Dynamic extensions of batch systems with cloud resources

Compute clusters use Portable Batch Systems (PBS) to distribute workload among individual cluster machines. To extend standard batch systems to Cloud infrastructures, a new service monitors the number of queued jobs and keeps track of the price of available resources. This meta-scheduler dynamically adapts the number of Cloud worker nodes according to the requirement profile. Two different worker node topologies are presented and tested on the Amazon EC2 Cloud service

Redefining risk research priorities for nanomaterials

Chemical-based risk assessment underpins the current approach to responsible development of nanomaterials (NM). It is now recognised, however, that this process may take decades, leaving decision makers with little support in the near term. Despite this, current and near future research efforts are largely directed at establishing (eco)toxicological and exposure data for NM, and comparatively little research has been undertaken on tools or approaches that may facilitate near-term decisions, some of which we briefly outline in this analysis. We propose a reprioritisation of NM risk research efforts to redress this imbalance, including the development of more adaptive risk governance frameworks, alternative/complementary tools to risk assessment, and health and environment surveillance

A microphysiological system model of therapy for liver micrometastases

Metastasis accounts for almost 90% of cancer-associated mortality. The effectiveness of cancer therapeutics is limited by the protective microenvironment of the metastatic niche and consequently these disseminated tumors remain incurable. Metastatic disease progression continues to be poorly understood due to the lack of appropriate model systems. To address this gap in understanding, we propose an all-human microphysiological system that facilitates the investigation of cancer behavior in the liver metastatic niche. This existing LiverChip is a 3D-system modeling the hepatic niche; it incorporates a full complement of human parenchymal and non-parenchymal cells and effectively recapitulates micrometastases. Moreover, this system allows real-time monitoring of micrometastasis and assessment of human-specific signaling. It is being utilized to further our understanding of the efficacy of chemotherapeutics by examining the activity of established and novel agents on micrometastases under conditions replicating diurnal variations in hormones, nutrients and mild inflammatory states using programmable microdispensers. These inputs affect the cues that govern tumor cell responses. Three critical signaling groups are targeted: the glucose/insulin responses, the stress hormone cortisol and the gut microbiome in relation to inflammatory cues. Currently, the system sustains functioning hepatocytes for a minimum of 15 days; confirmed by monitoring hepatic function (urea, α-1-antitrypsin, fibrinogen, and cytochrome P450) and injury (AST and ALT). Breast cancer cell lines effectively integrate into the hepatic niche without detectable disruption to tissue, and preliminary evidence suggests growth attenuation amongst a subpopulation of breast cancer cells. xMAP technology combined with systems biology modeling are also employed to evaluate cellular crosstalk and illustrate communication networks in the early microenvironment of micrometastases. This model is anticipated to identify new therapeutic strategies for metastasis by elucidating the paracrine effects between the hepatic and metastatic cells, while concurrently evaluating agent efficacy for metastasis, metabolism and tolerability.National Institutes of Health (U.S.) (Grant 1UH2TR000496-01)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039

All-human microphysical model of metastasis therapy

The vast majority of cancer mortalities result from distant metastases. The metastatic microenvironment provides unique protection to ectopic tumors as the primary tumors often respond to specific agents. Although significant interventional progress has been made on primary tumors, the lack of relevant accessible model in vitro systems in which to study metastases has plagued metastatic therapeutic development - particularly among micrometastases. A real-time, all-human model of metastatic seeding and cancer cells that recapitulate metastatic growth and can be probed in real time by a variety of measures and challenges would provide a critical window into the pathophysiology of metastasis and pharmacology of metastatic tumor resistance. To achieve this we are advancing our microscale bioreactor that incorporates human hepatocytes, human nonparenchymal liver cells, and human breast cancer cells to mimic the hepatic niche in three dimensions with functional tissue. This bioreactor is instrumented with oxygen sensors, micropumps capable of generating diurnally varying profiles of nutrients and hormones, while enabling real-time sampling. Since the liver is a major metastatic site for a wide variety of carcinomas and other tumors, this bioreactor uniquely allows us to more accurately recreate the human metastatic microenvironment and probe the paracrine effects between the liver parenchyma and metastatic cells. Further, as the liver is the principal site of xenobiotic metabolism, this reactor will help us investigate the chemotherapeutic response within a metabolically challenged liver microenvironment. This model is anticipated to yield markers of metastatic behavior and pharmacologic metabolism that will enable better clinical monitoring, and will guide the design of clinical studies to understand drug efficacy and safety in cancer therapeutics. This highly instrumented bioreactor format, hosting a growing tumor within a microenvironment and monitoring its responses, is readily transferable to other organs, giving this work impact beyond the liver. © 2013 BioMed Central Ltd

