High-level languages for small devices: A case study

In this paper we study, through a concrete case, the feasibility of using a high-level, general-purpose logic language in the design and implementation of applications targeting wearable computers. The case study is a "sound spatializer" which, given real-time signáis for monaural audio and heading, generates stereo sound which appears to come from a position in space. The use of advanced compile-time transformations and optimizations made it possible to execute code written in a clear style without efñciency or architectural concerns on the target device, while meeting strict existing time and memory constraints. The final executable compares favorably with a similar implementation written in C. We believe that this case is representative of a wider class of common pervasive computing applications, and that the techniques we show here can be put to good use in a range of scenarios. This points to the possibility of applying high-level languages, with their associated flexibility, conciseness, ability to be automatically parallelized, sophisticated compile-time tools for analysis and verification, etc., to the embedded systems field without paying an unnecessary performance penalty.

Towards high-level execution primitives for and-parallelism: preliminary results

Most implementations of parallel logic programming rely on complex low-level machinery which is arguably difflcult to implement and modify. We explore an alternative approach aimed at taming that complexity by raising core parts of the implementation to the source language level for the particular case of and-parallelism. Therefore, we handle a signiflcant portion of the parallel implementation mechanism at the Prolog level with the help of a comparatively small number of concurrency-related primitives which take care of lower-level tasks such as locking, thread management, stack set management, etc. The approach does not eliminate altogether modiflcations to the abstract machine, but it does greatly simplify them and it also facilitates experimenting with different alternatives. We show how this approach allows implementing both restricted and unrestricted (i.e., non fork-join) parallelism. Preliminary experiments show that the amount of performance sacriflced is reasonable, although granularity control is required in some cases. Also, we observe that the availability of unrestricted parallelism contributes to better observed speedups.

Towards a high-level implementation of flexible parallelism primitives for symbolic languages

An abstract is not available.

The Learning of the Mathematical Models to Aid Decision Making in the High Level Engineering Schools?

At present, in the University curricula in most countries, the decision theory and the mathematical models to aid decision making is not included, as in the graduate program like in Doctored and Master´s programs. In the Technical School of High Level Agronomic Engineers of the Technical University of Madrid (ETSIA-UPM), the need to offer to the future engineers training in a subject that could help them to take decisions in their profession was felt. Along the life, they will have to take a lot of decisions. Ones, will be important and others no. In the personal level, they will have to take several very important decisions, like the election of a career, professional work, or a couple, but in the professional field, the decision making is the main role of the Managers, Politicians and Leaders. They should be decision makers and will be paid for it. Therefore, nobody can understand that such a professional that is called to practice management responsibilities in the companies, does not take training in such an important matter. For it, in the year 2000, it was requested to the University Board to introduce in the curricula an optional qualified subject of the second cycle with 4,5 credits titled " Mathematical Methods for Making Decisions ". A program was elaborated, the didactic material prepared and programs as Maple, Lingo, Math Cad, etc. installed in several IT classrooms, where the course will be taught. In the course 2000-2001 this subject was offered with a great acceptance that exceeded the forecasts of capacity and had to be prepared more classrooms. This course in graduate program took place in the Department of Applied Mathematics to the Agronomic Engineering, as an extension of the credits dedicated to Mathematics in the career of Engineering.

Eccentric Exercise in Treatment of Patellar Tendinopathy in High Level Basketball Players. A Randomized Clinical Trial.

Chronic patellar tendinopathy is a common pathology in sporting population. To date, there is no agreed upon protocol as election treatment. Eccentric exercises have been used with satisfactory outcomes (3). The purpose of this trial was to compare the effects of two eccentric exercise protocols.

Eccentric exercise in treatment of patellar tendinopathy in high level basketball players. A randomized clinical trial

Chronic patellar tendinopathy is a common pathology in sporting population. To date, there is no agreed upon protocol as election treatment. Eccentric exercises have been used with satisfactory outcomes.

Systematic Process for Building a Fault Diagnoser Based on Petri Nets Applied to a Helicopter

This work presents a systematic process for building a Fault Diagnoser (FD), based on Petri Nets (PNs) which has been applied to a small helicopter. This novel tool is able to detect both intermittent and permanent faults. The work carried out is discussed from theoretical and practical point of view. The procedure begins with a division of the whole system into subsystems, which are the devices that have to be modeled by using PN, considering both the normal and fault operations. Subsequently, the models are integrated into a global Petri Net diagnoser (PND) that is able to monitor a whole helicopter and show critical variables to the operator in order to determine the UAV health, preventing accidents in this manner. A Data Acquisition System (DAQ) has been designed for collecting data during the flights and feeding PN diagnoser with them. Several real flights (nominal or under failure) have been carried out to perform the diagnoser setup and verify its performance. A summary of the validation results obtained during real flight tests is also included. An extensive use of this tool will improve preventive maintenance protocols for UAVs (especially helicopters) and allow establishing recommendations in regulations

