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This study investigates stock recommendations from the three largest finance subreddits on Reddit: wallstreetbets, investing and stocks. A simple strategy that buys recommended stocks weighted by the number of posts per day yields a portfolio with higher average returns at the expense of higher risks than the market for all holding periods, i.e., unfavorable Sharpe ratios. Furthermore, the strategy leads to positive (insignificant) short-term and negative (significant) long-term alphas when considering common risk factors. This is consistent with the idea of “meme stocks”, meaning that the recommended stocks are artificially inflated in the short term when they are recommended, and that the posts contain no information about long-term success. However, it is likely that Reddit users, especially on the subreddit wallstreetbets, have preferences for bets which are not captured by the mean–variance framework. Therefore, we draw on cumulative prospect theory (CPT). We find that the CPT-valuations of the Reddit portfolio exceed those of the market, which may explain the persistent attractiveness for investors to follow social media stock recommendations despite the unfavorable risk-return ratio.

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. Over the last decades, several alpha-emitting radionuclides have entered and left research topics towards their clinical translation. Especially

This paper examines whether stock returns are consistent with the value function of prospect theory. We find that beta given a gain yields positive conditional premiums on returns while beta given ...

Objective: The somatostatin receptor subtype 2 (SSTR2) is a suitable target for the diagnosis and therapy of neuroendocrine tumors using radiolabeled ligands [1]. BON-1S cells have been described to express SSTR2 receptors in vitro [2]. We therefore established 2D and 3D cell culture systems of BON-1S cells. For SSTR2 ligand binding, BON-1S cells cultured as monolayer or spheroids were incubated with an SSTR2 agonist (NODAGA-TATE) or an SSTR2 antagonist (NODAGA-JR11). Both were labeled with either 68Ga- or 64Cu and their respective binding and uptake were determined. Understanding the binding data is a prerequisite for using spheroids of BON-1S cells in a Micro Physiological System (MPS) [3]. Methods: Spheroids of SSTR2 containing BON-1S cells were created as follows: Freshly harvested cells were incubated with magnetic nanoparticles in RPMI medium overnight. After magnetic particle uptake, cells were split into a 24-well-plate (1.5 x 10-4 cells/well). In an incubator, the magnetic particles were moved via a magnetic drive for five days, to allow the formation of spheroids [4]. After incubation with the 68Ga- or 64Cu-labeled radioligands (RCY>95%), the BON-1S cells, either as monolayer or as spheroids, were washed and treated with acidic glycine buffer (pH 3.0) to remove the bound but not yet internalized molecules from the outer cellular membrane. After this washing step, the remaining radioligand molecules are assumed to represent internalized molecules [5]. In the monolayer, internalization was determined after 10 minutes, 1 hour and 3 hours after addition of the radioligand to the respective culture. Results: Saturation analysis of radiolabeled NODAGA-TATE as well as NODAGA-JR11 on BON-S1 monolayer yielded similar Kd values in the low nanomolar range (2.3 to 8.6 nM). Affinity of the respective radiolabeled ligand was much lower on BON-1S spheroids, with Kd values around 30 nM for both 64Cu-labeled ligands and almost 60 nM for the 68Ga-labeled ligands. The maximal binding capacity (Bmax) was higher on monolayers and spheroids for radiolabeled JR11 (NODAGA-TATE: monolayer 0.3 pmol/mg, spheroids 0.8 pmol/mg; NODAGA-JR11: monolayer and spheroids 1.2 pmol/mg). The internalization assay showed a ratio of internalized to surface bound radiolabeled NODAGA-TATE of about 80% to 20% for both forms of cell culture, for radiolabeled JR11 a ratio of 8% to 92% was determined, each after a 60 min-incubation time. The internalization after the three time points was ca. 10 times lower in case of radiolabeled JR11 (0.25% (TATE) versus maximal 0.03% (JR11) of administered activity amount/µg protein). Conclusions: Using monolayer or spheroids of BON-1S cells (the latter were generated by the iron nanoparticle method) we could estimate reliable and reproducible binding parameters for a radiolabeled agonist and antagonist of SSTR2. There are obvious differences in binding affinities of the examined radiolabeled conjugates in monolayer cell culture compared to the spheroids. Acknowledgements: The SSTR2 expressing BON-1S cells were kindly given by Prof. Dr. Wiedenmann, University Hospital Charité Berlin. References: [1] Eychenne, Molecules 2020, 25, 4012. [2] Exner, Front Endocrinol 2018, 9, 146. [3] Busek, J Sens Sens Syst 2016, 5, 228. [4] Noel, J Vis Exp 2017, 126, e56081. [5] Matzku, Cancer Res 1986, 46, 3848.

