Middleware support for many-task computing

Many-task computing aims to bridge the gap between two computing paradigms, high throughput computing and high performance computing. Many-task computing denotes high-performance computations comprising multiple distinct activities, coupled via file system operations. The aggregate number of tasks, quantity of computing, and volumes of data may be extremely large. Traditional techniques found in production systems in the scientific community to support many-task computing do not scale to today’s largest systems, due to issues in local resource manager scalability and granularity, efficient utilization of the raw hardware, long wait queue times, and shared/parallel file system contention and scalability. To address these limitations, we adopted a “top-down” approach to building a middleware called Falkon, to support the most demanding many-task computing applications at the largest scales. Falkon (Fast and Light-weight tasK executiON framework) integrates (1) multi-level scheduling to enable dynamic resource provisioning and minimize wait queue times, (2) a streamlined task dispatcher able to achieve orders-of-magnitude higher task dispatch rates than conventional schedulers, and (3) data diffusion which performs data caching and uses a data-aware scheduler to co-locate computational and storage resources. Micro-benchmarks have shown Falkon to achieve over 15K+ tasks/s throughputs, scale to hundreds of thousands of processors and to millions of queued tasks, and execute billions of tasks per day. Data diffusion has also shown to improve applications scalability and performance, with its ability to achieve hundreds of Gb/s I/O rates on modest sized clusters, with Tb/s I/O rates on the horizon. Falkon has shown orders of magnitude improvements in performance and scalability than traditional approaches to resource management across many diverse workloads and applications at scales of billions of tasks on hundreds of thousands of processors across clusters, specialized systems, Grids, and supercomputers. Falkon’s performance and scalability have enabled a new class of applications called Many-Task Computing to operate at previously so-believed impossible scales with high efficiency.     

Dual role of mesenchymal stem/stromal cells and their cell-free extracellular vesicles in colorectal cancer

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell–cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.     

Repetitive pulling catalyzes co-translocational unfolding of barnase during import through a mitochondrial pore

We present a computational study of barnase unfolding during import into mitochondria through a model translocon. In contrast to thermal (or chemical) unfolding, the major intermediates of co-translocational unfolding are mainly mediated by non-native interactions accompanying the protein configurations induced by pulling forces. These energy contributions, combined with backbone topological constraints imposed by the model pore, result in milestones along the unfolding pathways which are significantly different not only from those experienced during thermal (or chemical) denaturation, but also from those observed in single-molecule pulling by both ends without pore constraints. Two on-pathway major translocation intermediates trapped in long-lived states by significantly high unfolding barriers are identified. A fraction of these pathways can, however, skip such local kinetic traps and result in extremely fast translocations, leading to a dramatic kinetic partitioning spanning approximately four orders of magnitude. The fraction of fast translocation events is shown to increase upon switching the pull off and on, when compared to pulling at constant force. This suggests a "catalytic" mechanism by which the mitochondrial import machinery regulates this partitioning by repetitively pulling in cycles. A number of mutation sites that alter the kinetic "flow" of the unfolding trajectories are suggested and tested.     

The characterization of complex continuous norms of reaction

Recent focus on the array of phenotypes expressed under differing environmental conditions, or phenotypic plasticity, has led to increased understanding of its genetic basis as well as its adaptive significance. However, the quantification of plasticity has proven difficult, hampered by both the limited number of environments over which plasticity may typically be assessed and by the need to assume, a priori, the general form of reaction norms under study. Our understanding of the shapes of continuous norms of reaction and, consequently, the subtle differences that may exist in shapes among genotypes or populations is rudimentary. Here, we propose the use of the loess smoothing function to analyze complex norms of reaction and to quantify total plasticity over many environments. A thermogradient incubator offers an ideal means to provide many environments for a demonstration of the use of the loess method. We test seed germination in three populations of two monocarpic plant species for population differentiation in plasticity to temperature. First, we test for differentiation in norms of reaction to 30 temperature environments among three populations of the monocarpic perennial, Lobelia inflata . The second demonstration assesses plasticity to eight temperature environments of three populations of the arctic-alpine annual, Koenigia islandica . Our demonstration shows that the loess technique can detect significant genetic differentiation among populations in complex norms of reaction for both species studied, and suggests that the use of this procedure should be considered where the form of norms of reaction might be complex. The general applicability of the approach is discussed.     

Non-invasive label-free monitoring the cardiac differentiation of human embryonic stem cells in-vitro by Raman spectroscopy

Background

Online label-free monitoring of in-vitro differentiation of stem cells remains a major challenge in stem cell research. In this paper we report the use of Raman micro-spectroscopy (RMS) to measure time- and spatially-resolved molecular changes in intact embryoid bodies (EBs) during in-vitro cardiogenic differentiation.

Methods

EBs formed by aggregation of human embryonic stem cells (hESCs) were cultured in defined medium to induce differentiation towards cardiac phenotype and maintained in purpose-built micro-bioreactors on the Raman microscope for 5 days (between days 5 and 9 of differentiation) and spatially-resolved spectra were recorded at 24 h intervals.

