On-site residence time in a driven diffusive system: violation and recovery of mean-field

We investigate simple one-dimensional driven diffusive systems with open boundaries. We are interested in the average on-site residence time defined as the time a particle spends on a given site before moving on to the next site. Using mean-field theory, we obtain an analytical expression for the on-site residence times. By comparing the analytic predictions with numerics, we demonstrate that the mean-field significantly underestimates the residence time due to the neglect of time correlations in the local density of particles. The temporal correlations are particularly long-lived near the average shock position, where the density changes abruptly from low to high. By using Domain wall theory (DWT), we obtain highly accurate estimates of the residence time for different boundary conditions. We apply our analytical approach to residence times in a totally asymmetric exclusion process (TASEP), TASEP coupled to Langmuir kinetics (TASEP + LK), and TASEP coupled to mutually interactive LK (TASEP + MILK). The high accuracy of our predictions is verified by comparing these with detailed Monte Carlo simulations

Normal stresses in semiflexible polymer hydrogels

Biopolymer gels such as fibrin and collagen networks are known to develop tensile axial stress when subject to torsion. This negative normal stress is opposite to the classical Poynting effect observed for most elastic solids including synthetic polymer gels, where torsion provokes a positive normal stress. As recently shown, this anomalous behavior in fibrin gels depends on the open, porous network structure of biopolymer gels, which facilitates interstitial fluid flow during shear and can be described by a phenomenological two-fluid model with viscous coupling between network and solvent. Here we extend this model and develop a microscopic model for the individual diagonal components of the stress tensor that determine the axial response of semi-flexible polymer hydrogels. This microscopic model predicts that the magnitude of these stress components depends inversely on the characteristic strain for the onset of nonlinear shear stress, which we confirm experimentally by shear rheometry on fibrin gels. Moreover, our model predicts a transient behavior of the normal stress, which is in excellent agreement with the full time-dependent normal stress we measure.Comment: 12 pages, 8 figure

Porosity governs normal stresses in polymer gels

When sheared, most elastic solids such as metals, rubbers and polymer hydrogels dilate in the direction perpendicular to the shear plane. This well-known behaviour known as the Poynting effect is characterized by a positive normal stress [1]. Surprisingly, biopolymer gels made of fibrous proteins such as fibrin and collagen and many tissues exhibit the opposite effect, contracting under shear and displaying a negative normal stress [2, 3]. Here we show that this anomalous behaviour originates from the open network structure of biopolymer gels, which facilitates interstitial fluid flow during shear. Using fibrin networks with a controllable pore size as a model system, we show that the normal stress response to an applied shear is positive at short times, but decreases to negative values with a characteristic time scale set by pore size. Using a two-fluid model, we develop a quantitative theory that unifies the opposite behaviours encountered in synthetic and biopolymer gels. Synthetic polymer gels are impermeable to solvent flow and thus effectively incompressible at typical experimental time scales, whereas biopolymer gels are effectively compressible. Our findings suggest a new route to tailor elastic instabilities such as the die swell effect that often hamper processing of polymer materials and furthermore show that poroelastic effects play a much more important role in the mechanical properties of cells and tissues than previously anticipated

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Association of matrix metalloproteinase-1-1607 1g/2g and C-reactive protein-717 C/T gene polymorphisms in Iranian patients with chronic periodontitis: a clinical trial

