An Experimental and Simulation Study of Early Flame Development in a Homogeneous-Charge Spark-Ignition Engine

An integrated experimental and Large-Eddy Simulation (LES) study is presented for homogeneous premixed combustion in a spark-ignition engine. The engine is a single-cylinder two-valve optical research engine with transparent liner and piston: the Transparent Combustion Chamber (TCC) engine. This is a relatively simple, open engine configuration that can be used for LES model development and validation by other research groups. Pressure-based combustion analysis, optical diagnostics and LES have been combined to generate new physical insight into the early stages of combustion. The emphasis has been on developing strategies for making quantitative comparisons between high-speed/high-resolution optical diagnostics and LES using common metrics for both the experiments and the simulations, and focusing on the important early flame development period. Results from two different LES turbulent combustion models are presented, using the same numerical methods and computational mesh. Both models yield Cycle-to-Cycle Variations (CCV) in combustion that are higher than what is observed in the experiments. The results reveal strengths and limitations of the experimental diagnostics and the LES models, and suggest directions for future diagnostic and simulation efforts. In particular, it has been observed that flame development between the times corresponding to the laminar-to-turbulent transition and 1% mass-burned fraction are especially important in establishing the subsequent combustion event for each cycle. This suggests a range of temporal and spatial scales over which future experimental and simulation efforts should focus

Machine Learning Assisted Design of Experiments for Solid State Electrolyte Lithium Aluminum Titanium Phosphate

Lithium-ion batteries with solid electrolytes offer safety, higher energy density and higher long-term performance, which are promising alternatives to conventional liquid electrolyte batteries. Lithium aluminum titanium phosphate (LATP) is one potential solid electrolyte candidate due to its high Li-ion conductivity. To evaluate its performance, influences of the experimental factors on the materials design need to be investigated systematically. In this work, a materials design strategy based on machine learning (ML) is employed to design experimental conditions for the synthesis of LATP. In the variation of parameters, we focus on the tolerance against the possible deviations in the concentration of the precursors, as well as the influence of sintering temperature and holding time. Specifically, models built with different design selection strategies are compared based on the training data assembled from previous laboratory experiments. The best one is then chosen to design new experiment parameters, followed by measuring the corresponding properties of the newly synthesized samples. A previously unknown sample with ionic conductivity of 1.09 × 10$^{-3}$ S cm$^{-1}$ is discovered within several iterations. In order to further understand the mechanisms governing the high ionic conductivity of these samples, the resulting phase compositions and crystal structures are studied with X-ray diffraction, while the microstructures of sintered pellets are investigated by scanning electron microscopy. Our studies demonstrate the advantages of applying machine learning in designing experimental conditions by the synthesis of desired materials, which can effectively help researchers to reduce the number of required experiments

The double Ringel-Hall algebra on a hereditary abelian finitary length category

In this paper, we study the category $\mathscr{H}^{(\rho)}$ of semi-stable coherent sheaves of a fixed slope $\rho$ over a weighted projective curve. This category has nice properties: it is a hereditary abelian finitary length category. We will define the Ringel-Hall algebra of $\mathscr{H}^{(\rho)}$ and relate it to generalized Kac-Moody Lie algebras. Finally we obtain the Kac type theorem to describe the indecomposable objects in this category, i.e. the indecomposable semi-stable sheaves.Comment: 29 page

Phase diagram of two-lane driven diffusive systems

We consider a large class of two-lane driven diffusive systems in contact with reservoirs at their boundaries and develop a stability analysis as a method to derive the phase diagrams of such systems. We illustrate the method by deriving phase diagrams for the asymmetric exclusion process coupled to various second lanes: a diffusive lane; an asymmetric exclusion process with advection in the same direction as the first lane, and an asymmetric exclusion process with advection in the opposite direction. The competing currents on the two lanes naturally lead to a very rich phenomenology and we find a variety of phase diagrams. It is shown that the stability analysis is equivalent to an `extremal current principle' for the total current in the two lanes. We also point to classes of models where both the stability analysis and the extremal current principle fail

Imaging of adult leukodystrophies

Leukodystrophies are genetically determined white matter disorders. Even though leukodystrophies essentially affect children in early infancy and childhood, these disorders may affect adults. In adults, leukodystrophies may present a distinct clinical and imaging presentation other than those found in childhood. Clinical awareness of late-onset leukodystrophies should be increased as new therapies emerge. MRI is a useful tool to evaluate white matter disorders and some characteristics findings can help the diagnosis of leukodystrophies. This review article briefly describes the imaging characteristics of the most common adult leukodystrophies

Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs

The Tandem CARDs of NOD2: Intramolecular Interactions and Recognition of RIP2

Caspase recruitment domains (CARDs) are homotypic protein interaction modules that link the stimulus-dependent assembly of large signaling platforms such as inflammasomes to the activation of downstream effectors that often include caspases and kinases and thereby play an important role in the regulation of inflammatory and apoptotic signaling pathways. NOD2 belongs to the NOD-like (NLR) family of intracellular pattern recognition receptors (PRR) and induces activation of the NF-κB pathway in response to the recognition of bacterial components. This process requires the specific recognition of the CARD of the protein kinase RIP2 by the tandem CARDs of NOD2. Here we demonstrate that the tandem CARDs of NOD2 are engaged in an intramolecular interaction that is important for the structural stability of this region. Using a combination of ITC and pull-down experiments we identify distinct surface areas that are involved in the intramolecular tandem CARD interaction and the interaction with the downstream effector RIP2. Our findings indicate that while CARDa of NOD2 might be the primary binding partner of RIP2 the two CARDs of NOD2 do not act independently of one another but may cooperate to from a binding surface that is distinct from that of single CARDs

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses