Miracle-dz/UniFAR-FTUs huggingface dataset:
GCL loss in BRAO

Purpose Our recent publication used optical coherence tomography (OCT) to follow thinning of the retinal ganglion cell layer (GCL) in central retinal artery occlusion (CRAO). Thinning of the inner layers also occurs in patients with branch retinal artery occlusion (BRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of OCT images to follow the loss of retinal layers in BRAO compared to CRAO patients, and 2) predict the number of patients and days of observation needed for a clinical trial of a calpain inhibitor against BRAO. Methods A retrospective, case control study was conducted by computer-aided search in a medical records database for BRAO (ICD10 Code H34.239) with at least one OCT procedure (CPT: 92134). Non-proliferative, co-morbid eye diseases were allowed in the patient data base, and manual correction of auto-segmentation errors was performed. GCL thickness changes were followed over time and Cohen-d/sample size statistics were used to predict minimal patients needed for drug trials. Results The thickness of the GCL layer in BRAO decreased rapidly with time as in CRAO, but in more limited quadrants. The data, as fit to a single-phase decay curve, showed that GCL thickness could be used to provide sample size statistics in a clinical trial to test a calpain inhibitor. For example, a 60-day trial with a 60% effective inhibitor would need a minimum of 29 patients. Conclusions Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against BRAO and CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period. Translational relevance Measurement of GCL thickness would be a useful indicator of amelioration of BRAO and CRAO progression in a clinical trial of a putative inhibitor.
Outer retinal degeneration in a non-human primate model using temporary intravitreal tamponade with N-methyl-N-nitrosourea in cynomolgus monkeys

Objective: The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU). Approach: Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2–3 mg ml−1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed. Main results: Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved. Significance: Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.
Microfluidics in drug delivery: review of methods and applications

Abstract Microfluidics technology has emerged as a promising methodology for the fabrication of a wide variety of advanced drug delivery systems. Owing to its ability for accurate handling and processing of small quantities of fluidics as well as immense control over physicochemical properties of fabricated micro and nanoparticles (NPs), microfluidic technology has significantly improved the pharmacokinetics and pharmacodynamics of drugs. This emerging technology has offered numerous advantages over the conventional drug delivery methods for fabricating of a variety of micro and nanocarriers for poorly soluble drugs. In addition, a microfluidic system can be designed for targeted drug delivery aiming to increase the local bioavailability of drugs. This review spots the light on the recent advances made in the area of microfluidics including various methods of fabrication of drug carriers, their characterization, and unique features. Furthermore, applications of microfluidic technology for the robust fabrication and development of drug delivery systems, the existing challenges associated with conventional fabrication methodologies as well as the proposed solutions offered by microfluidic technology have been discussed in details. Highlights Microfluidic technology has revolutionized fabrication of tunable micro and nanocarriers. Microfluidic platforms offer several advantages over the conventional fabrication methods. Microfluidic devices hold great promise in controlling the physicochemical features of fabricated drug carriers. Micro and nanocarriers with controllable release kinetics and site-targeting efficiency can be fabricated. Drug carriers fabricated by microfluidic technology exhibited improved pharmacokinetic and pharmacodynamic profiles. Graphical Abstract
Social environment and brain structure in adolescent mental health: A cross-sectional structural equation modelling study using IMAGEN data

Adolescent mental health is impacted by a myriad of factors, including the developing brain, socioeconomic conditions and changing social relationships. Studies to date have neglected investigating those factors simultaneously, despite evidence of their interacting effects and distinct profiles for males and females. The current study addressed that gap by applying structural equation modelling to IMAGEN data from adolescents aged 14 years (n = 1950). A multi-group model split by sex was tested with the variables of socioeconomic stress, family support, peer problems, and brain structure as predictors, and emotional symptoms as the main outcome. Findings indicated that, for both sexes, peer problems were positively associated with emotional symptoms, and socioeconomic stress was negatively associated with family support. Additionally, there were sex-specific findings within the full models: ventromedial prefrontal cortex grey matter volume was negatively associated with emotional symptoms for males when corrected for whole brain volume, and socioeconomic stress was negatively associated with whole brain volume for females. This study underscores the importance of the peer environment for early adolescent emotional symptoms in both boys and girls, but goes further to suggest distinct gender associations with socioeconomic factors and brain structure which provides a multi-level view of risk and resilience. Future research could exploit existing IMAGEN longitudinal data to strengthen causal claims and to determine the potential longstanding impact of social environment and brain development on adolescent mental health.
Factors related to burnout and its effects on mental and physical symptoms and daytime dysfunction among female flight attendants

