Extracting Safe Thread Schedules from Incomplete Model Checking Results

Model checkers frequently fail to completely verify a concurrent program, even if partial-order reduction is applied. The verification engineer is left in doubt whether the program is safe and the effort toward verifying the program is wasted. We present a technique that uses the results of such incomplete verification attempts to construct a (fair) scheduler that allows the safe execution of the partially verified concurrent program. This scheduler restricts the execution to schedules that have been proven safe (and prevents executions that were found to be erroneous). We evaluate the performance of our technique and show how it can be improved using partial-order reduction. While constraining the scheduler results in a considerable performance penalty in general, we show that in some cases our approach—somewhat surprisingly—even leads to faster executions

Morphological alterations of exogenous surfactant inhibited by meconium can be prevented by dextran

BACKGROUND: Surfactant dysfunction due to inhibition is involved in the pathophysiology of meconium aspiration syndrome. Dextran addition has been shown to reverse exogenous surfactant inactivation by meconium, but the precise mechanisms and the morphological correlate of this effect are yet unknown. Morphological surfactant analysis by transmission electron microscopy (TEM) and stereology allows the differentiation of active (large aggregates = LA) and inactive (small aggregates = SA) subtypes. METHODS: To determine the in vitro effects of meconium and dextran addition on the morphology of a modified porcine natural surfactant (Curosurf), Curosurf samples were either incubated alone or together with meconium or with meconium and dextran, fixed and processed for TEM. Volume fractions of surfactant subtypes [lamellar body-like forms (LBL), multilamellar vesicles (MV), unilamellar vesicles (UV)] were determined stereologically. RESULTS: All preparations contained LBL and MV (corresponding to LA) as well as UV (corresponding to SA). The volume fraction of UV increased with addition of meconium and decreased with further addition of dextran. Correspondingly, the UV/(LBL+MV) ratio (resembling the SA/LA ratio) increased when meconium was added and decreased when dextran was added to the surfactant-meconium mixture. CONCLUSION: Meconium causes alterations in the ultrastructural composition of Curosurf that can be visualized and analyzed by TEM and stereology. These alterations resemble an increase in the SA/LA ratio and are paralleled by an increase in minimum surface tension. Dextran prevents these effects and may therefore be a useful additive to exogenous surfactant preparations to preserve their structural and functional integrity, thereby improving their resistance to inactivation

Experimental rat bladder urothelial cell carcinoma models

Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the second part of the paper the development of a potential new orthotopic rat bladder tumor model is described

Therapeutic lung lavages in children and adults

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excessive intra-alveolar accumulation of surfactant lipids and proteins. Therapeutic whole lung lavages are currently the principle therapeutic option in adults. Not much is known on the kinetics of the wash out process, especially in children. METHODS: In 4 pediatric and 6 adult PAP patients 45 therapeutic half lung lavages were investigated retrospectively. Total protein, protein concentration and, in one child with a surfactant protein C mutation, aberrant pro-SP-C protein, were determined during wash out. RESULTS: The removal of protein from the lungs followed an exponential decline and averaged for adult patients 2 – 20 g and <0.5 to 6 g for pediatric patients. The average protein concentration of consecutive portions was the same in all patient groups, however was elevated in pediatric patients when expressed per body weight. The amount of an aberrant pro-SP-C protein, which was present in one patient with a SP-C mutation, constantly decreased with ongoing lavage. Measuring the optical density of the lavage fluid obtained allowed to monitor the wash out process during the lavages at the bedside and to determine the termination of the lavage procedure at normal protein concentration. CONCLUSION: Following therapeutic half lung lavages by biochemical variables may help to estimate the degree of alveolar filling with proteinaceous material and to improve the efficiency of the wash out, especially in children

In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice

We describe a two-photon microscopy-based method to evaluate the in vivo systemic transport of compounds. This method comprises imaging of the intact liver, kidney and intestine, the main organs responsible for uptake and elimination of xenobiotics and endogenous molecules. The image quality of the acquired movies was sufficient to distinguish subcellular structures like organelles and vesicles. Quantification of the movement of fluorescent dextran and fluorescent cholic acid derivatives in different organs and their sub-compartments over time revealed significant dynamic differences. Calculated half-lives were similar in the capillaries of all investigated organs but differed in the specific sub-compartments, such as parenchymal cells and bile canaliculi of the liver, glomeruli, proximal and distal tubules of the kidney and lymph vessels (lacteals) of the small intestine. Moreover, tools to image immune cells, which can influence transport processes in inflamed tissues, are described. This powerful approach provides new possibilities for the analysis of compound transport in multiple organs and can support physiologically based pharmacokinetic modeling, in order to obtain more precise predictions at the whole body scale

Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas.</p> <p>Methods</p> <p>In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits.</p> <p>Results</p> <p>Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (r_s= 0.68 and r_s= 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (r_s= 0.64, p < 0.001).</p> <p>Conclusion</p> <p>Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.</p