas jovens que tiveram diagnóstico de ruptura completa do ligamento cruzado anterior (LCA). Dezoito joelhos de 18 atletas (14 homens e 4 mulheres) com idade média de 21,6 anos (16 - 32) foram avaliados com aparelho isocinético modelo Cybex 6000. O intervalo médio entre a lesão e a avaliação foi de 10,2 meses (2 - 48). Houve lesão meniscal associada em oito joelhos. Demais atletas com outro tipo de lesão associada, limitação ou bloqueio da amplitude articular, dor importante durante o exame e tempo de lesão com menos de dois meses foram excluídos do estudo. O parâmetro estudado foi o pico de torque (PT) e a relação flexo-extensora do PT nas velocidades angulares constantes de 60º/seg e 240º/seg . Foi realizado um aquecimento prévio com bicicleta ergométrica e adaptação com três repetições submáximas. O lado contra-lateral, que não apresentava lesão, foi usado como controle. O PT na velocidade constante de 60°/seg foi maior do que na velocidade de 240°/seg, seja nos joelhos com ou sem lesão. Não houve diferença significante entre o lado com e sem lesão, tanto a 60°/seg como a 240°/seg. O valor médio da relação flexo-extensora do PT na velocidade de 60º/seg no lado com lesão foi de 60 % (± 6) e no lado contra-lateral 57 % (±10). A 240º/seg no lado com lesão foi de 75 % (± 10) e no contra-lateral foi de 65 % (± 12). Como conclusões observou-se que os valores do equilíbrio flexo-extensor foram semelhantes na velocidade de 60º/seg, apesar da ruptura completa do LCA. À medida que ocorreu aumento da velocidade, ocorreu também um aumento da relação flexo-extensora do joelho, indicando leve tendência do grupo muscular flexor se aproximar do extensor, mais pronunciada no lado com lesão

Multidimensional Characterization of Soft-Tissue Sarcomas with FUS-TFCP2 or EWSR1-TFCP2 Fusions

ABSTRACTLinking clinical multi-omics analyses with mechanistic studies provides opportunities to explore the pathogenesis of rare cancers. We leveraged two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective systemic therapies. All tumors exhibited outlier expression of the ALK receptor tyrosine kinase, which was partly accompanied by intragenic deletions and aberrant splicing, resulting in truncated ALK variants that were oncogenic and sensitive to ALK inhibitors. Additional recurrent alterations included CKDN2A/MTAP co-deletions, providing a rationale for therapies targeting CDK4/6 and PRMT5. Functional studies showed that FUS-TFCP2 blocks myogenic differentiation and induces transcription of ALK and a truncated form of TERT through binding outside their regular promoters. Furthermore, FUS-TFCP2 inhibited DNA double-strand break repair. Consistent with this, and unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibited marked genomic instability and signs of defective homologous recombination. DNA methylation profiling indicated a close relationship with undifferentiated sarcomas rather than rhabdomyosarcoma. Finally, we identified patients in whom overt disease was preceded by benign lesions carrying TFCP2 fusions, providing insight into stepwise sarcomagenesis and suggesting new approaches to early detection and interception.SIGNIFICANCEMost rare cancers are poorly understood, and pathogenesis-directed therapies are often lacking, resulting in poor patient outcomes. This study illustrates the potential of linking precision oncology programs with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers that could improve the clinical management of such diseases.</jats:sec