Customizing the Computation Capabilities of Microprocessors.

Designers of microprocessor-based systems must constantly improve performance and increase computational efficiency in their designs to create value. To this end, it is increasingly common to see computation accelerators in general-purpose processor designs. Computation accelerators collapse portions of an application's dataflow graph, reducing the critical path of computations, easing the burden on processor resources, and reducing energy consumption in systems. There are many problems associated with adding accelerators to microprocessors, though. Design of accelerators, architectural integration, and software support all present major challenges. This dissertation tackles these challenges in the context of accelerators targeting acyclic and cyclic patterns of computation. First, a technique to identify critical computation subgraphs within an application set is presented. This technique is hardware-cognizant and effectively generates a set of instruction set extensions given a domain of target applications. Next, several general-purpose accelerator structures are quantitatively designed using critical subgraph analysis for a broad application set. The next challenge is architectural integration of accelerators. Traditionally, software invokes accelerators by statically encoding new instructions into the application binary. This is incredibly costly, though, requiring many portions of hardware and software to be redesigned. This dissertation develops strategies to utilize accelerators, without changing the instruction set. In the proposed approach, the microarchitecture translates applications at run-time, replacing computation subgraphs with microcode to utilize accelerators. We explore the tradeoffs in performing difficult aspects of the translation at compile-time, while retaining run-time replacement. This culminates in a simple microarchitectural interface that supports a plug-and-play model for integrating accelerators into a pre-designed microprocessor. Software support is the last challenge in dealing with computation accelerators. The primary issue is difficulty in generating high-quality code utilizing accelerators. Hand-written assembly code is standard in industry, and if compiler support does exist, simple greedy algorithms are common. In this work, we investigate more thorough techniques for compiling for computation accelerators. Where greedy heuristics only explore one possible solution, the techniques in this dissertation explore the entire design space, when possible. Intelligent pruning methods ensure that compilation is both tractable and scalable.Ph.D.Computer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/57633/2/ntclark_1.pd

Thin Fisher Zeroes

Biskup et al. [Phys. Rev. Lett. 84 (2000) 4794] have recently suggested that the loci of partition function zeroes can profitably be regarded as phase boundaries in the complex temperature or field planes. We obtain the Fisher zeroes for Ising and Potts models on non-planar (``thin'') regular random graphs using this approach, and note that the locus of Fisher zeroes on a Bethe lattice is identical to the corresponding random graph. Since the number of states appears as a parameter in the Potts solution the limiting locus of chromatic zeroes is also accessible.Comment: 10 pages, 4 figure

Do divorcing couples become happier by breaking up?

Divorce is a leap in the dark. The paper investigates whether people who split up actually become happier. Using the British Household Panel Survey, we can observe an individual's level of psychological well-being in the years before and after divorce. Our results show that divorcing couples reap psychological gains from the dissolution of their marriages. Men and women benefit equally. The paper also studies the effects of bereavement, of having dependant children and of remarriage. We measure well-being by using general health questionnaire and life satisfaction scores

Tree migration-rates : narrowing the gap between inferred post-glacial rates and projected rates

Faster-than-expected post-glacial migration rates of trees have puzzled ecologists for a long time. In Europe, post-glacial migration is assumed to have started from the three southern European peninsulas (southern refugia), where large areas remained free of permafrost and ice at the peak of the last glaciation. However, increasing palaeobotanical evidence for the presence of isolated tree populations in more northerly microrefugia has started to change this perception. Here we use the Northern Eurasian Plant Macrofossil Database and palaeoecological literature to show that post-glacial migration rates for trees may have been substantially lower (60–260 m yr–1) than those estimated by assuming migration from southern refugia only (115–550 m yr–1), and that early-successional trees migrated faster than mid- and late-successional trees. Post-glacial migration rates are in good agreement with those recently projected for the future with a population dynamical forest succession and dispersal model, mainly for early-successional trees and under optimal conditions. Although migration estimates presented here may be conservative because of our assumption of uniform dispersal, tree migration-rates clearly need reconsideration. We suggest that small outlier populations may be a key factor in understanding past migration rates and in predicting potential future range-shifts. The importance of outlier populations in the past may have an analogy in the future, as many tree species have been planted beyond their natural ranges, with a more beneficial microclimate than their regional surroundings. Therefore, climate-change-induced range-shifts in the future might well be influenced by such microrefugia

A versatile diffractive maskless lithography for single-shot and serial microfabrication

Abstract: We demonstrate a diffractive maskless lithographic system that is capable of rapidly performing both serial and single-shot micropatterning. Utilizing the diffractive properties of phase holograms displayed on a spatial light modulator, arbitrary intensity distributions were produced to form two and three dimensional micropatterns/structures in a variety of substrates. A straightforward graphical user interface was implemented to allow users to load templates and change patterning modes within the span of a few minutes. A minimum resolution of ~700 nm is demonstrated for both patterning modes, which compares favorably to the 232 nm resolution limit predicted by the Rayleigh criterion. The presented method is rapid and adaptable, allowing for the parallel fabrication of microstructures in photoresist as well as the fabrication of protein microstructures that retain functional activity

Characterization of glycan substrates accumulating in GM1 Gangliosidosis

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies

Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.

