Particle interactions and lattice dynamics: Scenarios for efficient bidirectional stochastic transport?

Intracellular transport processes driven by molecular motors can be described by stochastic lattice models of self-driven particles. Here we focus on bidirectional transport models excluding the exchange of particles on the same track. We explore the possibility to have efficient transport in these systems. One possibility would be to have appropriate interactions between the various motors' species, so as to form lanes. However, we show that the lane formation mechanism based on modified attachment/detachment rates as it was proposed previously is not necessarily connected to an efficient transport state and is suppressed when the diffusivity of unbound particles is finite. We propose another interaction mechanism based on obstacle avoidance that allows to have lane formation for limited diffusion. Besides, we had shown in a separate paper that the dynamics of the lattice itself could be a key ingredient for the efficiency of bidirectional transport. Here we show that lattice dynamics and interactions can both contribute in a cooperative way to the efficiency of transport. In particular, lattice dynamics can decrease the interaction threshold beyond which lanes form. Lattice dynamics may also enhance the transport capacity of the system even when lane formation is suppressed.Comment: 25 pages, 17 figures, 2 table

A demographic perspective on human wellbeing: Concepts, measurement and population heterogeneity

This introduction to the 2021 special issue of the Vienna Yearbook of PopulationResearch explores demographic perspectives on human wellbeing across time andspace. While the idea of relating demographic parameters to wellbeing has beenaround for a while, a more concrete research agenda on this topic has only recentlygained momentum. Reviewing the research presented in this volume, we show howexisting theoretical concepts and methodological tools in demography can be usedto make substantial advances in the study of wellbeing. We also touch upon themany challenges researchers face in defining and measuring wellbeing, with themost important debate being about whether the focus should be on objective orsubjective measures. The studies discussed here define wellbeing as health andmortality; as income, education or other resources; as happiness or life satisfaction;or as a combination thereof. They cover wellbeing in historical and contemporarypopulations in high- and low-income countries, and also point out important barriersto research on wellbeing, including the lack of good quality data in many regions.Finally, we highlight the value of considering population heterogeneities when studying wellbeing in order to identify population subgroups who are likely to fallbehind, which can have important policy implications

Mean field treatment of exclusion processes with random-force disorder

The asymmetric simple exclusion process with random-force disorder is studied within the mean field approximation. The stationary current through a domain with reversed bias is analyzed and the results are found to be in accordance with earlier intuitive assumptions. On the grounds of these results, a phenomenological random barrier model is applied in order to describe quantitatively the coarsening phenomena. Predictions of the theory are compared with numerical results obtained by integrating the mean field evolution equations.Comment: 21 pages, 14 figure

β-glucan-dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

The initial host response to fungal pathogen invasion is critical to infection establishment and outcome. However, the diversity of leukocyte-pathogen interactions is only recently being appreciated. We describe a new form of interleukocyte conidial exchange called "shuttling." In Talaromyces marneffei and Aspergillus fumigatus zebrafish in vivo infections, live imaging demonstrated conidia initially phagocytosed by neutrophils were transferred to macrophages. Shuttling is unidirectional, not a chance event, and involves alterations of phagocyte mobility, intercellular tethering, and phagosome transfer. Shuttling kinetics were fungal-species-specific, implicating a fungal determinant. β-glucan serves as a fungal-derived signal sufficient for shuttling. Murine phagocytes also shuttled in vitro. The impact of shuttling for microbiological outcomes of in vivo infections is difficult to specifically assess experimentally, but for these two pathogens, shuttling augments initial conidial redistribution away from fungicidal neutrophils into the favorable macrophage intracellular niche. Shuttling is a frequent host-pathogen interaction contributing to fungal infection establishment patterns

