Rapamycin but not FK506 inhibits the proliferation of mononuclear phagocytes induced by colony-stimulating factors

FK506, CsA, and rapamycin are potent inhibitors of T lymphocyte activation; relatively little is known of their effects on cells of the monocyte/macrophage lineage. Studies were undertaken to determine the effects of these drugs on the proliferative response of bone marrow-derived mononuclear phagocytes (BMMP) to CSFs. Rapamycin inhibited the proliferation of BMMP cultured in the presence of 10% L cellconditioned medium, used as a source of macrophage CSF. The inhibition by rapamycin was dose dependent and apparent at concentrations of 0.1 nM or greater. In a similar fashion, rapamycin inhibited the proliferation of BMMP stimulated by the recombinant forms of murine IL-3 and murine granulocyte-macrophage CSF, and human macrophage CSF. In contrast, neither FK506 nor CsA at concentrations as high as 1000 nM diminished the proliferation of BMMP cultured under identical conditions. FK506, but not CsA, blocked the inhibitory effects of rapamycin on the response of BMMP to CSFs. In summary, these data indicate that rapamycin inhibits the proliferation of BMMP in response to CSFs. These results imply that patients receiving rapamycin, but not FK506 or CsA, may have an impaired ability to generate a functional mononuclear phagocyte population. © 1994 by Williams and Wilkins

Positronium emission from mesoporous silica studied by laser-enhanced time-of-flight spectroscopy

The use of mesoporous silica films for the production and study of positronium (Ps) atoms has become increasingly important in recent years, providing a robust source of free Ps in vacuum that may be used for a wide variety of experiments, including precision spectroscopy and the production of antihydrogen. The ability of mesoporous materials to cool and confine Ps has also been utilized to conduct measurements of Ps–Ps scattering and Ps2 molecule formation, and this approach offers the possibility of making a sufficiently dense and cold Ps ensemble to realize a Ps Bose–Einstein condensate. As a result there is great interest in studying the dynamics of Ps atoms inside such mesoporous structures, and how their morphology affects Ps cooling, diffusion and emission into vacuum. It is now well established that Ps atoms are initially created in the bulk of such materials and are subsequently ejected into the internal voids with energies of the order of 1 eV, whereupon they rapidly cool via hundreds of thousands of wall collisions. This process can lead to thermalisation to the ambient sample temperature, but will be arrested when the Ps deBroglie wavelength approaches the size of the confining mesopores. At this point diffusion through the pore network can only proceed via tunneling, at a much slower rate. An important question then becomes, how long does it take for the Ps atoms to cool and escape into vacuum? In a direct measurement of this process, conducted using laser-enhanced positronium time-of-flight spectroscopy, we show that cooling to the quantum confinement regime in a film with approximately 5 nm diameter pores is nearly complete within 5 ns, and that emission into vacuum takes ~10 ns when the incident positron beam energy is 5 keV. The observed dependence of the Ps emission time on the positron implantation energy supports the idea that quantum confined Ps does not sample all of the available pore volume, but rather is limited to a subset of the mesoporous network

Selective Production of Rydberg-Stark States of Positronium

Rydberg positronium (Ps) atoms have been prepared in selected Stark states via two-step (1s→2p→nd/ns) optical excitation. Two methods have been used to achieve Stark-state selection: a field ionization filter that transmits the outermost states with positive Stark shifts, and state-selected photoexcitation in a strong electric field. The former is demonstrated for n=17 and 18 while the latter is performed for n=11 in a homogeneous electric field of 1.9  kV/cm. The observed spectral intensities and their dependence on the polarization of the laser radiation are in agreement with calculations that include the perturbations of the intermediate n=2 manifold. Our results pave the way for the generation of Rydberg Ps atoms with large electric dipole moments that are required for the realization of schemes to control their motion using inhomogeneous electric fields, an essential feature of some proposed Ps free-fall measurements requiring focused beams of long-lived atoms

Experience with posttransplant lymphoproliferative disorders in solid organ transplant recipients

Nearly 6000 solid organ transplants have been performed at the University of Pittsburgh since 1981. Posttransplant lymphoproliferative disorders (PTLD) have occurred in 131 patients, at a frequency of 2.2%. The majority of cases manifest within 6 months following allograft, but individual lesions may arise several years thereafter. From 1981 to 1989, cyclosporine-A (CsA) served as the primary immunosuppressant in this population. In March of 1989, FK506 was introduced for clinical trials. Since that time, 1421 patients have received FK506 either for primary immunosuppression or as rescue therapy. The frequency of PTLD in this subpopulation is 1.5%. PTLD arising under FK506-containing regimens have clinicopathologic features similar to those arising with CsA immunosuppression. The frequency of PTLD at this point in time is approximately 1%, in kidney allograft patients, 2.7% in liver, 3.3% in heart and 3.8%, in heart/lung or lung recipients. An understanding of the range of histologic appearance is important for the diagnosis of PTLD, especially when it involves the allograft itself. Immunoglobulin heavy chain gene analysis shows that lesions with no rearrangements or with a rearrangement in only a small proportion of cells are more likely to respond to reduced immunosuppression than are those with clonal rearrangement involving a high proportion of cells. However, this distinction is not absolute, and a trial of reduced immunosuppression appears to be indicated regardless of clonal status

