NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation

The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain-like structure in the predicted NH2 terminus, and a "kelch motif" in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110(RB)) is found to be associated with the nuclear matrix and overexpression of p110(RB) induces neuronal differentiation, we investigated whether NRP/B is associated with p110(RB). Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110(RB) during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110(RB) and participates in the regulation of neuronal process formation.     

Isoseparation curves: a mechanism for optimizing off-axis dose homogeneity of intact breast irradiation

The purpose of this paper is to determine whether using off-axis isoseparation curves to optimize the collimator rotation angle improves dose homogeneity. Eleven intact breast irradiation patients underwent computerized tomography (CT) treatment planning with 1 cm abutting slices. Central plane treatment planning, using 6 MV photons, tissue inhomogeneity corrections, and isocentric opposed tangent treatment fields, was performed. Collimators were rotated to match chest wall slope through the use of a beam's-eye-view setting. Patient separations were measured from the apex of the breast to the posterior field border on each axial CT slice. Sagittal-plane isoseparation curves were constructed from these measurements. Using these curves, the collimator rotation that minimized off-axis separation differences was determined. A comparison of off-axis dose inhomogeneity was performed for patients with a > or =10 degrees difference between this optimized collimator angle and the angle determined by chest wall slope. These comparative treatment plans differed only with respect to collimator angle rotation. The mean optimal collimator rotation angle differed significantly from the mean rotation angle which matched the chest wall slope (5.4 degrees vs. 11 degrees, respectively, P < 0.001). Four of the 11 patients had rotation angle differences of 10 degrees. In these patients, the optimization of collimator angle reduced the percentage of breast volume to "that" received > or =110% of the prescribed dose. For the patient with the largest breast size to the patient with the smallest breast size the decreases were, respectively, 5% (15% to 10%), 3% (24% to 21%), 1% (4% to 3%), and 1% (0.9% to 0%). The mean reduction in dose inhomogeneity was greatest in the inferior breast quadrants. At 6 cm and 4 cm off axis, the mean reductions in the percentages of the breast tissue to "that" received 110% of the prescribed dose were respectively 15.1% and 5.3 %. Optimizing the collimator angle through the use of isoseparation curves decreases dose inhomogeneity. The greatest improvements are in the inferior quadrants of the intact breast. The improved dose homogeneity may have clinical relevance in the treatment of patients with large breast sizes.     

Multidimensionality of oral health in dentate adults

OBJECTIVES: An understanding of the validity and usefulness of self-reported measures (as distinct from clinically determined measures) of oral health is emerging. These self-reported measures include self-rated oral health (SROH). Three objectives were to: (1) describe self-rated oral health in dentate adults, (2) quantify associations between self-rated oral health and other measures of oral health (oral disease and tissue damage, pain and discomfort, functional limitation, and disadvantage), and (3) assess the construct validity of a model of oral health proposed herein. METHODS: The Florida Dental Care Study is a longitudinal study of oral health, which included at baseline 873 subjects who had at least one tooth, were 45 years or older, and who participated for an interview and clinical examination. RESULTS: The prevalence of self-rated oral health decrements was substantial; approximately one fourth of subjects reported their oral health as only fair or poor. Bivariate and multivariate results provided consistent evidence of the construct validity of the proposed model of oral health. Additionally, the salience of one measure of dental appearance suggests that persons may use esthetic cues when rating their oral health. CONCLUSIONS: The proposed multidimensional model of oral health has construct validity. Self-rated oral health is affected by oral disease and tissue damage, oral pain and discomfort, oral functional limitation, and oral disadvantage. These self-reported measures and the proposed model should provide useful information for dental care effectiveness research. General health status has been disaggregated into the "physical" and the "mental;" an additional separation into the "oral" aspects of health seems warranted.     

Mast cells mediate acute inflammatory responses to implanted biomaterials

Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines-macrophage inflammatory protein 1alpha/monocyte chemoattractant protein 1-and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s. c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores "normal" inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials.     

Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions

Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227-->Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227-->Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227-->Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.     

Reduction rules for YAWL workflows with cancellation regions and OR-joins

As the need for concepts such as cancellation and OR-joins occurs naturally in business scenarios, comprehensive support in a workflow language is desirable. However, there is a clear trade-off between the expressive power of a language (i.e., introducing complex constructs such as cancellation and OR-joins) and ease of verification. When a workflow contains a large number of tasks and involves complex control flow dependencies, verification can take too much time or it may even be impossible. There are a number of different approaches to deal with this complexity. Reducing the size of the workflow, while preserving its essential properties with respect to a particular analysis problem, is one such approach. In this paper, we present a set of reduction rules for workflows with cancellation regions and OR-joins and demonstrate how they can be used to improve the efficiency of verification. Our results are presented in the context of the YAWL workflow language.     

Reliability of seizure classification using a semistructured interview

Methods for standardized classification of epileptic seizures are important for both clinical practice and epidemiologic research. In this study, we developed a strategy for standardized classification using a semistructured telephone interview and operational diagnostic criteria. We interviewed 1,957 adults with epilepsy ascertained from voluntary organizations. To confirm and expand the seizure history, we also interviewed a first-degree relative for 67% of subjects and obtained medical records for 59%. Three lay reviewers used all available information to classify seizures. To assess reliability, each reviewer classified a sample of subjects assigned to the others. In addition, an expert physician classified a sample of subjects assigned to two of the reviewers. Agreement was "moderate-substantial" for generalized-onset seizures, both for the comparisons between pairs of lay reviewers and for the neurologist versus lay reviewers. Agreement was "substantial-almost perfect" for partial-onset seizures, both for pairs of lay reviewers and for the neurologist versus lay reviewers. These results suggest that seizures can be reliably classified by lay reviewers, using operational criteria applied to symptoms ascertained in a semistructured telephone interview.     

Relative effects of bacterial and protozoan predators on survival of Escherichia coli in estuarine water samples

The relative effect of protozoan and bacterial predators on the survival of Escherichia coli in estuarine water samples was examined. Predacious protozoa exerted their major influence on E. coli destruction during the first 2 days of a 10-day-decline period. Inhibition of protozoa after day 2 had little effect on E. coli survival. Bacterial predators also contributed to E. coli destruction but in natural estuarine water samples were maintained at lower levels due to "grazing" by predacious protozoa.     

含有零值和负值的随机准备金模型

在准备金评估中,由于多数随机准备金模型基本假设的限制是不能直接处理含有零值和负值增量赔款三角形,本文利用一个变换和广义线性模型的混合模型去解决这种情况．     

Studies on the ultrastructure, histochemistry and cytochemistry of the uninfected digestive gland of Bithynia tentaculata (Mollusca: Gastropoda) and on the ultrastructure of this host organ in snails infected with larval digeneans

The structure and function of the digestive gland of the gastropod mollusc, Bithynia tentaculata, was investigated using ultrastructural, histochemical, and cytochemical techniques. The digestive gland was shown to be composed of two main cell types, the "digestive" cells and "secretory" cells. The digestive cells appeared to be concerned with the absorption and digestion of nutrients, while secretory cells produced digestive enzymes and calcareous concretions. Undifferentiated cells were scattered between these two main cell types. The pathological effects of larval digeneans on the digestive gland were also investigated, at the ultrastructural level. In such infected snails the digestive gland appeared to be degenerating. The significance of this tissue destruction was briefly discussed.