Surface Properties and RF Performance of Vapor Diffused Nb₃Sn On NB After Sequential Anneals Below 1000 °C

Nb₃Sn is a next-generation superconducting material that can be used for future superconducting radiofrequency (SRF) accelerator cavities, promising better performance, cost reduction, and higher operating temperature than Nb. The Sn vapor diffusion method is currently the most preferred and successful technique to coat niobium cavities with Nb₃Sn. Among post-coating treatments to optimize the coating quality, higher temperature annealing without Sn is known to degrade Nb₃Sn because of Sn loss. We have investigated Nb₃Sn/Nb samples briefly annealed at 800-1000 °C, for 10 and 20 minutes to potentially improve the surface to enhance the performance of Nb₃Sn-coated cavities. Following the sample studies, a coated single-cell cavity was sequentially annealed at 900 °C and tested its performance each time, improving the cavity’s quality factor relatively. This paper summarizes the sample studies and discusses the RF test results from sequentially annealed SRF Nb₃Sn/Nb cavity

Fabrication and Testing of a Prototype RF-Dipole Crabbing Cavity

Crabbing cavities are essential in particle colliders to compensate the luminosity degradation due to beam collision at a crossing angle. The 952.6 MHz 2-cell rf-dipole crabbing cavity system was proposed for the Jefferson Lab Electron-Ion Collider to restore the head-on collisions of electron and proton bunches at the interaction point. A prototype cavity was designed and developed to demonstrate the performance of multi-cell rf-dipole structures. This paper presents the fabrication process and cold test results of the first 2-cell rf-dipole prototype cavity

Nb\u3csub\u3e3\u3c/sub\u3eSn Coating of Twin Axis Cavity for SRF Applications

The twin axis cavity with two identical accelerating beams has been proposed for energy recovery linac (ERL) applications. Nb3Sn is a superconducting material with a higher critical temperature and a higher critical field as compared to Nb, which promises a lower operating cost due to higher quality factors. Two niobium twin axis cavities were fabricated at JLab and were proposed to be coated with Nb3Sn. Due to their more complex geometry, the typical coating process used for basic elliptical cavi-ties needs to be improved to coat these cavities. This development advances the current coating system at JLab for coating complex cavities. Two twin axis cavities were coated recently for the first time. This contribution dis-cusses initial results from coating of twin axis cavities, RF testing and witness sample analysis with an overview of the current challenges towards high performance Nb3Sn coated twin axis cavities

Development and Performance of RFD Crab Cavity Prototypes for HL-LHC AUP

The US will be contributing to the HL-LHC upgrade at CERN with the fabrication and qualification of RFD crabbing cavities in the framework of the HL-LHC Accelerator Upgrade Project (AUP) managed by Fermilab. AUP received Critical Decision 3 (CD-3) approval by DOE in December 2020 launching the project into the production phase. The electro-magnetic design of the cavity was inherited from the LHC Accelerator Research Program (LARP) but needed to be revised to meet new project requirements and to prevent issues encountered during beam tests performed at CERN in the R&D phase. Two prototype cavities were manufactured in industry and cold tested. Challenges specific to the RFD cavity were the stringent interface tolerances, the pole symmetry and the higher-order-mode impedance spectrum. Chemical processing and heat treatments were performed initially at FNAL/ANL and are now being transferred to industry for the production phase. HOM dampers are manufactured and validated by JLAB. A summary of cold test results with and without HOM dampers is presented

Influence of the initial chemical conditions on the rational design of silica particles

The influence of the water content in the initial composition on the size of silica particles produced using the Stöber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical Stöber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Feeding Cues and Injected Nutrients Induce Acute Expression of Multiple Clock Genes in the Mouse Liver

The circadian clock is closely associated with energy metabolism. The liver clock can rapidly adapt to a new feeding cycle within a few days, whereas the lung clock is gradually entrained over one week. However, the mechanism underlying tissue-specific clock resetting is not fully understood. To characterize the rapid response to feeding cues in the liver clock, we examined the effects of a single time-delayed feeding on circadian rhythms in the liver and lungs of Per2::Luc reporter knockin mice. After adapting to a night-time restricted feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule on the last day. The phase of the liver clock was delayed in all groups with delayed feeding, whereas the lung clock remained unaffected. We then examined the acute response of clock and metabolism-related genes in the liver using focused DNA-microarrays. Clock mutant mice were bred under constant light to attenuate the endogenous circadian rhythm, and gene expression profiles were determined during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed a similarly acute response in hepatic clock gene expression caused by feeding wild type mice after an overnight fast. In addition to Per2 and Dec1, the expression of Per1 increased, and that of Rev-erbα decreased in the liver within 1 h of feeding after fasting, whereas none of these clock genes were affected in the lung. Moreover, an intraperitoneal injection of glucose combined with amino acids, but not either alone, reproduced a similar hepatic response. Our findings show that multiple clock genes respond to nutritional cues within 1 h in the liver but not in the lung

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Innate Immune Suppression Enables Frequent Transfection with RNA Encoding Reprogramming Proteins

BACKGROUND: Generating autologous pluripotent stem cells for therapeutic applications will require the development of efficient DNA-free reprogramming techniques. Transfecting cells with in vitro-transcribed, protein-encoding RNA is a straightforward method of directly expressing high levels of reprogramming proteins without genetic modification. However, long-RNA transfection triggers a potent innate immune response characterized by growth inhibition and the production of inflammatory cytokines. As a result, repeated transfection with protein-encoding RNA causes cell death. METHODOLOGY/PRINCIPAL FINDINGS: RNA viruses have evolved methods of disrupting innate immune signaling by destroying or inhibiting specific proteins to enable persistent infection. Starting from a list of known viral targets, we performed a combinatorial screen to identify siRNA cocktails that could desensitize cells to exogenous RNA. We show that combined knockdown of interferon-beta (Ifnb1), Eif2ak2, and Stat2 rescues cells from the innate immune response triggered by frequent long-RNA transfection. Using this technique, we were able to transfect primary human fibroblasts every 24 hours with RNA encoding the reprogramming proteins Oct4, Sox2, Klf4, and Utf1. We provide evidence that the encoded protein is active, and we show that expression can be maintained for many days, through multiple rounds of cell division. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that suppressing innate immunity enables frequent transfection with protein-encoding RNA. This technique represents a versatile tool for investigating expression dynamics and protein interactions by enabling precise control over levels and timing of protein expression. Our finding also opens the door for the development of reprogramming and directed-differentiation methods based on long-RNA transfection