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Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility are collaborating on the design and construction of the next Electron Ion Collider (EIC) to be built at BNL. The EIC is a unique high-energy, high-luminosity, polarized electron-proton/ion collider. The EIC accelerator complex needs about 10 new rf and SRF systems with frequencies spanning 24 MHz to 1773 MHz, requiring more than 60 new high-power fundamental power couplers (FPCs). These couplers will operate in either pulsed mode or continuous wave mode with peak traveling wave power ranging from 10 s to 380 kW. Here we present our design for a 1-MW broadband rf window suitable for EIC rf and SRF systems with operating frequencies up to 591 MHz. This design takes advantage of the numerous synergies between the various rf and SRF systems to make it broadly applicable. The rf window design criteria are based on the requirement for the 591-MHz electron storage ring (ESR) SRF cavities, as it will operate at both the highest traveling wave power and the highest peak power over the EICrf/SRFcomplex. The results presented will detail the FPC power requirement, rf window choices, design criteria, and multiphysics performance in the most critical application, the ESR SRF cavity, and how the rf window design applies to other EICrf/SRFsystems.

We present a rare case of fistulation of a dermoid cyst with the transverse colon. We illustrate how an infected dermoid cyst can be diagnosed as an appendix abscess although the management of these is quite different. The general surgeon should be aware of this as a differential diagnosis for an appendix abscess.

Superconducting accelerators are large and complex systems requiring a central refrigerator and distributed transfer systems to supply 2-4 K liquid helium. Stand-alone, cryocooler-based systems are of interest both to scientific facilities and for industrial applications, as they do not require large cryogenic infrastructure and trained specialists for operation. Presented here is our approach to the challenge of using low-power commercially avail-able cryocoolers to operate niobium superconducting resonators at 4.4 K with high accelerating voltages and several watts of heating. Engineering and design results from RadiaBeam Systems, collaborating with Argonne National Laboratory, for a stand-alone liquid-cooled cryomodule with 10 Watts of 4.4 K cooling capacity housing a 72.75 MHz quarter-wave resonator operating at 2 MV for synchronous ions travelling at 7.7% of speed of light will be discussed.

Quantum computers (QC), if realized, could disrupt many computationally intense fields of science. The building block element of a QC is a quantum bit (qubit). Qubits enable the use of quantum superposition and multi-state entanglement in QC calculations, allowing a QC to simultaneously perform millions of computations at once. However, quantum states stored in a qubit degrade with decreased quality factors and interactions with the environment. One technical solution to improve qubit lifetimes and network interactions is a circuit comprised of a Josephson junction-based qubit located inside of a high Q-factor superconducting 3D cavity.It is known that niobium resonators can reach Q0>1011. However, existing cavity geometries are optimized for particle acceleration rather than hosting qubits. RadiaBeam Technologies, in collaboration with Argonne National Laboratory and The University of Chicago, has developed a niobium superconducting radio frequency quarter-wave resonant cavity (QWR) for quantum computation. A 6 GHz QWR was optimized to include tapering of the inner and outer conductors, a toroidal shape for the resonator shorting plane, and an inner conductor tip to reduce parasitic capacitance. In this paper, we present the results of the resonator design optimization, fabrication, processing, and testing.

Argonne National Laboratory has developed and is implementing a novel 2 K superconducting cavity cryomodule operating at 162.5 MHz. This cryomodule is designed for the acceleration of 2 mA H- proton beams from 2.1 to 10 MeV as part of the Fermilab Proton Improvement Project-II (PIP-II). This work is an evolution of techniques recently implemented in two previous heavy-ion accelerator cryomodules now operating at Argonne National Laboratory. The 2 K cryomodule is comprised of 8 half-wave cavities operated in the continuous wave mode with 8 superconducting magnets, one in front of each cavity. All of the solenoids and cavities operate off of a single gravity fed 2 K helium cryogenic system expected to provide up to 50 W of 2 K cooling. Here we review the mechanical design of the cavities and cryomodule which were developed using methods similar to those required in the ASME Boiler and Pressure Vessel Code. This will include an overview of the cryomodule layout, the alignment of the accelerator components via modifications of the cryomodule vacuum vessel and provide a status report on the cryomodule assembly.

Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery—Arf1, IRSp53 and actin—and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route. Moreno-Layseca et al. identify Swip1 as an integrin-specific endocytic adaptor controlling the dynamics of integrin adhesion complexes as well as the migration and invasion of breast cancer cells.

Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability. Fingolimod can cause undesirable effects as a result of its interaction with other S1PR subtypes, which are expressed in diverse tissues, including cardiac myocytes. As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303. Data from phase II trials and early results from phase III studies have been promising and will be presented in this review. Of special interest are results from the EXPAND study of siponimod, which suggest a potential role for S1PR modulators in secondary progressive MS.

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Suspension of therapy is followed by rebound of viral loads to high, pre-therapy levels. However, there is significant heterogeneity in speed of rebound, with some rebounds occurring within days, weeks, or sometimes years. We present a stochastic mathematical model to gain insight into these post-treatment dynamics, specifically characterizing the dynamics of short term viral rebounds (≤ 60 days). Li et al. (2016) report that the size of the expressed HIV reservoir, i.e., cell-associated HIV RNA levels, and drug regimen correlate with the time between ART suspension and viral rebound to detectable levels. We incorporate this information and viral rebound times to parametrize our model. We then investigate insights offered by our model into the underlying dynamics of the latent reservoir. In particular, we refine previous estimates of viral recrudescence after ART interruption by accounting for heterogeneity in infection rebound dynamics, and determine a recrudescence rate of once every 2-4 days. Our parametrized model can be used to aid in design of clinical trials to study viral dynamics following analytic treatment interruption. We show how to derive informative personalized testing frequencies from our model and offer a proof-of-concept example. Our results represent first steps towards a model that can make predictions on a person living with HIV (PLWH)'s rebound time distribution based on biomarkers, and help identify PLWH with long viral rebound delays.

Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.

Working memory (WM) span tasks-and in particular, counting span, operation span, and reading span tasks-are widely used measures of WM capacity. Despite their popularity, however, there has never been a comprehensive analysis of the merits of WM span tasks as measurement tools. Here, we review the genesis of these tasks and discuss how and why they came to be so influential. In so doing, we address the reliability and validity of the tasks, and we consider more technical aspects of the tasks, such as optimal administration and scoring procedures. Finally, we discuss statistical and methodological techniques that have commonly been used in conjunction with WM span tasks, such as latent variable analysis and extreme-groups designs.