25 research outputs found
Precise Measurements of Beam Spin Asymmetries in Semi-Inclusive production
We present studies of single-spin asymmetries for neutral pion
electroproduction in semi-inclusive deep-inelastic scattering of 5.776 GeV
polarized electrons from an unpolarized hydrogen target, using the CEBAF Large
Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator
Facility. A substantial amplitude has been measured in the
distribution of the cross section asymmetry as a function of the azimuthal
angle of the produced neutral pion. The dependence of this amplitude
on Bjorken and on the pion transverse momentum is extracted with
significantly higher precision than previous data and is compared to model
calculations.Comment: to be submitted PL
Inhibition of MYC translation through targeting of the newly identified PHB-eIF4F complex as therapeutic strategy in CLL
Dysregulation of messenger RNA (mRNA) translation, including preferential translation of mRNA with complex 5âČ untranslated regions such as the MYC oncogene, is recognized as an important mechanism in cancer. Here, we show that both human and murine chronic lymphocytic leukemia (CLL) cells display a high translation rate, which is inhibited by the synthetic flavagline FL3, a prohibitin (PHB)-binding drug. A multiomics analysis performed in samples from patients with CLL and cell lines treated with FL3 revealed the decreased translation of the MYC oncogene and of proteins involved in cell cycle and metabolism. Furthermore, inhibiting translation induced a proliferation arrest and a rewiring of MYC-driven metabolism. Interestingly, contrary to other models, the RAS-RAF-(PHBs)-MAPK pathway is neither impaired by FL3 nor implicated in translation regulation in CLL cells. Here, we rather show that PHBs are directly associated with the eukaryotic initiation factor (eIF)4F translation complex and are targeted by FL3. Knockdown of PHBs resembled FL3 treatment. Importantly, inhibition of translation controlled CLL development in vivo, either alone or combined with immunotherapy. Finally, high expression of translation initiationârelated genes and PHBs genes correlated with poor survival and unfavorable clinical parameters in patients with CLL. Overall, we demonstrated that translation inhibition is a valuable strategy to control CLL development by blocking the translation of several oncogenic pathways including MYC. We also unraveled a new and direct role of PHBs in translation initiation, thus creating new therapeutic opportunities for patients with CLL
Semi-inclusive pi(0) target and beam-target asymmetries from 6 GeV electron scattering with CLAS
We present precision measurements of the target and beam-target spin
asymmetries from neutral pion electroproduction in deep-inelastic scattering
(DIS) using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. We
scattered 6-GeV, longitudinally polarized electrons off longitudinally
polarized protons in a cryogenic NH target, and extracted double and
single target spin asymmetries for in
multidimensional bins in four-momentum transfer ( GeV),
Bjorken- (), hadron energy fraction (), transverse
pion momentum ( GeV), and azimuthal angle between the
lepton scattering and hadron production planes. We extracted asymmetries as a
function of both and , which provide access to transverse-momentum
distributions of longitudinally polarized quarks. The double spin asymmetries
depend weakly on . The moments are zero within
uncertainties, which is consistent with the expected suppression of the Collins
fragmentation function. The observed moments suggest that quark
gluon correlations are significant at large .Comment: 18 preprint pages, 3 figure
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and lowâmiddle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of âsingle-useâ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for lowâmiddle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both highâ and lowâmiddleâincome countries
IgM-producing chronic lymphocytic leukemia cells undergo immunogobulin isotype-switching without acquiring somatic mutations.
The malignant B cells in chronic lymphocytic leukemia (CLL) typically express low-density membrane IgM or IgM/IgD. In vitro experiments have shown that the CLL cells can be induced to differentiate into cells that secrete immunoglobulin (Ig) and can occasionally undergo heavy (H) chain class switching. We now show that the CLL cells also undergo isotype-switching in vivo, since gamma and/or alpha H chain transcripts with identical FW3/CDR3/FW4 regions as the mu CLL transcripts were detected in all of the 13 investigated patients with IgM+ CLL. In most cases switching had occurred to alpha1 and gamma3, but CLL transcripts corresponding to the other gamma chain isotypes were also detected. In one case both the productively and nonproductively rearranged allele were found to undergo H chain class switching. CLL gamma transcripts were also present in surface IgG+ sorted B cells, demonstrating that a small subset of the CLL cells express membrane IgG. In addition, transcripts encoding secretary gamma2 and gamma3 H chains were detected in two cases, which suggests that some serum IgG could be produced by the leukemic clone. Analysis of sorted PBL showed that isotype-switching occurs in CLL cells that express the CD5 antigen. Finally, nucleotide sequence analysis showed that the mu, alpha, and gamma CLL transcripts are identical, demonstrating that the CLL cells do not accumulate somatic mutations in their variable region genes after the H chain class switching. These data provide in vivo evidence that isotype-switching is a frequent phenomenon in CLL, and indicate that a subset of the CLL lymphocytes progress to later stages of B cell differentiation