Publications by authors named "Fredrickson E"

Adolescence is a natural time for sexual exploration; developmentally-appropriate sexual education is essential to promote healthy behaviors and prevent long-term morbidity. Adolescents may confide in their primary care clinicians, who are responsible for providing information and access to evidence-based care including family planning, contraception, and abortion. Clinicians are essential in sexually transmitted infection prevention, screening, treatment, risk mitigation, and harm reduction for sexually active adolescents.

View Article and Find Full Text PDF

Mutation analysis provides confirmation of a clinical and radiological diagnosis of thanatophoric dysplasia types I and II (TD I and II). We developed a single multiplexed PCR and a single-nucleotide extension (SNE) assay to identify 14 common mutations causing 99% of TD I and TD II, including the challenging three adjacent mutations in the stop codon of exon 18 of the FGFR3 gene. The assay design also provides a solution for resolving SNE PCR product sizing using performance optimized polymer-7.

View Article and Find Full Text PDF

Motivation: Detection of germline variants in next-generation sequencing data is an essential component of modern genomics analysis. Variant detection tools typically rely on statistical algorithms such as de Bruijn graphs or Hidden Markov models, and are often coupled with heuristic techniques and thresholds to maximize accuracy. Despite significant progress in recent years, current methods still generate thousands of false-positive detections in a typical human whole genome, creating a significant manual review burden.

View Article and Find Full Text PDF

Purpose: Pathways and Resources for Engagement and Participation (PREP) is an intervention to optimise individuals' participation by building problem-solving capacity and addressing environmental barriers. We investigated the feasibility of implementing PREP with young adults (18-30 years) with complex disability in Australia.

Materials And Methods: Explanatory sequential mixed methods study in three stages.

View Article and Find Full Text PDF

Background And Objectives: Family physicians are the most common health professional providing rural obstetric (OB) care, but the number of family physicians practicing OB is declining. To address rural/urban disparities in parental and child health, family medicine must provide robust OB training to prepare family physicians to care for parent-newborn dyads in rural communities. This mixed-methods study aimed to inform policy and practice solutions.

View Article and Find Full Text PDF

Background: Genetic disorders contribute to significant morbidity and mortality in critically ill newborns. Despite advances in genome sequencing technologies, a majority of neonatal cases remain unsolved. Complex structural variants (SVs) often elude conventional genome sequencing variant calling pipelines and will explain a portion of these unsolved cases.

View Article and Find Full Text PDF

Purpose: Non-ambulant adults with cerebral palsy are at risk of developing asymmetry affecting thoracic cage, pelvis and hips. The primary aim of this study was to establish intra-rater and inter-rater reliability of the Goldsmith Indices of Body Symmetry in non-ambulant adults with cerebral palsy. The secondary aim was to establish comparative data for the Goldsmith Indices of Body Symmetry in healthy adults.

View Article and Find Full Text PDF

Protein misfolding is a recurring phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should they persist. To counter this burden, cells have evolved protein quality control (PQC) mechanisms that manage misfolded proteins. Two classes of systems that function in PQC are chaperones that aid in protein folding and ubiquitin-protein ligases that ubiquitinate misfolded proteins for proteasomal degradation.

View Article and Find Full Text PDF

An operationally simple nickel-catalyzed hydroarylation reaction for alkynes is described. This three-component coupling reaction utilizes commercially available alkynes and aryl bromides, along with water and Zn. An air-stable and easily synthesized Ni(II) precatalyst is the only entity used in the reaction that is not commercially available.

View Article and Find Full Text PDF

Eukaryotic cells employ the ribosome-associated quality control complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, Rqc1p, and Rqc2p. Upon ribosome stalling and splitting, the RQC assembles on the 60S species containing unreleased peptidyl-tRNA (60S:peptidyl-tRNA).

View Article and Find Full Text PDF

Vms1 translocates to damaged mitochondria in response to stress, whereupon its binding partner, Cdc48, contributes to mitochondrial protein homeostasis. Mitochondrial targeting of Vms1 is mediated by its conserved mitochondrial targeting domain (MTD), which, in unstressed conditions, is inhibited by intramolecular binding to the Vms1 leucine-rich sequence (LRS). Here, we report a 2.

View Article and Find Full Text PDF

In this Letter we present data from experiments on the National Spherical Torus Experiment Upgrade, where it is shown for the first time that small amounts of high pitch-angle beam ions can strongly suppress the counterpropagating global Alfvén eigenmodes (GAE). GAE have been implicated in the redistribution of fast ions and modification of the electron power balance in previous experiments on NSTX. The ability to predict the stability of Alfvén modes, and developing methods to control them, is important for fusion reactors like the International Tokamak Experimental Reactor, which are heated by a large population of nonthermal, super-Alfvénic ions consisting of fusion generated α's and beam ions injected for current profile control.

View Article and Find Full Text PDF

A compact and multi-view solid state neutral particle analyzer (SSNPA) diagnostic based on silicon photodiode arrays has been successfully tested on the National Spherical Torus Experiment-Upgrade. The SSNPA diagnostic provides spatially, temporally, and pitch-angle resolved measurements of fast-ion distribution by detecting fast neutral flux resulting from the charge exchange (CX) reactions. The system consists of three 16-channel subsystems: t-SSNPA viewing the plasma mid-radius and neutral beam (NB) line #2 tangentially, r-SSNPA viewing the plasma core and NB line #1 radially, and p-SSNPA with no intersection with any NB lines.

View Article and Find Full Text PDF

Protein quality control (PQC) is a critical process wherein misfolded or damaged proteins are cleared from the cell to maintain protein homeostasis. In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiquitin-proteasome system. In the ubiquitin-proteasome system, ubiquitin-conjugating enzymes and ubiquitin ligases append polyubiquitin chains onto misfolded protein substrates signaling for their degradation.

View Article and Find Full Text PDF

An energy-channeling mechanism is proposed to explain flattening of the electron temperature profiles at a high beam power in the beam-heated National Spherical Torus Experiment (NSTX). Results of self-consistent simulations of neutral-beam-driven compressional Alfvén eigenmodes (CAEs) in NSTX are presented that demonstrate strong coupling of CAEs to kinetic Alfvén waves at the Alfvén resonance location. It is suggested that CAEs can channel energy from the beam ions to the location of the resonant mode conversion at the edge of the beam density profile, modifying the energy deposition profile.

View Article and Find Full Text PDF

Prairie dogs (Cynomys spp.) have been eliminated from over 95% of their historic range in large part from direct eradication campaigns to reduce their purported competition with cattle for forage. Despite the longstanding importance of this issue to grassland management and conservation, the ecological interactions between cattle and prairie dogs have not been well examined.

View Article and Find Full Text PDF

The application of static magnetic field perturbations to a tokamak plasma is observed to alter the dynamics of high-frequency bursting Alfvén modes that are driven unstable by energetic ions. In response to perturbations with an amplitude of δB/B∼0.01 at the plasma boundary, the mode amplitude is reduced, the bursting frequency is increased, and the frequency chirp is smaller.

View Article and Find Full Text PDF

New observations of the formation and dynamics of long-lived impurity-induced helical "snake" modes in tokamak plasmas have recently been carried out on Alcator C-Mod. The snakes form as an asymmetry in the impurity ion density that undergoes a seamless transition from a small helically displaced density to a large crescent-shaped helical structure inside q<1, with a regularly sawtoothing core. The observations show that the conditions for the formation and persistence of a snake cannot be explained by plasma pressure alone.

View Article and Find Full Text PDF

Ubiquitin-protein ligases (E3s) that ubiquitinate substrates for proteasomal degradation are often in the position of ubiquitinating themselves due to interactions with a charged ubiquitin-conjugating enzyme (E2). This can mediate the E3's proteasomal degradation. Many E3s have evolved means to avoid autoubiquitination, including protection by partner or substrate binding, preventative modifications, and deubiquitinating enzyme reversal of ubiquitination.

View Article and Find Full Text PDF

Misfolded proteins present an escalating deleterious challenge to cells over the course of their lifetime. One mechanism the cell possesses to prevent misfolded protein accumulation is their destruction by protein quality control (PQC) degradation systems. In eukaryotes, PQC degradation typically proceeds via multiple ubiquitin-protein ligases that act throughout the cell to ubiquitinate misfolded proteins for proteasome degradation.

View Article and Find Full Text PDF

Mixed-species stocking can foster sound landscape management while offering economic and ecological advantages compared with mono-species stocking. Producers contemplating a mixed-species enterprise should reflect on several considerations before implementing this animal management strategy. Factors applicable to a particular producer's landscape must be considered together with goals and economic constraints before implementing mixed-species stocking.

View Article and Find Full Text PDF

Eukaryotic ribosome biogenesis requires hundreds of trans-acting factors and dozens of RNAs. Although most factors required for ribosome biogenesis have been identified, little is known about their regulation. Here, we reveal that the yeast deubiquitinating enzyme Ubp10 is localized to the nucleolus and that ubp10Δ cells have reduced pre-rRNAs, mature rRNAs, and translating ribosomes.

View Article and Find Full Text PDF

Misfolded proteins are continuously produced in the cell and present an escalating detriment to cellular physiology if not managed effectively. As such, all organisms have evolved mechanisms to address misfolded proteins. One primary way eukaryotic cells handle the complication of misfolded proteins is by destroying them through the ubiquitin-proteasome system.

View Article and Find Full Text PDF

This paper describes techniques for measuring halo currents, and their associated toroidal peaking, in the National Spherical Torus Experiments [M. Ono et al., Nucl.

View Article and Find Full Text PDF

Protein quality control (PQC) degradation protects the cell by preventing the toxic accumulation of misfolded proteins. In eukaryotes, PQC degradation is primarily achieved by ubiquitin ligases that attach ubiquitin to misfolded proteins for proteasome degradation. To function effectively, PQC ubiquitin ligases must distinguish misfolded proteins from their normal counterparts by recognizing an attribute of structural abnormality commonly shared among misfolded proteins.

View Article and Find Full Text PDF