A DNA-binding element for a steroid receptor-binding factor is flanked by dual nuclear matrix DNA attachment sites in the c-myc gene promoter

The receptor-binding factor (RBF) for the avian oviduct progesterone (Pg) receptor (PR) has previously been shown to be a unique 10-kDa nuclear matrix protein that generates high affinity PR-binding sites on avian DNA. This paper describes the use of Southwestern blot and DNA gel shift analyses with RBF protein to identify a minimal 54-base pair RBF-binding element in the matrix-associated region (MAR) of the Pg-regulated c-myc gene promoter. This element contains a 5'-GC-rich domain and a 3'-AT-rich domain, the latter of which has a homopurine/homopyrimidine structure. The gel shift assays required the generation of an RBF-maltose fusion protein (RBF-MBP), which specifically binds this element and is supershifted when the anti-RBF polyclonal antibody is added. Computer analysis of the full-length amino acid sequence for RBF predicts a DNA-binding motif involving a beta-sheet structure at the N-terminal domain. Southern blot analyses using nuclear matrix DNA suggests that there are dual MAR sites in the c-myc promoter, which flank an intervening domain containing the RBF element. The co-transfection of this MAR sequence, containing the RBF element and cloned into a luciferase reporter vector, together with an RBF expression vector construct, into steroid treated human MCF-7 cells, results in a decrease of the c-myc promoter activity relative to control transfections containing only the parent vector of the RBF expression construct. These data suggest that a unique chromatin/nuclear matrix structure, composed of the RBF-DNA element complex which is flanked by nuclear matrix attachment sites, serves to bind the PR and repress the c-myc promoter.     

Bounding completion times of jobs with arbitrary release times,variable execution times and resource sharing

The workload of many real time systems can be characterized as a set of preemptable jobs with linear precedence constraints. Typically their execution times are only known to lie within a range of values. In addition, jobs share resources and access to the resources must be synchronized to ensure the integrity of the system. The paper is concerned with the schedulability of such jobs when scheduled on a priority driven basis. It describes three algorithms for computing upper bounds on the completion times of jobs that have arbitrary release times and priorities. The first two are simple but do not yield sufficiently tight bounds, while the last one yields the tightest bounds but has the greatest complexity     

Estimating the viewing parameters of random, noisy projections ofasymmetric objects for tomographic reconstruction

The ability to determine the viewing parameters of objects from their projections has enabled well established tomographic techniques to be employed in the 3D reconstruction of objects from images obtained via modalities where the orientation of the objects cannot be controlled. A method is described for the determination of the viewing parameters of randomly acquired projections of asymmetric objects. It extends upon the common lines algorithm by determining the relative orientation of projections from the location of lines of intersection among the Fourier transforms of the projections in 3D Fourier space. A new technique for finding the lines of intersection in the presence of translational displacement, and for subsequently finding the translational displacement, is presented. The complete algorithm is described and its efficacy is demonstrated using real data. A new technique for dealing with noise is also discussed     

Time-frequency plane Wiener filtering of the high-resolution ECG: background and time-frequency representations

The diel 'activity', i.e. availability, of Ixodes ricinus larvae, nymphs and adults was investigated in a meadow and a forest habitat near Stockholm during 1991-1993. Generally, the immature ticks were more prevalent in the forest than in the meadow. In the meadow, the mean larval and adult numbers varied significantly between 4 h time intervals with the peak activity from 2300 to 0300 h. In the forest, the tick numbers did not differ significantly between the time intervals. The association of the tick activity with certain meteorological variables was strongest in the meadow, where the mean numbers of all tick stages were negatively correlated with the temperature. The relative humidity was positively correlated only with the mean numbers of larvae. In contrast, the larval activity in the forest was positively and negatively correlated with the temperature and relative humidity, respectively, while the nymphal and adult activity showed no association with these climatic variables. The impact of the host activity on the tick diel activity is also discussed.     

Estimation of deformation gradient and strain from cine-PC velocity data

Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial velocity field measurements. These data allow densely spaced material points to be tracked throughout the whole heart cycle using, for example, the Fourier tracking algorithm. To process the tracking results for myocardial deformation and strain quantification, we developed a method that is based on fitting the tracking results to an appropriate local deformation model. We further analyzed the accuracy and precision of the method and provided performance predictions for several local models. In order to validate the method and the theoretical performance analysis, we conducted controlled computer simulations and a phantom study. The results agreed well with expectations. Human heart data were also acquired and analyzed, and provided encouraging results. At the signal-to-noise ratio (SNR) level and spatial resolution expected in clinical settings, the study predicts strain quantification accuracy and precision that may allow the technique to become a practical and powerful noninvasive approach for the study of cardiac function, although clinically acceptable data acquisition strategies for three-dimensional (3-D) data are still a challenge.     

Stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug

This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.     

Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis

BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease.