Pretargeted Molecular Imaging and Radioimmunotherapy

Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-hapten antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors

Effects of mu- and kappa-2 opioid receptor agonists on pain and rearing behaviors

<p>Abstract</p> <p>Background</p> <p>Management of pain involves a balance between inhibition of pain and minimization of side effects; therefore, in developing new analgesic compounds, one must consider the effects of treatment on both pain processing and behavior. The purpose of this study was to evaluate the effects of the mu and kappa-2 opioid receptor agonists on general and pain behavioral outcomes.</p> <p>Methods</p> <p>As a general behavioral assessment, we modified the cylinder rearing assay and recorded the number and duration of rearing events. Thermal sensitivity was evaluated using either a reflexive measure of hindpaw withdrawal latency to a radiant heat source or using an orofacial operant thermal assay. Acetic acid-induced visceral pain and capsaicin-induced neurogenic inflammatory pain were used as painful stimuli. The mu-opioid receptor agonist, morphine or the kappa-2 receptor agonist GR89696 was administered 30 min prior to testing. A general linear model repeated measures analysis was completed for baseline session comparisons and an analysis of variance was used to evaluate the effects of treatment on each outcome measure (SPSS Inc). When significant differences were found, post-hoc comparisons were made using the Tukey honestly significant difference test. *P < 0.05 was considered significant in all instances.</p> <p>Results</p> <p>We found that morphine and GR89,696 dose-dependently decreased the number of reaching events and rearing duration. Rearing behavior was not affected at 0.5 mg/kg for morphine, 1.25 × 10^-4mg/kg for GR89,696. Hindpaw thermal sensitivity was significantly increased only at the highest doses for each drug. At the highest dose that did not significantly influence rearing behavior, we found that visceral and neurogenic inflammatory pain was not affected following GR89,696 administration and morphine was only partially effective for blocking visceral pain.</p> <p>Conclusion</p> <p>This study demonstrated that high levels of the opioids produced significant untoward effects and made distinguishing an analgesic versus a more general effect more difficult. Quantification of rearing behavior in conjunction with standard analgesic assays can help in gaining a better appreciation of true analgesic efficacy of experimental drugs.</p

A MODEL ACCOUNTING PLAN FOR SPECIAL EDUCATION Current systems for monitoring the enrollments and status of special education programs do not meet current demands for increased account- ability. Project MAP (Model Accounting Plan) attempts to meet this dem

trict. Using existing pupil count data and a follow-up one year later, the MAP describes and predicts the paths special education students follow, taking into account the student&apos;s age, handicap, and instructional setting assignment. The MAP provides previously unavailable data to special educators and decision makers at all levels regarding program effectiveness and resource allocation and poses useful questions for further study

GRB 091127: The cooling break race on magnetic fuel

Using high-quality, broad-band afterglow data for GRB 091127, we investigate the validity of the synchrotron fireball model for gamma-ray bursts, and infer physical parameters of the ultra-relativistic outflow. We used multi-wavelength follow-up observations obtained with GROND and the XRT onboard the Swift satellite. The resulting afterglow light curve is of excellent accuracy, and the spectral energy distribution is well-sampled over 5 decades in energy. These data present one of the most comprehensive observing campaigns for a single GRB afterglow and allow us to test several proposed emission models and outflow characteristics in unprecedented detail. Both the multi-color light curve and the broad-band SED of the afterglow of GRB 091127 show evidence of a cooling break moving from high to lower energies. The early light curve is well described by a broken power-law, where the initial decay in the optical/NIR wavelength range is considerably flatter than at X-rays. Detailed fitting of the time-resolved SED shows that the break is very smooth with a sharpness index of 2.2 +- 0.2, and evolves towards lower frequencies as a power-law with index -1.23 +- 0.06. These are the first accurate and contemporaneous measurements of both the sharpness of the spectral break and its time evolution. The measured evolution of the cooling break (nu_c propto t^-1.2) is not consistent with the predictions of the standard model, wherein nu_c propto t^-0.5 is expected. A possible explanation for the observed behavior is a time dependence of the microphysical parameters, in particular the fraction of the total energy in the magnetic field epsilon_B. This conclusion provides further evidence that the standard fireball model is too simplistic, and time-dependent micro-physical parameters may be required to model the growing number of well-sampled afterglow light curves.Comment: accepted to A&A, 13 pages, 5 figure