Results

The Raman spectra showed that the onset of spontaneous beating of EBs at day 7 coincided with an increase in the intensity of the Raman bands at 1340 cm^− 1, 1083 cm^− 1, 937 cm^− 1, 858 cm^− 1, 577 cm^− 1 and 482 cm^− 1. The spectral maps corresponding to these bands had a high positive correlation with the expression of the cardiac-specific α-actinin obtained by immuno-fluorescence imaging of the same EBs. The spectral markers obtained here are also in agreement with previous studies performed on individual live hESC-derived CMs.

Conclusions

The intensity profile of these Raman bands can be used for label-free in-situ monitoring of EBs to estimate the efficacy of cardiogenic differentiation.

General significance

As the acquisition of the time-course Raman spectra did not affect the viability or the differentiation potential of the hESCs, this study demonstrates the feasibility of using RMS for on-line non-invasive continuous monitoring of such processes inside bioreactor culture systems.     

Cellulose extraction from orange peel using sulfite digestion reagents

Orange peel (OP) was used as raw material for cellulose extraction. Two different pulping reagents were used, sodium sulfite and sodium metabisulfite. The effect of the main process parameters, sulfite agent dosage and reaction duration, on cellulose yield was investigated. A central composite rotatable design involving two variables at five levels and response surface methodology were used for the optimization of cellulose recovery. Other two invariable parameters were reaction temperature and hydromodulus. The optimum yields, referred to the weight of double extracted OP, were 40.4% and 45.2% for sodium sulfite and sodium metabisulfite digestions, respectively. The crude celluloses were bleached with hypochlorite and oxygen. The physicochemical characterization data of these cellulose materials indicate good levels of purity, low crystallinities, good whitenesses, good water retention and moderate molecular weights. According to these specific properties the recovered celluloses could be used as fillers, water absorbents, or as raw materials for cellulose derivatives.     

Effects of Menadione, Hydrogen Peroxide, and Quercetin on Apoptosis and Delayed Luminescence of Human Leukemia Jurkat T-Cells

Menadione (MD) is an effective cytotoxic drug able to produce intracellularly large amounts of superoxide anion. Quercetin (QC), a widely distributed bioflavonoid, can exert both antioxidant and pro-oxidant effects and is known to specifically inhibit cell proliferation and induce apoptosis in different cancer cell types. We have investigated the relation between delayed luminescence (DL) induced by UV-laser excitation and the effects of MD, hydrogen peroxide, and QC on apoptosis and cell cycle in human leukemia Jurkat T-cells. Treatments with 500 μM H₂O₂ and 250 μM MD for 20 min produced 66.0 ± 4.9 and 46.4 ± 8.6% apoptotic cell fractions, respectively. Long-term (24 h) pre-exposure to 5 μM, but not 0.5 μM QC enhanced apoptosis induced by MD, whereas short-term (1 h) pre-incubation with 10 μM QC offered 50% protection against H₂O₂-induced apoptosis, but potentiated apoptosis induced by MD. Since physiological levels of QC in the blood are normally less than 10 μM, these data can provide relevant information regarding the benefits of flavonoid-combined treatments of leukemia. All the three drugs exerted significant effects on DL. Our data are consistent with (1) the involvement of Complex I of the mitochondrial respiratory chain as an important source of delayed light emission on the 10 μs–10 ms scale, (2) the ability of superoxide anions to quench DL on the 100 μs–10 ms scale, probably via inhibition of reverse electron transfer at the Fe/S centers in Complex I, and (3) the relative insensitivity of DL to intracellular OH^? and H₂O₂ levels.     

Yeast RAS2 affects cell viability,mitotic division and transient gene expression in Nicotiana species

Overexpression of the budding yeast RAS2 gene in Nicotiana plumbaginifolia cells revealed that RAS2 acted as a suicide gene in freshly isolated protoplasts from leaves and blocked cell proliferation in cell suspension-derived protoplasts. Among a series of genes tested (such as npt II, CDC35, PDE2), RAS2 was the only one to block the expression of the cat gene, as measured in a transient gene expression assay. Another ras gene, v-Ha-ras, had similar effects. Furthermore, the RAS2 effect was species-specific and depended on the modulation of hormonal metabolism in the transfected cells, while no differences were noticed between the normal and the activated val19 gene. Transfected plant cells are shown to synthesize a RAS2 protein of the same electrophoretic mobility as the yeast RAS2 product. The results are discussed in the broader context of the evolutionarily conserved ras genes involved in vital cellular functions.     

Investigations of the supramolecular structure of individual diphenylalanine nano- and microtubes by polarized Raman microspectroscopy

Polarized Raman microspectroscopy and atomic force microscopy were used to obtain quantitative information regarding the molecular structure of individual diphenylalanine (FF) nano- and microtubes. The frequencies of the Raman spectral bands corresponding to the amide I (1690 cm(-1)) and amide III (1249 cm(-1)) indicated that the FF-molecules interact by hydrogen bonding at the N-H and not at the C═O sites. The calculated mean orientation angles of the principal axes of the Raman tensors (PARTs) obtained from the polarized Raman spectral measurements were 41 ± 4° for the amide I and 59 ± 5° for amide III. On the basis of the orientation of the PART for the amide I mode, it was found that the C═O bond is oriented at an angle of 8 ± 4° to the tube axis. These values did not vary significantly with the diameter of the tubes (range 400-1700 nm) and were in agreement with the molecular structure proposed previously for larger crystalline specimens.