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Inspired by bacterial chromosome organization, we study the compaction and clustering of a heterogeneous ring polymer in a crowded medium using molecular dynamics simulations. The polymer consists of several large monomers interspersed along the backbone and small intervening monomers. In a crowded medium, the entropy of crowding particles or crowders favors the collapse of chain molecules, such as chromosomes. Our study shows that the compaction transition of heterogeneous polymers by crowders is well-correlated with the clustering of large monomers: when the large monomers are sufficiently large, both occur concomitantly in the same narrow (biologically relevant) range of the volume fraction of crowders. It also indicates that cylindrical confinement makes crowding effects more effective. The results presented here suggest that phase separation and clustering are essential features of bacterial chromosome organization. [ABSTRACT FROM AUTHOR]

Abstract Background Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker. Methods Of these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis. Results Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group. Conclusions Concurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

Abstract Real-time digital image processing to optimally enhance low vision is now realizable with recent advances in personal computers. This study aimed to evaluate the efficacy of a wearable smartphone-based low vision aid (LVA) with customizable vision enhancement in patients with visual impairment. We recruited 35 subjects with visual impairment and who were literate and cognitively capable. The subjects completed a training session and were provided a smartphone-based LVA for a 4-week use. Visual functions including binocular best-corrected distance, intermediate, and near visual acuities; reading performance (reading speed and accuracy); and facial recognition performance were measured at baseline and after 4-weeks use. All subjects also completed the Low Vision Quality of Life (LVQOL) Questionnaire. Thirty-four subjects (mean age, 43.82 ± 15.06 years) completed the study. Significant improvements in binocular best-corrected distance, intermediate, and near visual acuities were observed after smartphone-based LVA use (all p

Abstract We evaluated the reliability and validity of the 5-scale grading system to interpret the point-of-care immunoassay for tear matrix metalloproteinase (MMP)-9. Six observers graded red bands of photographs of the readout window in MMP-9 immunoassay kit (InflammaDry) two times with 2-week interval based on the 5-scale grading system (i.e. grade 0–4). Interobserver and intraobserver reliability were evaluated using intraclass correlation coefficients. The interobserver agreements were analyzed according to the severity of tear MMP-9 expression. To validate the system, a concentration calibration curve was made using MMP-9 solutions with reference concentrations, then the distribution of MMP-9 concentrations was analyzed according to the 5-scale grading system. Both intraobserver and interobserver reliability was excellent. The readout grades were significantly correlated with the quantified colorimetric densities. The interobserver variance of readout grades had no correlation with the severity of the measured densities. The band density continued to increase up to a maximal concentration (i.e. 5000 ng/mL) according to the calibration curve. The difference of grades reflected the change of MMP-9 concentrations sensitively, especially between grade 2 and 4. Together, our data indicate that the subjective 5-scale grading system in the point-of-care MMP-9 immunoassay is an easy and reliable method with acceptable accuracy.

Many macromolecules of biological and technological interest are both chiral and semi-flexible. DNA and collagen are good examples. Such molecules often form chiral nematic (or cholesteric) phases, as is well-documented in collagen and chitin. This work presents a method for studying cholesteric phases in the highly successful self-consistent field theory of worm-like chains, offering a new way of studying many biologically relevant molecules. The method involves an effective Hamiltonian with a chiral term inspired by the Oseen–Frank (OF) model of liquid crystals. This method is then used to examine the formation of cholesteric phases in chiral-nematic worm-like chains as a function of polymer flexibility, as well as the optimal cholesteric pitch and distribution of polymer segment orientations. Our approach not only allows for the determination of the isotropic–cholesteric transition and segment distributions, beyond what the OF model promises, but also explicitly incorporates polymer flexibility into the study of the cholesteric phase, offering a more complete understanding of the behavior of semiflexible chiral-nematic polymers. [ABSTRACT FROM AUTHOR]

Long chain molecules can be entropically compacted in a crowded medium. We study the compaction transition of a heterogeneous polymer with ring topology by crowding effects in a free or confined space. For this, we use molecular dynamics simulations in which the effects of crowders are taken into account through effective interactions between chain segments. Our parameter choices are inspired by the Escherichia coli chromosome. The polymer consists of small and big monomers; the big monomers dispersed along the backbone are to mimic the binding of RNA polymerases. Our results show that the compaction transition is a two-step process: initial compaction induced by the association (clustering) of big monomers followed by a gradual overall compaction. They also indicate that cylindrical confinement makes the initial transition more effective; for representative parameter choices, the initial compaction accounts for about 60% reduction in the chain size. Our simulation results support the view that crowding promotes clustering of active transcription units into transcription factories. [ABSTRACT FROM AUTHOR]

Translocation of a polymer through a nano-pore is relevant in a variety of contexts such as passage of RNAs through a nuclear pore and transportation of proteins across a membrane. An essential step in polymer translocation is for the end monomers to search the pore. This process requires a characteristic time, referred to as the "attempt time" in this work. Here, we study the attempt time τ of a confined polymer inside a spherical surface by combining a scaling approach and Langevin dynamics simulations. For a moderately to strongly confined polymer, our results suggest that τ ∼ R3.67 for R > P and τ ∼ R2.67 for R < P, where R is the radius of the spherical surface and P is the persistence length of the polymer. All simulation data obtained for an intermediate range of the volume fraction of monomers ϕ(≲ 0.2) tend to collapse onto each other. This implies that τ does not explicitly depend on ϕ, in agreement with the theoretical predictions. These results will be useful for interpreting translocation as a two-step process: the initial attempt to find the pore and eventual pore crossing. [ABSTRACT FROM AUTHOR]

The phase behavior of semi-flexible polymers is integral to various contexts, from materials science to biophysics, many of which utilize or require specific confinement geometries as well as the orientational behavior of the polymers. Inspired by collagen assembly, we study the orientational ordering of semi-flexible polymers, modeled as Maier–Saupe worm-like chains, using self-consistent field theory. We first examine the bulk behavior of these polymers, locating the isotropic–nematic transition and delineating the limit of stability of the isotropic and nematic phases. This effort explains how nematic ordering emerges from the isotropic phase and offers insight into how different (e.g., mono-domain vs multi-domain) nematic phases form. We then clarify the influence of planar confinement on the nematic ordering of the polymers. We find that while the presence of a single confining wall does not shift the location of nematic transition, it aligns the polymers in parallel to the wall; above the onset of nematic transition, this preference tends to propagate into the bulk phase. Introducing a second, perpendicular, wall leads to a nematic phase that is parallel to both walls, allowing the ordering direction to be uniquely set by the geometry of the experimental setup. The advantage of wall-confinement is that it can be used to propagate mono-domain nematic phases into the bulk phase. [ABSTRACT FROM AUTHOR]