Interplay of tidal and fluvial processes in an early Pleistocene, delta-fed, strait margin (Calabria, Southern Italy)

The architecture and morphodynamics of modern and ancient tidal straits and in particular the deposits of strait-margin zones, have been significantly understudied compared to other marginal marine settings, even though many reservoirs in the North Sea and the Norwegian Continental Shelf are developed in narrow grabens or seaways. This paper presents a detailed sedimentological and stratigraphic analysis of an early Pleistocene marginal-marine succession deposited along the northern margin of the Siderno paleostrait (southern Italy). This area represents an excellent case study of sedimentation along a tidal strait margin, interpreted to record the interaction of fluvial and tidal processes. Here, syn-depositional tectonics produced a complex coastal morphology, significantly influencing sedimentation and hydrodynamic processes. Along the strait margin, the emplacement of an isolated tectonic high (Piano Fossati) created a ca. 3.5 km-wide local passageway. This morpho-structural element induced interplays between fluvio-deltaic processes (fed from the northern strait margin) and tidal current reworking (active within the marine strait).The field-based facies analysis reported here documents an initial stage of non-tidal shallow-marine sedimentation across the strait. A subsequent regression caused river-generated hyperpycnal flows and the transfer of large volumes of pebbly and shelly sandstones into deeper water. Tidal currents became amplified in the strait, and, in the delta-front area, they were able to rework river-derived sediments generating large dune fields. Following the local tidal transport pathway, strong tidal currents skewed the delta front (causing it to be asymmetrical) and elongated sand bodies in a direction parallel to the marine strait axis. Differently from the classical tide-influenced deltas in which onshore-offshore tidal flow predominates, coast-parallel deflection and strong asymmetry of delta-front deposits is a typical feature of deltas entering tide-dominated seaways and straits, where strong tidal currents are capable of dispersing large volumes of sand for significant distances along the coast and along the strait axis. This process became progressively enhanced during the following transgression, when tide-modulated currents reworked biocalcarenitic sands over the previous delta deposits, generating southeasterly migrating dunes. At the end of the transgression, strandplain deposits formed in this area. This last stage of sedimentation was followed by a dramatic regional-scale structural uplift, which ended any marine circulation within the strait. This work provides new insights on sedimentation in a tide-dominated strait, and helps to predict sandbody distribution along the strait margin and axis. These findings can be applied to any other setting characterized by a narrow (possibly structurally-confined) basin dominated by tidal currents

Kinematics of Metal-Poor Stars in the Galaxy. II. Proper Motions for a Large Non-Kinematically Selected Sample

We present a revised catalog of 2106 Galactic stars, selected without kinematic bias, and with available radial velocities, distance estimates, and metal abundances in the range 0.0 <= [Fe/H] <= -4.0. This update of the Beers and Sommer-Larsen (1995) catalog includes newly-derived homogeneous photometric distance estimates, revised radial velocities for a number of stars with recently obtained high-resolution spectra, and refined metallicities for stars originally identified in the HK objective-prism survey (which account for nearly half of the catalog) based on a recent re-calibration. A subset of 1258 stars in this catalog have available proper motions, based on measurements obtained with the Hipparcos astrometry satellite, or taken from the updated Astrographic Catalogue (AC 2000; second epoch positions from either the Hubble Space Telescope Guide Star Catalog or the Tycho Catalogue), the Yale/San Juan Southern Proper Motion (SPM) Catalog 2.0, and the Lick Northern Proper Motion (NPM1) Catalog. Our present catalog includes 388 RR Lyrae variables (182 of which are newly added), 38 variables of other types, and 1680 non-variables, with distances in the range 0.1 to 40 kpc.Comment: 31 pages, including 8 figures, to appear in AJ (June 2000), full paper with all figures embedded available at http://pluto.mtk.nao.ac.jp/people/chiba/preprint/halo4