Zirconium-89 (
Zr) is an ideal radiometal isotope for antibody-based positron emission tomography (immunoPET) as its physical half-life (3.27 days) is a good match with the biological half-life of ...larger molecular weight targeting molecules, such as antibodies (3-4 days), and its positron emission (BR = 100% EC/β
, E
= 395.5 keV) is suited for high resolution PET imaging. Concerns over the in vivo stability of the most commonly used
Zr-chelator, desferrioxamine B (DFO), have spurred efforts into the development of alternative
Zr-chelators that withstand the release of osteophilic
Zr
. Herein we report the new chelator 1,3-propanediamine-N,N,N',N'-tetrakis(2-(aminomethyl)-3-hydroxy-1,6-dimethyl-4(1H)-pyridinone)acetamide (THPN) based on four 3-hydroxy-4-pyridinone (3,4-HOPO) coordinating groups, as a potentially superior chelator over DFO. THPN has been demonstrated to quantitatively form a monometallic complex with Zr
within 10 min at ambient temperature at as low as 10
M concentrations of the chelator. The resulting complexes were studied in vitro and in vivo. The
Zr-THPN complex was stable in serum and outperformed the
Zr-DFO complex in a direct transchelation challenge. Healthy mice excreted
Zr-THPN rapidly without signs of demetalation or residual organ uptake. This renders THPN as a promising alternative to DFO and introduces the first octadentate 3,4-HOPO chelator to the field.
Recent advances in visual data analysis are well suited to gain insights into dynamical processes in the atmosphere. We apply novel methods for
three-dimensional (3-D) interactive visual data ...analysis to investigate marine cold air outbreaks (MCAOs) and polar lows (PLs) in the recently released ERA5 reanalysis data. Our study aims at revealing 3-D perspectives on MCAOs and PLs in ERA5 and at improving the diagnostic indices to capture these weather events in long-term assessments on seasonal and climatological timescales. Using an extended version of the open-source visualization framework Met.3D, we explore 3-D perspectives on the structure and dynamics of MCAOs and PLs and relate these to previously used diagnostic indices. Motivated by the 3-D visual analysis of selected MCAO and PL cases, we conceptualize alternative index variants that capture the vertical extent of MCAOs and their distance to the dynamical tropopause. The new index variants are evaluated, along with previously used indices, with a focus on their skill as a proxy for the occurrence of PLs. Testing the association of diagnostic indices with observed PLs in the Barents and the Nordic seas for the years 2002–2011 shows that the new index variants based on the vertical structure of cold air masses are more skilful in distinguishing the times and locations of PLs, compared with conventional indices based on sea–air temperature difference only. We thus propose using the new diagnostics for further analyses in climate predictions and climatological studies. The methods for visual data analysis applied here are available as an open-source tool and can be used generically for interactive 3-D visual analysis of atmospheric processes in ERA5 and other gridded meteorological data.
Even today the remediation of organic contaminant source zones poses significant technical and economic challenges. Nanoscale zero-valent iron (NZVI) injections have proved to be a promising approach ...especially for source zone treatment. We present the development and the characterization of a new kind of NZVI with several advantages on the basis of laboratory experiments, model simulations and a field test. The developed NZVI particles are manufactured by milling, consist of 85 % Fe(0) and exhibit a flake-like shape with a thickness of <100 nm. The mass normalized perchloroethylene (PCE) dechlorination rate constant was 4.1 × 10⁻³ L/g h compared to 4.0 × 10⁻⁴ L/g h for a commercially available reference product. A transport distance of at least 190 cm in quartz sand with a grain size of 0.2–0.8 mm and Fe(0) concentrations between 6 and 160 g/kg (sand) were achieved without significant indications of clogging. The particles showed only a low acute toxicity and had no longterm inhibitory effects on dechlorinating microorganisms. During a field test 280 kg of the iron flakes was injected to a depth of 10–12 m into quaternary sand layers with hydraulic conductivities ranging between 10⁻⁴ and 10⁻⁵ m/s. Fe(0) concentrations of 1 g/kg (sand) or more up to 100 g/kg (sand) were achieved in 80 % of the targeted area. The iron flakes have so far remained reactive for more than 1 year and caused a PCE concentration decrease from 20.000–30.000 to 100–200 µg/L. Integration of particle transport processes into the OpenGeoSys model code proved suitable for site-specific 3D prediction and optimization of iron flake injections.
