Together is better: mRNA co-encapsulation in lipoplexes is required to obtain ratiometric co-delivery and protein expression on the single cell level

Liposomes can efficiently deliver messenger RNA (mRNA) into cells. When mRNA cocktails encoding different proteins are needed, a considerable challenge is to efficiently deliver all mRNAs into the cytosol of each individual cell. In this work, two methods are explored to co-deliver varying ratiometric doses of mRNA encoding red (R) or green (G) fluorescent proteins and it is found that packaging mRNAs into the same lipoplexes (mingle-lipoplexes) is crucial to efficiently deliver multiple mRNA types into the cytosol of individual cells according to the pre-defined ratio. A mixture of lipoplexes containing only one mRNA type (single-lipoplexes), however, seem to follow the "first come - first serve" principle, resulting in a large variation of R/G uptake and expression levels for individual cells leading to ratiometric dosing only on the population level, but rarely on the single-cell level. These experimental observations are quantitatively explained by a theoretical framework based on the stochasticity of mRNA uptake in cells and endosomal escape of mingle- and single-lipoplexes, respectively. Furthermore, the findings are confirmed in 3D retinal organoids and zebrafish embryos, where mingle-lipoplexes outperformed single-lipoplexes to reliably bring both mRNA types into single cells. This benefits applications that require a strict control of protein expression in individual cells.Drug Delivery Technolog

Phosphorescent Energy Downshifting for Diminishing Surface Recombination in Silicon Nanowire Solar Cells

Molecularly engineered Ir(III) complexes can transfer energy from short-wavelength photons (lambda < 450 nm) to photons of longer wavelength (lambda > 500 nm), which can enhance the otherwise low internal quantum efficiency (IQE) of crystalline Si (c-Si) nanowire solar cells (NWSCs) in the shortwavelength region. Herein, we demonstrate a phosphorescent energy downshifting system using Ir(III) complexes at short wavelengths (300-450 nm) to diminish the severe surface recombination that occurs in c-Si NWSCs. The developed Ir(III) complexes can be considered promising energy converters because they exhibit superior intrinsic properties such as a high quantum yield, a large Stokes shift, a long exciton diffusion length in crystalline film, and a reproducible synthetic procedure. Using the developed 1011) complexes, highly crystalline energy downshifting layers were fabricated by ultrasonic spray deposition to enhance the photoluminescence efficiency by increasing the radiative decay. With the optimized energy downshifting layer, our 1cm(2) c-Si NWSCs with Ir(III) complexes exhibited a higher IQE value for short-wavelength light (300-450 nm) compared with that of bare Si NWSCs without Ir(III) complexes, resulting in a notable increase in the short-circuit current density (from 34.4 mA.cm(-2) to 36.5 mA.cm(-2) )

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species? holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species. Variation in frontal sinus shape and dimensions has high potential for phylogenetic discussion when studying human evolution

Frontal sinuses and human evolution.

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species' holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of 'Homo erectus'. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species’ holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species

The lognormal and gamma distribution models for estimating molecular weight distributions of polymers using PGSE NMR

We present comprehensive derivations for the statistical models and methods for the use of pulsed gradient spin echo (PGSE) NMR to characterize the molecular weight distribution of polymers via the well-known scaling law relating diffusion coefficients and molecular weights. We cover the lognormal and gamma distribution models and linear combinations of these distributions. Although the focus is on methodology, we illustrate the use experimentally with three polystyrene samples, comparing the NMR results to gel permeation chromatography (GPC) measurements, test the accuracy and noise-sensitivity on simulated data, and provide code for implementation

Hand grip strength is associated with forced expiratory volume in 1 second among subjects with COPD: report from a population-based cohort study

Viktor Johansson Strandkvist,1,2 Helena Backman,2 Jenny Röding,1 Caroline Stridsman,3 Anne Lindberg4 1Division of Health and Rehabilitation, Department of Health Science, Luleå University of Technology, Luleå, 2Division of Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, The Obstructive Lung disease in Northern Sweden Unit, Umeå University, Umeå, 3Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, 4Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden Background: Cardiovascular diseases and skeletal muscle dysfunction are common comorbidities in COPD. Hand grip strength (HGS) is related to general muscle strength and is associated with cardiovascular disease and all-cause mortality, while the results from small selected COPD populations are contradictory. The aim of this population-based study was to compare HGS among the subjects with and without COPD, to evaluate HGS in relation to COPD severity, and to evaluate the impact of heart disease.Subjects and methods: Data were collected from the Obstructive Lung disease in Northern Sweden COPD study, where the subjects with and without COPD have been invited to annual examinations since 2005. In 2009–2010, 441 subjects with COPD (postbronchodilator forced expiratory volume in 1 second [FEV1]/ vital capacity <0.70) and 570 without COPD participated in structured interviews, spirometry, and measurements of HGS.Results: The mean HGS was similar when comparing subjects with and without COPD, but those with heart disease had lower HGS than those without. When compared by Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, the subjects with GOLD 3–4 had lower HGS than those without COPD in both sexes (females 21.4 kg vs 26.9 kg, P=0.010; males 41.5 kg vs 46.3 kg, P=0.038), and the difference persisted also when adjusted for confounders. Among the subjects with COPD, HGS was associated with FEV1% of predicted value but not heart disease when adjusted for height, age, sex, and smoking habits, and the pattern was similar among males and females.Conclusion: In this population-based study, the subjects with GOLD 3–4 had lower HGS than the subjects without COPD. Among those with COPD, HGS was associated with FEV1% of predicted value but not heart disease, and the pattern was similar in both sexes. Keywords: muscle strength, muscle strength dynamometer, pulmonary disease, COPD, heart diseases, epidemiolog

The pseudo 2-D relaxation model for obtaining T1-T2 relationships from 1-D T1 and T2 measurements of fluid in porous media

NMR spin-lattice (T1) and spin-spin (T2) relaxation times and their inter-relation possess information on fluid behaviour in porous media. To elicit this information we utilize the pseudo 2-D relaxation model (P2DRM), which deduces the T1-T2 functional relationship from independent 1-D T1 and T2 measurements. Through model simulations we show empirically that the P2DRM accurately estimates T1-T2 relationships even when the marginal distributions of the true joint T1-T2 distribution are unknown or cannot be modeled. Estimates of the T1:. T2 ratio for fluid interacting with pore surfaces remain robust when the P2DRM is applied to simulations of rapidly acquired data. Therefore, the P2DRM can be useful in situations where experimental time is limited