Dietary inorganic nitrate prevents aspects of cardiac mitochondrial dysfunction induced by hypoxia, although the mechanism is not completely understood. In both heart and skeletal muscle, nitrate increases fatty acid oxidation capacity, and in the latter case, this involves up-regulation of peroxisome proliferator-activated receptor (PPAR)α expression. Here, we investigated whether dietary nitrate modifies mitochondrial function in the hypoxic heart in a PPARα-dependent manner. Wild-type (WT) mice and mice without PPARα (Ppara-/-) were given water containing 0.7 mM NaCl (control) or 0.7 mM NaNO3 for 35 d. After 7 d, mice were exposed to normoxia or hypoxia (10% O2) for the remainder of the study. Mitochondrial respiratory function and metabolism were assessed in saponin-permeabilized cardiac muscle fibers. Environmental hypoxia suppressed mass-specific mitochondrial respiration and additionally lowered the proportion of respiration supported by fatty acid oxidation by 18% (P < 0.001). This switch away from fatty acid oxidation was reversed by nitrate treatment in hypoxic WT but not Ppara-/- mice, indicating a PPARα-dependent effect. Hypoxia increased hexokinase activity by 33% in all mice, whereas lactate dehydrogenase activity increased by 71% in hypoxic WT but not Ppara-/- mice. Our findings indicate that PPARα plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation.-Horscroft, J. A., O'Brien, K. A., Clark, A. D., Lindsay, R. T., Steel, A. S., Procter, N. E. K., Devaux, J., Frenneaux, M., Harridge, S. D. R., Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα

Euthanasia-related strain and coping strategies in animal shelter employees

Objective—To identify and evaluate coping strategies advocated by experienced animal shelter workers who directly engaged in euthanizing animals. Design—Cross-sectional study. Sample Population—Animal shelters across the United States in which euthanasia was conducted (5 to 100 employees/shelter). Procedures—With the assistance of experts associated with the Humane Society of the United States, the authors identified 88 animal shelters throughout the United States in which animal euthanasia was actively conducted and for which contact information regarding the shelter director was available. Staff at 62 animal shelters agreed to participate in the survey. Survey packets were mailed to the 62 shelter directors, who then distributed them to employees. The survey included questions regarding respondent age, level of education, and role and asked those directly involved in the euthanasia of animals to provide advice on strategies for new euthanasia technicians to deal with the related stress. Employees completed the survey and returned it by mail. Content analysis techniques were used to summarize survey responses. Results—Coping strategies suggested by 242 euthanasia technicians were summarized into 26 distinct coping recommendations in 8 categories: competence or skills strategies, euthanasia behavioral strategies, cognitive or self-talk strategies, emotional regulation strategies, separation strategies, get-help strategies, seek long-term solution strategies, and withdrawal strategies. Conclusions and Clinical Relevance—Euthanizing animals is a major stressor for many animal shelter workers. Information regarding the coping strategies identified in this study may be useful for training new euthanasia technicians

Retention Time Variability as a Mechanism for Animal Mediated Long-Distance Dispersal

Long-distance dispersal (LDD) events, although rare for most plant species, can strongly influence population and community dynamics. Animals function as a key biotic vector of seeds and thus, a mechanistic and quantitative understanding of how individual animal behaviors scale to dispersal patterns at different spatial scales is a question of critical importance from both basic and applied perspectives. Using a diffusion-theory based analytical approach for a wide range of animal movement and seed transportation patterns, we show that the scale (a measure of local dispersal) of the seed dispersal kernel increases with the organisms' rate of movement and mean seed retention time. We reveal that variations in seed retention time is a key determinant of various measures of LDD such as kurtosis (or shape) of the kernel, thinkness of tails and the absolute number of seeds falling beyond a threshold distance. Using empirical data sets of frugivores, we illustrate the importance of variability in retention times for predicting the key disperser species that influence LDD. Our study makes testable predictions linking animal movement behaviors and gut retention times to dispersal patterns and, more generally, highlights the potential importance of animal behavioral variability for the LDD of seeds