The cyclotron-based (100)Mo(p,2n)(99m)Tc reaction has been proposed as an alternative method for solving the shortage of (99m)Tc. With this production method, however, even if highly enriched ...molybdenum is used, various radioactive and stable isotopes will be produced simultaneously with (99m)Tc. In order to optimize reaction parameters and estimate potential patient doses from radiotracers labeled with cyclotron produced (99m)Tc, the yields for all reaction products must be estimated. Such calculations, however, are extremely complex and time consuming. Therefore, the objective of this study was to design a graphical user interface (GUI) that would automate these calculations, facilitate analysis of the experimental data, and predict dosimetry. The resulting GUI, named Cyclotron production Yields and Dosimetry (CYD), is based on Matlab®. It has three parts providing (a) reaction yield calculations, (b) predictions of gamma emissions and (c) dosimetry estimations. The paper presents the outline of the GUI, lists the parameters that must be provided by the user, discusses the details of calculations and provides examples of the results. Our initial experience shows that the proposed GUI allows the user to very efficiently calculate the yields of reaction products and analyze gamma spectroscopy data. However, it is expected that the main advantage of this GUI will be at the later clinical stage when entering reaction parameters will allow the user to predict production yields and estimate radiation doses to patients for each particular cyclotron run.
Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17beta-estradiol (E2), the ACI rat exhibits a genetically ...conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain. In both (ACI x COP)F(2) and (COP x ACI)F(2) populations, we find strong evidence for a major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5. Our data are most consistent with a model in which the ACI allele of this locus, termed Emca1 (estrogen-induced mammary cancer 1), acts in an incompletely dominant manner to increase both tumor incidence and tumor multiplicity as well as to reduce tumor latency in these populations. We also find evidence suggestive of a second locus, Emca2, on chromosome 18 in the (ACI x COP)F(2) population. The ACI allele of Emca2 acts in a dominant manner to increase incidence and decrease latency. Together, Emca1 and Emca2 act independently to modify susceptibility to E2-induced mammary cancer.
A radiographic analysis of the cervical spine of 70 patients diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with Klippel-Feil (KF) syndrome was conducted.
The objectives ...of this study were to describe cervical spine abnormalities in patients with FOP, to compare and contrast those findings with the malformations in patients with KF syndrome, and to examine the possible etiology of these abnormalities.
Congenital features of diseases often provide seminal clues to underlying etiology and developmental pathways. While progressive metamorphosis of connective tissue to heterotopic bone is the most dramatic and disabling feature of FOP, less severe congenital anomalies of the skeleton are also present. Vertebral fusions observed in KF are consistent with defects in embryonic segmentation.
The cervical spine plain films of 70 FOP patients and 33 KF patients with documented congenital abnormalities were reviewed.
Generalized neck stiffness and decreased range of motion were noted in most children with FOP. In the FOP patient group, characteristic anomalies, including large posterior elements, tall narrow vertebral bodies,and fusion of the facet joints between C2 and C7, were observed. Most notably, these characteristic anomalies of the cervical spine in patients with FOP were distinctly different from those of 33 patients with KF that were examined but were strikingly similar to those seen in mice with homozygous deletions of the gene-encoding noggin, a bone morphogenetic protein (BMP) antagonist.
FOP patients exhibit a characteristic set of congenital spine malformations. While the noggin gene (NOG) is not mutated in patients who have FOP, these findings extend a growing body of evidence implicating overactivity of the BMP signaling pathway in the molecular pathogenesis of FOP.
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