Alteration of Gallium Biodistribution Using Indium Complexes for Enhanced Early Imaging

Radiopharmaceutical compositions and methods for tumor tomography in mammals are disclosed, wherein radioactive gallium and non-radioactive indium are injected into said mammals whereby the affinity of said radioactive gallium for non-tumor tissues is decreased, resulting in enhanced imaging characteristics

Synthesis and Use of Diagnostic Radio-Pharmaceuticals Comprising Radioactive Isotopes of Bromine with Dyes

A process for preparing bromine-containing dyes labelled with gamma-emitting isotopes of bromine, and the product thereof which is useful as an imaging agent for the hepato-biliary system, particularly in dynamic imaging methods. The dyes prepared are from the class of triarylmethane dyes, and also from the phthalein subclass of the class of xanthene dyes, and the labelling thereof is effected with 76Br, 77 Br or 82 Br. The process for preparing these dyes involves reacting the non-brominated dye precursor with either 76 Br2, 77 Br2 or 82 Br2. This is a substitution type of reaction in which a ring hydrogen is substituted by either 76 Br, 77 Br or 82 Br

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Dual Anti-OX40/IL-2 Therapy Augments Tumor Immunotherapy via IL-2R-Mediated Regulation of OX40 Expression

The provision of T cell co-stimulation via members of the TNFR super-family, including OX40 (CD134) and 4-1BB (CD137), provides critical signals that promote T cell survival and differentiation. Recent studies have demonstrated that ligation of OX40 can augment T cell-mediated anti-tumor immunity in pre-clinical models and more importantly, OX40 agonists are under clinical development for cancer immunotherapy. OX40 is of particular interest as a therapeutic target as it is not expressed on naïve T cells but rather, is transiently up-regulated following TCR stimulation. Although TCR engagement is necessary for inducing OX40 expression, the downstream signals that regulate OX40 itself remain unclear. In this study, we demonstrate that OX40 expression is regulated through a TCR and common gamma chain cytokine-dependent signaling cascade that requires JAK3-mediated activation of the downstream transcription factors STAT3 and STAT5. Furthermore, combined treatment with an agonist anti-OX40 mAb and IL-2 augmented tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8 T cells in mice with long-term well-established (>5 wks) tumors, leading to increased survival of the tumor-bearing hosts. Together, these data reveal the ability of TCR/common gamma chain cytokine signaling to regulate OX40 expression and demonstrate a novel means of augmenting cancer immunotherapy by providing dual anti-OX40/common gamma chain cytokine-directed therapy

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes

The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described

Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run

Peer reviewe

Challenges for Deep Vadose Zone Remediation at the Hanford Site

ABSTRACT The "deep vadose zone" is defined as the region below the practical depth of surface remedy influence (e.g., excavation or barrier). At the Hanford Site, this region of the Central Plateau poses unique challenges for characterization and remediation. Currently, deep vadose zone characterization efforts and remedy selection are spread over multiple waste site Operable Units and tank farm Waste Management Areas. A particular challenge for this effort is the situation in which past leaks from single-shell tanks have become commingled with discharges from nearby liquid disposal sites. In addition, tests of potentially viable remediation technologies will be initiated in the next few years. The Hanford Site is working with all affected parties, including the Washington State Department of Ecology, the Environmental Protection Agency, DOE-RL, DOE-ORP, and multiple contractor organizations to develop remediation approaches. This effort addresses the complex and challenging technical and is evaluating the best strategy or combination of strategies for focusing technical investigations, including treatability studies to facilitate deep vadose zone remediation at the Hanford Site