Along-the-channel modeling and analysis of PEFCs at low stoichiometry: Development of a 1+2D model

Water management remains a key challenge in polymer-electrolyte fuel cells. In this work, a pseudo 3-D (1+2D) model is developed to account better for changes of water management along the channel, as well as verify the possibilities of using differential cells for data capture and translation to integral cell performance. An accurate 2-D membrane-electrode-assembly model is developed for differential cell modeling, which is combined with an along-the-channel stepping algorithm to account for down the channel changes in pressure, temperature, reactant concentration, and relative humidity. Variations in cell performance along the channel due to changes in operating conditions are characterized quantitatively and optimized, where drier feed conditions demonstratively require such an approach. Overall, the study identifies gaps between differential and integral cells including those related to flow velocity and highlights the need for better models to understand and link integral cell performance and water management

Forman's Ricci curvature - From networks to hypernetworks

Networks and their higher order generalizations, such as hypernetworks or multiplex networks are ever more popular models in the applied sciences. However, methods developed for the study of their structural properties go little beyond the common name and the heavy reliance of combinatorial tools. We show that, in fact, a geometric unifying approach is possible, by viewing them as polyhedral complexes endowed with a simple, yet, the powerful notion of curvature - the Forman Ricci curvature. We systematically explore some aspects related to the modeling of weighted and directed hypernetworks and present expressive and natural choices involved in their definitions. A benefit of this approach is a simple method of structure-preserving embedding of hypernetworks in Euclidean N-space. Furthermore, we introduce a simple and efficient manner of computing the well established Ollivier-Ricci curvature of a hypernetwork.Comment: to appear: Complex Networks '18 (oral presentation

Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions

The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs

The diplomat's dilemma: Maximal power for minimal effort in social networks

Closeness is a global measure of centrality in networks, and a proxy for how influential actors are in social networks. In most network models, and many empirical networks, closeness is strongly correlated with degree. However, in social networks there is a cost of maintaining social ties. This leads to a situation (that can occur in the professional social networks of executives, lobbyists, diplomats and so on) where agents have the conflicting objectives of aiming for centrality while simultaneously keeping the degree low. We investigate this situation in an adaptive network-evolution model where agents optimize their positions in the network following individual strategies, and using only local information. The strategies are also optimized, based on the success of the agent and its neighbors. We measure and describe the time evolution of the network and the agents' strategies.Comment: Submitted to Adaptive Networks: Theory, Models and Applications, to be published from Springe

A family case of fertile human 45,X,psu dic(15;Y) males

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Variation in life history traits and transcriptome associated with adaptation to diet shifts in the ladybird Cryptolaemus montrouzieri

Background: Despite the broad diet range of many predatory ladybirds, the mechanisms involved in their adaptation to diet shifts are not completely understood. Here, we explored how a primarily coccidophagous ladybird Cryptolaemus montrouzieri adapts to feeding on aphids. Results: Based on the lower survival rate, longer developmental time, and lower adult body weight and reproduction rate of the predator, the aphid Megoura japonica proved being less suitable to support C. montrouzieri as compared with the citrus mealybug Planococcus citri. The results indicated up-regulation of genes related to ribosome and translation in fourth instars, which may be related to their suboptimal development. Also, several genes related to biochemical transport and metabolism, and detoxification were up-regulated as a result of adaptation to the changes in nutritional and non-nutritional (toxic) components of the prey. Conclusion: Our results indicated that C. montrouzieri succeeded in feeding on aphids by regulation of genes related to development, digestion and detoxification. Thus, we argue that these candidate genes are valuable for further studies of the functional evolution of ladybirds led by diet shifts

The Classical Harmonic Vibrations of the Atomic Centers of Mass with Micro Amplitudes and Low Frequencies Monitored by the Entanglement between the Two Two-level Atoms in a Single mode Cavity

We study the entanglement dynamics of the two two-level atoms coupling with a single-mode polarized cavity field after incorporating the atomic centers of mass classical harmonic vibrations with micro amplitudes and low frequencies. We propose a quantitative vibrant factor to modify the concurrence of the two atoms states. When the vibrant frequencies are very low, we obtain that: (i) the factor depends on the relative vibrant displacements and the initial phases rather than the absolute amplitudes, and reduces the concurrence to three orders of magnitude; (ii) the concurrence increases with the increase of the initial phases; (iii) the frequency of the harmonic vibration can be obtained by measuring the maximal value of the concurrence during a small time. These results indicate that even the extremely weak classical harmonic vibrations can be monitored by the entanglement of quantum states.Comment: 10 pages, 3 figure

Beyond Volume: The Impact of Complex Healthcare Data on the Machine Learning Pipeline

From medical charts to national census, healthcare has traditionally operated under a paper-based paradigm. However, the past decade has marked a long and arduous transformation bringing healthcare into the digital age. Ranging from electronic health records, to digitized imaging and laboratory reports, to public health datasets, today, healthcare now generates an incredible amount of digital information. Such a wealth of data presents an exciting opportunity for integrated machine learning solutions to address problems across multiple facets of healthcare practice and administration. Unfortunately, the ability to derive accurate and informative insights requires more than the ability to execute machine learning models. Rather, a deeper understanding of the data on which the models are run is imperative for their success. While a significant effort has been undertaken to develop models able to process the volume of data obtained during the analysis of millions of digitalized patient records, it is important to remember that volume represents only one aspect of the data. In fact, drawing on data from an increasingly diverse set of sources, healthcare data presents an incredibly complex set of attributes that must be accounted for throughout the machine learning pipeline. This chapter focuses on highlighting such challenges, and is broken down into three distinct components, each representing a phase of the pipeline. We begin with attributes of the data accounted for during preprocessing, then move to considerations during model building, and end with challenges to the interpretation of model output. For each component, we present a discussion around data as it relates to the healthcare domain and offer insight into the challenges each may impose on the efficiency of machine learning techniques.Comment: Healthcare Informatics, Machine Learning, Knowledge Discovery: 20 Pages, 1 Figur