ABSTRACT In this study, risk factors were identified to assess the impact of burnout on the health and daytime function of 412 female flight attendants from an international airline from 2017 to 2018 with convenience sampling. Data were obtained from self-administered questionnaires. Analysis of variance, Pearson’s correlation analysis, and independent t-tests were used to assess the relationships between burnout and demographic and work-related factors. A structural equation model analysis was performed to assess the effect of burnout impact factors on mental health using the Brief Symptom Rating Scale, six common physical symptoms, and daytime dysfunction (a subscale of the Athens Insomnia Scale). The results showed a moderate level of burnout, as reported by 19.2 percent of the participants. Personal and work-related characteristics, including marital status and working hours, were not significantly associated with burnout. Smoking behavior was the only significant risk factor (T = −3.64). The impact model of burnout revealed a moderate direct effect of burnout on mental health symptoms (95 percent CI: 0.27, 0.47) and daytime dysfunction (95 percent CI: 0.04, 0.11) and a small direct effect on physical symptoms (95 percent CI: 0.28, 0.47). Our findings increase our understanding of the risk and impact factors related to burnout in female flight attendants.
HP1 proteins regulate nucleolar structure and function by secluding pericentromeric constitutive heterochromatin

Abstract Nucleoli are nuclear compartments regulating ribosome biogenesis and cell growth. In embryonic stem cells (ESCs), nucleoli containing transcriptionally active ribosomal genes are spatially separated from pericentromeric satellite repeat sequences packaged in largely repressed constitutive heterochromatin (PCH). To date, mechanisms underlying such nuclear partitioning and the physiological relevance thereof are unknown. Here we show that repressive chromatin at PCH ensures structural integrity and function of nucleoli during cell cycle progression. Loss of heterochromatin proteins HP1α and HP1β causes deformation of PCH, with reduced H3K9 trimethylation (H3K9me3) and HP1γ levels, absence of H4K20me3 and upregulated major satellites expression. Spatially, derepressed PCH aberrantly associates with nucleoli accumulating severe morphological defects during S/G2 cell cycle progression. Hp1α/β deficiency reduces cell proliferation, ribosomal RNA biosynthesis and mobility of Nucleophosmin, a major nucleolar component. Nucleolar integrity and function require HP1α/β proteins to be recruited to H3K9me3-marked PCH and their ability to dimerize. Correspondingly, ESCs deficient for both Suv39h1/2 H3K9 HMTs display similar nucleolar defects. In contrast, Suv4-20h1/2 mutant ESCs lacking H4K20me3 at PCH do not. Suv39h1/2 and Hp1α/β deficiency-induced nucleolar defects are reminiscent of those defining human ribosomopathy disorders. Our results reveal a novel role for SUV39H/HP1-marked repressive constitutive heterochromatin in regulating integrity, function and physiology of nucleoli.
A Size-Structured Population-Model with Dispersion

Abstract We propose a model for size structured populations which allows growth rates to vary with individuals (growth rate distribution across all possible growth rates). After establishing existence and uniqueness of the solutions of our model equations we present a numerical algorithm for computing the solutions and prove its convergence. Finally, we show that this approximation scheme can be used for estimating the growth rate distribution from size structured population data and illustrate the applicability of our ideas by an example.
Tin filter compared to low kV protocols - optimizing sinonasal imaging in computed tomography

Objectives Paranasal sinus imaging due to chronic inflammatory disease is one of the most common examinations in head and neck radiology with CT imaging considered the current gold standard. In this phantom study we analyzed different low dose CT protocols in terms of image quality, radiation exposure and subjective evaluation in order to establish an optimized scanning protocol. Methods In a phantom study, an Alderson phantom was scanned using 12 protocols between 70–120 kV and 25–200 mAs with and without tin filtration. For all datasets, iterative reconstruction was used. Data were objectively evaluated (image noise, (dose-weighted) contrast-to-noise ratio) and for subjective evaluation an online survey using a Likert scale was performed to reach a large group of clinically experienced reader (n = 62). The protocol was considered diagnostically insufficient if the median score was 4 and above and if more than 10% of raters scored 4 and above on the Likert scale. For an interreader agreement an ICC was calculated. To compare clinical value in relation to the applied dose and the objective image parameters, we calculated a figure of merit (FOM) and ranked the protocols accordingly. Results There was an overall moderate agreement between the 62 readers for the 12 examined CT protocols. In this phantom study, protocols with 100 kV with spectral shaping and 50–100 mAs obtained the best results for its combination of dose, image quality and clinical information value for diagnosing sinusitis (FOM 1st– 2nd place) with the 70 kV and 50 mAs as a good alternative as well (Sinusitis: FOM shared 2nd). For preoperative planning, where a higher dose is necessary, 100 kV with spectral shaping and 100 mAs achieved the overall best results (FOM 1st place) with 70 kV and 50 mAs ranking 4th. Conclusion 100-kV protocols with spectral shaping or low kV protocols (70 kV) with a similarly low dose showed the best figure of merit for imaging sinonasal disease and preoperative planning. With modern scanner technology available, spectral shaping or low KV protocols should be used for sinusitis imaging.
The geometry of Kato Grassmannians

We discuss Fredholm pairs of subspaces and associated Grassmannians in a Hilbert space. Relations between several existing definitions of Fredholm pairs are established as well as some basic geometric properties of the Kato Grassmannian. It is also shown that the so-called restricted Grassmannian can be endowed with a natural Fredholm structure making it into a Fredholm Hilbert manifold.
Numerical study on the motion of microscopic oil droplets in high intensity isotropic turbulence

The rise of small oil droplets in water under isotropic turbulence conditions is analyzed computationally. The effort focuses on the puzzling behavior observed by Friedman and Katz [Phys. Fluids 14, 3059 (2002)], namely, that the rise velocity of droplets smaller than 800μm in diameter is enhanced by turbulence, whereas the rise of larger droplets is suppressed. Specifically, the study explores whether these effects can be captured or explained using a simplified one-way coupling model that combines direct numerical simulation of the turbulent flow field with Lagrangian tracking of the droplets using a dynamical equation that accounts for buoyancy, virtual mass, pressure, drag, lift, and history forces. The computational method used is adapted from the model of Snyder et al. [Phys. Fluids 19, 065108 (2007)], which showed excellent correlation between computational results and extensive experimental data for microbubbles in isotropic turbulence. The computed results indicate that, using the quasisteady, em.
Sea Breeze Theory and Applications

Abstract The linearized Boussinesq equations with rotation, viscosity, conduction, and a mean stratification are used to model the sea breeze in two dimensions. The motion is forced by a prescribed surface temperature function. The linear model produces a sea breeze with realistic velocities and spatial dimensions. Hydrostatic solutions are found to differ very little from nonhydrostatic solutions. The only distinguishing feature of the solution at the inertial latitude is an amplitude maximum far from the coastline. Both the phase and the amplitude depend on the mean atmospheric stability. The computed vertical heat fluxes, when summed along the coastlines of the principal land masses, indicate that the sea breeze effect can account for several percent of the globally averaged vertical flux of sensible heat at a height of several hundred meters. The land-sea temperature difference required by the model to create a net onshore flow in opposition to a basic current agrees well with the empirical criterion .
Does Prolonged Weight Relief Increase the Chances of a Favourable Outcome After Containment for Perthes Disease?

We have been treating children with Legg-Calvé-Perthes disease (LCPD) with a femoral varus osteotomy (PFVO) and weight relief till the disease evolves to the latter part of the stage of reconstitution (Stage IIIb). This entails weight relief for 18 to 24 months. We undertook this case-control study to test if a shorter period of weight relief would compromise the chance of retaining the spherical shape of the femoral head when the disease healed. Forty-one children diagnosed in the early stages of LCPD (Stages Ia, Ib, and IIa), were treated by PFVO and non–weight-bearing for a period of 6 months following surgery (6m group). Eighty-two children with LCPD matched for age, sex, and stage at surgery, who resumed weight-bearing only once they reached Stage IIIb, served as the control group (3b group). Both groups were followed up till the disease healed. The sphericity deviation score was calculated, and the height and width of the epiphysis were measured on the first radiograph designated as Stage IV. The median sphericity deviation score value at healing was 3 in the 3b group and 11 in the 6m group (P<0.001). The frequency of spherical heads was 76% in the 3b group and 49% in the 6m group (P<0.003). The Odds Ratio of the disease healing with an aspherical head in 6-month group was 3.05 (CI: 1.28 to 7.22) compared with the 3b group. The percentage increase in width of the femoral epiphysis at healing was greater in the 6 group (111.5±8.5% vs. 106.5±7.2%; P<0.001). The study confirms that containment by PFVO performed early in the course of LCPD combined with weight relief till the disease has evolved to Stage IIIb is likely to result in spherical hips in 75% of children. Reducing the period of weight relief to 6 months may yield significantly poorer results with only 49% spherical femoral heads.
Exciton dynamics in $alpha$-particle tracks in organic crystals: magnetic field study of the scintillation in tetracene crystals

The mechanisms of scintillation of organic crystals bombarded by $alpha$ particles are discussed in terms of the current knowledge of exciton dynamics, which has been derived from a study of the photofluorescence of crystals such as anthracene and tetracene. The scintillation of tetracene excited by 4.4-MeV $alpha$ particles incident in a direction perpendicular to the ab plane has been studied in the presence of external magnetic fields (0 to 4000 G) and compared with the scintillation of crystalline anthracene. At 298$sup 0$K, the magnetic field effect on the total scintillation yield is (+2.5 +- 0.5) percent in tetracene and displays a typical fissionlike (fission of one singlet exciton into two triplets) dependence. At low temperatures when fission is suppressed, a fusionlike dependence (reverse of fission) appears with a (-4 to -5) percent effect at 4000 G at 148$sup 0$K. In anthracene, the fusionlike dependence is observed with a (-4 to -5) percent effect at 4000 G at 148$sup 0$K. In anthracene, the fusionlike dependence is observed at all temperatures in the range studied (148 to 298$sup 0$K). Using appropriate kinetic equations, expressions are derived for the prompt (L/sub P) and delayed (L/sub D/) components of the total scintillation yield Lmore » = L/sub P/ + L/sub D/. These expressions describe the temperature and magnetic field dependence of L, which arises because of the temperature and magnetic field dependence of the exciton fission and fusion rate constants in tetracene. In tetracene, L/sub D/ appears to be strongly temperature dependent, while L/sub P/ is not. This is explained in terms of the high density of transient singlet exciton quenchers in the $alpha$-particle track. The density of these transient quenchers is estimated to be in the range of 3 x 10$sup 17$--5 x 10$sup 18$ cm$sup -3$, and they are identified, in accord with a previous suggestion by Schott, as triplet excitons which are created by random recombination of electrons and holes in the $alpha$- particle track. (auth)« less
Immunochemical characterisation of styrene maleic acid lipid particles prepared from Mycobacterium tuberculosis plasma membrane

Membrane proteins of Mycobacterium tuberculosis (Mtb) can be targeted for the development of therapeutic and prophylactic interventions against tuberculosis. We have utilized the unique membrane-solubilising properties of the styrene maleic acid copolymer (SMA) to prepare and characterise ‘styrene maleic acid lipid particles’ from the native membrane of Mtb (MtM-SMALPs). When resolved by SDS-PAGE and visualised with coomassie blue, the molecular weights of Mtb membrane (MtM) proteins solubilised by SMA were mostly in the range of 40–70 kDa. When visualised by transmission electron microscopy, MtM-SMALPs appeared as nanoparticles of discrete shapes and sizes. The discoid nanoparticles exhibited a range of diameters of ~10–90 nm, with largest portion (~61%) ranging from 20–40 nm. MtM proteins of a molecular weight-range overlapping with that of MtM-SMALPs were also amenable to chemical cross-linking, revealing protein complex formation. Characterisation using monoclonal antibodies against seven MtM-associated antigens confirmed the incorporation of the inner membrane protein PRA, membrane-associated proteins PstS1, LpqH and Ag85, and the lipoglycan LAM into MtM-SMALPs. Conversely, the peripheral membrane proteins Acr and PspA were nearly completely excluded. Furthermore, although MtM showed an abundance of Con A-binding glycoproteins, MtM-SMALPs appeared devoid of these species. Immune responses of healthcare workers harbouring ‘latent TB infection’ provided additional insights. While MtM-SMALPs and MtM induced comparable levels of the cytokine IFN-γ, only MtM-SMALPs could induce the production of TNF-α. Antibodies present in the donor sera showed significantly higher binding to MtM than to MtM-SMALPs. These results have implications for the development of MtM-based immunoprophylaxis against tuberculosis.
DENSE SETS IN WEAK STRUCTURE AND MINIMAL STRUCTURE

This paper is an attempt to study and introduce the notion of -dense set in weak structures and the notion of m-dense set in minimal structures. We have also investigate the relationships between -dense sets, -dense sets, sets, sets, sets, sets, m-semiopen sets and -preopen sets. Further we give some representations of the above generalized sets in minimal structures as well as in weak structures.
A Confirmatory Snowfall Enhancement Project in the Snowy Mountains of Australia. Part II: Primary and Associated Analyses

AbstractThe Snowy Precipitation Enhancement Research Project (SPERP) was undertaken in winters from May 2005 to June 2009 in the Snowy Mountains region of southeastern Australia. Part I of this paper describes the design and implementation of the project, as well as the characteristics of the key datasets collected during the field phase. The primary analysis in this paper (Part II) shows an unequivocal impact on the targeting of seeding material, with the maximum level of silver in snow samples collected from the primary target area found to be significantly greater in seeded than unseeded experimental units (EUs). A positive but not statistically significant impact on precipitation was found. Further analysis shows that a substantial source of uncertainty in the estimation of the impacts of seeding on precipitation is associated with EUs where the seeding generators operated for relatively few hours. When the analysis is repeated using only EUs with more than 45 generator hours, the increase in precipit.