Quantitative modeling of stochastic systems in molecular biology by using stochastic Petri nets

An integrated understanding of molecular and developmental biology must consider the large number of molecular species involved and the low concentrations of many species in vivo. Quantitative stochastic models of molecular interaction networks can be expressed as stochastic Petri nets (SPNs), a mathematical formalism developed in computer science. Existing software can be used to define molecular interaction networks as SPNs and solve such models for the probability distributions of molecular species. This approach allows biologists to focus on the content of models and their interpretation, rather than their implementation. The standardized format of SPNs also facilitates the replication, extension, and transfer of models between researchers. A simple chemical system is presented to demonstrate the link between stochastic models of molecular interactions and SPNs. The approach is illustrated with examples of models of genetic and biochemical phenomena where the UltraSAN package is used to present results from numerical analysis and the outcome of simulations.

Chromosomal arm replacement generates a high level of intraspecific polymorphism in the terminal inverted repeats of the linear chromosomal DNA of Streptomyces ambofaciens

The chromosomal DNA of the bacteria Streptomyces ambofaciens DSM40697 is an 8-Mb linear molecule that ends in terminal inverted repeats (TIRs) of 210 kb. The sequences of the TIRs are highly variable between the different linear replicons of Streptomyces (plasmids or chromosomes). Two spontaneous mutant strains harboring TIRs of 480 and 850 kb were isolated. The TIR polymorphism seen is a result of the deletion of one chromosomal end and its replacement by 480 or 850 kb of sequence identical to the end of the undeleted chromosomal arm. Analysis of the wild-type sequences involved in these rearrangements revealed that a recombination event took place between the two copies of a duplicated DNA sequence. Each copy was mapped to one chromosomal arm, outside of the TIR, and encoded a putative alternative sigma factor. The two ORFs, designated hasR and hasL, were found to be 99% similar at the nucleotide level. The sequence of the chimeric regions generated by the recombination showed that the chromosomal structure of the mutant strains resulted from homologous recombination events between the two copies. We suggest that this mechanism of chromosomal arm replacement contributes to the rapid evolutionary diversification of the sequences of the TIR in Streptomyces.

Low- and high-level transgenic expression of β2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gαq-overexpressing mice

Transgenic overexpression of Gαq in the heart triggers events leading to a phenotype of eccentric hypertrophy, depressed ventricular function, marked expression of hypertrophy-associated genes, and depressed β-adrenergic receptor (βAR) function. The role of βAR dysfunction in the development of this failure phenotype was delineated by transgenic coexpression of the carboxyl terminus of the βAR kinase (βARK), which acts to inhibit the kinase, or concomitant overexpression of the β2AR at low (≈30-fold, Gαq/β2ARL), moderate (≈140-fold, Gαq/β2ARM), and high (≈1,000-fold, Gαq/β2ARH) levels above background βAR density. Expression of the βARK inhibitor had no effect on the phenotype, consistent with the lack of increased βARK levels in Gαq mice. In marked contrast, Gαq/β2ARL mice displayed rescue of hypertrophy and resting ventricular function and decreased cardiac expression of atrial natriuretic factor and α-skeletal actin mRNA. These effects occurred in the absence of any improvement in basal or agonist-stimulated adenylyl cyclase (AC) activities in crude cardiac membranes, although restoration of a compartmentalized β2AR/AC signal cannot be excluded. Higher expression of receptors in Gαq/β2ARM mice resulted in salvage of AC activity, but hypertrophy, ventricular function, and expression of fetal genes were unaffected or worsened. With ≈1,000-fold overexpression, the majority of Gαq/β2ARH mice died with cardiomegaly at 5 weeks. Thus, although it appears that excessive, uncontrolled, or generalized augmentation of βAR signaling is deleterious in heart failure, selective enhancement by overexpressing the β2AR subtype to limited levels restores not only ventricular function but also reverses cardiac hypertrophy.

Histones H3 and H4 are components of upstream activation factor required for the high-level transcription of yeast rDNA by RNA polymerase I

RNA polymerase I (Pol I) transcription in the yeast Saccharomyces cerevisiae is greatly stimulated in vivo and in vitro by the multiprotein complex, upstream activation factor (UAF). UAF binds tightly to the upstream element of the rDNA promoter, such that once bound (in vitro), UAF does not readily exchange onto a competing template. Of the polypeptides previously identified in purified UAF, three are encoded by genes required for Pol I transcription in vivo: RRN5, RRN9, and RRN10. Two others, p30 and p18, have remained uncharacterized. We report here that the N-terminal amino acid sequence, its mobility in gel electrophoresis, and the immunoreactivity of p18 shows that it is histone H3. In addition, histone H4 was found in UAF, and myc-tagged histone H4 could be used to affinity-purify UAF. Histones H2A and H2B were not detectable in UAF. These results suggest that histones H3 and H4 probably account for the strong binding of UAF to DNA and may offer a means by which general nuclear regulatory signals could be transmitted to Pol I.

