User's manual for the sisyphus simulation environment

Journal ArticleThis report describes how to create and simulate a design with Sisyphus. Inasmuch as Sisyphus is written in Symbolics-Lisp, some familiarity with both Lisp and with Symbolics computers is presumed. In addition, the concepts presented here presume an acquaintance with [3]. First, a disclaimer ? this report is neither a user's manual nor a reference manual, but rather a combination of the two. As such, it is neither a s detailed as a reference manual, nor as conversational as a tutorial. Further, this report describes yet another hardware description language and, in this author's humble opinion, there are already far too many HDLs and hence very little justification for writing more. To quote from the eminent numerician C.W. Gear's Forsythe award lecture [1]

Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion

Morphogenesis, the establishment and repair of emergent complex anatomy by groups of cells, is a fascinating and biomedically-relevant problem. One of its most fascinating aspects is that a developing embryo can reliably recover from disturbances, such as splitting into twins. While this reliability implies some type of goal-seeking error minimization over a morphogenic field, there are many gaps with respect to detailed, constructive models of such a process being used to implement the collective intelligence of cellular swarms. We describe a closed-loop negative-feedback system for creating reaction-diffusion (RD) patterns with high reliability. It uses a cellular automaton to characterize a morphogen pattern, then compares it to a goal and adjusts accordingly, providing a framework for modeling anatomical homeostasis and robust generation of target morphologies. Specifically, we create a RD pattern with N repetitions, where N is easily changeable. Furthermore, the individual repetitions of the RD pattern can be easily stretched or shrunk under genetic control to create, e.g., some morphological features larger than others. Finally, the cellular automaton uses a computation wave that scans the morphogen pattern unidirectionally to characterize the features that the negative feedback then controls. By taking advantage of a prior process asymmetrically establishing planar polarity (e.g., head vs. tail), our automaton is greatly simplified. This work contributes to the exciting effort of understanding design principles of morphological computation, which can be used to understand evolved developmental mechanisms, manipulate them in regenerative medicine settings, or embed a degree of synthetic intelligence into novel bioengineered constructs.Comment: 20 pages, 3 tables, 5 figure

Closing the loop on morphogenesis: a mathematical model of morphogenesis by closed-loop reaction-diffusion

Morphogenesis, the establishment and repair of emergent complex anatomy by groups of cells, is a fascinating and biomedically-relevant problem. One of its most fascinating aspects is that a developing embryo can reliably recover from disturbances, such as splitting into twins. While this reliability implies some type of goal-seeking error minimization over a morphogenic field, there are many gaps with respect to detailed, constructive models of such a process. A common way to achieve reliability is negative feedback, which requires characterizing the existing body shape to create an error signal–but measuring properties of a shape may not be simple. We show how cells communicating in a wave-like pattern could analyze properties of the current body shape. We then describe a closed-loop negative-feedback system for creating reaction-diffusion (RD) patterns with high reliability. Specifically, we use a wave to count the number of peaks in a RD pattern, letting us use a negative-feedback controller to create a pattern with N repetitions, where N can be altered over a wide range. Furthermore, the individual repetitions of the RD pattern can be easily stretched or shrunk under genetic control to create, e.g., some morphological features larger than others. This work contributes to the exciting effort of understanding design principles of morphological computation, which can be used to understand evolved developmental mechanisms, manipulate them in regenerative-medicine settings, or engineer novel synthetic morphology constructs with desired robust behavior