This paper describes a model in which a network of interbank loans leads to a severe amplification of the previously unanticipated insolvency of one bank. Banks that cannot rule out an indirect hit react by selling assets and hoarding liquidity. While this potentially lowers illiquidity risks, it depresses market liquidity and prices. This leads to a negative externality by which sales to acquire liquidity simultaneously lead to lower global sale proceeds and thus to a greater number of insolvencies inducing deadweight losses. Thus, the distribution of information on the network has a direct impact on welfare by itself. Der Zusammenhang zwischen unvollständigen Informationen über das Banknetzwerk und Adressenausfallrisiken Zusammenfassung In dieser Arbeit wird ein Modell betrachtet, in dem das Netzwerk aus Interbankenkrediten die Folgen der unerwarteten Insolvenz einer einzelnen Bank drastisch verstärkt. Banken, die indirekte Verluste nicht ausschließen können, reagieren mit dem Verkauf von Vermögenswerten und dem Horten von Liquidität. Dies führt zwar potenziell zu ­einer Senkung der Illiquiditätsrisiken, drückt aber die Marktliquidität und Preise. Es kommt zu einem negativen externen Effekt, da die Verkäufe zur Liquiditätsbeschaffung gleichzeitig zu geringeren Verkaufserlösen und damit zu einer größeren Anzahl von Insolvenzen, die Wohlfahrtsverluste mit sich bringen, führen. Demnach hat die Informa­tionsverteilung im Bankennetzwerk einen direkten Einfluss auf die Wohlfahrt. JEL Classification: G01, G11, G21, G33

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. Over the last decades, several alpha-emitting radionuclides have entered and left research topics towards their clinical translation. Especially, 225Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [225Ac]Ac-PSMA-617. While PSMA-617 carries the DOTA moiety as the complexing agent, the chelator macropa as a macrocyclic alternative provides even more beneficial properties regarding labeling and complex stability in vivo. Lanthanum-133 is an excellent positron-emitting diagnostic lanthanide to radiolabel macropa-functionalized therapeutics since 133La forms a perfectly matched theranostic pair of radionuclides with the therapeutic radionuclide 225Ac, which itself can optimally be complexed by macropa as well. 133La was thus produced by cyclotron-based proton irradiation of an enriched 134Ba target. The target (30 mg of [134Ba]BaCO3) was irradiated for 60 min at 22 MeV and 10–15 µA beam current. Irradiation side products in the raw target solution were identified and quantified: 135La (0.4%), 135mBa (0.03%), 133mBa (0.01%), and 133Ba (0.0004%). The subsequent workup and anion-exchange-based product purification process took approx. 30 min and led to a total amount of (1.2–1.8) GBq (decay-corrected to end of bombardment) of 133La, formulated as [133La]LaCl3. After the complete decay of 133La, a remainder of ca. 4 kBq of long-lived 133Ba per 100 MBq of 133La was detected and rated as uncritical regarding personal dose and waste management. Subsequent radiolabeling was successfully performed with previously published macropa-derived PSMA inhibitors at a micromolar range (quantitative labeling at 1 µM) and evaluated by radio-TLC and radio-HPLC analyses. The scale-up to radioactivity amounts that are needed for clinical application purposes would be easy to achieve by increasing target mass, beam current, and irradiation time to produce 133La of high radionuclide purity (>99.5%) regarding labeling properties and side products.

In metal chalcogenide nanocrystals (NCs), the cations can be partially or fully replaced with other cations through the so-called cation exchange (CE) reactions. Here, we took advantage of these CE reactions to replace the cations on different chalcogenides NCs with 64Cu ions in order to radiolabel them. With respect to other approaches reported in the literature, our CE protocol is easily transferable to the clinic. It requires indeed one single step, in which the water-soluble NCs are mixed with a 64Cu copper(II) chloride solution of high specific activity, in the presence of vitamin C used as a reducing agent for Cu(II) to Cu(I)). Given the quantitative replacement of the cations of the NCs with 64Cu(I), a high radiochemical yield up to 90-95% can be reached. Provided that there is no free 64Cu, no purification step is needed, making the protocol straightforward. At the same time, the amount of NCs required for the exchange is so low (in the range of μg) that the dose of NCs shows no intrinsic cytotoxicity. This protocol works on different types of metal chalcogenide NCs. In ZnSe and ZnS NCs, the Zn(II) ions are exchanged with 64Cu (I) ions, and in CuFeS2 NCs the Fe(III) ions are exchanged with 64Cu(I). To ensure the stability of the NCs during and after the CE reaction, a multi-anchoring coating procedure based on PEG, cysteamine and poly-maleic anhydride was proven to be more efficient than the use of monothiol PEG ligands. With our approach we managed to achieve an unprecedented high specific activity, i.e. the amount of 64Cu radionuclide loaded per NC dose, to dispatch remarkable ionizing effects. Indeed, by exploiting a volumetric cations exchange, our strategy enables to concentrate a large dose of 64Cu (18.5 MBq) in a small NC dose (0.4 μg), reaching a specific activity of about 50 TBq/g. Remarkably, for CuFeS2 NCs even after the CE, the radiolabeled 64Cu:CuFeS2 NCs still show the characteristic dielectric resonance that enables the generation of heat under laser exposure for clinical use (1 W/cm2). The synergic toxicity of photo-ablation and 64Cu radiation exposure is here demonstrated in an in vitro study on glioblastoma and epidermoid carcinoma tumor cells.

The epidermal growth factor receptor (EGFR) represents an important molecular target for both radiotracer-based diagnostic imaging and radionuclide therapy of various cancer entities. For the delivery of radionuclides to the tumor, peptides hold great potential as a transport vehicle. With respect to EGFR, the peptide YHWYGYTPQNVI (GE11) has been reported to bind the receptor with high specificity and affinity. In the present study, GE11 with β-alanine (β-Ala-GE11) was conjugated to the chelating agent p-SCN-Bn-NOTA and radiolabeled with 64Cu for the first radio pharmacological evaluation as a potential probe for positron emission tomography (PET)-based cancer imaging. For better water solubility, an ethylene glycol-based linker was introduced between the peptide’s N terminus and the radionuclide chelator. The stability of the 64Cu-labeled peptide conjugate and its binding to EGFR-expressing tumor cells was investigated in vitro and in vivo, and then compared with the 64Cu-labeled EGFR-targeting antibody conjugate NOTA-cetuximab. The GE11 peptide conjugate [64Cu]Cu-NOTA-linker-β-Ala-GE11 ([64Cu]Cu-1) was stable in a buffer solution for at least 24 h but only 50% of the original compound was detected after 24 h of incubation in human serum. Stability could be improved by amidation of the peptide’s C terminus (β-Ala-GE11-NH2 (2)). Binding assays with both conjugates, [64Cu]Cu-1 and [64Cu]Cu-2, using the EGFR-expressing tumor cell lines A431 and FaDu showed no specific binding. A pilot small animal PET investigation in FaDu tumor-bearing mice revealed only low tumor uptake (standard uptake value (SUV)

Recent research suggests that competition is reduced by common ownership. Based on this idea, we build a model in which strategic investors have an incentive to reduce the correlation between companies they have invested in. Therefore, we hypothesize that pairwise correlations between stock returns decrease with increasing common strategic ownership. To test this hypothesis empirically, we construct a measure that captures the presence of strategic investors in both companies. Using NYSE data and several control variables, we find a negative relation between this measure and pairwise correlations. This result provides support for the anticompetitive effects of common ownership.

Unnatural mirror image l-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. Their high metabolic stability and negligible unspecific binding to endogenous targets are superior characteristics in comparison to their d-configured analogs. In this study, a radiopharmacological evaluation of a new l-ONs based pretargeting system using the epidermal growth factor receptor (EGFR) specific antibody cetuximab (C225) as target-seeking component is presented. An optimized PEGylated 17mer-L-DNA was conjugated with p-SCN-Bn-NOTA (NOTA′) to permit radiolabeling with the radionuclide 64Cu. C225 was modified with the complementary 17mer-L-DNA (c-L-DNA) strand as well as with NOTA′ for radiolabeling and use for posi...

Radiolabeled α-melanocyte-stimulating hormone (α-MSH) derivatives have a high potential for diagnosis and treatment of melanoma, because of high specificity and binding affinity to the melanocortin-1 receptor (MC1R). Hence, the α-MSH-derived peptide NAP-NS1 with a β-Ala linker (ε-Ahx-β-Ala-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH

Regardless of its high positron energy

Through the choice of appropriate layer thicknesses, the bandgap of InAs/Ga(As)Sb type II superlattices (T2SLs) can be engineered in a wide range covering the mid-wavelength and long-wavelength infrared (MWIR, 3 μm - 5 μm and LWIR, 8 μm - 12 μm) spectral regions. Using this material system, Fraunhofer IAF develops bi-spectral MWIR image sensors based on homojunction photodiodes for missile warning applications and pursues modern heterojunction approaches as well as heteroepitaxial growth of T2SLs on GaAs. We discuss topics arising from efforts to improve the manufacturability of our bi-spectral arrays and report on the progress of the integration with MWIR heterojunction designs that exhibit reduced dark currents.

The epidermal growth factor receptor (EGFR) represents an important molecular target for both radiotracer-based diagnostic imaging and radionuclide therapy of various cancer entities. For the delivery of radionuclides to the tumor, peptides hold great potential as a transport vehicle. With respect to EGFR, the peptide YHWYGYTPQNVI (GE11) has been reported to bind the receptor with high specificity and affinity. In the present study, GE11 with β-alanine (β-Ala-GE11) was conjugated to the chelating agent p-SCN-Bn-NOTA and radiolabeled with

Price-taking behavior seems to contradict rationality if a price effect is to be expected. This paper identifies a strategic effect between price-takers and non-price-takers on financial markets. It results from the liquidity reduction non-price-taking induces. Thus, a trade-off between the benefits of calculating price impacts correctly and market liquidity exists. It is shown that price-takers may benefit more from trading than their fully rational counterparts do. Moreover, it is demonstrated that when the choice of behavior is unobservable and decision costs exist an investor would profit more as a non-price-taker when his trading potential is large, and more as a price-taker when it is small. However, when the choice of behavior is observable it is the other way around. If various rounds of trading take place, an investor’s terminal endowment converges to his risk tolerance share. Thus, an efficient allocation is obtained. Furthermore, a paradox concerning the endogenous choice of manners of calculation is identified.

