Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels

A two-step exocytosis/endocytosis protocol was used in rat pancreatic acini to study membrane trafficking events at the apical plasma membrane (APM) as a function of extracellular pH. Exocytosis, as measured by cholecystokinin (CCK)-8-induced release of amylase into the incubation medium, was relatively insensitive to changes in extracellular pH from 5.5 to 9.0. In contrast, endocytosis, as measured by temperature-dependent uptake of horseradish peroxidase (HRP), was robust at pH values between 6.5 and 8.3 but abolished at acidic pH values of 5.5 to 6.0. Energy metabolism and cell viability were maintained during pH 6-induced cessation of HRP uptake, and the vesicular block could be reversed upon raising the luminal pH to 7.4. Histochemical and morphometric studies of HRP uptake examined by electron microscopy indicated that extracellular pH regulates endocytosis at the apical plasma membrane. At pH 6.0 in prestimulated cells, HRP uptake at the APM was abolished, and acinar lumen membranes remained markedly dilated with decreased density of microvilli and "arrested" exocytic images. At pH 7.4, HRP was taken up into endolysosomal structures within the Golgi complex, and acinar lumen membranes were contracted. Cleavage of GP2, a glycosyl phosphatidylinositol-anchored protein, was associated with the pH-dependent activation of HRP uptake. These studies demonstrate that acinar lumen pH regulates endocytic but not exocytic activity at the APM and suggest that alkalinization of the acinar lumen by duct cells is required for retrieval of exocytic membranes into the acinar cell via vesicular uptake mechanisms. The role of acid-base interactions within the acinar lumen provides a novel basis for understanding the cellular and luminal defects observed within the exocrine pancreas in cystic fibrosis.     

T-matrix computations of light scattering by red blood cells

The electromagnetic far field, as well as the near field, originating from light interaction with a red blood cell (RBC)volume-equivalent spheroid, was analyzed by utilizing theT-matrix theory. This method is a powerful tool thatmakes it possible to study the influence of cell shape on the angulardistribution of scattered light. General observations were that thethree-dimensional shape, as well as the optical thickness apparent tothe incident field, affects the forward scattering. Thebackscattering was influenced by the shape of the surface facing theincident beam. Furthermore sphering as well as elongation of anoblate RBC into a volume-equivalent sphere or a prolate spheroid, respectively, was theoretically modeled to imitate physiologicalphenomena caused, e.g., by heat or the increased shear stress offlowing blood. Both sphering and elongation were shown to decreasethe intensity of the forward-directed scattering, thus yielding lowerg factors. The sphering made the scattering patternindependent of azimuthal scattering angle phi(s), whereas the elongation induced more apparent phi(s)-dependent patterns. The lightscattering by a RBC volume-equivalent spheroid was thus found to behighly influenced by the shape of the scattering object. Anear-field radius r(nf) was evaluated as thedistance to which the maximum intensity of the total near field haddecreased to 2.5 times that of the incident field. It was estimatedto 2-24.5 times the maximum radius of the scattering spheroid, corresponding to 12-69 mum. Because the near-field radiuswas shown to be larger than a simple estimation of the distance betweenthe RBC's in whole blood, the assumption of independent scattering, frequently employed in optical measurements on whole blood, seemsinappropriate. This also indicates that one cannot extrapolate theresults obtained from diluted blood to whole blood by multiplying witha simple concentration factor.     

Monocyte activation in patients with non-seminomatous germ cell tumour of the testis before and after tumour eradication

AIMS: To investigate the kinetics of normalisation of monocyte oxidative activity following tumour eradication. METHODS: Whole blood lucigenin enhanced chemiluminescence was studied in patients with non-seminomatous germ cell tumours. Group 1 comprised 14 patients who had been "cured" of their cancer (the term "cured" as used in this report denotes a relapse free period of at least three years). Group 2 comprised 15 patients who were followed from diagnosis to up to two years after the start of treatment. RESULTS: Lucigenin enhanced chemiluminescence of whole blood in the "cured" patients was similar to that of controls and lower than that in patients who had not yet received chemotherapy (group 2). After treatment, chemiluminescence decreased slowly and did not normalise until 18 months after the start of treatment. Tumour necrosis factor alpha (TNF alpha) concentrations were normal in "cured" patients but were raised in those who had not yet received treatment. TNF alpha was normalised 12 months after start of treatment. Alpha-fetoprotein concentrations were raised in most patients but normalised rapidly after tumour eradication. CONCLUSIONS: The activity of blood monocytes, as measured by whole blood lucigenin enhanced chemiluminescence, is increased in cancer. This activity may be a consequence of the presence of tumour cells. Immunocompetent cells remain active for over a year after eradication of the tumour.     

Importance of participation rate in sampling of data in population based studies, with special reference to bone mass in Sweden

OBJECTIVE: To study the effects of participation rate in sampling on "normative" bone mass data. DESIGN: This was a comparison between two randomly selected samples from the same population. The participation rates in the two samples were 61.9% and 83.6%. Measurements were made of bone mass at different skeletal sites and of muscle strength, as well as an assessment of physical activity. SETTING: Malm?, Sweden. SUBJECTS: There were 230 subjects (117 men, 113 women), aged 21 to 42 years. RESULTS: Many subjects participated in both studies (163). Those who took part only in the study with the higher participation rate (67) almost invariably had higher values for bone mass density at the sites measured (up to 7.6% for men) than participants in the study with the lower participation rate. No differences in muscle strength were recorded. CONCLUSION: A high degree of compliance is important to achieve a reliable result in determining normal values in population based studies.     

Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues

Using PCR with degenerate primers and screening of a human B-cell lymphoblast cDNA library, a full-length cDNA encoding a 375-amino-acid protein was isolated. It contains seven regions of hydrophobic amino acids probably representing membrane-spanning domains of a novel heptahelix receptor, tentatively named CMKRL2. It shows nearly 30% overall identity with the high-affinity IL8 receptor and similar degree of homology with other chemoattractant receptors, including the "fusin" coreceptors for HIV1. Measurements of various transduction pathways following application of a panel of chemokines to transfected cells failed to evoke any reproducible response. Although the natural ligand for CMKRL2 could, thus, not be identified, receptor expression in spleen and lymph nodes as well as in Burkitt's lymphoma (irrespective of EBV status) supports a functional role in activated B-cells. Receptor message was ubiquitously distributed in normal peripheral tissues and CNS, suggesting that CMKRL2 is expressed in widespread cell populations, such as macrophages and neuroglia.     

A new heuristic to solve the one-warehouse N-retailer problem

We deal with a multi-echelon inventory system in which one warehouse supplies an item to multiple retailers. Customer demand arrives at each retailer at a constant rate. The retailers replenish their inventories from the warehouse that in turn orders from an outside supplier. It is assumed that shortages are not allowed and lead times are negligible. The goal is to determine replenishment policies that minimize the overall cost in the system. We develop a heuristic to compute efficient policies, which also can easily be used in a spreadsheet application. The main idea consists of finding a balance between the replenishment and the inventory holding costs at each installation. This new heuristic we compare with two other approaches proposed in the literature; the computational studies show that in most of the instances generated the new method provides lower costs.     

A framework for developing measurement systems and its industrial evaluation

As in every engineering discipline, metrics play an important role in software development, with the difference that almost all software projects need the customization of metrics used. In other engineering disciplines, the notion of a measurement system (i.e. a tool used to collect, calculate, and report quantitative data) is well known and defined, whereas it is not as widely used in software engineering. In this paper we present a framework for developing custom measurement systems and its industrial evaluation in a software development unit within Ericsson. The results include the framework for designing measurement systems and its evaluation in real life projects at the company. The results show that with the help of ISO/IEC standards, measurement systems can be effectively used in software industry and that the presented framework improves the way of working with metrics. This paper contributes with the presentation of how automation of metrics collection and processing can be successfully introduced into a large organization and shows the benefits of it: increased efficiency of metrics collection, increased adoption of metrics in the organization, independence from individuals and standardized nomenclature for metrics in the organization.     

Design patterns for user interface for mobile applications

The topic of this paper is a collection of user interface (UI) design patterns for mobile applications. In the paper we present the structure of the patterns collection – the patterns are suggested solutions to problems that are grouped into a set of problem areas that are further grouped into three main problem areas – a structure which is valuable both as an index to identifying patterns to use, and it gives a fairly comprehensive overview of issues when designing user interfaces for mobile applications. To show the breadth of the patterns collection we present six individual problems with connected design patterns in some detail – each coming from different problem areas. They represent important and relevant problems, and are on different levels of abstraction, thus showing how patterns may be used to present problems and solutions on different levels of detail. To show the relevance and usefulness of the patterns collection for usability professionals with a mixed background, we present some relevant findings from a validation of the patterns collection. In addition to verifying the relevance and usefulness of the patterns collection, it also shows both expected and surprising correlations between background and perceived relevance and usefulness. One important finding from the validation is an indication that the patterns collection is best suited for experienced UI developers wanting to start developing mobile UIs. Using a patterns collection for documenting design knowledge and experience has been a mixed experience, so we discuss pros and cons of this. Finally, we present related work and future research.     

Competitive exploration of rectilinear polygons

Exploring a polygon with robots when the robots do not have knowledge of the surroundings can be viewed as an online problem. Typical for online problems is that decisions must be made based on past events without complete information about the future. In our case the robots do not have complete information about the environment. Competitive analysis can be used to measure the performance of methods solving online problems. The competitive ratio of such a method is the ratio between the method's performance and the performance of the best method having full knowledge of the future. We prove constant competitive strategies and lower bounds for exploring a simple rectilinear polygon in the _L1$L_1$ metric.