Harnessing parallelism in multicore clusters with the All-Pairs,Wavefront, and Makeflow abstractions

Both distributed systems and multicore systems are difficult programming environments. Although the expert programmer may be able to carefully tune these systems to achieve high performance, the non-expert may struggle. We argue that high level abstractions are an effective way of making parallel computing accessible to the non-expert. An abstraction is a regularly structured framework into which a user may plug in simple sequential programs to create very large parallel programs. By virtue of a regular structure and declarative specification, abstractions may be materialized on distributed, multicore, and distributed multicore systems with robust performance across a wide range of problem sizes. In previous work, we presented the All-Pairs abstraction for computing on distributed systems of single CPUs. In this paper, we extend All-Pairs to multicore systems, and introduce the Wavefront and Makeflow abstractions, which represent a number of problems in economics and bioinformatics. We demonstrate good scaling of both abstractions up to 32 cores on one machine and hundreds of cores in a distributed system.     

Role of WASP in cell polarity and podosome dynamics of myeloid cells

The integrin-dependent migration of myeloid cells requires tight coordination between actin-based cell membrane protrusion and integrin-mediated adhesion to form a stable leading edge. Under this mode of migration, polarised myeloid cells including dendritic cells, macrophages and osteoclasts develop podosomes that sustain the extending leading edge. Podosome integrity and dynamics vary in response to changes in the physical and biochemical properties of the cell environment. In the current article we discuss the role of various factors in initiation and stability of podosomes and the roles of the Wiskott Aldrich Syndrome Protein (WASP) in this process. We discuss recent data indicating that in a cellular context WASP is crucial not only for localised actin polymerisation at the leading edge and in podosome cores but also for coordination of integrin clustering and activation during podosome formation and disassembly.     

Frozen Cord Blood Hematopoietic Stem Cells Differentiate into Higher Numbers of Functional Natural Killer Cells In Vitro than Mobilized Hematopoietic Stem Cells or Freshly Isolated Cord Blood Hematopoietic Stem Cells

Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC) has become an alluring option for NK cell therapy, with umbilical cord blood (UCB) and mobilized peripheral blood (PBCD34⁺) being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34⁺) and frozen PBCD34⁺ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34⁺ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34⁺ cultures. NK cells generated from CBCD34⁺ and PBCD34⁺ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34⁺-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34⁺-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34⁺ for the production of NK cells in vitro results in higher cell numbers than PBCD34⁺, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.     

Optimization in the recovery of a labile intracellular enzyme

A high molecular weight intracellular enzyme of Bacillus brevis ATCC 9999 is released when the organism is disrupted by sonication of homogenization. However, both processes also degrade the enzyme. Assays for protein release and specific enzymatic activity of the released protein indicate that both release and degradation can be represented by first-order kinetic models. Utilization of the difference between the kinetics of release and degradation allows optimization in the recovery of this enzyme for both the sonication and homogenization processes.     

High productivity tank fermentation for gramicidin S synthetases

A high productivity tank fermentation for gramicidin S synthetases has been developed to supply biocatalyst for a preparative-scale ATP-driven cell-free enzymatic synthesis employing the polypeptide antibiotic, gramicidin S, as a model product. A rich, complex medium supports rapid and dense growth of the enzyme-producing microorganism, Bacillus brevis ATCC 9999, accompanied by the appearance of excellentenzyme activities. Under conditions used, the two enzyme fractions of the gramicidin S synthesizing system, as well as the total enzymatic activity for synthesis of gramicidin S, all reach their maxima simultaneously at the point where growth enters the stationary phase. Successful batch enzyme fermentations have been performed at the bench (14 liter) and pilot (180 liter)scales.     

Carbon monoxide oxygenase activity of cytochrome cd1

Cytochrome cd1 from the denitrifying bacterium Pseudomonas aeruginosa catalyzes the oxygenation of carbon monoxide by dioxygen. A minimum estimate of the turnover number for this activity is 7 mol of carbon dioxide produced per hour per mole of cytochrome subunit at 30 degrees C and pH 7. The reaction is 98% inhibited by 2.5 mM cyanide, but catalase has no effect. The reaction accounts for the unusual reduction of ferric cytochrome in the presence of carbon monoxide, but no additional reducing agent. The reaction is independent of the steady-state oxidation level of the cytochrome during turnover. Under anaerobic conditions, ferricyanide plus water may substitute for dioxygen as the source of oxidizing equivalents and atomic oxygen.     

Regulation of rat liver phosphofructokinase levels in Morris hepatomas.

The levels of the major liver phosphofructokinase isozyme (PFK-L₂) and the PFK regulatory factor were measured in adult and fetal liver as well as Morris hepatomas of different differentiation states. The results indicate that both the PFK-L₂ activity and the PFK regulatory factor levels in well and highly differentiated hepatomas are not statistically different from the amounts found in adult liver. In the poorly differentiated hepatomas and fetal liver, the levels of both PFK-L₂ and PFK regulatory factor are approximately 2 and 3 fold greater, respectively, than what was found in adult liver.