RadiomercuryA good accordance between measurements and simulations was found for planar and SPECT imaging. Simulations allowed the decomposition of the detected energy spectrum into photon origins. Measurements and simulations for the bar phantom revealed that for the LEHR collimator, the 6-mm pattern could be resolved, whereas for the HEGP collimator, the resolution is about 10 mm. Furthermore, we found that no significant image distortion results from high-energy photons when using the LEHR collimator.We demonstrated the imaging capabilities of

In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of en passant mutagenesis was used. Targeted mutations within ORF36 and/or ORF28 and an autonomously expressed gene of the monomeric red fluorescent protein for plaque identification were introduced into the European wild-type VZV strain HJO. Plaque reduction assays revealed that the amino acid substitutions with unknown functions in TK, Q303stop, N334stop, A163stop, and the deletion of amino acids 7 to 74 aa (Δaa 7 to 74), were associated with resistance against acyclovir (ACV), penciclovir, or brivudine, whereas the L73I substitution and the Pol substitutions T237K and A955T revealed sensitive viral phenotypes. The results were confirmed by quantitative PCR by measuring the viral load under increasing ACV concentrations. In conclusion, analyzing the enzymatic activities of recombinant TK proteins represent a useful tool for evaluating the significance of amino acid substitutions in the antiviral resistance of clinical VZV strains. However, direct testing of replication-competent viruses by the introduction of nonsynonymous mutations in a VZV bacterial artificial chromosome using en passant mutagenesis led to reliable phenotypic characterization results.

Two-photon quantum well infrared photodetectors (QWIPs) are nonlinear detectors for the mid-infrared and terahertz regimes optimized for resonant two-photon absorption. Here we present first results on two-photon QWIP samples based on the GaAs/AlGaAs material system with intersubband energies between 25 and 12 meV (6–3 THz) confirmed by photocurrent spectra. The dark current showed large discontinuities, presumably caused by impact ionization. We performed interferometric autocorrelation experiments at the free-electron laser FELBE and observed nonlinear interferograms for all samples.

We show coherent wireless transmission at carrier frequencies within 0.30+0.02 THz using up to 20 QPSK-modulated subcarriers with a symbol rate of 0.75 GBd each, leading to an aggregate line rate of 30 Gbit/s. We exploit optoelectronic techniques, both for THz generation and coherent reception.

Improved aluminum-gallium-nitride (Al x Ga 1-x N) p-i-n photodetectors with different active regions are reported, designed for the measurement of UV-A (315 to 380 nm), UV-B (280 to 315 nm), and UV-C (

Reactor-produced Hg-197 had previous medical use for imaging[1] but was discontinued due to low stability and low specific-activity. Cyclotron-produced Hg-197(m) can overcome the toxicity problem, due to much higher molar activity[2], allowing access to the radiometal’s useful decay modes (γ for SPECT-imaging. Conversion & auger electrons for therapy) at sub-toxic Hg-concentrations. Development in Hg ligands for medicinal applications necessitates stability in vivo but the poor long-term stability of Mercury compounds in solution is an ongoing issue[3]. Hg-organometallics show good water-stability and bypass the issue of Hg-S bonds suffering from competition by common biomolecules, e.g. cysteine. Therefore, our focus is on Hg-C chemistry, specifically the strongest bond kind: the mercury-phenyl bond[4]. As prior research has shown that the synthetically simpler route of monodentate ligands (κ1-L2Hg) suffers from significant cleavage[5], this research is centred on the syntheses of bidentate chelators benefitting from entropic stability. Purification of the Hg-197(m) leaves it in an acidic aqueous medium as the chloride salt, thus transmetallation, via stannyl or boronic acid derivatives, was chosen as a viable option for mercury attachment. Chelator designs began with a dibenzylisophthalamide template but low selectivity for the 1:1-compound encouraged a better fitting structure. Recent radio-labelling experiments show promise for specific binding with a design based on the bispidine backbone (attractive for being known in co-ordination chemistry for a variety of metals[6] and possessing bridge linking-functionalisation). Analyses are performed through radio-TLC and HPLC, whilst stable mercury compound analysis includes Hg-199 NMR. References : (1) Sodee. J. Nucl. Med. 1968; 9: 645. (2) Walther et al. Appl. Radiat. Isot. 2015; 97: 177–181. (3) Henke et al. Wat. Res. 2000; 34: 3005-3013. (4) Dean. Lange’s Handbook of Chemistry, 15th ed.; McGraw-Hill Inc, 1998; 606. (5) Wilhelm. et al. Z. Naturforsch. 2000; 55b: 35–38. (6) Comba et al. Inorg. Chem. 2009; 48: 6604–6614.

Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using (18)F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these (18)F- and (68)Ga-labelled tracers and of (64)Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG) was primarily absorbed at the sites of bone growth. (64)Cu chloride and a (68)Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the (68)Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model.

We report on the development of high-performance InAs/GaSb superlattice (SL) infrared (IR) detectors for the mid-wavelength (MWIR, 3–5 μm) and long-wavelength (LWIR, 8–12 μm) transmission window of the atmosphere. With a refined process technology, we are now able to fabricate dual-color focal plane arrays for the MWIR that excel at a very low number of noisy pixels. In an effort to correlate dark current and noise data of a larger number of devices, we found that for the description of the behavior in the white noise part of the spectrum, both, in InAs/GaSb SL photodiodes for the MWIR and the LWIR McIntyre’s well-known model for excess noise of avalanche photodiodes is, in general, much more suited than the commonly used shot noise model. The analysis of dark current contributions is a convenient method to identify limiting mechanisms and extract material parameters such as the minority carrier lifetime. We show that even in large area devices the contribution of the sidewall leakage path should not be ignored for this kind of investigation. Finally, we present our Al-free heterojunction device concept for reduced dark current.

