Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism

We have performed cDNA sequencing and homology analyses to elucidate the complete amino acid composition for a superficial zone protein (SZP) from human and bovine cartilage which has previously been shown to be a proteoglycan specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining cells. The results of this study indicate that cartilage SZP is homologous with a glycoprotein first described as the precursor protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and analyses indicate that (i) the amino acid composition of SZP is highly conserved between bovine and human species, (ii) SZP contains structural motifs at the N- and C-termini which are similar to those found in vitronectin and which may impart cell-proliferative and matrix-binding properties to the molecule, and (iii) SZP contains large and small mucin-like repeat domains composed of the sequences KEPAPTTT/P (76-78 repeats) and XXTTTX (6-8 repeats), respectively, which occur within a large central region of approximately 940 amino acids. The mucin-like domains are likely to be substituted with O-linked oligosaccharides which would impart lubricating properties to SZP which in part accumulates at the articular cartilage-synovial fluid interface. Additionally, we have shown that interleukin-1 inhibits the biosynthesis of chondrocyte SZP, while TGF-beta and IGF-1 increase its biosynthesis, and that in pathological (osteoarthritic) human articular cartilage SZP mRNA can be expressed as an alternatively spliced variant lacking exons 4 and 5 which encode a potential heparin binding domain. The occurrence of different SZP alternative splice variants and the differential expression of SZP in the presence of cytokines and growth factors suggest that SZP may play an important cytoprotective role by preventing cellular adhesion to the articular cartilage surface in normal cartilage metabolism. Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and invasion of pannus observed in inflammatory joint diseases.     

An implicit finite element material model for energetic particulate composite materials

The predisposition of energetic particulate composite materials, or high explosives (HE), to ignition by bulk heating (cookoff) poses serious safety problems. Because unexpected initiation of HE must be a major consideration in any activity involving employment of the material, its behaviour under a variety of conditions is of much interest. The formulation of a numerical constitutive model that can be employed in an implicit finite element code to predict the mechanical and ignition behaviour of HE is presented. The capability of the developed material model is then demonstrated through its implementation in the ABAQUS finite element code to simulate the response of HE test configurations. The simulated response is found to compare favourably with the physical test results, in the cases where test data exist. Copyright © 2000 John Wiley & Sons, Ltd.     

Factor structure of the Graduate Record Examinations General Test in handicapped and nonhandicapped groups.

We used confirmatory factor analysis to investigate the structure of the Graduate Record Examinations General Test across handicapped and nonhandicapped groups. A simple three-factor model, consisting of verbal, quantitative, and analytical item types, was posed and tested for model fit. In addition, a higher order factor solution was computed to investigate the meaning of General Test total scores and to probe observed discrepancies in factor structure. Results suggested that the three-factor model fit better than simpler models but less well than a four-factor solution. The three-factor model showed particular problems in fit for visually impaired students taking a large-type examination and for physically impaired examinees taking a standard administration. For these groups, the item types composing the Analytical factor did not appear to function effectively as a single factor. For the large-type group, in particular, these item types exhibited different relations with the other factors, had different relations with the test's general factor, and appeared to produce different scale units. Results suggest that Analytical scores and total scores (Verbal?+?Quantitative?+?Analytical) may have different meanings across handicapped and nonhandicapped groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of HTLV-1-specific CTL directed against synthetic and naturally processed peptides in HLA-B*3501 transgenic mice

Most human breast tumors start as estrogen-dependent, but during the course of the disease become refractory to hormone therapy. The transition of breast tumors from estrogen dependent to independent behavior may be regulated by autocrine and/or paracrine growth factor(s) that are independent of the estrogen receptor (ER). We have investigated the role(s) of NDF (neu-differentiation factor) in the biology of estrogen positive breast cancer cells by using MCF-7 cells as a model system. Treatment of MCF-7 cells with human recombinant NDF-beta 2 (NDF) inhibited the ER expression by 70% and this was associated with growth stimulation in an estrogen-independent manner. To explore the mechanism(s) of action of NDF in MCF-7 cells, we examined the expression of NDF-inducible gene products. We report here that NDF stimulated the levels of expression of a 46 kD protein (p46) (in addition to few minor proteins) in ER positive breast cancer cells including MCF-7, T-47-D, and ZR-75-R cells but not in ER negative breast cancer cells including MDA-231, SK-BR-3, and MDA-468 cells. This effect of NDF was due to induction in the rate of synthesis of new p46. The observed NDF-mediated induction of p46 expression was specific as there was no such effect by epidermal growth factor or 17-beta-estradiol, and inclusion of actinomycin D partially inhibited the p46 induction elicited by NDF. NDF-inducible stimulation of p46 expression was an early event (2-6 h) which preceded the period of down-regulation of ER expression by NDF. These results support the existence of NDF-responsive specific cellular pathway(s) that may regulate ER, and these interactions could play a role(s) in hormone-independence of ER positive breast cancer cells.     

The AP-3 complex: a coat of many colours

A new adaptor protein complex, termed AP-3, has recently been identified in mammalian cells, and genetic studies in yeast have revealed a functional role for the AP-3 complex in cargo-selective transport via a new alternative trafficking pathway from the Golgi to the vacuole/lysosome. Here, the authors review what is currently known about the AP-3 complex and discuss recent insight into its function in multicellular organisms that has come from the finding that mutations in AP-3 subunits correspond to classical mutations in Drosophila and mice.     

Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials

Eight randomized controlled trials (RCTs) of screening mammography have been conducted involving women aged 40-49 at entry. Current data are now available from these trials at 10.5 to 18 years of follow-up (average follow-up time: 12.7 years). Meta-analysis has been performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women aged 40-49 at entry, including new follow-up data presented at the NIH Consensus Development Conference held January 21-23, 1997. Combining the most recent follow-up data on women aged 40-49 at entry into all eight RCTs yields a statistically significant 18% mortality reduction among women invited to screening mammography (relative risk: 0.82; 95% confidence interval: 0.71-0.95). Combining all current follow-up data on women aged 40-49 at entry into the five Swedish RCTs yields a statistically significantly 29% mortality reduction among women invited to screening (relative risk: 0.71; 95% confidence interval: 0.57-0.89). Meta-analysis including the most recent follow-up data from all eight RCTs involving women aged 40-49 at entry demonstrates for the first time a statistically significant mortality reduction due to regular screening mammography in women of this age group.     

Hole and electron mobilities in heavily doped silicon: comparison of theory and experiment

Most device models for npn or pnp transistors assume that hole (electron) mobilities in n-type and p-type silicon are equal. Partial-wave phase shift calculations for the contributions of carrier-dopant ion scattering to the carrier mobilities lead to unequal minority hole (electron) and majority hole (electron) mobilities at the same doping density. These calculations are valid over the doping range of 2 x 10¹⁹ to 8 x 10¹⁹ cm⁻³ in n-type and p-type silicon and contain the assumptions that the holes and electrons move in isotropic parabolic energy bands and are scattered by the screened Coulomb potentials of the dopant ions. When the effects of carrier-acoustic phonon and carrier-carrier scatterings are included, these calculations agree to within the spread of experimental value for the majority mobilities reported in the literature. This agreement is a substantial improvement by factors of 2–4 over the results of earlier theories such as first order Born and nondegenerate theories. The results of this work, particularly the inequality of minority and majority carrier mobilities, have implications for the modeling of both bipolar and field effect transistors.     

RF and AMS

The paper shows four basic circuit functions which are RF transceiver, AMS, power amplifier (PA) and power management (PM), and digital signal processor (DSP). In this article, the authors emphasize the first three circuit functions, which drive analog and RF technology needs. Each of those three major parts in a RF front-end for a wireless system are discussed in a separate section with special emphasis on the device needs and technology choices for those blocks and with main focus on the frequency range from 0.8 to 10 GHz. A section on millimeter wave circuits and devices cover device and technology integration issues for applications in the frequency range starting from 10-100 GHz. Finally, we discuss the evolution of technology choices, integration issues, and potentially new emerging devices, all within the time-frame for the 2003 ITRS roadmap (2003-2018).     

Fasciola hepatica Gastrodermal Cells Selectively Release Extracellular Vesicles via a Novel Atypical Secretory Mechanism

The liver fluke, Fasciola hepatica, is an obligate blood-feeder, and the gastrodermal cells of the parasite form the interface with the host’s blood. Despite their importance in the host–parasite interaction, in-depth proteomic analysis of the gastrodermal cells is lacking. Here, we used laser microdissection of F. hepatica tissue sections to generate unique and biologically exclusive tissue fractions of the gastrodermal cells and tegument for analysis by mass spectrometry. A total of 226 gastrodermal cell proteins were identified, with proteases that degrade haemoglobin being the most abundant. Other detected proteins included those such as proton pumps and anticoagulants which maintain a microenvironment that facilitates digestion. By comparing the gastrodermal cell proteome and the 102 proteins identified in the laser microdissected tegument with previously published tegument proteomic datasets, we showed that one-quarter of proteins (removed by freeze–thaw extraction) or one-third of proteins (removed by detergent extraction) previously identified as tegumental were instead derived from the gastrodermal cells. Comparative analysis of the laser microdissected gastrodermal cells, tegument, and F. hepatica secretome revealed that the gastrodermal cells are the principal source of secreted proteins, as well as showed that both the gastrodermal cells and the tegument are likely to release subpopulations of extracellular vesicles (EVs). Microscopical examination of the gut caeca from flukes fixed immediately after their removal from the host bile ducts showed that selected gastrodermal cells underwent a progressive thinning of the apical plasma membrane which ruptured to release secretory vesicles en masse into the gut lumen. Our findings suggest that gut-derived EVs are released via a novel atypical secretory route and highlight the importance of the gastrodermal cells in nutrient acquisition and possible immunomodulation by the parasite.