The Small Molecule GAL-201 Efficiently Detoxifies Soluble Amyloid β Oligomers: New Approach towards Oral Disease-Modifying Treatment of Alzheimer’s Disease

Soluble amyloid β (Aβ) oligomers have been shown to be highly toxic to neurons and are considered to be a major cause of the neurodegeneration underlying Alzheimer’s disease (AD). That makes soluble Aβ oligomers a promising drug target. In addition to eliminating these toxic species from the patients’ brain with antibody-based drugs, a new class of drugs is emerging, namely Aβ aggregation inhibitors or modulators, which aim to stop the formation of toxic Aβ oligomers at the source. Here, pharmacological data of the novel Aβ aggregation modulator GAL-201 are presented. This small molecule (288.34 g/mol) exhibits high binding affinity to misfolded Aβ_1-42 monomers (K_D = 2.5 ± 0.6 nM). Pharmacokinetic studies in rats using brain microdialysis are supportive of its oral bioavailability. The Aβ oligomer detoxifying potential of GAL-201 has been demonstrated by means of single cell recordings in isolated hippocampal neurons (perforated patch experiments) as well as in vitro and in vivo extracellular monitoring of long-term potentiation (LTP, in rat transverse hippocampal slices), a cellular correlate for synaptic plasticity. Upon preincubation, GAL-201 efficiently prevented the detrimental effect on LTP mediated by Aβ_1-42 oligomers. Furthermore, the potential to completely reverse an already established neurotoxic process could also be demonstrated. Of particular note in this context is the self-propagating detoxification potential of GAL-201, leading to a neutralization of Aβ oligomer toxicity even if GAL-201 has been stepwise removed from the medium (serial dilution), likely due to prion-like conformational changes in Aβ_1-42 monomer aggregates (trigger effect). The authors conclude that the data presented strongly support the further development of GAL-201 as a novel, orally available AD treatment with potentially superior clinical profile.     

Microcavity-integrated graphene photodetector

There is an increasing interest in using graphene (1, 2) for optoelectronic applications. (3-19) However, because graphene is an inherently weak optical absorber (only ≈2.3% absorption), novel concepts need to be developed to increase the absorption and take full advantage of its unique optical properties. We demonstrate that by monolithically integrating graphene with a Fabry-Pérot microcavity, the optical absorption is 26-fold enhanced, reaching values >60%. We present a graphene-based microcavity photodetector with responsivity of 21 mA/W. Our approach can be applied to a variety of other graphene devices, such as electro-absorption modulators, variable optical attenuators, or light emitters, and provides a new route to graphene photonics with the potential for applications in communications, security, sensing and spectroscopy.     

Formal Translation of Bytecode into BoogiePL

Many modern program verifiers translate the program to be verified and its specification into a simple intermediate representation and then compute verification conditions on this representation. Using an intermediate language improves the interoperability of tools and facilitates the computation of small verification conditions. Even though the translation into an intermediate representation is critical for the soundness of a verifier, this step has not been formally verified. In this paper, we formalize the translation of a small subset of Java bytecode into an imperative intermediate language similar to BoogiePL. We prove soundness of the translation by showing that each bytecode method whose BoogiePL translation can be verified, can also be verified in a logic that operates directly on bytecode.     

Rückblicke und Ausblicke auf die Konstitutionsaufklärung der Cellulose

Ohne Zusammenfassung Mitteilung über makromolekulare Verbindungen 582. Mitt. vgl. Makromolekulare Chem. Bd.10 (1955), H. 2; zugl. 113, Mitt. über Cellulose.     

Polarographische Untersuchungen an 1,3-Thiazinthionen

Polarographic Investigations of 1,3-Thiazinthiones 1,3-Thiazine-6-thiones are stepwise reduced in aprotic media to the corresponding radical anions and dianions. In the case of the 2,4-diphenyl derivative ( 1a ) the radical anion is stable in dimethylformamide, whereas the dianion reacts further to yield the bithiazinylidene ( 4 ) among other products. The effect of substituents on the reduction potentials is discussed.     

Nanoporous gold bumps for low temperature bonding

Nanoporous gold bumps have been deposited on silicon wafers by electroplating a silver–gold alloy followed by etching the silver. An open-porous cellular structure of gold at meso-scale is left on top of the bumps. For flip chip bonding we found low temperature and low force bonding conditions. The porous interconnects have very promising properties, like compressibility and reduced stiffness, which should result in higher bond yield and extended reliability.