Maximum Likelihood Estimation for Single Particle, Passive Microrheology Data with Drift

Volume limitations and low yield thresholds of biological fluids have led to widespread use of passive microparticle rheology. The mean-squared-displacement (MSD) statistics of bead position time series (bead paths) are either applied directly to determine the creep compliance [Xu et al (1998)] or transformed to determine dynamic storage and loss moduli [Mason & Weitz (1995)]. A prevalent hurdle arises when there is a non-diffusive experimental drift in the data. Commensurate with the magnitude of drift relative to diffusive mobility, quantified by a P\'eclet number, the MSD statistics are distorted, and thus the path data must be "corrected" for drift. The standard approach is to estimate and subtract the drift from particle paths, and then calculate MSD statistics. We present an alternative, parametric approach using maximum likelihood estimation that simultaneously fits drift and diffusive model parameters from the path data; the MSD statistics (and consequently the compliance and dynamic moduli) then follow directly from the best-fit model. We illustrate and compare both methods on simulated path data over a range of P\'eclet numbers, where exact answers are known. We choose fractional Brownian motion as the numerical model because it affords tunable, sub-diffusive MSD statistics consistent with typical 30 second long, experimental observations of microbeads in several biological fluids. Finally, we apply and compare both methods on data from human bronchial epithelial cell culture mucus.Comment: 29 pages, 12 figure

Pretenuring for Java

Pretenuring is a technique for reducing copying costs in garbage collectors. When pretenuring, the allocator places long-lived objects into regions that the garbage collector will rarely, if ever, collect. We extend previous work on profiling-driven pretenuring as follows. (1) We develop a collector-neutral approach to obtaining object lifetime profile information. We show that our collection of Java programs exhibits a very high degree of homogeneity of object lifetimes at each allocation site. This result is robust with respect to different inputs, and is similar to previous work on ML, but is in contrast to C programs, which require dynamic call chain context information to extract homogeneous lifetimes. Call-site homogeneity considerably simplifies the implementation of pretenuring and makes it more efficient. (2) Our pretenuring advice is neutral with respect to the collector algorithm, and we use it to improve two quite different garbage collectors: a traditional generational collector and an older-first collector. The system is also novel because it classifies and allocates objects into 3 categories: we allocate immortal objects into a permanent region that the collector will never consider, long-lived objects into a region in which the collector placed survivors of the most recent collection, and shortlived objects into the nursery, i.e., the default region. (3) We evaluate pretenuring on Java programs. Our simulation results show that pretenuring significantly reduces collector copying for generational and older-first collectors. 1

The Utilization of Yucca for the Maintenance of Cattle.

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Micro-heterogeneity metrics for diffusion in soft matter

Enhanced metrics to detect and quantify micro-heterogeneity from microbead tracking data in soft matter

Patient-reported outcomes of periacetabular osteotomy from the prospective ANCHOR cohort study

BACKGROUND: Current literature describing the periacetabular osteotomy (PAO) is mostly limited to retrospective case series. Larger, prospective cohort studies are needed to provide better clinical evidence regarding this procedure. The goals of the current study were to (1) report minimum 2-year patient-reported outcomes (pain, hip function, activity, overall health, and quality of life), (2) investigate preoperative clinical and disease characteristics as predictors of clinical outcomes, and (3) report the rate of early failures and reoperations in patients undergoing contemporary PAO surgery. METHODS: A large, prospective, multicenter cohort of PAO procedures was established, and outcomes at a minimum of 2 years were analyzed. A total of 391 hips were included for analysis (79% of the patients were female, and the average patient age was 25.4 years). Patient-reported outcomes, conversion to total hip replacement, reoperations, and major complications were documented. Variables with a p value of ≤0.10 in the univariate linear regressions were included in the multivariate linear regression. The backward stepwise selection method was used to determine the final risk factors of clinical outcomes. RESULTS: Clinical outcome analysis demonstrated major clinically important improvements in pain, function, quality of life, overall health, and activity level. Increasing age and a body mass index status of overweight or obese were predictive of improved results for certain outcome metrics. Male sex and mild acetabular dysplasia were predictive of lesser improvements in certain outcome measures. Three (0.8%) of the hips underwent early conversion to total hip arthroplasty, 12 (3%) required reoperation, and 26 (7%) experienced a major complication. CONCLUSIONS: This large, prospective cohort study demonstrated the clinical success of contemporary PAO surgery for the treatment of symptomatic acetabular dysplasia. Patient and disease characteristics demonstrated predictive value that should be considered in surgical decision-making. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain

Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels