Scale Domain Research Articles

Nutrient Signaling-Dependent Quaternary Structure Remodeling Drives the Catalytic Activation of metazoan PASK.

The Per-Arnt-Sim (PAS) domains are characterized by diverse sequences and feature tandemly arranged PAS and PAS-associated C-terminal (PAC) motifs that fold seamlessly to generate the metabolite-sensing PAS domain. Here, using evolutionary scale sequence, domain mapping, and deep learning-based protein structure analysis, we deconstructed the sequence-structure relationship to unearth a novel example of signal-regulated assembly of PAS and PAC subdomains in metazoan PAS domain-regulated kinase (PASK). By comparing protein sequence, domain architecture, and computational protein models between fish, bird, and mammalian PASK orthologs, we propose the existence of previously unrecognized third PAS domain of PASK (PAS-C) formed through long-range intramolecular interactions between the N-terminal PAS fold and the C-terminal PAC fold. We experimentally validated this novel structural design using residue-level cross-linking assays and showed that the PAS-C domain assembly is nutrient-responsive. Furthermore, by combining structural phylogeny approaches with residue-level cross-linking, we revealed that the PAS-C domain assembly links nutrient sensing with quaternary structure reorganization in PASK, stabilizing the kinase catalytic core of PASK. Thus, PAS-C domain assembly likely integrates environmental signals, thereby relaying sensory information for catalytic control of the PASK kinase domain. In conclusion, we theorize that during their horizontal transfer from bacteria to multicellular organisms, PAS domains gained the capacity to integrate environmental signals through dynamic modulation of PAS and PAC motif interaction, adding a new regulatory layer suited for multicellular systems. We propose that metazoan PAS domains are likely to be more dynamic in integrating sensory information than previously considered, and their structural assembly could be targeted by regulatory signals and exploited to develop therapeutic strategies.

Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study.

Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown. This study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD. Participants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants' smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age. The CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P<.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P<.001 in all cases). These findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change.

Cause-and-effect chain analysis of combustion cyclic variability in a spark-ignition engine using large-eddy simulation, Part I: From tumble compression to flame initiation

Understanding, modeling, and reducing the cycle-to-cycle variability (CCV) of combustion in internal combustion engines (ICE) is a critical challenge to design engines of high efficiency and low emissions. A high level of CCV may contribute to partial burn, misfire, and knock in extreme engine cycles, which affects engine performance and eventually damages the engine. The origins of CCV have been studied both experimentally and numerically, and the variability of in-cylinder aerodynamics is recognized as one of the most important sources of CCV. However, a detailed and quantitative explanation of how in-cylinder flow CCV is generated is not yet clear. The objective of the present study is to develop a methodology to localize inside the chamber of a spark-ignition engine (SIE) the origins of flow variabilities and to identify some driving mechanisms leading to combustion variabilities. Multi-cycle wall-modeled large-eddy simulations (LES) for the TU Darmstadt optical engine under fired conditions are performed using the CFD solver Converge 3.0. The evolution of organized large-scale structures and the small-scale turbulence of the in-cylinder flow are analyzed using a developed methodology that includes the empirical mode decomposition (EMD) method adapted for 2D and 3D flow fields, and a vortex identification tool Γ3p. The contributions of different parts of the flow to CCV are quantified. In Part I of this work, the LES framework is validated against experimental data, and CCV of large-scale structures is characterized at spark timing. In Part II, the overall flow development during compression and intake strokes are quantitatively analyzed, and links are built between different engine phases to establish the cause-and-effect chain. Other CCV factors, such as spray injection and exhaust gas recirculation, are not included in the current study. However, the developed methodology for in-cylinder flow analysis could be used in studies on other engine configurations to improve the development of engine designs.Novelty and significance statementIn this work, the cycle-to-cycle variability (CCV) of combustion in a spark ignition engine is investigated to give a deeper understanding of CCV generation. The present study focuses on CCV caused by the stochastic nature of internal turbulent flow structures. LES approach is chosen due to its ability to capture CCV. The LES methodology was validated in a motored case in Ding et al. (2023). In the present study, it is validated in a reactive case against experimental in-cylinder pressures and velocity fields.A first novelty is the application of EMD methods combined with topology-based techniques to reactive LES results to characterize flow structures of different scales in the three-dimensional domain and to quantify separately their impacts on combustion.A second novelty and important finding is that a link is established between the combustion speed and the tumble formation and destabilization near BDC.Throughout our analyses in Part I and II, starting from the spark-ignition timing and going back to the early intake phase, a cause-and-effect chain is finally established between the development of in-cylinder flow and the combustion variability.

