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K3Lu(PO4)2:Ce single crystals have been studied under gamma, X-ray, VUV, and UV excitation. For all of the excitation forms, the luminescence of these materials is dominated by the d–f emission bands of Ce3+. The shape and position of these bands, however, depends on the form of the excitation and on temperature due to crystallographic structural phase changes and multiple types of Lu3+ ions sites in the which the Ce3+ ion can substitute for Lu. The highly efficient and fast scintillation of these materials is based on radiative recombination of electron-hole pairs via Ce ions, and the scintillation characteristics identify K3Lu(PO4)2:Ce as a promising fast and efficient scintillator. [Copyright &y& Elsevier]

LuPO4:Nd and YPO4:Nd represent new and very fast potential scintillator materials. For most types of ionizing excitation, the luminescence of these materials is dominated by an emission band whose maximum intensity occurs at ∼192 nm. The origin of this band is the fast 5d–4f transitions of the Nd3+ ions. An additional emission contribution due to host-defect emission varies for different samples. These defects appear to be responsible for the limited light yield of LuPO4:Nd. [Copyright &y& Elsevier]

Presents results for neodymium-activated lutetium and yttrium orthophosphates grown in single-crystal form. Motives for the interest in the potential applications of neodymium doped materials as scintillators; Way of obtaining the energy spectra used to measure the scintillation light yield; Use of digital oscilloscope.

Discusses a study which focused on the scintillation and spectroscopic properties of YAG crystals activated with earth ions. Areas in which rare earth ions are found; Measurements that were obtained at various temperatures under the pulsed synchrotron excitation; Reason for the assumption that all scintillation components can be attributed to radioluminiscence.

Abstract: The scintillation properties of Ce-activated alkali-lutetium double phosphate single crystals that vary with the alkali ion type and activation level are summarized and compared. The materials investigated here have been identified as fast and efficient scintillators for the detection of X-ray and γ radiation, and in case of Li3Lu(PO4)2:Ce, for thermal neutron detection as well. [Copyright &y& Elsevier]

A new scintillator material consisting of a methanol adduct of cerium trichloride with the composition CeCl3(CH3OH)4 has been discovered and crystallized in the form of large single crystals by solution growth in methanol. The peak emission of the x-ray-excited luminescence spectrum occurs at ∼364 nm. A light yield of up to ∼16 600 photons/MeV and an energy resolution of 11.4% were obtained using 662 keV gamma-ray photons. The scintillator decay time for 662 keV gamma-ray excitation was measured using the time-correlated, single-photon-counting method, and a nominal value of 64.4 ns was obtained. The molecular adduct CeCl3(CH3OH)4 represents the first example of a rare-earth, metal-organic scintillator that is applicable to gamma ray, x ray, and neutron detection. [ABSTRACT FROM AUTHOR]

The chronological history of the important discoveries leading to our present understanding of the essential clinical, biological, biochemical, and molecular features of chronic myelogenous leukemia (CML) are first reviewed, focusing in particular on abnormalities that are responsible for the massive myeloid expansion. CML is an excellent target for the development of selective treatment because of its highly consistent genetic abnormality and qualitatively different fusion gene product, p210[SUPbcr-abl]. It is likely that the multiple signaling pathways dysregulated by p210[SUPbcr-abl] are sufficient to explain all the initial manifestations of the chronic phase of the disease, although understanding of the circuitry is still very incomplete. Evidence is presented that the signaling pathways that are constitutively activated in CML stem cells and primitive progenitors cooperate with cytokines to increase the proportion of stem cells that are activated and thereby increase recruitment into the committed progenitor cell pool, and that this increased activation is probably the primary cause of the massive myeloid expansion in CML. The cooperative interactions between Bcr-Abl and cytokine-activated pathways interfere with the synergistic interactions between multiple cytokines that are normally required for the activation of stem cells, while at the same time causing numerous subtle biochemical and functional abnormalities in the later progenitors and precursor cells. The committed CML progenitors have discordant maturation and reduced proliferative capacity compared to normal committed progenitors, and like them, are destined to die after a limited number of divisions. Thus, the primary goal of any curative strategy must be to eliminate all Philadelphia positive (Ph+) primitive cells that are capable of symmetric division and thereby able to expand the Ph+ stem cell pool and recreate the disease. Several highly potent and moderately selective inhibitors of... [ABSTRACT FROM AUTHOR]

