Quality Control System Response to Stochastic Growth of Amyloid Fibrils

We introduce a stochastic model describing aggregation of misfolded proteins and degradation by the protein quality control system in a single cell. In analogy with existing literature, aggregates can grow, nucleate and fragment stochastically. We assume that the quality control system acts as an enzyme that can degrade aggregates at different stages of the growth process, with an efficiency that decreases with the size of the aggregate. We show how this stochastic dynamics, depending on the parameter choice, leads to two qualitatively different behaviors: a homeostatic state, where the quality control system is stable and aggregates of large sizes are not formed, and an oscillatory state, where the quality control system periodically breaks down, allowing for the formation of large aggregates. We discuss how these periodic breakdowns may constitute a mechanism for the sporadic development of neurodegenerative diseases.Comment: 14 pages, 4 figures, submitte

Fundamental bounds on transmission through periodically perforated metal screens with experimental validation

This paper presents a study of transmission through arrays of periodic sub-wavelength apertures. Fundamental limitations for this phenomenon are formulated as a sum rule, relating the transmission coefficient over a bandwidth to the static polarizability. The sum rule is rigorously derived for arbitrary periodic apertures in thin screens. By this sum rule we establish a physical bound on the transmission bandwidth which is verified numerically for a number of aperture array designs. We utilize the sum rule to design and optimize sub-wavelength frequency selective surfaces with a bandwidth close to the physically attainable. Finally, we verify the sum rule and simulations by measurements of an array of horseshoe-shaped slots milled in aluminum foil.Comment: 10 pages, 11 figures. Updated Introduction and Conclusion

An Observational Registry Of Carotid Endarterectomy And Carotid Artery Stenting In Brazil: Study Protocol

Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. CEA has been considered the first-line treatment for carotid stenosis worldwide, and the safety and efficacy of CAS compared to CEA remains in question. Objective: The purpose of this study is to compare the practice and outcomes of CAS and CEA in a real-world setting within public university hospitals in Brazil. Methods: This study will be a prospective 5-year analysis of treatment for atherosclerotic carotid stenosis with CEA and CAS performed at 5 centers affiliated with the Vascular Study Group at public university hospitals in Brazil. The indications for the procedures will be determined by each surgeon's individual discretion, in accordance with preoperative risk evaluation. The primary outcome measures will be (1) any in-hospital stroke or death, and (2) any per-procedural stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery will be excluded from the study. Multivariate logistic regression will be performed to identify predictors of stroke or death in patients undergoing CEA and CAS. All tests of significance will be performed at the .05 level. This study was approved by the Committee of Ethics in Research at the University Hospital of Ribeirao Preto Medical School, and in all other participating institutions linked to National Research System and National Board of Health in Brazil (Process 15695/2011). Results: This study is currently in the recruitment phase, and the final patient is expected to be enrolled by the end of 2018. We hope to recruit approximately 800 patients to the study. Analyses will focus on primary end points for patients that are allocated to each treatment group. During the per-procedural period, the occurrence of the primary end point components (stroke, MI, or death) for CAS and CEA will be analyzed for symptomatic or asymptomatic subjects. Conclusions: The analyses of the primary endpoints (and all others variables of the study) are expected to be published in 2019 in a peer reviewed journal, and results will be presented at scientific meetings, with summary results published online. This study will obtain new data related to the quality of treatment for carotid disease in Brazil at the primary training centers of future vascular surgeons, but the initial data that will be obtained and published (with the outcomes and complications) are restricted to the first 30 days postprocedure. This time restriction limits the comparison of the results that relate to the main goal of treatment, which is to decrease the risk of stroke over 5 years. The purpose of the study group is to continue the monitoring of patient records, and evaluate the follow-up data in the 5 years following the initial evaluation. This study protocol will contribute very significantly to improving the care of patients with carotid disease, in addition to qualifying the level of assistance provided in public university hospitals in the state of Sao Paulo, Brazil.54Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paul

Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle. The main components from the IBA nozzle were implemented in the FLUKA MC code. We calibrated and verified the following entities to experimental measurements: range of pristine Bragg peaks (PBPs) and spread-out Bragg peaks (SOBPs), energy spread, lateral profiles, compensator range degradation, and absolute dose. We recalculated two patients with different field setups, comparing FLUKA vs. treatment planning system (TPS) dose, also obtaining LET and variable RBE doses. We achieved good agreement between FLUKA and measurements. The range differences between FLUKA and measurements were for the PBPs within ±0.9 mm (83% ≤ 0.5 mm), and for SOBPs ±1.6 mm (82% ≤ 0.5 mm). The differences in modulation widths were below 5 mm (79% ≤ 2 mm). The differences in the distal dose fall off (D80%–D20%) were below 0.5 mm for all PBPs and the lateral penumbras diverged from measurements by less than 1 mm. The mean dose difference (RBE = 1.1) in the target between the TPS and FLUKA were below 0.4% in a three-field plan and below 1.4% in a four-field plan. A dose increase of 9.9% and 7.2% occurred when using variable RBE for the two patients, respectively. We presented a method to recalculate DS proton plans in the FLUKA MC code. The implementation was used to obtain LET and variable RBE dose and can be used for investigating variable RBE for previously treated patients.publishedVersio

Herglotz functions and applications in electromagnetics

Herglotz functions inevitably appear in pure mathematics, mathematical physics, and engineering with a wide range of applications. In particular, they are the pertinent functions to model passive systems, and thus appear in modeling of electromagnetic phenomena in circuits, antennas, materials, and scattering. In this chapter, we review the basic theory of Herglotz functions and its applications to determine sum rules and physical bounds for passive systems.Peer reviewe

Haptic Transparency and Interaction Force Control for a Lower-Limb Exoskeleton

Controlling the interaction forces between a human and an exoskeleton is crucial for providing transparency or adjusting assistance or resistance levels. However, it is an open problem to control the interaction forces of lower-limb exoskeletons designed for unrestricted overground walking. For these types of exoskeletons, it is challenging to implement force/torque sensors at every contact between the user and the exoskeleton for direct force measurement. Moreover, it is important to compensate for the exoskeleton's whole-body gravitational and dynamical forces, especially for heavy lower-limb exoskeletons. Previous works either simplified the dynamic model by treating the legs as independent double pendulums, or they did not close the loop with interaction force feedback. The proposed whole-exoskeleton closed-loop compensation (WECC) method calculates the interaction torques during the complete gait cycle by using whole-body dynamics and joint torque measurements on a hip-knee exoskeleton. Furthermore, it uses a constrained optimization scheme to track desired interaction torques in a closed loop while considering physical and safety constraints. We evaluated the haptic transparency and dynamic interaction torque tracking of WECC control on three subjects. We also compared the performance of WECC with a controller based on a simplified dynamic model and a passive version of the exoskeleton. The WECC controller results in a consistently low absolute interaction torque error during the whole gait cycle for both zero and nonzero desired interaction torques. In contrast, the simplified controller yields poor performance in tracking desired interaction torques during the stance phase.Comment: 17 pages, 12 figure

A case-control study of linear energy transfer and relative biological effectiveness related to symptomatic brainstem toxicity following pediatric proton therapy

Background and purpose A fixed relative biological effectiveness (RBE) of 1.1 (RBE1.1) is used clinically in proton therapy even though the RBE varies with properties such as dose level and linear energy transfer (LET). We therefore investigated if symptomatic brainstem toxicity in pediatric brain tumor patients treated with proton therapy could be associated with a variable LET and RBE. Materials and methods 36 patients treated with passive scattering proton therapy were selected for a case-control study from a cohort of 954 pediatric brain tumor patients. Nine children with symptomatic brainstem toxicity were each matched to three controls based on age, diagnosis, adjuvant therapy, and brainstem RBE1.1 dose characteristics. Differences across cases and controls related to the dose-averaged LET (LETd) and variable RBE-weighted dose from two RBE models were analyzed in the high-dose region. Results LETd metrics were marginally higher for cases vs. controls for the majority of dose levels and brainstem substructures. Considering areas with doses above 54 Gy(RBE1.1), we found a moderate trend of 13% higher median LETd in the brainstem for cases compared to controls (P =.08), while the difference in the median variable RBE-weighted dose for the same structure was only 2% (P =.6). Conclusion Trends towards higher LETd for cases compared to controls were noticeable across structures and LETd metrics for this patient cohort. While case-control differences were minor, an association with the observed symptomatic brainstem toxicity cannot be ruled out.publishedVersio

Musik for de Gusind hiem

Collection that includes six pieces for piano and one for voice with piano accompaniment. Sold by C. Rabe. Plate numbers 2644, 314, 1585, 2645, 129, 2643, 2646. Pieces include: Nocturne, Carmencita-Polka, A F Erotikon , Chant du Printemps, Ned ad Floden Den Fluss hinab, Andante, and Haandvaerkersvendens sang Gjennem Skoven. Published between 1895 and 1897.https://scholarexchange.furman.edu/krohn-album2/1006/thumbnail.jp