Positronium emission from mesoporous silica studied by laser-enhanced time-of-flight spectroscopy

The use of mesoporous silica films for the production and study of positronium (Ps) atoms has become increasingly important in recent years, providing a robust source of free Ps in vacuum that may be used for a wide variety of experiments, including precision spectroscopy and the production of antihydrogen. The ability of mesoporous materials to cool and confine Ps has also been utilized to conduct measurements of Ps–Ps scattering and Ps2 molecule formation, and this approach offers the possibility of making a sufficiently dense and cold Ps ensemble to realize a Ps Bose–Einstein condensate. As a result there is great interest in studying the dynamics of Ps atoms inside such mesoporous structures, and how their morphology affects Ps cooling, diffusion and emission into vacuum. It is now well established that Ps atoms are initially created in the bulk of such materials and are subsequently ejected into the internal voids with energies of the order of 1 eV, whereupon they rapidly cool via hundreds of thousands of wall collisions. This process can lead to thermalisation to the ambient sample temperature, but will be arrested when the Ps deBroglie wavelength approaches the size of the confining mesopores. At this point diffusion through the pore network can only proceed via tunneling, at a much slower rate. An important question then becomes, how long does it take for the Ps atoms to cool and escape into vacuum? In a direct measurement of this process, conducted using laser-enhanced positronium time-of-flight spectroscopy, we show that cooling to the quantum confinement regime in a film with approximately 5 nm diameter pores is nearly complete within 5 ns, and that emission into vacuum takes ~10 ns when the incident positron beam energy is 5 keV. The observed dependence of the Ps emission time on the positron implantation energy supports the idea that quantum confined Ps does not sample all of the available pore volume, but rather is limited to a subset of the mesoporous network

Investment in Authentic Sustainable Cultural Tourism : Planning for the Future Benefit of Waikato-Tainui along the Waikato River, Case Studies at Tūrangawaewae and Te Awamārahi Marae

“Tērā ōkū hoa kei ngā tōpito e whā o te ao - My friends will come from all parts of the world” – Kīngi Tāwhiao 1822-1894 This doctorate is guided by the visions of the second Māori king, Kīngi Tāwhiao, which reflect the importance of global connections, relationships (Turongo House, 2000:109) and investment to achieve the ultimate goal of authentic or ‘true’ sustainability throughout the world. The strategic process will require a balance between humans and the natural environment to ensure long-term growth and survival. This research will investigate whether investment in Authentic Sustainable Cultural Tourism (ASCT) will provide long-term and sustainable benefits for tribes throughout New Zealand, using a study of Waikato-Tainui. ASCT, if practiced correctly, must be driven by whānau of marae, hapū and iwi alongside ideal long-term partners to ultimately achieve indigenous autonomy. ASCT prioritises the wellbeing of indigenous and local communities, cultural preservation and environmental sustainability while providing secure economic returns to key stakeholders. Today, tourism is New Zealand’s largest and fastest growing industry; total tourism expenditure is forecast to increase from $34.7b in 2016, an increase of 12.2$41b by 2025. The natural landscape is the main reason why international travellers visit New Zealand, followed by an interest in Māori culture (Tourism Industry Association, 2015). Unfortunately, there is sparse funding for Māori tourism development (New Zealand Māori Tourism, 2015; Goulter, 2015) compared to mainstream tourism and Māori are the most impoverished people in New Zealand (Statistics New Zealand, 2011). Cultural tourism has existed in New Zealand for more than 150 years and has a vital role in New Zealand’s tourism industry. Te Kīngitanga and the Waikato River are the main aspects that make Waikato unique in New Zealand, however, there is very little cultural tourism in the region. As a descendant of Waikato-Tainui, I work with my people at the marae level to inform tribal governance about the significant opportunities available to whānau compared to current mainstream investments by the tribe. Using Kaupapa Māori and critical realism, the methods used in this research include an investigation of government tourism organisations, interviews with Waikato-Tainui governance groups, case studies at Tūrangawaewae and Te Awamārahi Marae, case studies at fourteen successful Māori tourism providers throughout New Zealand, and an international comparison of best practices in indigenous tourism.

Poiseuille geometry shear flow apparatus for small-angle scattering experiments

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