The PET radionuclide (61)Cu is accessible through several nuclear reactions. Besides the common production route via (61)Ni(p,n)(61)Cu the (64)Zn(p,α)(61)Cu reaction offers some advantages. Especially the comparatively cheap enriched (64)Zn makes this process economical. For fast product purification and recycling of target material an ion exchange cascade was developed. In addition a separation technique with a copper selective resin was tested. (61)Cu with specific activities up to 1000 GBq/μmol was produced with these methods.

A removal, as far as possible, of the GaSb substrate is needed to optimize the quantum efficiency and the longevity, i.e., the maximum number of cool down cycles, of dual-colour InAs/GaSb superlattice focal plane array detectors for the mid-wavelength infrared atmospheric transmission window at 3-5 µm. For this purpose, three different vertical detector structures have been investigated and are compared in the present paper. A basic structure, comprising only the essential layers is evaluated against two more advanced structures, which include a lattice-matched InAsSb etch stop layer. For the basic structure the remaining substrate thickness amounts to roughly 20 µm. With a second structure, which employs an etch stop separated from the active diode structure by a sufficiently thick GaSb spacer layer, the substrate and the etch stop layer can be completely removed by combining mechanical lapping and polishing as well as different wet chemical etchants. Here, only epitaxially grown layers remain, but the spacer is still common to all pixels. A third structure combined with further optimized front- and backside processes is suited for the complete mechanical separation of dual-colour detector pixels in the focal plane array arrangement (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Bombesins (BN) containing (99m)Tc '4+1' complexes may be useful to detect tumors expressing the gastrin-releasing peptide receptor (GRPR). Derivatives of the formula [(99m)Tc(NS(3)R)(L2-BN(st))] were synthesized, in which Tc(III) is coordinated by an isocyanide L2-BN(st) bearing the peptide (BN(st)=βAla-βAla-Gln-Trp-Ala-Val-Gly-His-Cha-Nle-NH(2)) and a tetradentate chelator NS(3)R. NS(3)R consists of 2,2',2″-nitrilotriethanethiol (NS(3)) bearing a crown ether (NS(3)crown), an aliphatic amine (NS(3)en) and a tricarboxylic acid (NS(3)(COOH)(3)). Non-radioactive Re compounds were prepared and analysed by electrospray ionization mass spectrometry. The structural similarity to the (99m)Tc conjugates was demonstrated by their identical HPLC elution profiles. The lipophilicity of [(99m)Tc(NS(3)R)(L2-BN(st))] decreased depending on the coligands NS(3)crown (log D(O/W), pH=7.4, 0.98 ± 0.11), NS(3)en (-0.49 ± 0.07) and NS(3)(COOH)(3) (-2.01 ± 0.09). Biodistribution in normal rats was characterized by an increasing kidney uptake and a decreasing uptake into the liver corresponding to the reduced lipophilicity of the conjugates. The pancreatic uptake expressed by the organ/blood ratio of standardized uptake values at 60 min p.i. in rats was 8.6 ± 1.2 for [(99m)Tc(NS(3)en)(L2-BN(st))] and higher compared to the other conjugates. The pancreas/liver ratio of the SUV at 60 min p.i. in rats was highest for [(99m)Tc(NS(3)(COOH)(3))(L2-BN(st))] at 8.4 ± 1.3. [(99m)Tc(NS(3)en)(L2-BN(st))] was further studied in tumor-bearing mice and its pancreas/blood and pancreas/liver ratios were lower, however the pancreas/kidney ratios were higher in mice compared to rats. The activity uptake of [(99m)Tc(NS(3)en)(L2-BN(st))] into the PC-3 tumor xenografts was low (%ID/g: 0.83 ± 0.18 at 60 min; SUV: 0.21 ± 0.05 at 60 min) but specific.

Within a very few years, InAs/GaSb superlattice technology has proven its suitability for high-performance infrared imaging detector arrays. At the Fraunhofer Institute for Applied Solid State Physics (IAF) and AIM Infrarot-Module GmbH, efforts have been focused on developing mature fabrication technology for dual-color InAs/GaSb superlattice focal-plane arrays for simultaneous, colocated detection at 3 µm to 4 µm and 4 µm to 5 µm in the mid-wavelength infrared atmospheric transmission window. Integrated into a wide-field-of-view missile approach warning system for an airborne platform, a very low number of pixel outages and cluster defects is mandatory for bispectral detector arrays. Process refinements, intense root-cause analysis, and specific test methodologies employed at various stages during the process have proven to be the key for yield enhancements.

We examined the production, separation, and characterization of (89)Zr, including supplementation of a commercial Cyclone(®) 18/9 with a self-made Solid Target System (STS). Obtained [(89)Zr]Zr-oxalate was used for the labeling of anti-B cell antibodies with desferrioxamine-p-SCN as a bifunctional chelator. (89)Zr-labeled antibodies were injected in DBA/1 mice to examine usability for detection of B cells in vivo. PET measurements showed binding of (89)Zr-labeled anti-B cell antibodies in tissues with high frequencies of B cells, i.e. in spleen and lymph nodes.

We present the InAs/GaSb type-II superlattice dual-color technology developed at Fraunhofer IAF. This includes insights into some of the test methodologies employed at various stages during the fabrication process, which ensure that the basic requirements for achieving high detector performance are met. Much effort is put in improving and monitoring the quality of the substrate and the epilayers. We also present performance data from a dual-color mid-wavelength infrared (MWIR) camera which incorporates the latest backside process technology.

The development of high brightness lasers was pushed enormously in the last five years. Two different trends can be noticed. Beside the continuous growing laser power in the multi mode sector up to 100kW, diffraction limited laser systems are available in the range up to 10kW [1]. High power diffraction limited lasers deliver a new quantity of laser power induced aberrations [2]. Currently no online measurement equipment for optical aberrations is available. This paper describes an alternative online method to capture the optical aberrations of lenses. The developed tool allows a comparing benchmark of different optical components.

A sophisticated coligand strategy is presented for peptide-derived radioconjugates based on (99m)Tc '4 + 1' mixed-ligand complexes. The new pharmacologically active coligands are assessed for (99m)Tc-labeling of the RGD-peptide cyclo(Arg-Gly-Asp-D-Tyr-Lys) which is an established vehicle to target alpha(v)beta(3) integrins playing a crucial part in tumor pathogenesis. Complexes of the general formula [(99m)Tc(NS(3)R)X] were synthesized and evaluated, in which Tc(III) is coordinated by NS(3)R, a derivative of the tetradentate chelator 2,2',2''-nitrilotriethanethiol (NS(3)), and by X, a monodentate binding isocyanide bearing the biomolecule. The novel tetradentate chelators (NS(3)R = NS(3)crown, NS(3)en, NS(3)(COOH)(3)) constitute NS(3) with a crown ether, an amine or a tricarboxylic acid as pharmacological modifiers. The isocyanides (X = L2-RGD, L2-Lys) contained the linker isocyanobutanoic acid (L2) coupled to N(6)-Lys of the RGD-peptide and additionally to a single Lys. The lipophilicity (distribution coefficient log D(O)(/W), pH = 7.4) of the RGD-containing radiotracers decreased in the order of the coligands NS(3)crown (-1.7 +/- 0.1), NS(3)en (-2.7 +/- 0.1) and NS(3)(COOH)(3) (-3.3 +/- 0.1). In the same order of the coligands, the biodistribution of the series [(99m)Tc(NS(3)R)(L2-RGD)] in normal rats showed a decrease of hepatobiliary and an increase of urinary excretion. The ratio of specifically to unspecifically uptaken activity (sum of surface bound and internalized activity) in alpha(v)beta(3) integrin-expressing M21 cells was in the range of approximately 4-5 and comparable for all [(99m)Tc(NS(3)R)(L2-RGD)] tracers. The biodistribution of [(99m)Tc(NS(3)en)(L2-RGD)] in nu/nu mice bearing M21 and M21L (control) tumor xenografts exhibited a specific tumor uptake with a low target-background ratio. The metabolic stability of the [(99m)Tc(NS(3)R)(L2-RGD)] tracers in normal rats was high, since 75-87% of the radioactivity in the plasma extract was assigned to the injected radiotracers 60 min after intravenous application in a rat. The hypothetical metabolites [(99m)Tc(NS(3)R)(L2-Lys)] were not found. These results demonstrate a considerable improvement of in vivo properties of (99m)Tc '4 + 1' peptide conjugates and open up the possibility of applying the labeling approach for further radiodiagnostic peptides.

Introduction Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [ 99m Tc]"4+1" FA. Methods Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP −/− mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography. Results The largest fraction of tissue radioactivity was associated with cytosol [79.69±8.88% of infused dose]. About 9.07±0.95% and 3.43±1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [ 123 I]-labeled 15-( p -iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction ( P 99m Tc]"4+1" FA could be detected in any isolated heart. Conclusions Myocardial [ 99m Tc]"4+1" FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.

The present issue of physica status solidi (c) contains papers presented at the 35th International Symposium on Compound Semiconductors (ISCS 2008). The symposium was held 21–24 September 2008 at the Europa-Park in Rust, Germany. This conference is one in an annual series, which has in the past rotated between the United States, Europe and Asia and was organized for the second time at the Europa-Park. The last three conferences were held in Kyoto, Japan (2007), Vancouver, Canada (2006) and Rust, Germany (2005). The history of the symposium goes back to 1966 when the first “International Symposium on GaAs and Related Compounds” took place in Reading, England. The scope of the meeting includes both science and technology and the entire spectrum of III–V and II–VI compound semiconductors as well as SiGe, SiC and carbon related materials. The symposium was attended by 130 registered participants from 17 countries with 26% from Asia, 12% from America and 62% from Europe. A total of 101 papers were presented at the symposium including 4 plenary talks, 13 invited talks, 41 contributed talks and 43 poster presentations. The conference was opened with a plenary session to highlight current research activities within the German “excellence initiative” at the Universities of Aachen, Karlsruhe and Konstanz. Reinhart Proprawe opened this series with his view on “Reaching excellence in university R&D – The institutional strategy of RWTH Aachen 2020”, followed by a presentation on “Photonic metamaterials: Optics starts walking on two feet” by Martin Wegener from the University of Karlsruhe. Alfred Leitenstorfer highlighted application oriented research in a paper entitled “The Konstanz center for Applied Photonics: Bridging the gap between fundamental research and high tech industry”, followed by the industrial view of Stefan Illek on “Light from crystals – Light emitting diodes are penetrating our everyday life”. Three prestigious research awards were presented at the symposium, the Welker Award, the Quantum Device Award, and the Young Scientist Award. We thank all the participants as well as the Program Committee members of ISCS 2008 for contributing to the success of the meeting. Finally, we extend our thanks to the Local Organizing Committee for the excellent organization of the symposium. The 36th International Symposium on Compound Semiconductors will be organized by Umesh Mishra and will be held at the University of California at Santa Barbara, on 31 August–2 September 2009 (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The preparation and use of bispidine derivatives (3,7-diazabicyclo[3.3.1]nonane) as chelate ligands for radioactive copper isotopes for diagnosis (64Cu) or therapy (67Cu) are reported. Starting from the hexadentate bispidine-based bis(amine)tetrakis(pyridine) ligand 1 with a keto and two ester substituents, the corresponding mono-ol 2 and two dicarboxylic acid derivatives 3 and 5 have been synthesized. A range of techniques, including single-crystal X-ray structure analysis, UV/vis spectroscopy, cyclic voltammetry, thin-layer- (TLC), and high-performance liquid chromatography (HPLC), have been used to characterize the structure and stability of the copper(II)-bispidine complexes. A rapid formation (within 1 min) of stable copper(II)-bispidine complexes under mild conditions (ambient temperature, aqueous solution) has been observed. Challenge experiments of these complexes in the presence of a high excess of competing ligands, such as glutathione, cyclam, or superoxide dismutase (SOD), as well as in rat plasma, gave no evidence of demetalation or transchelation. The bifunctional bispidine derivative 5 can be readily functionalized with biologically active molecules at the pendant carboxylate groups. The coupling of a bombesin analogue ßhomo-Glu-ßAla-ßAla-[Cha13,Nle14]BBN(7-14), by condensation of a carboxylate of the bispidine backbone with the N-terminus of the peptide produced the bifunctional ligand 6. The radiocopper(II) complex of this bombesin-bispidine conjugate has a considerable hydrophilicity (log Do/w < -2.4), and this leads to a very fast blood clearance (blood: 0.28 +/- 0.02 SUV, 1 h p.i.), low liver tissue accumulation (liver: 1.20 +/- 0.27 SUV, 1 h p.i.), and rapid renal-urinary excretion (kidneys: 6.06 +/- 2.96 SUV, 1 h p.i.) as shown by biodistribution studies of 64Cu-6 in Wistar rats. Preliminary in vivo studies of 64Cu-6 in NMRI nu/nu mice, bearing the human prostate tumor PC-3 showed an accumulation of the conjugate in the tumor (2.25 +/- 0.13 SUV, 12.5 min p.i.; 0.94 +/- 0.05 SUV, 55 min p.i.) and allowed a clear visualization of the gastrin-releasing peptide receptor distribution by positron emission tomography (PET).

A new ligand derivative of 1,4,7-triazacyclononane (TACN), 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (6), has been synthesized and its complexation behavior towards Cu2+ ions investigated. The ligand 6 has been characterized by spectroscopic methods and a molecular structure of a corresponding Cu(II) complex has been elucidated by single crystal X-ray analysis. The suitability of 6 for conjugation to peptide substrates has been shown by amide coupling of 6 to the stabilized derivative of bombesin (BN), βAla-βAla-[Cha13, Nle14]BN(7-14), to give the conjugate 8. The free ligand 6 and the bioconjugate 8 were labeled with 64Cu2+ and the resulting complexes, 64Cu . 6 and 64Cu . 8, were found to be stable in the presence of a large excess of a competing ligand (cyclam) or the copper-seeking superoxide dismutase (SOD), as well as in rat plasma. Biodistribution studies of 64Cu . 8 in Wistar rats showed a high activity uptake into the pancreas (5.76 ± 0.25 SUV, 5 min p.i.; 3.93 ± 0.25 SUV, 1 h p.i.), which is the organ with high levels of gastrin-releasing peptide receptor (GRPR). This receptor is over-expressed in a large number of breast and prostate carcinomas. The novel 64Cu . 6 complex had a dominating influence on the non-specific activity biodistribution of its BN conjugate, since the distribution data of 64Cu . 6 are similar to 64Cu . 8. The 64Cu complexes exhibited a low activity accumulation in the liver tissue and an extensive renal clearance, which was distinctively different to the biodistribution of 64CuCl2, suggesting that 64Cu . 6 does not undergo significant demetalation, but rather exhibits high in vivo stability.