Glucose absorption during continuous ambulatory peritoneal dialysis

Glucose absorption during continuous ambulatory peritoneal dialysis. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are exposed to a continuous infusion of glucose via their peritoneal cavity. We performed studies to quantitate the amount of energy derived from dialysate glucose. Net glucose absorption averaged 182 ± (SD) 61 g/day in 19 studies with a dialysate dextrose concentration of 1.5 or 4.25 g/dl. The amount of glucose absorbed per liter of dialysate (y) varied with the concentration of glucose in dialysate (x), (y = 11.3x - 10.9, r = 0.96), The amount of glucose absorbed per day during a given dialysis regimen was constant. Energy intake from dialysate glucose was 8.4 ± 2.8 kcal/kg of body wt per day, or 12 to 34% of total energy intake. This additional energy may contribute to the anabolic effect reported during CAPD. The ability to vary glucose absorption by altering the dialysate glucose concentration may prove a useful tool to modify energy intake.Absorption de glucose au cours de la dialyse péritonéale continue ambulatoire. Les malades soumis à la dialyse péritonéale continue ambulatoire (CAPD) sont exposés à une administration continue de glucose via leur cavité péritonéale. La quantité d'énergie qui dérive du glucose du dialysat a été quantifiée. L'absorption nette de glucose est en moyenne de 182 ± (SD) 61 g/jour au cours de 19 études avec un dialysat contenant du dextrose, 1,5 ou 4,25 g/dl. La quantité de glucose absorbée par litre de dialysat (y) varie avec la concentration de glucose dans le dialysat (x), (y = 11,3x - 10,9, r = 0,96). La quantité de glucose absorbée par jour pour un type donné de dialyse a été constante. L'entrée d'énergie à partir du glucose du dialysat était de 8,4 ± 2,8 kcal/kg de poids par jour, soit 12 à 34% de l'entrée totale d'énergie. Cette énergie supplémentaire peut contribuer à l'effet anabolique rapporté au cours de CAPD. La possibilité de faire varier l'absorption de glucose en modifiant la concentration de glucose dans le dialysat peut être un moyen utile pour influencer l'entrée d'énergie

Cumulative Exposure to Lead in Relation to Cognitive Function in Older Women

Background: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. Objective: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. Methods: Patella and tibia bone lead—measures of cumulative exposure over many years—and blood lead, a measure of recent exposure, were assessed in 587 women 47–74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. Results: Mean ± SD lead levels in tibia, patella, and blood were 10.5 ± 9.7 μg/g bone, 12.6 ± 11.6 μg/g bone, and 2.9 ± 1.9 μg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: −0.099 to −0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. Conclusions: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Sisyphus, an environment for simulation

technical reportSisyphus is an environment for the simulation of integrated circuits (ICs). It supports hierarchical simulation from the functional block level down to circuit analysis. Sisyphus develops a new hierarchical wire model (based on that of Sable) which facilitates the accurate simulation of incomplete designs. Sisyphus provides a testbed for the coding of new algorithms; the coding of existing algorithms has been accomplished, using Sisyphus resources, in a fraction of the effort needed elsewhere. It also supports a wide range of simulation algorithms including Iterated Timing Analysis and Mossim; different simulation algorithms are integrated via partitioning a circuit into subnetworks, and simulating each with the most appropriate algorithms. The possibility of combining multiple simulation algorithms, each where it is most effective, is shown to result in significantly faster or more accurate simulation The design perspective of Sisyphus, its implementation, and the results of using Sisyphus are examined here

Logic Decomposition During Technology Mapping

Abstract—A problem in technology mapping is that the quality of the final implementation depends significantly on the initially provided circuit structure. This problem is critical, especially for mapping with tight and complicated constraints. In this paper, we propose a procedure which takes into account a large number of circuit structures during technology mapping. A set of circuit structures is compactly encoded in a single graph, and the procedure dynamically modifies the set during technology mapping by applying simple local transformations to the graph. State-of-the-art technology mapping algorithms are naturally extended, so that the procedure finds an optimal tree implementation over all of the circuit structures examined. We show that the procedure effectively explores the entire solution space obtained by applying algebraic decomposition exhaustively. However, the run time is proportional to the size of the graph, which is typically logarithmic in the number of circuit structures encoded. The procedure has been implemented and used for commercial design projects. We present experimental results on benchmark examples to demonstrate its effectiveness. I