Nanostructure Accelerators: Novel concept and path to its realization

TeV/m acceleration gradients using crystals as originally envisioned by R. Hofstadter, an early pioneer of HEP, have remained unrealizable. Fundamental obstacles that have hampered efforts on particle acceleration using bulk-crystals arise from collisional energy loss and emittance degradation in addition to severe beam disruption despite the favorable effect of particle channeling along interatomic planes in bulk. We aspire for the union of nanoscience with accelerator science to not only overcome these problems using nanostructured tubes to avoid direct impact of the beam on bulk ion-lattice but also to utilize the highly tunable characteristics of nanomaterials. We pioneer a novel surface wave mechanism in nanostructured materials with a strong electrostatic component which not only attains tens of TeV/m gradients but also has focusing fields. Under our initiative, the proof-of-principle demonstration of tens of TeV/m gradients and beam nanomodulation is underway. Realizable nanostructure accelerators naturally promise new horizons in HEP as well as in a wide range of areas of research that utilize beams of high-energy particles or photons.Comment: submission to Snowmass'21 Accelerator Frontie

Approaching Petavolts per meter plasmonics using structured semiconductors

A new class of strongly excited plasmonic modes that open access to unprecedented Petavolts per meter electromagnetic fields promise wide-ranging, transformative impact. These modes are constituted by large amplitude oscillations of the ultradense, delocalized free electron Fermi gas which is inherent in conductive media. Here structured semiconductors with appropriate concentration of n-type dopant are introduced to tune the properties of the Fermi gas for matched excitation of an electrostatic, surface "crunch-in" plasmon using readily available electron beams of ten micron overall dimensions and hundreds of picoCoulomb charge launched inside a tube. Strong excitation made possible by matching results in relativistic oscillations of the Fermi electron gas and uncovers unique phenomena. Relativistically induced ballistic electron transport comes about due to relativistic multifold increase in the mean free path. Acquired ballistic transport also leads to unconventional heat deposition beyond the Ohm's law. This explains the absence of observed damage or solid-plasma formation in experiments on interaction of conductive samples with electron bunches shorter than $\rm 10^{-13} seconds$. Furthermore, relativistic momentum leads to copious tunneling of electron gas allowing it to traverse the surface and crunch inside the tube. Relativistic effects along with large, localized variation of Fermi gas density underlying these modes necessitate the kinetic approach coupled with particle-in-cell simulations. Experimental verification of acceleration and focusing of electron beams modeled here using tens of Gigavolts per meter fields excited in semiconductors with $\rm 10^{18}cm^{-3}$ free electron density will pave the way for Petavolts per meter plasmonics.Comment: 16 pages, 10 figure

Long-term safety and efficacy of Eculizumab in Aquaporin-4 IgG-positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088–109

Nanostructure Accelerators: Novel concept and path to its realization

TeV/m acceleration gradients using crystals as originally envisioned by R. Hofstadter, an early pioneer of HEP, have remained unrealizable. Fundamental obstacles that have hampered efforts on particle acceleration using bulk-crystals arise from collisional energy loss and emittance degradation in addition to severe beam disruption despite the favorable effect of particle channeling along interatomic planes in bulk. We aspire for the union of nanoscience with accelerator science to not only overcome these problems using nanostructured tubes to avoid direct impact of the beam on bulk ion-lattice but also to utilize the highly tunable characteristics of nanomaterials. We pioneer a novel surface wave mechanism in nanostructured materials with a strong electrostatic component which not only attains tens of TeV/m gradients but also has focusing fields. Under our initiative, the proof-of-principle demonstration of tens of TeV/m gradients and beam nanomodulation is underway. Realizable nanostructure accelerators naturally promise new horizons in HEP as well as in a wide range of areas of research that utilize beams of high-energy particles or photons

Proximity biotinylation to define the local environment of the protein kinase A catalytic subunit in adrenal cells

Summary: Mutant protein kinase A catalytic subunit (PKAc) drives adrenal Cushing’s syndrome, though its signaling interactions remain unclear. This protocol details steps to use live-cell proximity labeling to identify subcellular compartments and proteins closely associated with variants of PKAc in human adrenal cells. We include instructions for clonal cell line generation, live biotin labeling of proximal proteins, isolation of biotinylated proteins, and sample processing for proteomic analysis using the biotin ligase miniTurbo with wild-type and mutant PKAc.1,2For complete details on the use and execution of this protocol, please refer to Omar et al. (2022).3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics