247,164 research outputs found

    Mediated population protocols

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    We extend here the Population Protocol (PP) model of Angluin et al. (2004, 2006) [2,4] in order to model more powerful networks of resource-limited agents that are possibly mobile. The main feature of our extended model, called the Mediated Population Protocol (MPP) model, is to allow the edges of the interaction graph to have states that belong to a constant-size set. We then allow the protocol rules for pairwise interactions to modify the corresponding edge state. The descriptions of our protocols preserve both the uniformity and anonymity properties of PPs, that is, they do not depend on the size of the population and do not use unique identifiers. We focus on the computational power of the MPP model on complete interaction graphs and initially identical edges. We provide the following exact characterization of the class MPS of stably computable predicates: a predicate is in MPS iff it is symmetric and is in NSPACE(n2). © 2010 Elsevier B.V. All rights reserved

    Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

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    A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection

    A Pre-transplant Blood-based Lipid Signature for Prediction of Antibody-mediated Rejection in Kidney Transplant Patients

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    Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients. Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to create Linear Discrimination Analysis with regularized correction (RLDA). Changes over time were estimated using sparse partial least square method which is validated by permutation testing. T-test was performed to compare two time points for the same group and groups at matched time points. JMP Pro 13 and MetaboAnalyst were used in the analysis of the Data. Results. A comparison of lipids classes on the day of transplant revealed PLs relative concentration differences between SC and AMR. Concentration of phosphatidylcholine (PC) was significantly diminished in AMR, while there was a trend for increased concentration of lysophosphatidylcholine (LPC). AMR group also showed significantly lower concentration of phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), plasmanylethanolamine (PE-O), and plasmenylethanolamine (PE-P). Our data demonstrated that there are significant differences in the lipidome between SC and AMR on the day of transplant. The analysis identified 7 distinct lipids that discriminated between AMR and SC (AUC) =0.95 (95%CI=0.84- 0.98), R2=0.63 (95%CI=0.4-0.8). A sPLSDA analysis of the data revealed a statistically significant alteration in the lipid profile at 6 months post-transplant compared to the day of transplant. The analysis revealed a panel of 13 lipids that were found to differentiate the two groups at 6 month post-transplant . Further data analysis confirms the presence of a sustained lipid metabolic difference between SC and AMR over time that distinguish between the patients with favorable and non-favorable transplant outcomes. Conclusion. This study demonstrates the potential of the pre-transplant lipidome towards determining AMR in kidney transplant patients, raising the possibility of using this information in risk stratification of patients about to undergo transplant.https://scholarscompass.vcu.edu/gradposters/1086/thumbnail.jp

    Passively Mobile Communicating Logarithmic Space Machines

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    We propose a new theoretical model for passively mobile Wireless Sensor Networks. We call it the PALOMA model, standing for PAssively mobile LOgarithmic space MAchines. The main modification w.r.t. the Population Protocol model is that agents now, instead of being automata, are Turing Machines whose memory is logarithmic in the population size n. Note that the new model is still easily implementable with current technology. We focus on complete communication graphs. We define the complexity class PLM, consisting of all symmetric predicates on input assignments that are stably computable by the PALOMA model. We assume that the agents are initially identical. Surprisingly, it turns out that the PALOMA model can assign unique consecutive ids to the agents and inform them of the population size! This allows us to give a direct simulation of a Deterministic Turing Machine of O(nlogn) space, thus, establishing that any symmetric predicate in SPACE(nlogn) also belongs to PLM. We next prove that the PALOMA model can simulate the Community Protocol model, thus, improving the previous lower bound to all symmetric predicates in NSPACE(nlogn). Going one step further, we generalize the simulation of the deterministic TM to prove that the PALOMA model can simulate a Nondeterministic TM of O(nlogn) space. Although providing the same lower bound, the important remark here is that the bound is now obtained in a direct manner, in the sense that it does not depend on the simulation of a TM by a Pointer Machine. Finally, by showing that a Nondeterministic TM of O(nlogn) space decides any language stably computable by the PALOMA model, we end up with an exact characterization for PLM: it is precisely the class of all symmetric predicates in NSPACE(nlogn).Comment: 22 page

    Exercise-Derived Microvesicles: A Review of the Literature

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    Initially suggested as simple cell debris, cell-derived microvesicles (MVs) have now gained acceptance as recognized players in cellular communication and physiology. Shed by most, and perhaps all, human cells, these tiny lipid-membrane vesicles carry bioactive agents, such as proteins, lipids and microRNA from their cell source, and are produced under orchestrated events in response to a myriad of stimuli. Physical exercise introduces systemic physiological challenges capable of acutely disrupting cell homeostasis and stimulating the release of MVs into the circulation. The novel and promising field of exercise-derived MVs is expanding quickly, and the following work provides a review of the influence of exercise on circulating MVs, considering both acute and chronic aspects of exercise and training. Potential effects of the MV response to exercise are highlighted and future directions suggested as exercise and sports sciences extend the realm of extracellular vesicles

    The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells

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    We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM
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