The 9;22 chromosomal translocation characteristic of CML results in a fused bcr/abl gene and an abnormal fusion protein, p210bcr/abl. Relative to normal c-abl, p210bc1/abl has elevated tyrosine kinase activity that is essential for its transforming activity. We recently reported a prominent 62 kDa GAP-associated P-tyr protein and five additional consistent but less prominent P-tyr proteins as well as five more minor P-tyr proteins that are constitutively tyrosine phosphorylated in primary primitive lineage negative (lin-) chronic phase CML blasts but not in comparable primary lin- normal blasts. The GAP-associated p62 protein has now been purified, sequenced and its gene has been cloned; it is a previously unidentified protein and is currently being characterized. In analyzing P-tyr proteins in primary lin- normal blasts in response to various hematopoietic cytokines, we found a striking similarity in the tyrosine phosphorylation of four major and three minor proteins after stimulation with c-kit ligand (KL) and the P-tyr proteins that are constitutively phosphorylated in primary primitive lin- chronic phase CML blasts. Other cytokines tested (ie GM-CSF, G-CSF, IL-3, FLT3 ligand, TPO, EPO) were much less active or stimulated phosphorylation of other proteins. KL/c-kit and bcr/abl have some similar activities including enhancing survival and expansion of hematopoietic progenitor cells, probably acting primarily on early progenitors at the time of lineage commitment rather than on self-renewing stem cells. Activation of growth factor receptors promote a cascade of protein phosphorylations that can ultimately result in a wide range of cellular responses. Sustained activation of discrete signaling pathways in some types of cells results in differentiation, whereas transient activation instead causes a proliferative response; in other cell types, the converse is true. It may be postulated that stem cells and primitive progenitors are at a particularly susceptible stage of development that renders them especially responsive to sustained bcr/abl-induced phorphorylation of a number of signaling proteins that are components of critical regulatory pathways, including c-kit. The affected pathways control and coordinate multiple diverse cell processes including proliferation, differentiation, maturation and apoptosis, processes that are normally tightly regulated and integrated. Perturbation of these key pathways in primitive progenitors would be expected to seriously disrupt orderly hematopoiesis and could also explain the multiple subtle pleiotropic biological abnormalities characteristically observed in later maturing CML compartments that we have collectively designated 'discordant maturation'. The true situation is undoubtedly very complex and involves interaction of multiple cytokines and signaling pathways that we are now trying to define. Constitutive downstream activation of critical pathways in susceptible early progenitors that normally require KL or other factors for activation could explain most if not all features of the disease. [ABSTRACT FROM AUTHOR]

A new scintillator material for the detection of fast neutrons that consists of a methanol adduct of cerium trichloride with the composition CeCl3(CH3OH)4 has been characterized using 14.1 MeV neutrons from a deuterium-tritium neutron generator and fast neutrons from a bare instrumented 252Cf source. The timing resolution of the scintillator for fast neutrons was found to be ~ 1 ns. Neutron interactions in the CeCl3(CH3OH)4 composition were simulated using the MCNP-PoliMi code. These simulations indicate that proton recoils account for most of the deposited energy in CeCl3(CH3OH)4. The crystalline molecular adduct CeCl3(CH3OH)4 represents a rare-earth metal-organic scintillator that can be applied to both fast neutron and gamma-ray detection. [ABSTRACT FROM AUTHOR]

The primary virulence factor of Bacillus anthrads is a secreted zinc-dependent metalloprotease toxin known as lethal factor (LF) that is lethal to the host through disruption of signaling pathways, cell destruction, and circulatory shock. Inhibition of this proteolytic-based LF toxemia could be expected to provide therapeutic value in combination with an antibiotic during and immediately after an active anthrax infection. Herein is shown the crystal structure of an intimate complex between a hydroxamate, (2R)-2-[(4-fluoro-3-methyl phenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, and LF at the LF-active site. Most importantly, this molecular interaction between the hydroxamate and the IF active site resulted in (0 inhibited LF protease activity in an enzyme assay and protected macrophages against recombinant LF and protective antigen in a cell-based assay, (10100% protection in a lethal mouse toxemia model against recombinant LE and protective antigen, (iii) 50% survival advantage to mice given a lethal challenge of B. anthracis Sterne vegetative cells and to rabbits given a lethal challenge of B. anthracis Ames spores and doubled the mean time to death in those that died in both species, and (iv) 100% protection against B. anthrads spore challenge when used in combination therapy with ciprofloxacin in a rabbit "point of no return" model for which ciprofloxacin alone provided 50% protection. These results indicate that a small molecule, hydroxamate IF inhibitor, as revealed herein, can ameliorate the toxemia characteristic of an active B. anthrads infection and could be a vital adjunct to our ability to combat anthrax. [ABSTRACT FROM AUTHOR]