Small Time Asymptotics on the Diagonal for Hörmander’s Type Hypoelliptic Operators

We compute the small time asymptotics of the fundamental solution of Hörmander’s type hypoelliptic operators with drift, on the diagonal at a point x ₀. We show that the order of the asymptotics depends on the controllability of an associated control problem and of its approximating system. If the control problem of the approximating system is controllable at x ₀, then so is also the original control problem, and in this case we show that the fundamental solution blows up as \(\phantom {\dot {i}\!}t^{-\mathcal {N}/2}\), where \(\phantom {\dot {i}\!}\mathcal {N}\) is a number determined by the Lie algebra at x ₀ of the fields, that define the hypoelliptic operator.     

The iterative group implicit algorithm for parallel transient finite element analysis

The Iterative Group Implicit (IGI) algorithm is developed for the parallel solution of general structural dynamic problems. In this method the original structure is partitioned into a number of a subdomains. Each subdomain is solved independently and therefore concurrently, using any traditional direct solution method. The IGI algorithm is an extension of the Group Implicit (GI) algorithm, and similarly to that method compatibility of the interface degrees of freedom is restored using a mass averaging rule. However, unlike the GI algorithm, in the IGI algorithm an iterative procedure is devised to restore equilibrium at the interface degrees of freedom. The IGI method has the same algorithmic characteristics as the underlying solution method used to solve each subdomain. Furthermore, the solution obtained by this method, once the iteration converges, is the same as the one obtained if the subdomain solution method is used to solve the whole structure. Numerical studies are carried out which demonstrate that the performance of the IGI algorithm is superior to that of the GI algorithm both in terms of accuracy and efficiency. Finally, the IGI method is highly modular and scalable, and therefore very well suited for distributed and parallel computing. Copyright © 2000 John Wiley & Sons, Ltd.     

Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk

Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting. Immune activation is a shared pathophysiology across several different developmental stressors and may thus be a targetable treatment to mitigate the later behavioral deficits. In this review, we explore different types of prenatal and perinatal stressors and their contribution to disease risk and underlying molecular mechanisms. We highlight the impact of developmental stressors on microglia biology because of their early infiltration into the brain, their critical role in brain development and function, and their long-lived status in the brain throughout life. Furthermore, we introduce innate immune memory as a potential underlying mechanism for developmental stressors’ impact on disease. Finally, we highlight the molecular and epigenetic reprogramming that is known to underlie innate immune memory and explain how similar molecular mechanisms may be at work for cells to retain a long-term perturbation after exposure to developmental stressors.     

Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56^dimCD16⁻ and CD56^brightCD16⁻ NK cells represent the predominant NK cell subpopulations in AML, while the CD56^dimCD16⁺ NK cells are significantly reduced compared to HDs. Moreover, TIGIT⁺ and PVRIG⁺ cells cluster on the CD56^dimCD16⁺ subset whereas CD39⁺ and CD38⁺ cells do so on CD56^brightCD16⁻ NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.     

Effect of chitosan coating in preventing deterioration and preserving the quality of fresh‐cut papaya ‘Maradol’

BACKGROUND: Chitosan can form antimicrobial, semi‐permeable barriers that limit gas exchange and reduces water loss in fruits. Consumer interest in fresh‐cut papaya fruit is leading to increasing demand because of its sensorial and antioxidant properties. However, papaya is a highly perishable product that is prone to loss of weight, loss of firmness and microbial attack. The aim of this study was to evaluate the effect of chitosan coatings on the overall quality of fresh‐cut papaya. Chitosan coatings of low (LMWC), medium (MMWC) and high (HMWC) molecular weights, at concentrations of 0.01 and 0.02 g mL^?1, were applied to fresh‐cut papaya cubes. The treated cubes were stored at 5 °C and changes in quality were evaluated. RESULTS: MMWC maintained the highest color values (L* and b*) and firmness. Chitosan coatings suppressed mesophilic plate count, and the growth of molds and yeast, compared to controls. The MMWC coatings at 0.02 g mL^?1 resulted in the highest antimicrobial activity and decreased the activity of the enzymes polygalacturonase and pectin methylesterase, followed by low and high MW chitosan coatings at 0.02 g mL^?1. CONCLUSION: The application of the MMWC treatment at 0.02 g mL^?1 could be used to reduce deteriorative processes, maintain quality and increase the shelf life of fresh‐cut papaya stored at 5 °C. Copyright © 2008 Society of Chemical Industry     

Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.     

Modeling of the polluting emissions from a cement production plant by partial least-squares, principal component regression, and artificial neural networks

A Portland cement process was taken into consideration and monitored for one month with respect to polluting emissions, fuel and raw material physical-chemical properties, and operative conditions. Soft models, based on linear (partial least-squares, PLS, and principal component regression, PCR) and nonlinear (artificial neural networks, ANNs) approaches, were employed to predict the polluting emissions. The predictive ability of the three regression methods was evaluated by means of the partition of the dataset by Kohonen self-associative maps into both a training and a test set. Then, a "leave-more-out" approach, based on the use of a training set, a test set, and a production set, was adopted. The training set was used to build the models, the test set was used to select the number of latent variables or the neural network training endpoint, and the production set was used to produce genuine predictions. ANNs proved to be much more effective in prediction with respect to PLS and PCR and, at least in the case of SO2 and dust, provided a predictive ability comparable with the experimental estimated uncertainty of the response. This showed that it is possible to satisfactorily predict the two responses. Such a prediction will result in the prevention of environmental and legal problems connected to the polluting emissions.     

Effects of long-term heavy metal contamination on soil microbial characteristics

In this study, total heavy metal content and its effects on soil microbiological characteristics were investigated in soil samples from an area with known long-term pollution problems. The total heavy metal concentrations of contaminated soil samples were 109 and 1,558 mg/kg for Hg and As, respectively. Key microbiological parameters measured included dehydrogenase activity, ATP content and number of culturable aerobic bacteria, actinomycetes, fungi and asymbiotic nitrogen-fixers. Quantitative analysis of soil microbial populations shows a marked decrease in total culturable numbers of the different microbial groups of the contaminated soil samples. Certain groups of soil microbes were particularly sensitive to long-term contamination (asymbiotic nitrogen-fixers and heterotrophic bacteria). Dehydrogenase activity was found to be a sensitive assay for determining the effect of heavy metals on physiologically active soil microbial biomass and sustains the high applicability of this parameter for soil ecotoxicological testing as reported by other authors.     

Features of the mechanical properties of phosphate glasses doped with rare earth elements under indentation

The microstructure, as well as the mechanical and thermal properties, of phosphate glasses (PhGs) doped with rare earth elements (REEs), namely, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, and Yb, were studied in the present paper. The strength parameters of the PhGs and their dependence on the load value modification were estimated by the dynamic indentation method. Three specific stages were revealed in the deformation process, including nano-, submicro-, and microdeformation. The factors responsible for each stage were determined. It was shown that the strength properties (Young’s modulus and hardness) and the thermal characteristics (the lower and upper annealing temperature, the softening temperature, and the vitrification temperature) exhibit no evident relationship with the atomic mass and ionic radius of an REE. An assumption was made that the elastic and plastic properties of PhGs can be determined by the internal structure of the glasses.