A detailed understanding of limiting dark current mechanisms in InAs/GaSb type-II superlattice (T2SL) infrared detectors is key to improve the electrooptical performance of these devices. We present a six-component dark current analysis which, for the first time, takes account of sidewall-related dark current contributions in mesa-etched T2SL photodiodes. In a wide temperature range from 30K to 130K, the paper compares limiting mechanisms in two homojunction T2SL photodiode wafers for the long-wavelength infrared regime. While the two epi wafers were fabricated with nominally the same frontside process they were grown on different molecular beam epitaxy systems. In the available literature a limitation by S hockley-Read-Hall processes in the space charge region giving rise to generation-recombination (GR) dark current is the prevailing verdict on the bulk dark current mechanism in T2SL homojunction photodiodes around 77K. In contrast, we find that investigated photodiode wafers are instead limited by the diffusion mechanism and the ohmic shunt component, respectively. Furthermore, our in-depth analysis of the various dark current components has led to an interesting observation on the temperature dependence of the shunt resistance in T2SL homojunction photodiodes. Our results indicate that the GR and the shunt mechanism share the same dependence on bandgap and temperature, i.e. , a proportionality to exp(- E

Technetium-labeled fatty acids intended for myocardial metabolism imaging and the respective rhenium model complexes were synthesized according to the "4 + 1" mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive rhenium model complexes were characterized by NMR, IR, and EA, and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single-crystal X-ray analyses. To estimate the diagnostic value of the 99mTc-labeled fatty acids, the compounds were investigated in experiments in vitro and in biodistribution studies using male Wistar rats. The new fatty acid tracers contain the metal core in the oxidation states +3, well-wrapped in a trigonal-bipyramidal coordination moiety, which is attached at the omega-position of a fatty acid chain. This structural feature is considered to be a good imitation of the well-established iodinated phenyl fatty acids. High heart extraction in perfused heart studies (up to 26% injected dose (ID)) and noticeable heart uptake of the 99mTc tracers in vivo being in the order of 2% ID/g at 5 min (postinjection, pi.), accompanied by a good heart to blood ratio of 8, confirms that the new Tc compounds are suitable as fatty acid tracers.

Focal Plane Arrays for high-performance thermal imaging systems operating in the mid-infrared spectral range between 3–5 µm have been realized by type-II InAs/GaSb short-period superlattices. A fully operational 256 × 256 camera system showing a noise equivalent temperature difference below 10 mK is presented. The suitability of InAs/GaSb type-II superlattices for next generation thermal imagers is demonstrated with the first 288 × 384 dual color demonstrator camera which features a simultaneous and spatially coincident acquisition of two separate spectral regimes in the mid-infrared. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

A series of novel S,N-heterocyclic (thiazolyl) substituted carboximidamides 3 and 4 was synthesized in yields up to 82% from specific triazinium salts 1 and primary or secondary amines 2 which additionally bear pyridine or imidazole units. These carboximidamides are used as tailor-made ligands for the complexation of Cu(II) and Zn(II). The coordination behavior of 3 and 4 and the properties of the resulting metal complexes are affected a significant extent especially by the nature of these amine substituents. The most important structural feature of the novel complexes is that the ligation of the metal cations is achieved by a 1,3,5-triazapentadienyl anion system, compare the X-ray structure of the model complex Cu-4d. Analogous Zn(II) complexes 5, 6a, 6b, 6c, 7a, and 7b were obtained from carboximidamides 3, 4a, 4b, 4c, 4d, and 4e after reaction with diethylzinc. Interestingly, these Zn(II) complexes possess an intrinsic activity to catalyze the copolymerization of cyclohexene oxide and carbon dioxide to...

Starting with bis([1,3,4]thiadiazolo)[1,3,5]triazinium halides 1 , a novel class of heterocyclic compounds, the [1,3,4]thiadiazolo[2,3-d][1,2,4]triazolo[1,5-a][1,3,5]triazinium halides 5 were prepared. The reaction between 5 and primary or secondary amines 6 yielded highly substituted guanidines 8 and fused tricyclic bis([1,2,4]triazolo)[1,5-a:1′,5′-d][1,3,5]triazinium halides 9 . The formation of the reactive triazinium-imidothioate zwitterions 7 , which is controlled by the influence of negative hyperconjugation, was proven by NMR data and the X-ray structure of 7c . The subsequent ring-closure/ring-opening steps can be understood in terms of an S N (ANRORC) process accompanied by intramolecular proton-transfer reactions. The zwitterions 7 were reacted with EtI forming cationic derivatives 10 or hydrolyzed at pH 6–7 to give novel heterocyclic ethanethioamides 11 .

The formation of highly reactive zwitterionic triaziniumimidothioate intermediates 10 from bis(1,3,4-thiadiazolo)-1,3,5-triazinium halides is reported. These intermediates are the first structures to be isolated from the reaction pathway between bis(1,3,4-thiadiazolo)-1,3,5-triazinium halides 1 and benzylamines 2. The reaction between 1 and 2 has a very complicated hypersurface and can yield unusual bis(1,2,4-triazolo)-1,3,5-triazinium halides 6, [1,2,4]triazolo[1,3,4]thiadiazolo[1,3,5]triazinium halides 7 or highly substituted guanidines 5. The formation of 6 and 7 can be understood in terms of an SN(ANRORC) process. As could be demonstrated for the tricyclic cations 6, these compounds, together with 7, could be interesting in further synthetic applications. The salts 6 react with KOH/tBuOK to give novel aminals 16 in good to excellent yields. Most of the important steps in the course of the transformation of 1 into 5, 6 and 7 are supported by B3LYP/6−311++G(d,p) calculations and the X-ray structures of 6a, 7b, 14b and 16c. From an electronic point of view, the more important reaction steps are governed by the conformation-controlling effect of negative hyperconjugation, accompanied by intramolecular proton-transfer reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)