Design and implementation of electron diverters for lobster eye space-based X-ray optics.

Micropore optics have recently been implemented in a lobster eye geometry as a compact X-ray telescope. Fields generated by rare-earth magnets are used to reduce the flux of energetic electrons incident upon the focal plane detector in such a setup. We present the design and implementation of the electron diverters for X-ray telescopes of two upcoming missions: the microchannel X-ray telescope onboard the space-based multiband astronomical variable objects monitor and the soft X-ray instrument onboard the solar wind magnetosphere ionosphere link explorer. Electron diverters must be configured to conform to stringent limits on their total magnetic dipole moment and be compensated for any net moment arising from manufacturing errors. The two missions have differing designs, which are presented and evaluated in terms of the fractions of electrons reaching the detector, as determined by relativistic calculations of electron trajectories. The differential flux of electrons to the detector is calculated, and the integrated electron background is determined for both designs.

Expression of terminal differentiation proteins defines stages of mouse mammary gland development.

Immunohistochemical analysis using paraffin-embedded specimens is the method of choice to evaluate protein expression at a cellular level while preserving tissue architecture in normal and neoplastic tissues. Current knowledge of the expression of terminal differentiation markers in the mouse mammary gland relies on the evaluation of frozen tissues by use of immunofluorescence. We assessed changes in patterns of expression of terminal differentiation markers throughout the development of the mouse mammary gland in paraffin-embedded tissues. The expression of alpha-smooth muscle actin (SMA) and keratins (K) 5, 8/18, and 14 was influenced by the development stage of the mammary gland. Expression of K5 and SMA was restricted to basal cells. Keratin 14 was consistently expressed by mammary basal cells, and was detected in scattered luminal cells from 13.5 days after conception through puberty. Labeling for K8/18 of luminal cells was heterogeneous at all times. Heterogeneous expression patterns in luminal cells suggest this layer has cells with a variety of biological functions. The absence of K6 expression at any stage of the development of the mammary gland was confirmed by use of reverse transcriptase-polymerase chain reaction analysis, which indicates that this intermediate filament is not a marker of the mammary gland stem cell. Finally, consistent with results of earlier studies, keratins 1, 10, 13, and 15, and filaggrin, involucrin, and loricrin were not detected at any stage of mammary gland development.

IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo.

IGF-I, a ubiquitous polypeptide, plays a key role in longitudinal bone growth and acquisition. The most predominant effect of skeletal IGF-I is acceleration of the differentiation program for osteoblasts. However, in vivo studies using recombinant human (rh) IGF-I and/or rhGH have demonstrated stimulation of both bone formation and resorption, thereby potentially limiting the usefulness of these peptides in the treatment of osteoporosis. In this study, we hypothesized that IGF-I modulates bone resorption by regulating expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) in bone cells. Using Northern analysis in ST2 cells, we found that human IGF-I suppressed OPG mRNA in a time- and dose-dependent manner: 100 micro g/LIGF-I (13 nM) decreased OPG expression by 37.0 +/- 1.8% (P < 0.002). The half maximal inhibitory dose of IGF-I was reached at 50 micro g/liter ( approximately 6.5 nM) with no effect of IGF-I on OPG message stability. Conditioned media from ST2 cells confirmed that IGF-I decreased secreted OPG, reducing levels by 42%, from 12.1-7 ng/ml at 48 h (P < 0.05). Similarly, IGF-I at 100 micro g/liter (13 nM) increased RANKL mRNA expression to 353 +/- 74% above untreated cells as assessed by real-time PCR. In vivo, low doses of rhGH when administered to elderly postmenopausal women only modestly raised serum IGF-I (to concentrations of 18-26 nM) and did not affect circulating OPG concentrations; however, administration of rhIGF-I (30 micro g/kg.d) for 1 yr to older women resulted in a significant increase in serum IGF-I (to concentrations of 39-45 nM) and a 20% reduction in serum OPG (P < 0.05). In summary, we conclude that IGF-I in a dose- and time-dependent manner regulates OPG and RANKL in vitro and in vivo. These data suggest IGF-I may act as a coupling factor in bone remodeling by activating both bone formation and bone resorption; the latter effect appears to be mediated through the OPG/RANKL system in bone.

Mouse genetic model for bone strength and size phenotypes: NZB/B1NJ and RF/J inbred strains.

The relationships of bone size, bone strength, and bone formation were investigated in two strains of mice, NZB/B1NJ and RF/J. Measurement of the femur midshaft size by peripheral quantitative computed tomography (pQCT) showed that the RF/J mice had a 32% greater cross-sectional area than NZB/B1NJ mice at 10 weeks of age, and a 38% greater cross-sectional area at 22 weeks of age. Body weight in the RF/J mice was 10% higher at 10 weeks but 9% lower at 22 weeks. Bone strength was determined by a three-point bending method. In agreement with the difference in bone cross-sectional area, the femurs of the RF/J mice were stronger (80% greater) and stiffer (80% greater) than the bones of the NZB/B1NJ mice. To determine whether periosteal bone formation played a role in the greater size of the RF/J mice, the mice were injected with tetracycline to label areas of new bone formation. Histomorphometrical analysis of the femur diaphysis demonstrated higher rates of periosteal bone formation (131% greater) and of periosteal forming surface (81% greater) in RF/J than in NZB/B1NJ mice. We conclude that a high rate of periosteal bone formation increases bone size and strength in RF/J mice when compared with NZB/B1NJ mice. The NZB/B1NJ and RF/J mice should be an excellent model to investigate the genes that regulate femur size and strength.