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Using a high-energy laser to produce a super-Alfvénic carbon-ion beam in a strongly magnetized helium plasma, we expect to be able to observe the formation of a collisionless parallel shock inside the Large Plasma Device. We compare early magnetic-field measurements of the resonant right-hand instability with analytical predictions and find excellent agreement. Hybrid simulations show that the carbon ions couple to the background plasma and compress it, although so far the background ions are mainly accelerated perpendicular to the mean-field direction.

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

We present two-dimensional hybrid kinetic/magnetohydrodynamic simulations of planned laser-ablation experiments in the Large Plasma Device (LAPD). Our results, based on parameters which have been validated in previous experiments, show that a parallel collisionless shock can begin forming within the available space. Carbon-debris ions that stream along the magnetic-field direction with a blow-off speed of four times the Alfven velocity excite strong magnetic fluctuations, eventually transfering part of their kinetic energy to the surrounding hydrogen ions. This acceleration and compression of the background plasma creates a shock front, which satisfies the Rankine-Hugoniot conditions and can therefore propagate on its own. Furthermore, we analyze the upstream turbulence and show that it is dominated by the right-hand resonant instability.

Collisionless coupling between super Alfv\\'{e}nic ions and an ambient plasma parallel to a background magnetic field is mediated by a set of electromagnetic ion/ion-beam instabilities including the resonant right hand instability (RHI). To study this coupling and its role in parallel shock formation, a new experimental configuration at the University of California, Los Angeles utilizes high-energy and high-repetition-rate lasers to create a super-Alfv\\'{e}nic field-aligned debris plasma within an ambient plasma in the Large Plasma Device (LAPD). We used a time-resolved fluorescence monochromator and an array of Langmuir probes to characterize the laser plasma velocity distribution and density. The debris ions were observed to be sufficiently super-Alfv\\'{e}nic and dense to excite the RHI. Measurements with magnetic flux probes exhibited a right-hand circularly polarized frequency chirp consistent with the excitation of the RHI near the laser target. We compared measurements to 2D hybrid simulations of the experiment.

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB and JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 and its role in LMP1 signalling remains elusive. Here we demonstrate that TRAF6 interacts directly with a viral TRAF6 binding motif within CTAR2. Functional and NMR studies supported by molecular modeling provide insight into the architecture of the LMP1-TRAF6 complex, which differs from that of CD40-TRAF6. The direct recruitment of TRAF6 to LMP1 is essential for NF-κB activation by CTAR2 and the survival of LMP1-driven lymphoma. Disruption of the LMP1-TRAF6 complex by inhibitory peptides interferes with the survival of EBV-transformed B cells. In this work, we identify LMP1-TRAF6 as a critical virus-host interface and validate this interaction as a potential therapeutic target in EBV-associated cancer. Epstein-Barr virus causes lymphoma. Here the authors describe a direct complex of the viral oncoprotein LMP1 with the cellular TRAF6 protein as a critical virus-host interface for lymphoma survival and validate this complex as a potential therapeutic target.

Pioneer factors are transcription factors sharing the fascinating ability to bind to compact chromatin and thereby alter its transcriptional fate. Most pioneer factors are known for their importance during embryonic development, for instance, in inducing zygotic genome activation or cell fate decision. Some pioneer factors are actively induced or downregulated by viral infection. With this, viruses are capable to modulate different signaling pathways resulting for example in MHC-receptor up/downregulation which contributes to viral immune evasion. In this article, we review the current state of research on how different viruses (Herpesviruses, Papillomaviruses and Hepatitis B virus) use pioneer factors for their viral replication and persistence in the host, as well as for the development of viral cancer.

18F-galacto-RGD (18F-RGD) is a PET tracer binding to alpha v beta 3 integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial 18F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. METHODS: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with 18F-RGD to evaluate alpha v beta 3 integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by 13N-ammonia PET and MRI, respectively. RESULTS: One week after MI, 18F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 plus or minus 0.05 vs. 0.06 plus or minus 0.03 and 0.07 plus or minus 0.04, P < 0.001). At this time, 18F-RGD uptake was associated with capillary density in histologic sections. Average 18F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 plus or minus 0.07 vs. 0.21 plus or minus 0.05, P < 0.05). In a multivariable logistic regression analysis, low 18F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). CONCLUSION: High levels of 18F-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that alpha v beta 3 integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.

To develop and implement a multidisciplinary early activation mechanism and bundle of care (eHIP) to improve adherence to ACSQHC standards in a regional trauma centre. Barriers to implementation were categorised using the Theoretical Domains Framework, then linked to specific strategies guided by the Behaviour Change Wheel and Behaviour Change Technique Taxonomy (BCTT). The resulting implementation strategies were assessed using Affordable, Practical, Effective, Acceptable, had Side-effects (APEASE) criteria. Eighty-three barriers to implementation of the hip fracture care bundle were identified. The behaviour change wheel process resulted in the identification of 41 techniques to address these barriers. The predominant mechanisms to achieve this were development and implementation of 1) formal policy that outlines eHIP roles; 2) video promotion; 3) pager group; 4) fascia iliaca block enabling; 5) eMR modifications; 6) face-to-face reinforcement and modelling; 7) communication and prompts; 8) environmental restructuring. We applied behaviour change theory through a pragmatic evidence-based process. This resulted in a codesigned strategy to overcome staff and organisational barriers to the implementation of a multidisciplinary early activation mechanism and bundle of care (eHIP). Future work will include evaluation of the uptake and clinical impact of the care bundle.

To measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI). ECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[18F]fluoro-d-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDGBP), and also from the later myocardial uptake (FDGMyo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer 68Ga-albumin (AlbBP) and again by FDG (FDGMyo2) in one setting. Cine-MRI examination provided the reference standard measurement. The mean LV ejection fractions (LVEF) were 56 ± 3 (FDGBP), 55 ± 3 (FDGMyo), 56 ± 3 (FDGMyo2), 57 ± 3 (AlbBP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDGBP (r = 0.71), FDGMyo (r = 0.86) and AlbBP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDGMyo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDGMyo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDGMyo and FDGMyo2 (P = .50). Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer 68Ga-albumin.

^sup 18^F-galacto-RGD (^sup 18^F-RGD) is a PET tracer binding to α^sub v^β^sub 3^ integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial ^sup 18^F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. Methods: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with ^sup 18^F-RGD to evaluate α^sub v^β^sub 3^ integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by 13N-ammonia PET and MRI, respectively. Results: One week after MI, ^sup 18^F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 0.04, P < 0.001). At this time, ^sup 18^F-RGD uptake was associated with capillary density in histologic sections. Average ^sup 18^F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 ± 0.07 vs. 0.21 ± 0.05, P < 0.05). In a multivariable logistic regression analysis, low ^sup 18^F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). Conclusion: High levels of ^sup 18^FRGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that α^sub v^β^sub 3^ integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information. [PUBLICATION ABSTRACT]