Improvement in Measures of Quality of Life and Symptoms of Anxiety and Depression in Patients with Severe Alopecia Areata Achieving Sustained Scalp Hair Regrowth with Baricitinib.

Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials. This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics. In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104. This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.

Magnetoelectric coupling at the domain level in polycrystalline hexagonal ErMnO3

We explore the impact of a magnetic field on the ferroelectric domain pattern in polycrystalline hexagonal ErMnO3 at cryogenic temperatures. Utilizing piezoelectric force microscopy measurements at 1.65 K, we observe modifications of the topologically protected ferroelectric domain structure induced by the magnetic field. These alterations likely result from strain induced by the magnetic field, facilitated by intergranular coupling in polycrystalline multiferroic ErMnO3. Our findings give insights into the interplay between electric and magnetic properties at the domain scale and represent a so far unexplored pathway for manipulating topologically protected ferroelectric vortex patterns in hexagonal manganites.

Translation, adaptation, and cross-cultural validation of the CDQ-24 scale in patients with primary blepharospasm under botulinum toxin treatment, pilot test

BackgroundBenign essential blepharospasm (BEB) is the most common adult-onset focal facial dystonia and its treatment of choice is periodic application of botulinum toxin (BtA). It has a higher incidence in middle and late adulthood, especially in women between 40 and 60 years of age. ObjectiveTo carry out the translation and cross-cultural adaptation of the CDQ24 questionnaire in its Spanish version in patients diagnosed with BEB who have been treated with BtA in an ophthalmologic center in Bogotá - Colombia. Materials and methodsPilot test of validation study and adaptation of a scale assembled in a prospective cohort of the CDQ24 instrument to Spanish in adult patients with primary blepharospasm treated with botulinum toxin in Bogota, Colombia. ResultsWe obtained a sample of 26 patients to whom the instrument was applied after translation and retranslation of the original document, composed of 19 (73%) women with a median age of 64.5 years; the average time to answer the survey was 4.93 min. The internal consistency of the scale evaluated by Cronbach's Alpha had a total score of 0.78. Criterion validity between the CDQ24 scale and the WHOQOL-BREF quality of life scale was determined by determining correlation between the Emotional Well-Being and Phsychological domains of both scales. ConclusionsThe translation and cross-cultural adaptation of the CDQ-24 scale into Spanish allowed the applicability of the instrument to the Spanish-speaking population during the pilot test, which allows us to continue the relevant studies in the study population.

ROSE: Multi-level super-resolution-oriented semantic embedding for 3D microvasculature segmentation from low-resolution images

Current state-of-the-art segmentation methods often require high-resolution input to attain the high performance, which pushes the limit of data acquisition and brings large computation budgets. Instead, we present an end-to-end deep learning-based method, ROSE, for robust and precise segmentation of high-quality 3D super-resolution (SR) microvasculatures from low-resolution (LR) images as input, which can transform data from the LR imaging domain to the SR semantic domain (cross different modalities and scales). More specifically, a multi-tasking two-stream deep learning framework is proposed to learn the high-fidelity microvasculature SR image and semantic hybrid features simultaneously. During the proposed joint learning process, the high-resolution features of microvasculatures are further enhanced by the learned fine-grained structural/textural features from the microvasculature SR stream with a multi-level embedding scheme through the oriented feature aggregation at different fusion stages. In the constructed joint multi-level hybrid embedding spaces, the instance semantic embedding and the SR imaging embedding can be connected and integrated synergistically. We have conducted extensive experiments using public and real patient micro-cerebrovascular image datasets and compare our framework with traditional 3D vessel segmentation methods and the other state-of-the-art in deep learning. This robust and precise microvascular visualization in different brain regions by our method demonstrates its potential impact in magnetic resonance (MR) angiography and venography for the diagnosis of microvascular disease.

Multifractal detrended fluctuation analysis on the fracture surface of polycarbonate and acrylonitrile-butadiene-styrene alloy

Multifractal detrended fluctuation analysis (MF-DFA) has been carried out to evaluate the multifractal properties of the fracture morphology for Polycarbonate (PC) and Acrylonitrile-butadiene-styrene (ABS) alloy, and the relationship between the long-range correlation parameter of the samples fracture - Hurst exponent and fractal dimension was explored and analyzed. The results suggest that the existence of multifractal properties within the micrometer scale domain we investigated for the fracture surface of PC/ABS alloy samples. The Hurst exponent and fractal dimension can both be used to measure and characterize the fracture surface morphology of the PC/ABS alloys. As the content of compatibilizer PP-g-MAH increased, the tensile strength of PC/ABS alloy decreased, the fracture surface peaks tend to dominate, the Hurst exponent increased, the fractal dimension decreased, and its strength retention rate increases, displaying persistence.

Satisfaction With and Adherence to Off-Label Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis: Results of a Web-Based Survey in the United States.

We assessed satisfaction with and adherence to off-label corticosteroids in patients with eosinophilic esophagitis (EoE) in the United States. EoE is a chronic inflammatory disease for which there are currently no US Food and Drug Administration-approved swallowed topical corticosteroids. This noninterventional, cross-sectional, web-based survey included caregivers of adolescents (aged 11 to 17 y) and adults (aged 18 years or older) with a self-reported [or caregiver-reported (adolescents)] physician diagnosis of EoE who were receiving corticosteroids. Participants were recruited through 2 nonprofit, patient advocacy groups. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used to assess satisfaction across effectiveness, convenience, and global satisfaction domains (scale: 1 to 100 per domain); higher scores indicated greater satisfaction. The 4-item Morisky Green Levine Medication Adherence Scale (MGL-4) was used to assess adherence; an MGL-4 score of <3 indicated adherence. Participants also reported reasons for nonadherence. Overall, 201 participants (caregivers of adolescents, n=98; adults, n=103) were included in this study. Mean TSQM-9 scores indicated low satisfaction with off-label corticosteroids across all 3 satisfaction domains in adolescents (≤61.1) and adults (≤55.7). Slightly fewer adolescents (37.1%) than adults (40.8%) were considered adherent. Forgetfulness was the most frequently reported reason for nonadherence; some patients chose not to take their medications, owing to poor palatability (adolescents), difficulty taking medications at specific times (adults), or feeling depressed/overwhelmed (adolescents and adults). Satisfaction with and adherence to off-label corticosteroids were low in this web-based survey of adolescents and adults with EoE in the United States.

Ambush strategy enhances organisms’ performance in rock–paper–scissors games

We study a five-species cyclic system wherein individuals of one species strategically adapt their movements to enhance their performance in the spatial rock–paper–scissors game. Environmental cues enable the awareness of the presence of organisms targeted for elimination in the cyclic game. If the local density of target organisms is sufficiently high, individuals move towards concentrated areas for direct attack; otherwise, they employ an ambush tactic, maximising the chances of success by targeting regions likely to be dominated by opponents. Running stochastic simulations, we discover that the ambush strategy enhances the likelihood of individual success compared to direct attacks alone, leading to uneven spatial patterns characterised by spiral waves. We compute the autocorrelation function and measure how the ambush tactic unbalances the organisms’ spatial organisation by calculating the characteristic length scale of typical spatial domains of each species. We demonstrate that the threshold for local species density influences the ambush strategy’s effectiveness, while the neighbourhood perception range significantly impacts decision-making accuracy. The outcomes show that long-range perception improves performance by over 60%, although there is potential interference in decision-making under high attack triggers. Understanding how organisms’ adaptation their environment enhances their performance may be helpful not only for ecologists, but also for data scientists, aiming to improve artificial intelligence systems.

Transcription factor shapes chromosomal conformation and regulates gene expression in bacterial adaptation.

Genomic mutations allow bacteria to adapt rapidly to adverse stress environments. The three-dimensional conformation of the genome may also play an important role in transcriptional regulation and environmental adaptation. Here, using chromosome conformation capture, we investigate the high-order architecture of the Zymomonas mobilis chromosome in response to genomic mutation and ambient stimuli (acetic acid and furfural, derived from lignocellulosic hydrolysate). We find that genomic mutation only influences the local chromosome contacts, whereas stress of acetic acid and furfural restrict the long-range contacts and significantly change the chromosome organization at domain scales. Further deciphering the domain feature unveils the important transcription factors, Ferric uptake regulator (Fur) proteins, which act as nucleoid-associated proteins to promote long-range (>200 kb) chromosomal communications and regulate the expression of genes involved in stress response. Our work suggests that ubiquitous transcription factors in prokaryotes mediate chromosome organization and regulate stress-resistance genes in bacterial adaptation.

Teachers' Perspectives on Public School Principals' Instructional Leadership Practices: An Assessment Using the Hallinger Scale

Teachers' Perspectives on Public School Principals' Instructional Leadership Practices: An Assessment Using the Hallinger Scale

Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Authentic Behavior and Job Satisfaction among Child Welfare Caseworkers.

This study was designed to investigate the relationship between authentic behavior and job satisfaction among child welfare caseworkers in Pennsylvania. Confirmatory factor analysis was conducted to validate the domains of the Authentic Behavior Scale (balanced processing, relational transparency, and internalized morality) and Job Satisfaction Scale, and the results provided consistent support for the factorial structure of the scales across child welfare caseworkers. The findings of this study revealed a positive correlation between authentic behavior and job satisfaction. To further explore this relationship, a path model was developed that included the elements of authentic behavior, job satisfaction, and demographic variables. The results indicated an association between the type of agency and internalized morality, impacting job satisfaction. Private workers showed a higher level of authentic behavior compared with public workers, with authentic behavior associated with greater job satisfaction. The findings suggest that authentic behavior can play a crucial role in social work practice and warrants considerable attention.

Processing and Evaluation of Bio-Based Paramylon Ester/Poly(butylene succinate) Blends for Industrial Applications

Poly(butylene succinate) (PBS) was melt-blended with paramylon based mixed ester, paramylon propionate hexanoate (PaPrHe) and characterized for its morphology, thermal and mechanical properties. The PBS/PaPrHe blends were found to be immiscible throughout the loading range of PaPrHe (10–90 wt%), with individual glass transition peaks. Due to the immiscibility, there was phase separation observed in the bulk, evident by sea-island morphology. However, further observation of the micro-structure revealed that, in low PaPrHe loading (10–30 wt%), there was a micron to sub-micron order distribution of PBS particles and partially miscible PBS/PaPrHe phase. On increasing the PaPrHe to 50 wt% and beyond, the sub-micron scale domains fused to form a co-continuous morphology. As a result, the impact strength of PBS increased from 6.6 to 16.4 kJ/m2 in the 50/50 blend. Under tensile loading, the strength at break and elongation decreased after the introduction of less-flexible PaPrHe particles in the blend. This could be countered by uniaxially stretching the blended films with 10–30 wt% PaPrHe, after which the tensile strength increased by up to 380% (from 33–52 MPa to 165–200 MPa) compared to the unstretched films, attributable to the increased degree of orientation of the molecular chains. In terms of thermal processability, all the blend ratios had high thermal degradation temperature (>350 °C), higher than the melt-flow temperature (124–133 °C) providing a wide processing window. Overall, PBS/PaPrHe blend is a novel bio-based blend with properties suitable for packaging, mulching, and related applications.

Parent/Guardian- and Self-Report Versions of the Irritability Domain of the Concise Associated Symptom Tracking Scale: Evaluation of Psychometric Properties and Potential Clinical Utility in the Texas Youth Depression and Suicide Research Network

Parent/Guardian- and Self-Report Versions of the Irritability Domain of the Concise Associated Symptom Tracking Scale: Evaluation of Psychometric Properties and Potential Clinical Utility in the Texas Youth Depression and Suicide Research Network

Quality of life and its association with predictors in lung transplant recipients: a latent profile analysis.

