Detectum velum Mosaicum Judaeorum nostri temporis : Das ist: Jüdischer Deckmantel dess Mosaischen Gesetzes, unter welchem die Juden jetzigen Zeit allerley Bubenstück, Laster, Schand und Finantzerey, & üben und treiben, auffgehoben und entdecket

durch Dietherichen Schwaben ...

Space-based space surveillance and tracking demonstrator: mission and system design

This paper presents the capabilities of a Space-Based Space Surveillance (SBSS) demonstration mission for Space Surveillance and Tracking (SST) based on a micro-satellite platform. The results have been produced in the frame of ESA’s "Assessment Study for Space Based Space Surveillance Demonstration Mission" performed by the Airbus Defence and Space consortium. The assessment of SBSS in an SST system architecture has shown that both an operational SBSS and also already a well- designed space-based demonstrator can provide substantial performance in terms of surveillance and tracking of beyond-LEO objects. Especially the early deployment of a demonstrator, possible by using standard equipment, could boost initial operating capability and create a self-maintained object catalogue. Furthermore, unique statistical information about small-size LEO debris (mm size) can be collected in-situ. Unlike classical technology demonstration missions, the primary goal is the demonstration and optimisation of the functional elements in a complex end-to-end chain (mission planning, observation strategies, data acquisition, processing, etc.) until the final products can be offered to the users and with low technological effort and risk. The SBSS system concept takes the ESA SST System Requirements into account and aims at fulfilling SST core requirements in a stand-alone manner. Additionally, requirements for detection and characterisation of small-sizedLEO debris are considered. The paper presents details of the system concept, candidate micro-satellite platforms, the instrument design and the operational modes. Note that the detailed results of performance simulations for space debris coverage and cataloguing accuracy are presented in a separate paper “Capability of a Space-based Space Surveillance System to Detect and Track Objects in GEO, MEO and LEO Orbits” by J. Silha (AIUB) et al., IAC-14, A6, 1.1x25640.

Dissertatio philologica de Cabbala : maxime Ebraeorum ; cui appendicis loco ... acc. in fine: Hierorgraphicum ... cuius haec sit ... interpretatio Latina: deus virginem concipere faciet: et illa pariet filium

Wittenbergae, Univ., Diss., 1655

Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate

Purpose The radiolanthanide 161Tb (T 1/2 = 6.90 days, Eβ− av = 154 keV) was recently proposed as a potential alternative to 177Lu (T 1/2 = 6.71 days, Eβ− av = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare 161Tb and 177Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). Methods 161Tb-cm09 and 177Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo 161Tb-cm09 and 177Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using 99mTc-dimercaptosuccinic acid (DMSA). Results To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for 161Tb-cm09 (IC50 ~0.014 MBq/ml and ~2.53 MBq/ml) compared to 177Lu-cm09 (IC50 ~0.063 MBq/ml and ~4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies 161Tb-cm09 reduced tumour growth more efficiently than 177Lu-cm09. These findings were in line with the higher absorbed tumour dose for 161Tb-cm09 (3.3 Gy/MBq) compared to 177Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Conclusion Compared to 177Lu-cm09 we demonstrated equal imaging features for 161Tb-cm09 but an increased therapeutic efficacy for 161Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical studies using other tumour-targeting radioconjugates are clearly necessary to draw final conclusions about the future clinical perspectives of 161Tb.

Elementale Hebraicum, et Chaldaicum : cui annexae sunt utriusque linguae conjugationes

[Christoph Helwig]

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues.

PURPOSE Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the (125)iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer (125)I-GLP-1(7-36)amide. METHODS Receptor autoradiography studies with (125)I-GLP-1(7-36)amide agonist or (125)I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. RESULTS The antagonist (125)I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer (125)I-GLP-1(7-36)amide. For comparison, (125)I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. CONCLUSION The GLP-1 receptor antagonist exendin(9-39) labelled with (125)I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients.

A complete-pelvis segmentation framework for image-free total hip arthroplasty (THA): methodology and clinical study

Background Complete-pelvis segmentation in antero-posterior pelvic radiographs is required to create a patient-specific three-dimensional pelvis model for surgical planning and postoperative assessment in image-free navigation of total hip arthroplasty. Methods A fast and robust framework for accurately segmenting the complete pelvis is presented, consisting of two consecutive modules. In the first module, a three-stage method was developed to delineate the left hemipelvis based on statistical appearance and shape models. To handle complex pelvic structures, anatomy-specific information processing techniques were employed. As the input to the second module, the delineated left hemi-pelvis was then reflected about an estimated symmetry line of the radiograph to initialize the right hemi-pelvis segmentation. The right hemi-pelvis was segmented by the same three-stage method, Results Two experiments conducted on respectively 143 and 40 AP radiographs demonstrated a mean segmentation accuracy of 1.61±0.68 mm. A clinical study to investigate the postoperative assessment of acetabular cup orientations based on the proposed framework revealed an average accuracy of 1.2°±0.9° and 1.6°±1.4° for anteversion and inclination, respectively. Delineation of each radiograph costs less than one minute. Conclusions Despite further validation needed, the preliminary results implied the underlying clinical applicability of the proposed framework for image-free THA.

DNA with Hydrophobic Base Substitutes: A Stable, Zipperlike Recognition Motif Based On Interstrand-Stacking Interactions

No Abstract

Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic drivers of clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.

Towards tailored radiopeptide therapy.

PURPOSE Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. METHODS Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination. RESULTS (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. CONCLUSIONS Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.