A sharp-front moving boundary model for malignant invasion

We analyse a novel mathematical model of malignant invasion which takes the form of a two-phase moving boundary problem describing the invasion of a population of malignant cells into a population of background tissue, such as skin. Cells in both populations undergo diffusive migration and logistic proliferation. The interface between the two populations moves according to a two-phase Stefan condition. Unlike many reaction-diffusion models of malignant invasion, the moving boundary model explicitly describes the motion of the sharp front between the cancer and surrounding tissues without needing to introduce degenerate nonlinear diffusion. Numerical simulations suggest the model gives rise to very interesting travelling wave solutions that move with speed $c$, and the model supports both malignant invasion and malignant retreat, where the travelling wave can move in either the positive or negative $x$-directions. Unlike the well-studied Fisher-Kolmogorov and Porous-Fisher models where travelling waves move with a minimum wave speed $c \ge c^* > 0$, the moving boundary model leads to travelling wave solutions with $|c| < c^{**}$. We interpret these travelling wave solutions in the phase plane and show that they are associated with several features of the classical Fisher-Kolmogorov phase plane that are often disregarded as being nonphysical. We show, numerically, that the phase plane analysis compares well with long time solutions from the full partial differential equation model as well as providing accurate perturbation approximations for the shape of the travelling waves.Comment: 48 pages, 21 figure

Functional Cellular Anti-Tumor Mechanisms are Augmented by Genetic Proteoglycan Targeting.

While recent research points to the importance of glycans in cancer immunity, knowledge on functional mechanisms is lacking. In lung carcinoma among other tumors, anti-tumor immunity is suppressed; and while some recent therapies boost T-cell mediated immunity by targeting immune-checkpoint pathways, robust responses are uncommon. Augmenting tumor antigen-specific immune responses by endogenous dendritic cells (DCs) is appealing from a specificity standpoint, but challenging. Here, we show that restricting a heparan sulfate (HS) loss-of-function mutation in the HS sulfating enzyme Ndst1 to predominantly conventional DCs (Ndst1f/f CD11cCre+ mutation) results in marked inhibition of Lewis lung carcinoma growth along with increased tumor-associated CD8+ T cells. In mice deficient in a major DC HS proteoglycan (syndecan-4), splenic CD8+ T cells showed increased anti-tumor cytotoxic responses relative to controls. Studies examining Ndst1f/f CD11cCre + mutants revealed that mutation was associated with an increase in anti-tumor cytolysis using either splenic CD8+ T cells or tumor-infiltrating (TIL) CD8+ T cells purified ex-vivo, and tested in pooled effector-to-target cytolytic assays against tumor cells from respective animals. On glycan compositional analysis, HS purified from Ndst1f/f CD11cCre + mutant DCs had reduced overall sulfation, including reduced sulfation of a tri-sulfated disaccharide species that was intriguingly abundant on wildtype DC HS. Interestingly, antigen presentation in the context of major histocompatibility complex class-I (MHC-I) was enhanced in mutant DCs, with more striking effects in the setting of HS under-sulfation, pointing to a likely regulatory role by sulfated glycans at the antigen/MHC-I - T-cell interface; and possibly future opportunities to improve antigen-specific T cell responses by immunologic targeting of HS proteoglycans in cancer

Predictors of breastfeeding duration among women in Kuwait: results of a prospective cohort study

The purposes of this paper are to report the prevalence of breastfeeding to six months among women in Kuwait and to determine the factors that are associated with the duration of breastfeeding. A cohort of 373 women recruited from maternity wards in four hospitals in Kuwait city were followed from birth to 26 weeks postpartum. The association of any and full breastfeeding duration and predictor variables were explored using multivariate Cox’s proportional hazards models. At six months, 39% of all infants were receiving some breast milk and only 2% of infants had been fully breastfed to 26 weeks. Women born in other Arab countries were less likely to discontinue breastfeeding than women born in Kuwait. Other factors positively associated with breastfeeding duration were level of maternal education, higher parity, infant being demand fed in hospital and a preference for breastfeeding on the part of the infant’s father and maternal grandmother. The introduction of a pacifier before four weeks of age and the mother intending to return to work by six months were negatively associated with duration. These findings present a number of opportunities for prolonging breastfeeding duration in Kuwait

Quantification of the performance of iterative and non-iterative computational methods of locating partial discharges using RF measurement techniques

Partial discharge (PD) is an electrical discharge phenomenon that occurs when the insulation materialof high voltage equipment is subjected to high electric field stress. Its occurrence can be an indication ofincipient failure within power equipment such as power transformers, underground transmission cableor switchgear. Radio frequency measurement methods can be used to detect and locate discharge sourcesby measuring the propagated electromagnetic wave arising as a result of ionic charge acceleration. Anarray of at least four receiving antennas may be employed to detect any radiated discharge signals, thenthe three dimensional position of the discharge source can be calculated using different algorithms. These algorithms fall into two categories; iterative or non-iterative. This paper evaluates, through simulation, the location performance of an iterative method (the standardleast squares method) and a non-iterative method (the Bancroft algorithm). Simulations were carried outusing (i) a "Y" shaped antenna array and (ii) a square shaped antenna array, each consisting of a four-antennas. The results show that PD location accuracy is influenced by the algorithm's error bound, thenumber of iterations and the initial values for the iterative algorithms, as well as the antenna arrangement for both the non-iterative and iterative algorithms. Furthermore, this research proposes a novel approachfor selecting adequate error bounds and number of iterations using results of the non-iterative method, thus solving some of the iterative method dependencies

(S)norlaudanosoline synthase. the first enzyme in the benzylisoquinoline biosynthetic pathway

1. introduction Isoquinoline alkaloids form the largest group of alkaloids in the plant kingdom. Numerous publications deal with aspects of the biosynthesis of these compounds in vivo [ 11, while isoquinoline biosynthesis at the cell-free level had hardly been touched [Z]. The initial reaction in isoquinoline biosynthesis has long [3] been assumed to be a condensation of two aromatic units, both derived from tyrosine, namely dopamine and 3,4-d~ydroxyphenylacet~dehyde [4]. This scheme was later modified [5] where it was reported that condensation of dopamine with 3,4-dihydroxyphenylpyruvate would lead to an amino acid, norlaudanosoline-l-carboxylic acid, which in turn, by decarboxylation, would yield norlaudanosoline

The Breathing Human Infrastructure: Integrating Air Quality, Traffic, And Social Media Indicators

Outdoor air pollution is a complex system that is responsible for the deaths of millions of people annually, yet the integration of interdisciplinary data necessary to assess air quality\u27s multiple metrics is still lacking. This case study integrates atmospheric indicators (concentrations of criteria pollutants including particulate matter and gaseous pollutants), traffic indicators (permanent traffic monitoring station data), and social indicators (community responses in Twitter archives) representing the interplay of the three critical pillars of the United Nations\u27 Triple Bottom Line: environment, economy, and society. During the watershed moment of the COVID-19 pandemic lockdowns in Florida, urban centers demonstrated the gaps and opportunities for understanding the relationships, through correlations rather than causations, between urban air quality, traffic emissions, and public perceptions. The relationship between the perception and the traffic variables were strongly correlated, however no correlation was observed between the perception and actual air quality indicators, except for NO2. These observations might consequently infer that traffic serves as people\u27s proxy for air quality, regardless of actual air quality, suggesting that social media messaging around asthma may be a way to monitor traffic patterns in areas where no infrastructure currently exists or is prohibited to build. It also indicates that people are less likely to be reliable sensors to accurately measure air quality due to bias in their observations of traffic volume and/or confirmation biases in broader social discourse. Results presented herein are of significance in demonstrating the capacity for interdisciplinary studies to consider the predictive capacities of social media and air pollution, its use as both lever and indicator of public support for air quality legislation and clean-air transitions, and its ability to overcome limitations of surface monitoring stations

Linking the chemical speciation of cerium to its bioavailability in water for a freshwater alga

Over the past decade, researchers have begun to use metals of the lanthanide family for numerous applications, including liquid crystal display (LCD) screens, optical fibers, and laser technology. Unfortunately, little is presently known about their bioavailability or the mechanisms by which they might cause toxicity. The present study focuses on cerium (Ce), one of the most widely used lanthanides, and on validating the biotic ligand model as a means to predict Ce bioaccumulation. Short-term exposures to Ce were performed using the unicellular alga Chlamydomonas reinhardtii, to better relate Ce bioavailability to its chemical speciation in solution. Maximum uptake fluxes (Jmax) and affinity constants for the binding of Ce to the biological uptake sites (KS) were established at pH 5.0 and pH 7.0. An apparent affinity constant of 1.8 × 107 M–1 was observed at pH 5.0, with a larger value obtained at pH 7.0 (6 × 107 M–1), albeit under conditions where equilibrium could not be confirmed. By evaluating Ce speciation using centrifugal ultrafiltration and single-particle inductively coupled plasma spectrometry, it could be concluded that very little (∼30%) Ce was truly dissolved at pH 7.0, with the majority of the metal being present in colloidal species. Speciation was also monitored by fluorescence to evaluate Ce complexation by natural organic matter (NOM). The presence of NOM decreased Ce bioaccumulation in line with free Ce concentrations. Finally, competition with calcium for the metal uptake sites was shown to result in a decrease in Ce uptake by C. reinhardtii