Improving quality of life (QOL) is one of the main aims of lung transplantation (LTx). There is a need to identify those who have poor quality of life early. However, research addressing inter individual quality of life variability among them is lacking. This study aims to identify group patterns in quality of life among lung transplant recipients and examine the predictors associated with quality of life subgroups. In total, 173 lung transplant recipients were recruited from one hospital in Guangdong Province between September 2022 and August 2023. They were assessed using the Lung Transplant Quality of Life scale (LT-QOL), Mindful Attention Awareness Scale (MAAS), Life Orientation Test-Revised scale (LOT-R), and Positive and Negative Affect Scale (PANAS). Latent profile analysis was used to identify QOL subtypes, and logistic regression analysis was used to examine the associations between latent profiles and sociodemographic and psychosocial characteristics. Two distinct QOL profiles were identified: "low HRQOL" profile [N = 53 (30.94%)] and "high HRQOL" profile [N = 120 (69.06%)]. Single lung transplant recipients, and patients who reported post-transplant infection, high levels of negative emotion or low levels of mindfulness and optimism were significantly correlated with the low QOL subgroup. Using the domains of the LT-QOL scale, two profiles were identified among the lung transplant recipients. Our findings highlighted that targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to patients who have undergone single lung transplantation, have had a hospital readmission due to infection, exhibit low levels of optimism, low levels of mindfulness or high negative emotions.

Development and psychometric testing of the lymphedema self-management support scale for breast cancer survivors

ObjectiveEffective self-management support should be tailored to the individual. To provide personalized and targeted self-management support, a rigorous assessment tool is needed to screen the actual degree of lymphedema self-management support received by breast cancer survivors. This study aims to develop and psychometrically test the Lymphedema Self-Management Support Scale for Breast Cancer Survivors (LSMS-BCs). MethodsThis study involves two phases: scale development and psychometric testing. In the scale development phase, preliminary items and domains were identified through a qualitative meta-synthesis, a quantitative systematic review, and reference to previous similar scales. Expert consultation and pilot study were conducted to refine the scale and evaluate the content validity. The psychometric characteristics were tested with 447 participants using item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability assessments, as well as measurement invariance. ResultsA preliminary 21-item scale with four domains, basic management support, management support for limb volume reduction, role management support, and emotional management support, was constructed in the scale development phase and well supported by EFA and CFA. The scale-level content validity index was 0.983. Cronbach's α coefficient for overall scale and subscales ranged from 0.732 to 0.949. McDonald's ω ranged from 0.848 to 0.955. Excellent known-groups validity, concurrent validity, predictive validity, and measurement invariance were demonstrated. ConclusionsThe LSMS-BCs is psychometrically valid and reliable. It can serve as a valuable tool for assessing and understanding the lymphedema self-management support received by breast cancer survivors.

Numerical Validation of the Inverse Cascade of Surface Gravity Wave Action.

We report numerical simulations of surface gravity waves forced at small scale and the subsequent inverse cascade of wave action. We combine the spectral approach to simulating weakly nonlinear waves with the capabilities of modern graphics processing units to reach unprecedented scale separation between the forcing and domain scales. The resulting broad inertial range allows for an unambiguous confirmation of the theoretical prediction for the spectrum in the inverse cascade regime, both in terms of spectral index and dependence of the spectral level on the action flux.

Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation.

Local mutation rates in human are highly heterogeneous, with known variability at the scale of megabase-sized chromosomal domains, and, on the other extreme, at the scale of oligonucleotides. The intermediate, kilobase-scale heterogeneity in mutation risk is less well characterized. Here, by analyzing thousands of somatic genomes, we studied mutation risk gradients along gene bodies, representing a genomic scale spanning roughly 1-10 kb, hypothesizing that different mutational mechanisms are differently distributed across gene segments. The main heterogeneity concerns several kilobases at the transcription start site and further downstream into 5' ends of gene bodies; these are commonly hypomutated with several mutational signatures, most prominently the ubiquitous C>T changes at CpG dinucleotides. The width and shape of this mutational coldspot at 5' gene ends is variable across genes, and corresponds to variable interval of lowered DNA methylation depending on gene activity level and regulation. Such hypomutated loci, at 5' gene ends or elsewhere, correspond to DNA hypomethylation that can associate with various landmarks, including intragenic enhancers, Polycomb-marked regions, or chromatin loop anchor points. Tissue-specific DNA hypomethylation begets tissue-specific local hypomutation. Of note, direction of mutation risk is inverted for AID/APOBEC3 cytosine deaminase activity, whose signatures are enriched in hypomethylated regions.