Structure and function in rhodopsin: high level expression of a synthetic bovine opsin gene and its mutants in stable mammalian cell lines.

Stable mammalian cell lines harboring a synthetic bovine opsin gene have been derived from the suspension-adapted HEK293 cell line. The opsin gene is under the control of the immediate-early cytomegalovirus promoter/enhancer in an expression vector that also contains a selectable marker (Neo) governed by a relatively weak promoter. The cell lines expressing the opsin gene at high levels are selected by growth in the presence of high concentrations of the antibiotic geneticin. Under the conditions used for cell growth in suspension, opsin is produced at saturated culture levels of more than 2 mg/liter. After reconstitution with 11-cis-retinal, rhodopsin is purified to homogeneity in a single step by immunoaffinity column chromatography. Rhodopsin thus prepared (> 90% recovery at concentrations of up to 15 microM) is indistinguishable from rhodopsin purified from bovine rod outer segments by the following criteria: (i) UV/Vis absorption spectra in the dark and after photobleaching and the rate of metarhodopsin II decay, (ii) initial rates of transducin activation, and (iii) the rate of phosphorylation by rhodopsin kinase. Although mammalian cell opsin migrates slower than rod outer segment opsin on SDS/polyacrylamide gels, presumably due to a different N-glycosylation pattern, their mobilities after deglycosylation are identical. This method has enabled the preparation of several site-specific mutants of bovine opsin in comparable amounts.

Histone H1 overexpressed to high level in tobacco affects certain developmental programs but has limited effect on basal cellular functions.

Histone H1, a major structural component of chromatin fiber, is believed to act as a general repressor of transcription. To investigate in vivo the role of this protein in transcription regulation during development of a multicellular organism, we made transgenic tobacco plants that overexpress the gene for Arabidopsis histone H1. In all plants that overexpressed H1 the total H1-to-DNA ratio in chromatin increased 2.3-2.8 times compared with the physiological level. This was accompanied by 50-100% decrease of native tobacco H1. The phenotypic changes in H1-overexpressing plants ranged from mild to severe perturbations in morphological appearance and flowering. No correlation was observed between the extent of phenotypic change and the variation in the amount of overexpressed H1 or the presence or absence of the native tobacco H1. However, the severe phenotypic changes were correlated with early occurrence during plant growth of cells with abnormally heterochromatinized nuclei. Such cells occurred considerably later in plants with milder changes. Surprisingly, the ability of cells with highly heterochromatinized nuclei to fulfill basic physiological functions, including differentiation, was not markedly hampered. The results support the suggestion that chromatin structural changes dependent on H1 stoichiometry and on the profile of major H1 variants have limited regulatory effect on the activity of genes that control basal cellular functions. However, the H1-mediated chromatin changes can be of much greater importance for the regulation of genes involved in control of specific developmental programs.

Identification of a minimal sequence of the mouse pro-alpha 1(I) collagen promoter that confers high-level osteoblast expression in transgenic mice and that binds a protein selectively present in osteoblasts.

Based on our previous transgenic mice results, which strongly suggested that separate cell-specific cis-acting elements of the mouse pro-alpha 1(I) collagen promoter control the activity of the gene in different type I collagen-producing cells, we attempted to delineate a short segment in this promoter that could direct high-level expression selectively in osteoblasts. By generating transgenic mice harboring various fragments of the promoter, we identified a 117-bp segment (-1656 to -1540) that is a minimal sequence able to confer high-level expression of a lacZ reporter gene selectively in osteoblasts when cloned upstream of the proximal 220-bp pro-alpha 1(I) promoter. This 220-bp promoter by itself was inactive in transgenic mice and unable to direct osteoblast-specific expression. The 117-bp enhancer segment contained two sequences that appeared to have different functions. The A sequence (-1656 to -1628) was required to obtain expression of the lacZ gene in osteoblasts, whereas the C sequence (-1575 to -1540) was essential to obtain consistent and high-level expression of the lacZ gene in osteoblasts. Gel shift assays showed that the A sequence bound a nuclear protein present only in osteoblastic cells. A mutation in the A segment that abolished the binding of this osteoblast-specific protein also abolished lacZ expression in osteoblasts of transgenic mice.

High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease.

Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase and dihydrofolate reductase genes. Following transfection in dihydrofolate reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and amplification with methotrexate, a cell line producing high levels of the alpha-glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with 5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91 micrograms.ml-1 in the medium (activity, > 22.6 mumol.hr-1.ml-1). This enzyme has a pH optimum similar to that of the mature form, but a lower Vmax and Km for 4-methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts from Pompe patients, restoring normal levels of acid alpha-glucosidase and glycogen. The uptake is blocked by mannose 6-phosphate. Following intravenous injection, high enzyme levels are seen in heart and liver. An efficient production system now exists for recombinant human acid alpha-glucosidase targeted to heart and capable of correcting fibroblasts from patients with Pompe disease.