Exploiting design patterns to automate validation of class invariants

In this paper, techniques are presented that exploit two design patterns, the Visitor pattern and the Decorator pattern, to validate invariants about the data attributes in a C++ class automatically. To investigate the pragmatics involved in using the two patterns, a study of an existing, well‐tested application, keystone, a parser and front‐end for the C++ language, is presented. Results from the study indicate that these two patterns provide flexibility in terms of the frequency and level of granularity of validation of the class invariants, which are expressed in the Object Constraint Language (OCL). The quantitative results measure the impact of these approaches and the additional faults uncovered through validation of the case study. Copyright © 2005 John Wiley & Sons, Ltd.     

A computer filtering method to drive out tiny genes from the yeast genome

The authors of the first yeast chromosome sequence defined a minimum threshold requirement of 100 codons, above which an open reading frame (ORF) is retained as a putative coding sequence. However, at least 58 yeast genes shorter than 100 codons have an assigned protein function. Therefore, the yeast genome may contain other tiny but functionally important genes that are discarded from analyses by this simple filtering rule. We have established discriminant functions from the in-phase hexamer frequencies of functional genes and of simulated ORFs derived from a stationary Markov chain model. Fifty-two out of the 58 genes were recognized as coding ORFs by our discriminating method. The test was also applied to all the small ORFs (36 to 100 codons) found in the intergenic regions of published chromosomes. It retained 140 new potential tiny coding sequences, among which we identified seven new genes by similarity searches. Our method, used conjointly with similarity searches, can also highlight sequencing errors resulting from the disruption of the coding frame of longer ORFs. This method, by its ability to detect potential coding ORFs, can be a very useful tool for functional analysis.     

A New Strategy to Preserve and Assess Oxygen Consumption in Murine Tissues

Mitochondrial dysfunctions are implicated in several pathologies, such as metabolic, cardiovascular, respiratory, and neurological diseases, as well as in cancer and aging. These metabolic alterations are usually assessed in human or murine samples by mitochondrial respiratory chain enzymatic assays, by measuring the oxygen consumption of intact mitochondria isolated from tissues, or from cells obtained after physical or enzymatic disruption of the tissues. However, these methodologies do not maintain tissue multicellular organization and cell-cell interactions, known to influence mitochondrial metabolism. Here, we develop an optimal model to measure mitochondrial oxygen consumption in heart and lung tissue samples using the XF24 Extracellular Flux Analyzer (Seahorse) and discuss the advantages and limitations of this technological approach. Our results demonstrate that tissue organization, as well as mitochondrial ultrastructure and respiratory function, are preserved in heart and lung tissues freshly processed or after overnight conservation at 4 °C. Using this method, we confirmed the repeatedly reported obesity-associated mitochondrial dysfunction in the heart and extended it to the lungs. We set up and validated a new strategy to optimally assess mitochondrial function in murine tissues. As such, this method is of great potential interest for monitoring mitochondrial function in cohort samples.     

New insights into the negative regulation of hematopoiesis by chemokine platelet factor 4 and related peptides

Platelet factor 4 (PF4) has been recognized as an inhibitor of myeloid progenitors. However, the mechanism of action of this chemokine remains poorly understood. The present study was designed to determine its structure/function relationship. A series of peptides overlapping the C-terminal and central regions of PF4 were analyzed in vitro for their action on murine hematopoietic progenitor growth to assess the minimal sequence length required for activity. The peptides p17-58 and p34-58 possessed an increased hematopoietic inhibitory activity when compared with PF4, whereas the shorter peptides p47-58 and p47-70 were equivalent to the native molecule and the peptide p58-70 was inactive. The PF4 functional motif DLQ located in 54-56 was required for the activity of these peptides. The peptide p34-58 impaired to a similar extent the growth of colony-forming unit-megakaryocyte (CFU-MK) as well as burst-forming unit-erythroid (BFU-E) and colony-forming unit-granulocyte-macrophage (CFU-GM), whereas PF4 was more active on CFU-MK. In the experiments using purified murine CD34(+) marrow cells, statistically significant inhibition induced by p34-58 was shown at concentrations of 2.2 nmol/L or greater for progenitors of the three lineages, whereas that induced by PF4 was seen at 130 nmol/L for CFU-MK and 650 nmol/L for CFU-GM and BFU-E, indicating that the p34-58 acts directly on hematopoietic progenitors and its activity is approximately 60- to 300-fold higher than PF4. The p34-58, unlike PF4, lacked affinity for heparin and its inhibitory activity could not be abrogated by the addition of heparin. In addition, an antibody recognizing p34-58 neutralized the activity of p34-58 but not whole PF4 molecule. These results demonstrate that PF4 contains a functional domain in its central region, which is independent of the heparin binding properties, and provide evidence for a model of heparin-dependent and independent pathways of PF4 in inhibiting hematopoiesis.     

Neuropsychologic prediction of performance measures of daily living skills in geriatric patients.

The current study examined the capacity of an abbreviated neuropsychologic (NP) battery to predict performance-based activities of daily living (ADLs) in a psychogeriatric sample. Inpatients of a geriatric evaluation unit (34 men and 74 women), mean age 74, underwent neuropsychologic assessment and performance assessment of ADLs. Results revealed a strong overall relation between NP assessment and ADL performance. Multiple regressions were significant for 4 of 5 instrumental ADLs, with the NP battery accounting for 14% to 32% of the variance in ADL performance. Visuospatial ability was the best predictor of functional dependence across each ADL domain, followed by memory performance. The findings provide validation for the use of specific NP tests in making judgments about dependence in instrumental ADLs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measuring concentration within and co-concentration between informetric distributions: An empirical study

Summary There is a well-established literature on the use of concentration measures in informetrics. However, these works have usually been devoted to measures of concentration within a productivity distribution. In a pair of recent papers the author introduced two new measures, both based on the Gini ratio, for measuring the similarity of concentration of productivity between two different informetric distributions. The first of these was derived from Dagum's notion of relative economic affluence; the second - in some ways analogous to the correlation coefficient - is completely new. The purpose of this study is to develop a purely empirical approach to comparative studies of concentration between informetric data sets using both within and between measures thereby greatly extending the original study which considered just two data sets for purposes of illustration of the methods of calculation of the measures.     

Intraocular pressure regulation after combined glaucoma and cataract operation

BACKGROUND: The success rate of combined glaucoma and small incision cataract surgery is not yet established. PATIENTS AND METHODS: Therefore, 56 eyes of 52 patients (mean age 79.0 years) having trabeculectomy combined with phacoemul-sification and implantation of a silicone posterior chamber lens were retrospectively investigated. RESULTS: The mean follow-up was 21.6 weeks. Due to the combined surgery the mean intraocular pressure decreased significantly (p < 0.001) from 21.8 to 14.8 mmHg. Seventy-five percent of the patients did not need any antiglaucomatous medication, while 25% still had to use a local medication, but less frequently. The overall visual acuity increased significantly (p < 0.001) from a preoperative value of 0.24 to 0.52 postoperatively. CONCLUSIONS: The results of combined glaucoma and cataract surgery seem as good as those reported for two separate glaucoma and cataract procedures.     

Evaluation of Elastin-Fibrin biomaterial in experimental pancreatic surgery

Artificial connective soft tissue, so-called Elastin-Fibrin biomaterial, was investigated to reinforce a pancreato-jejunum anastomosis in the dog. The ambiguous results invite us, however, to improve the quality of the material, especially against proteolytic degradation: elastinolysis and fibrinolysis. Antibiotic was also added. The improved material was tested, first in rabbit then in dog, to repair a large loss of substance in the duodenum, just in front of the Wirsung duct. In view of the successful results, we are now attempting an evaluation in humans, for all indications throughout the digestive system.     

The complexity of scheduling for data cache optimization

The performance of the memory hierarchy, and in particular the data cache, can significantly impact program execution speed. Thus, instruction reordering to minimize data cache misses is an important consideration for optimizing compilers. In this paper, we prove that the problem of instruction reordering for data cache miss minimization belongs to the class of NP-complete problems. The framework that we develop for the proof exposes the symbiotic relationship among the references to the cache. This symbiosis exists because a single cache reference lengthens the life span of its neighbors in the cache, and thus provides opportunity for additional cache hits through reference to the neighbors. We present a greedy heuristic designed to exploit this symbiotic relationship to improve data cache performance for general-purpose programs. Experiments with a prototype implementation of the heuristic show that we can improve data cache performance in many cases.     

Unclogging improvement based on interdate and interreach comparison of water release monitoring (Durance,France)

Large‐scale flow release experiments are becoming common for improving aquatic habitat quality downstream of dams. Because of the naturally high fine sediment load in the Durance River, France due to inputs from torrential tributaries draining badlands, unpredictable high flow events with dam overspill are not always sufficient to prevent clogging, which can lead to habitat degradation (especially spawning habitats) in bypassed reaches. Therefore, large‐scale flow experiments were conducted on four reaches to test the efficacy of clear‐water releases to improve aquatic habitat conditions. Continuous measurements of water depth, suspended sediment concentrations, and turbidity were conducted during twelve releases and compared on nine. Before and after each release, superficial clogging was measured. The study shows that there is a link between the volume of suspended sediments carried by water releases and the initial clogging. The volumes carried were low compared with the river's annual transport. The effect on clogging can vary significantly from one release to another. In particular, the hydrological context surrounding the releases has a significant influence on clogging. Comparisons of monitoring showed that releases are more effective on reaches that are more severely regulated (high hydrological control) than on those that are less well‐controlled. The areas with the highest initial clogging tend to unclog more than those with lower initial clogging; however, the latter zones are most impacted by ineffective releases. Performing a release on environments with low initial clogging can therefore be environmentally damaging. To ensure that releases are successful and that intervention is warranted, initial clogging should be measured in the field and releases should only be performed if the clogging is judged to be unfavourable.