Background: An imbalance in the expression of matrix metalloproteinases (MMPs) and tissue inhibitor metalloproteinases initiate the destructive process in chronic periodontitis (CP). C-reactive protein (CRP) is a systemic inflammatory mediator that reflects an acute immune response.Objectives: The purpose of this investigation was to analyze the association between the MMP-1 -16071G/2G (rs1799750) and CRP 717 A/G (rs2794521) gene polymorphisms and chronic periodontitis in Iran.Methods: This analytical case-control study was performed among 141 participants including 63 CP cases and 78 matched healthy individuals. Five milliliters of peripheral blood was collected for DNA isolation. Restriction fragment length polymorphism- polymerase chain reaction (RFLP-PCR) was performed for single-nucleotide polymorphism (SNP) analysis. The frequencies were analyzed by chi-squared test (95% CI, P < 0.05). In addition, genetic data were assessed by the Hardy-Weinberg principle, linkage disequilibrium, and haplotype analysis.Results: Our findings presented no significant relationship between genotype/alleles of MMP-1 -16071G/2G (rs1799750) (0.73: 0.27-1.95, P = 0.48) or CRP 717 A/G (rs2794521) (0.384: 0.104 -1.414, P = 0.303) and the presence of CP (P = 0.47 and P = 0.30, respectively). The analysis of genetic distribution among various severities of CP and controls revealed no significant association between various severities of CP and MMP-1 -16071G/2G (rs1799750) (P = 0.52) and CRP 717 A/G (rs2794521) (P = 0.67).Conclusions: Our results suggest no association between the occurrence or severity of chronic periodontitis and MMP-1-16071G/2G (rs1799750) and CRP 717 A/G (rs2794521) polymorphisms. Further studies with larger sample sizes may provide a more generalizable evidence-based overview of the relationship between these gene polymorphisms and periodontitis

Isolation and in vitro Characterization of Mesenchymal Stem Cells Derived from the Pulp Tissue of Human Third Molar Tooth

Background: It is still controversial that the stem cells isolatedfrom human dental pulp meets the criteria for mesenchymalstem cells (MSCs). The aim of the present study wasto examine whether or not they are MSCs, or are distinct stemcells population residing in tooth pulp.Methods: Adherent fibroblastic cells in the culture of pulptissue from human third molars were propagated through severalsuccessive subcultures. Passaged-3 cells with a tendencyto differentiate into odontoblastic cells were used to examinethe key properties of MSCs including typical tripotent differentiationpotential into bone, cartilage and adipose cell lineagesand the expression of typical surface antigens. Moreover,they were examined for growth capacity in culture.Results: Dental pulp stem cells successfully progressed towardsdifferentiation among three skeletal cell lineages. Morethan 90% of the cell population exhibited the expression ofsurface antigens known to be found on mesenchymal lineagessuch as CD105, CD90, CD44, and CD73, while only less than2% expressed endothelial-hematopoietic epitopes includingCD56, CD11b, CD34, CD31, CD33, and CD45. The cells exhibiteda relatively high proliferation capacity with populationdoubling time of about 21.9 hours.Conclusion: The dental pulp stem cells are of MSC population,and may be considered suitable for use in regenerativemedicine, owing to their relatively rapid rate of in vitro propagation

Comparison of antimicrobial effect of Ziziphora tenuior, Dracocephalum moldavica, Ferula gummosa, and Prangos ferulacea essential oil with chlorhexidine on Enterococcus faecalis: An in vitro study

Background: Different irrigating solutions with high antimicrobial activity have been introduced for cleaning of the root canal system. However, effects of Prangos ferulacea (PF), Ziziphora tenuior (ZT), Dracocephalum moldavica (DM), and Ferula gummosa (FG) on oral and dental pathogens have not been extensively evaluated due to their optimal biocompatibility and insignificant side effects. The aim of this study was to evaluate the antibacterial effects of essential oils of mentioned plants on Enterococcus faecalis. Materials and Methods: In this in vitro study the plants were collected from Zanjan Province, Iran. Analysis of the essential oil was carried out by gas chromatography/mass chromatography. Micro-broth dilution and disc diffusion methods were used for assessment of the antimicrobial activity, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. Results: All the four essential oils had antibacterial effects on E. faecalis, and ZT had the greatest antibacterial activity. Assessment of the mean diameter of the growth inhibition zone showed higher antibacterial activity of PF and ZT than that of chlorhexidine. The MIC and MBC of ZT showed that the antimicrobial activity of ZT against E. faecalis was greater than that of other plants evaluated in this study. Conclusion: The results of this study indicated significant antibacterial effects of the mentioned plants on E. faecalis. The greatest antimicrobial activity belonged to ZT. The current study suggests extraction of effective compounds in these medicinal plants to use them in the clinical setting