Immunomodulation by Different Types of N-Oxides in the Hemocytes of the Marine Bivalve Mytilus galloprovincialis

The potential toxicity of engineered nanoparticles (NPs) for humans and the environment represents an emerging issue. Since the aquatic environment represents the ultimate sink for NP deposition, the development of suitable assays is needed to evaluate the potential impact of NPs on aquatic biota. The immune system is a sensitive target for NPs, and conservation of innate immunity represents an useful basis for studying common biological responses to NPs. Suspension-feeding invertebrates, such as bivalves, are particularly at risk to NP exposure, since they have extremely developed systems for uptake of nano and microscale particles integral to intracellular digestion and cellular immunity. Evaluation of the effects of NPs on functional parameters of bivalve immunocytes, the hemocytes, may help understanding the major toxic mechanisms and modes of actions that could be relevant for different NP types in aquatic organisms.In this work, a battery of assays was applied to the hemocytes of the marine bivalve Mytilus galloprovincialis to compare the in vitro effects of different n-oxides (n-TiO2, n-SiO2, n-ZnO, n-CeO2) chosen on the basis of their commercial and environmental relevance. Physico-chemical characterization of both primary particles and NP suspensions in artificial sea water-ASW was performed. Hemocyte lysosomal and mitochondrial parameters, oxyradical and nitric oxide production, phagocytic activity, as well as NP uptake, were evaluated. The results show that different n-oxides rapidly elicited differential responses hemocytes in relation to their chemical properties, concentration, behavior in sea water, and interactions with subcellular compartments. These represent the most extensive data so far available on the effects of NPs in the cells of aquatic organisms. The results indicate that Mytilus hemocytes can be utilized as a suitable model for screening the potential effects of NPs in the cells of aquatic invertebrates, and may provide a basis for future experimental work for designing environmentally safer nanomaterials

Cd2+ Toxicity to a Green Alga Chlamydomonas reinhardtii as Influenced by Its Adsorption on TiO2 Engineered Nanoparticles

In the present study, Cd2+ adsorption on polyacrylate-coated TiO2 engineered nanoparticles (TiO2-ENs) and its effect on the bioavailability as well as toxicity of Cd2+ to a green alga Chlamydomonas reinhardtii were investigated. TiO2-ENs could be well dispersed in the experimental medium and their pHpzc is approximately 2. There was a quick adsorption of Cd2+ on TiO2-ENs and a steady state was reached within 30 min. A pseudo-first order kinetics was found for the time-related changes in the amount of Cd2+ complexed with TiO2-ENs. At equilibrium, Cd2+ adsorption followed the Langmuir isotherm with the maximum binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO2-EN concentration was 1, 10, and 100 mg/l, respectively. On the other hand, Cd2+ toxicity was alleviated in the presence of TiO2-ENs. Algal growth was less suppressed in treatments with comparable total Cd2+ concentration but more TiO2-ENs. However, such toxicity difference disappeared and all the data points could be fitted to a single Logistic dose-response curve when cell growth inhibition was plotted against the free Cd2+ concentration. No detectable amount of TiO2-ENs was found to be associated with the algal cells. Therefore, TiO2-ENs could reduce the free Cd2+ concentration in the toxicity media, which further lowered its bioavailability and toxicity to C. reinhardtii