Modeling genomic diversity and tumor dependency in malignant melanoma

The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors

Automatic determination of Greulich and Pyle bone age in healthy Dutch children

Background: Bone age (BA) assessment is a routine procedure in paediatric radiology, for which the Greulich and Pyle (GP) atlas is mostly used. There is rater variability, but the advent of automatic BA determination eliminates this. Objective: To validate the BoneXpert method for automatic determination of skeletal maturity of healthy children against manual GP BA ratings. Materials and methods: Two observers determined GP BA with knowledge of the chronological age (CA). A total of 226 boys with a BA of 3-17 years and 179 girls with a BA of 3-15 years were included in the study. BoneXpert's estimate of GP BA was calibrated to agree on average with the manual ratings based on several studies, including the present study. Results: Seven subjects showed a deviation between manual and automatic BA in excess of 1.9 years. They were re-rated blindly by two raters. After correcting these seven ratings, the root mean square error between manual and automatic rating in the 405 subjects was 0.71 years (range 0.66-0.76 years, 95% CI). BoneXpert's GP BA is on average 0.28 and 0.20 years behind the CA for boys and girls, respectively. Conclusion: BoneXpert is a robust method for automatic determination of BA

Effect of Thiamine Status on Probability of Lake Ontario Chinook Salmon Spawning in the Upper or Lower Sections of Salmon River, New York

Consumption of thiaminase‐containing forage fishes reduces egg and muscle thiamine content and impairs the spawning migration of Cayuga Lake (New York) rainbow trout Oncorhynchus mykiss. Because some Chinook salmon O. tshawytscha from Lake Ontario have been shown to produce eggs low in thiamine, we examined the relationship between the migration of Chinook salmon and the thiamine content of their eggs spawned in the lower and upper sections of the Salmon River, a major tributary to Lake Ontario, in 2003–2006. Eggs from the upper section of the river were collected from 79 salmon returning to the state hatchery 25 river kilometers from the mouth. Eggs from 25 salmon in the lower section were collected from redds or females angled on redds approximately 1–3 km from the mouth. For all years combined, we found the mean thiamine concentration in eggs spawned in the lower section to be significantly lower than that for eggs spawned in the upper section; however, the annual differences in thiamine content of eggs between the upper and lower sections were significant only in 2003 and 2006. Binary logistic regression showed that the odds of spawning in the upper section was increased by 96% (95% confidence interval, 21–217%) for every nanomole of increase in the thiamine content of eggs. Therefore, the migratory achievement of Chinook salmon was significantly dependent on their thiamine status.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142217/1/nafm0895.pd

Expanding the evolutionary explanations for sex differences in the human skeleton

While the anatomy and physiology of human reproduction differ between the sexes, the effects of hormones on skeletal growth do not. Human bone growth depends on estrogen. Greater estrogen produced by ovaries causes bones in female bodies to fuse before males\u27 resulting in sex differences in adult height and mass. Female pelves expand more than males\u27 due to estrogen and relaxin produced and employed by the tissues of the pelvic region and potentially also due to greater internal space occupied by female gonads and genitals. Evolutionary explanations for skeletal sex differences (aka sexual dimorphism) that focus too narrowly on big competitive men and broad birthing women must account for the adaptive biology of skeletal growth and its dependence on the developmental physiology of reproduction. In this case, dichotomizing evolution into proximate‐ultimate categories may be impeding the progress of human evolutionary science, as well as enabling the popular misunderstanding and abuse of it

Evaluating the Dimensionality of First-Grade Written Composition

Purpose—We examined dimensions of written composition using multiple evaluative approaches such as an adapted 6+1 trait scoring, syntactic complexity measures, and productivity measures. We further examined unique relations of oral language and literacy skills to the identified dimensions of written composition. Method—A large sample of first grade students (N = 527) was assessed on their language, reading, spelling, letter writing automaticity, and writing in the spring. Data were analyzed using a latent variable approach including confirmatory factor analysis and structural equation modeling. Results—The seven traits in the 6+1 trait system were best described as two constructs: substantive quality, and spelling and writing conventions. When the other evaluation procedures such as productivity and syntactic complexity indicators were included, four dimensions emerged: substantive quality, productivity, syntactic complexity, and spelling and writing conventions. Language and literacy predictors were differentially related to each dimension in written composition. Conclusions—These four dimensions may be a useful guideline for evaluating developing beginning writer’s compositions

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes