We provide an integrated dynamic view on a eukaryotic osmolyte system, linking signaling with regulation of gene expression, metabolic control and growth. Adaptation to osmotic changes enables cells to adjust cellular activity and turgor pressure to an altered environment. The yeast Saccharomyces cerevisiae adapts to hyperosmotic stress by activating the HOG signaling cascade, which controls glycerol accumulation. The Hog1 kinase stimulates transcription of genes encoding enzymes required for glycerol production (Gpd1, Gpp2) and glycerol import (Stl1) and activates a regulatory enzyme in glycolysis (Pfk26/27). In addition, glycerol outflow is prevented by closure of the Fps1 glycerol facilitator. In order to better understand the contributions to glycerol accumulation of these different mechanisms and how redox and energy metabolism as well as biomass production are maintained under such conditions we collected an extensive dataset. Over a period of 180 min after hyperosmotic shock we monitored in wild type and different mutant cells the concentrations of key metabolites and proteins relevant for osmoadaptation. The dataset was used to parameterize an ODE model that reproduces the generated data very well. A detailed computational analysis using time-dependent response coefficients showed that Pfk26/27 contributes to rerouting glycolytic flux towards lower glycolysis. The transient growth arrest following hyperosmotic shock further adds to redirecting almost all glycolytic flux from biomass towards glycerol production. Osmoadaptation is robust to loss of individual adaptation pathways because of the existence and upregulation of alternative routes of glycerol accumulation. For instance, the Stl1 glycerol importer contributes to glycerol accumulation in a mutant with diminished glycerol production capacity. In addition, our observations suggest a role for trehalose accumulation in osmoadaptation and that Hog1 probably directly contributes to the regulation of the Fps1 glycerol facilitator. Taken together, we elucidated how different metabolic adaptation mechanisms cooperate and provide hypotheses for further experimental studies.

Simultaneous backscattering measurements with radar and sonar in the large wind wave facility in Marseilles, France shows that bound and free waves coexist on the water surface. By observing the surface from above and below, we were able to show definitively that the bound waves ride on the front face of the dominant wave in the tank. Because of the large width of the tank, we were able to vary the azimuth angle of both the radar and sonar, which viewed a common surface area, and observe the dependence of both free and bound waves on azimuth angle.

Many optimizing compilers perform global register allocation using a Chaitin-style graph coloring algorithm. Live ranges that cannot be allocated to registers are spilled to memory. The amount of code required to spill the live range depends on the spilling heuristic used. Chaitin's spilling heuristic offers some guidance in reducing the amount of spill code produced. However, this heuristic does not allow the partial spilling of live ranges and the reduction in spill code is limited to a local level. In this paper, we present a global technique called interference region spilling that improves the spilling granularity of any local spilling heuristic. Our technique works above the local spilling heuristic, limiting the normal insertion of spill code to a portion of each spilled live range. By partially spilling live ranges, we can achieve large reductions in dynamically executed spill code; up to 75% in some cases and an average of 33.6% across the benchmarks tested. 1 Introduction Gl...

Array and pointer references are often ambiguous in that compile time analysis cannot always determine if distinct references are to the same object. Ambiguously aliased objects are not allocated to registers by conventional compilers due to the cost of the loads and stores required to keep register copies consistent with memory and each other. There are several hardware and software strategies that can be used to solve the ambiguous alias problem; we have implemented one such scheme called CRegs in a compiler and instruction level simulator. We present a modification to Briggs' Optimistic Coloring Algorithm that allows us to allocate local and parameter arrays to CRegs. The CRegs register file operation and instruction set modifications required to implement this scheme are discussed. Underlying hardware issues such as pipeline impact and chip area are briefly discussed. Several benchmarks are compared in terms of dynamic instructions executed for two CReg set sizes. The measured reduction in memory operations is significant, averaging 23% for the benchmarks shown.