Vasodilatory effect of pentoxifylline in isolated equine digital veins

The direct vasodilatory action of pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) and its signalling pathway was evaluated in equine digital veins. Cumulative concentration-response curves to pentoxifylline (1 nM to 300 μM) were recorded in phenylephrine-precontracted equine digital vein rings under different experimental conditions. Relaxation to pentoxifylline was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (a non-xanthine adenosine receptor antagonist; 3 μM). Nitric oxide synthase (NOS), soluble guanylate cyclase and cyclooxygenase (COX) inhibitors (Nω-nitro-L-arginine methyl ester (100 μM), ODQ (30 μM) and indomethacin (10 μM), respectively) significantly reduced the maximum relaxation induced by pentoxifylline. Moreover, pentoxifylline-induced relaxation was strongly reduced by Rp-8-Br-PET-cyclic guanosine monophosphate-S (a protein kinase G inhibitor; 3 μM), but remained unaffected by H-89 (a protein kinase A inhibitor; 2 μM). Pentoxifylline-induced relaxation was associated with a 3.4-fold increase in tissue cGMP content. To investigate whether pentoxifylline can affect cAMP- and cGMP-mediated relaxations, curves to forskolin, to sodium nitroprusside (SNP) and 8-bromo-cGMP were also recorded in endothelium-denuded equine digital vein rings pretreated with pentoxifylline (10 and 100 μM). Pentoxifylline only potentiated the SNP-mediated relaxation at the highest concentration (100 μM). Thus, pentoxifylline relaxed equine digital veins via endothelium-dependent and endothelium-independent components. The effect was mediated through both the NOS and COX pathways and could also result from inhibition of cGMP specific-phosphodiesterase activity at the highest concentrations used

First Measurement of Timeline Compton Scattering

We present the first measurement of the timelike Compton scattering process, p →p′∗(∗→e+e−), obtained with the CLAS12 detector at Jefferson Lab. The photon beam polarization and the decay lepton angular asymmetries are reported in the range of timelike photon virtualities 2.25 \u3c Q2 \u3c 9  GeV2, squared momentum transferred 0.1 \u3c −t \u3c 0.8  GeV2, and average total center-of-mass energy squared s = 14.5  GeV2 . The photon beam polarization asymmetry, similar to the beam-spin asymmetry in deep virtual Compton scattering, is sensitive to the imaginary part of the Compton form factors and provides a way to test the universality of the generalized parton distributions. The angular asymmetry of the decay leptons accesses the real part of the Compton form factors and thus the D-term in the parametrization of the generalized parton distributions

Photoproduction of K+K− meson pairs on the proton

The exclusive reaction γp→pK+K− was studied in the photon energy range 3.0–3.8  GeV and momentum transfer range 0.6<−t<1.3  GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. In this kinematic range the integrated luminosity was approximately 20  pb−1. The reaction was isolated by detecting the K+ and the proton in CLAS, and reconstructing the K− via the missing-mass technique. Moments of the dikaon decay angular distributions were extracted from the experimental data. Besides the dominant contribution of the ϕ meson in the P wave, evidence for S−P interference was found. The differential production cross sections dσ/dt for individual waves in the mass range of the ϕ resonance were extracted and compared to predictions of a Regge-inspired model. This is the first time the t-dependent cross section of the S-wave contribution to the elastic K+K− photoproduction has been measured

Artificial Intelligence for the Electron Ion Collider (AI4EIC)

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R&D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments.Comment: 27 pages, 11 figures, AI4EIC workshop, tutorials and hackatho

Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequence

The epigenetic code of DNA methylation is interpreted chiefly by methyl cytosine binding domain (MBD) proteins which in turn recruit multiprotein co-repressor complexes. We previously isolated one such complex, MBD2-NuRD, from primary erythroid cells and have shown it contributes to embryonic/fetal β-type globin gene silencing during development. This complex has been implicated in silencing tumor suppressor genes in a variety of human tumor cell types. Here we present structural details of chicken MBD2 bound to a methylated DNA sequence from the ρ-globin promoter to which it binds in vivo and mediates developmental transcriptional silencing in normal erythroid cells. While previous studies have failed to show sequence specificity for MBD2 outside of the symmetric mCpG, we find that this domain binds in a single orientation on the ρ-globin target DNA sequence. Further, we show that the orientation and affinity depends on guanine immediately following the mCpG dinucleotide. Dynamic analyses show that DNA binding stabilizes the central β-sheet, while the N- and C-terminal regions of the protein maintain mobility. Taken together, these data lead to a model in which DNA binding stabilizes the MBD2 structure and that binding orientation and affinity is influenced by the DNA sequence surrounding the central mCpG

First measurements of the double-polarization observables F, P, and H in ω photoproduction off transversely polarized protons in the N* resonance region

First measurements of double-polarization observables in ω photoproduction off the proton are presented using transverse target polarization and data from the CEBAF Large Acceptance Spectrometer (CLAS) FROST experiment at Jefferson Lab. The beam-target asymmetry F has been measured using circularly polarized, tagged photons in the energy range 1200–2700 MeV, and the beam-target asymmetries H and P have been measured using linearly polarized, tagged photons in the energy range 1200–2000 MeV. These measurements significantly increase the database on polarization observables. The results are included in two partial-wave analyses and reveal significant contributions from several nucleon (N∗) resonances. In particular, contributions from new N∗ resonances listed in the Review of Particle Properties are observed, which aid in reaching the goal of mapping out the nucleon resonance spectrum

Beam Charge Asymmetries for Deeply Virtual Compton Scattering on the Proton at CLAS12

The parameterization of the nucleon structure through Generalized Parton Distributions (GPDs) shed a new light on the nucleon internal dynamics. For its direct interpretation, Deeply Virtual Compton Scattering (DVCS) is the golden channel for GPDs investigation. The DVCS process interferes with the Bethe-Heitler (BH) mechanism to constitute the leading order amplitude of the $eN \to eN\gamma$ process. The study of the $ep\gamma$ reaction with polarized positron and electron beams gives a complete set of unique observables to unravel the different contributions to the $ep \gamma$ cross section. This separates the different reaction amplitudes, providing a direct access to their real and imaginary parts which procures crucial constraints on the model dependences and associated systematic uncertainties on GPDs extraction. The real part of the BH-DVCS interference amplitude is particularly sensitive to the $D$-term which parameterizes the Gravitational Form Factors of the nucleon. The separation of the imaginary parts of the interference and DVCS amplitudes provides insights on possible higher-twist effects. We propose to measure the unpolarized and polarized Beam Charge Asymmetries (BCAs) of the $\vec{e}^{\pm}p \to e^{\pm}p \gamma$ process on an unpolarized hydrogen target with {\tt CLAS12}, using polarized positron and electron beams at 10.6~GeV. The azimuthal and $t$-dependences of the unpolarized and polarized BCAs will be measured over a large $(x_B,Q^2)$ phase space using a 100 day run with a luminosity of 0.66$\times 10^{35}$cm$^{-2}\cdot$s$^{-1}$.Comment: Proposal to the Jefferson Lab Program Advisory Committee (PAC51