Automated Synthesis of 68Ga-Labeled DOTA-MGS8 and Preclinical Characterization of Cholecystokinin-2 Receptor Targeting

The new minigastrin analog DOTA-MGS8 targeting the cholecystokinin-2 receptor (CCK2R) used in this study displays the combination of two site-specific modifications within the C-terminal receptor binding sequence together with an additional N-terminal amino acid substitution preventing fast metabolic degradation. Within this study, the preparation of ⁶⁸Ga-labeled DOTA-MGS8 was validated using an automated synthesis module, describing the specifications and analytical methods for quality control for possible clinical use. In addition, preclinical studies were carried out to characterize the targeting potential. [⁶⁸Ga]Ga-DOTA-MGS8 showed a high receptor-specific cell internalization into AR42J rat pancreatic cells (~40%) with physiological expression of rat CCK2R as well as A431-CCK2R cells transfected to stably express human CCK2R (~47%). A favorable biodistribution profile was observed in BALB/c nude mice xenografted with A431-CCK2R cells and mock-transfected A431 cells as control. The high tumor uptake of ~27% IA/g together with low background activity and limited uptake in non-target tissue confirms the potential for high-sensitivity positron emission tomography of stabilized MG analogs in patients with MTC and other CCK2R-related malignancies.     

The analysis of the error statistics in a 5 × 40 Gbit/s fibre link with hybrid amplification

We quantify the error statistics and patterning effects in a 5 × 40 Gbit/s WDM RZ-OOK SMF/DCF fibre link using hybrid Raman/EDFA amplification. By extensive use of a numerical model, we determine how the error statistics change with the transmission distance. This knowledge is used as a basis for a constrained coding technique in order to improve the transmission error rate. We propose an adaptive constrained code for mitigation of the patterning effects and demonstrate that this approach can substantially reduce the bit error rate (BER) even for very large values of the channel BER (BER > 10^− 1). The proposed technique can be used in combination with forward error correction schemes (FEC) to extend the range of channel BERs that an FEC scheme is effective over.     

Observation of mixed fermionic-bosonic helium clusters by transmission grating diffraction

Small weakly bound boson-fermion 4He(m) 3He(n) clusters formed in a free jet expansion are identified using nondestructive transmission grating diffraction. The observations confirm the existence of more than 11 very tenuous complexes including the three-body halo molecule 4He2 3He and the pseudo-Borromean complex 4He2 3He2. Effective cluster formation temperatures, extracted from a sudden freeze model for cluster growth using theoretical binding energies, increase smoothly with cluster size, thereby confirming the calculations with the possible exception of 4He2 3He2.     

Chern–Simons,Wess–Zumino and other cocycles from Kashiwara–Vergne and associators

Descent equations play an important role in the theory of characteristic classes and find applications in theoretical physics, e.g., in the Chern–Simons field theory and in the theory of anomalies. The second Chern class (the first Pontrjagin class) is defined as \(p= \langle F, F\rangle \) where F is the curvature 2-form and \(\langle \cdot , \cdot \rangle \) is an invariant scalar product on the corresponding Lie algebra \(\mathfrak g\). The descent for p gives rise to an element \(\omega =\omega _3+\omega _2+\omega _1+\omega _0\) of mixed degree. The 3-form part \(\omega _3\) is the Chern–Simons form. The 2-form part \(\omega _2\) is known as the Wess–Zumino action in physics. The 1-form component \(\omega _1\) is related to the canonical central extension of the loop group LG. In this paper, we give a new interpretation of the low degree components \(\omega _1\) and \(\omega _0\). Our main tool is the universal differential calculus on free Lie algebras due to Kontsevich. We establish a correspondence between solutions of the first Kashiwara–Vergne equation in Lie theory and universal solutions of the descent equation for the second Chern class p. In more detail, we define a 1-cocycle C which maps automorphisms of the free Lie algebra to one forms. A solution of the Kashiwara–Vergne equation F is mapped to \(\omega _1=C(F)\). Furthermore, the component \(\omega _0\) is related to the associator \(\Phi \) corresponding to F. It is surprising that while F and \(\Phi \) satisfy the highly nonlinear twist and pentagon equations, the elements \(\omega _1\) and \(\omega _0\) solve the linear descent equation.     

Majorization in de Branges spaces I. Representability of subspaces

In this series of papers we study subspaces of de Branges spaces of entire functions which are generated by majorization on subsets D of the closed upper half-plane. The present, first, part is addressed to the question which subspaces of a given de Branges space can be represented by means of majorization. Results depend on the set D where majorization is permitted. Significantly different situations are encountered when D is close to the real axis or accumulates to i∞.     

Recurrence of Ancestral Lines and Offspring Trees in Time Stationary Branching Populations

For time stationary Galton- Watson-branching populations on a general type space, the structure of the “individually positive recurrent part” of the system is described: its building blocks consist of finitely many “clans” with positive recurrent trunks. Conditions are given when this nubsystem is void, and when it equals the full system. In addition, positive recurrence on the clan level is characterized. Whereas individual positive recurrence turns out to be a symmetric concept with respect to forward and backward time direction (i. e., with respect to anceatral lines and offspring trees), with individual null recurrence this symmetry can fail even in the absence of branching, i.e., for independently migrating particle systems (Example 13.1). For discrete type spaces a classification of types as to the various individual recurrence concepts (positive, null, forward and backward in time) is proposed and illustrated by a couple of results and examples. For finite type spaces conditiom on the branching dynamics and its mean matrix for the existence of nontrivial equilibria are given.     

Towards experiments with highly charged ions at HESR

The atomic physics collaboration SPARC is a part of the APPA pillar at the future Facility for Antiproton and Ion Research. It aims at atomic-physics research across virtually the full range of atomic matter. An emphasis of this contribution are the atomic physics experiments addressing the collision dynamics in strong electro-magnetic fields as well as the fundamental interactions between electrons and heavy nuclei at the HESR. Here we give a short overview about the central instruments for SPARC experiments at this storage ring.     

Organoboron Derivatives of Stereoregular Phenylcyclosilsesquioxanes

This study presents the synthesis of organoboron derivatives of stereoregular 4-, 6-, and 12-unit phenylcyclosilsesquioxanes. All compounds obtained were isolated in good yields (70–80 %) and were fully characterized by ¹H, ¹³C, ²⁹Si, ¹¹B NMR, IR spectroscopy, HRMS ESI, and elemental microanalysis. The structure of the key modifier, obtained for the first time, 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) dimethylvinylsilane, was also confirmed by single-crystal XRD.     

Aliphatic hydroxylation and epoxidation of capsaicin by cytochrome P450 CYP505X

Microbial cytochrome P450 enzymes (CYPs) are able to mimic the metabolism of human CYPs. One challenge is to identify the respective drug metabolites and to compare substrate specificities to those of the human enzymes. In this study, a class VIII self-sufficient CYP from Aspergillus fumigatus (CYP505X) and variants of this enzyme were heterologously expressed in E. coli. The substrate scope of the variants was determined using active pharmaceutical ingredients (APIs) and (hetero)cyclic compounds. Capsaicin – the active compound in chili peppers – was oxidized most efficiently (4.36?μM/min) in a whole cell mediated biotransformation. The products were isolated, purified and their structures elucidated by 1D and 2D NMR. The two major metabolites showed modifications on the lipophilic side chain. Specifically, capsaicin was hydroxylated at position 8 to give (E)-8-hydroxy-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide and epoxidized at the double bond to give N-(4-hydroxy-3-methoxybenzyl)-5-(3-isopropyloxiran-2-yl)-pentanamide.