Teil III. Edelgasdetektoren,Indirekter Elektron-Mobility-Detektor und Schlußfolgerungen

Die Multiplikation von Ladungsträgern durch feldbeschleunigte Elektronen erfolgt im Bereich der unselbständigen Entladung. Sie wurde von Lovelock [1] erstmals für β-Argondetektoren zur Steigerung der Empfindlichkeit E_N angewandt. Detektoren im Bereich der selbständigen Entladung [2] haben sich nicht bewährt.     

Ethynylphosphonamidates for the Rapid and Cysteine‐Selective Generation of Efficacious Antibody–Drug Conjugates

Requirements for novel bioconjugation reactions for the synthesis of antibody–drug conjugates (ADCs) are exceptionally high, since conjugation selectivity as well as the stability and hydrophobicity of linkers and payloads drastically influence the performance and safety profile of the final product. We report Cys‐selective ethynylphosphonamidates as new reagents for the rapid generation of efficacious ADCs from native non‐engineered monoclonal antibodies through a simple one‐pot reduction and alkylation. Ethynylphosphonamidates can be easily substituted with hydrophilic residues, giving rise to electrophilic labeling reagents with tunable solubility properties. We demonstrate that ethynylphosphonamidate‐linked ADCs have excellent properties for next‐generation antibody therapeutics in terms of serum stability and in vivo antitumor activity.     

Electrochemical Hydroxylation of Arenes Catalyzed by a Keggin Polyoxometalate with a Cobalt(IV) Heteroatom

The sustainable, selective direct hydroxylation of arenes, such as benzene to phenol, is an important research challenge. An electrocatalytic transformation using formic acid to oxidize benzene and its halogenated derivatives to selectively yield aryl formates, which are easily hydrolyzed by water to yield the corresponding phenols, is presented. The formylation reaction occurs on a Pt anode in the presence of [Co^IIIW₁₂O₄₀]^5? as a catalyst and lithium formate as an electrolyte via formation of a formyloxyl radical as the reactive species, which was trapped by a BMPO spin trap and identified by EPR. Hydrogen was formed at the Pt cathode. The sum transformation is ArH+H₂O→ArOH+H₂. Non‐optimized reaction conditions showed a Faradaic efficiency of 75 % and selective formation of the mono‐oxidized product in a 35 % yield. Decomposition of formic acid into CO₂ and H₂ is a side‐reaction.     

Monitoring FET flow control and wall adsorption of charged fluorescent dye molecules in nanochannels integrated into a multiple internal reflection infrared waveguide

Using Si as the substrate, we have fabricated multiple internal reflection infrared waveguides embedded with a parallel array of nanofluidic channels. The channel width is maintained substantially below the mid-infrared wavelength to minimize infrared scattering from the channel structure and to ensure total internal reflection at the channel bottom. A Pyrex slide is anodically bonded to the top of the waveguide to seal the nanochannels, while simultaneously enabling optical access in the visible range from the top. The Si channel bottom and sidewalls are thermally oxidized to provide an electrically insulating barrier, and the Si substrate surrounding the insulating SiO(2) layer is selectively doped to function as a gate. For fluidic field effect transistor (FET) control, a DC potential is applied to the gate to manipulate the surface charge on SiO(2) channel bottom and sidewalls and therefore their zeta-potential. Depending on the polarity and magnitude, the gate potential can accelerate, decelerate, or reverse the flow. Here, we demonstrate that this nanofluidic infrared waveguide can be used to monitor the FET flow control of charged, fluorescent dye molecules during electroosmosis by multiple internal reflection Fourier transform infrared spectroscopy. Laser scanning confocal fluorescence microscopy is simultaneously used to provide a comparison and verification of the IR analysis. Using the infrared technique, we probe the vibrational modes of dye molecules, as well as those of the solvent. The observed infrared absorbance accounts for the amount of dye molecules advancing or retracting in the nanochannels, as well as adsorbing to and desorbing from the channel bottom and sidewalls.     

Development of a capillary electrophoresis-based assay of sirtuin enzymes

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent enzymes catalyzing the deacetylation of acetyl-lysine residues of histones and other proteins. Three 9-fluorenylmethoxycarbonyl (Fmoc)-labeled peptide substrates derived from the amino acid sequence of p53, i.e. Fmoc-KK(Ac)-NH(2), Fmoc-KK(Ac)L-NH(2) and Fmoc-RHKK(Ac)-NH(2), were synthesized and evaluated as substrates of the human isoenzyme SIRT1. The acetylated and respective deacetylated peptides as well as nicotinamide as the reaction product of nicotinamide adenine dinucleotide were separated by capillary electrophoresis in a fused-silica capillary using 200 mM phosphate-Tris buffer, pH 2.7. Sodium hydroxide-mediated sample stacking was performed in order to overcome peak asymmetry due to the high salt and acid content of the sample as well as to enhance UV detection sensitivity. The assay was subsequently validated. Upon incubation of the acetylated peptides for 60 min in the presence of 2.5 U of SIRT1 at least 87% of the peptides was deacetylated, indicating that the new derivatives are efficient substrates of the enzyme.     

Human reaction to vibrations from blasting activity – Norwegian exposure–effect relationships

Rock blasting may cause disturbances, fear, and annoyance in residential and community areas affected by such activities. These community reactions can be quite strong, even when the blasting activities and the resulting vibrations are unlikely to cause physical damage to building foundations or buildings. A socio-vibrational survey was undertaken to assess residential reactions to blasting activities. Vibration velocities were obtained for 520 respondent dwellings located in seven study areas, and compared to the residents’ assessments of environment quality. Even at low vibration values, many people report annoyance. Exposure–effect relationships with acceptable statistical error bands were obtained. The level of annoyance from long-term blasting activities (quarry blasting) was not higher than from finite periods of more intense blasting activities (road and rail tunnels). Providing information in advance of the blasting activities, can reduce community reactions. Self-reported sensitivity to vibrations was associated with significantly increased annoyance. Sensitivity to vibrations was uncorrelated with exposure to vibrations. Sensitivity to noise and sensitivity to vibration were moderately correlated.     

The Synthesis and Characterization of the Tri-rhenium(VI) Capped Wells–Dawson Polyoxometalate, [{(C4H9)4N)5(C2H5)3NH}{Re3P2W15O62}]

The tri-rhenium(VI) capped Wells–Dawson polyoxometalate, [Re₃P₂W₁₅O₆₂]^6– with quaternary ammonium cations was synthesized by reacting the trivacant lacunary species, [P₂W₁₅O₅₆]^12– with [ReOCl₃(PPh₃)₂] in an organic solvent. Elemental analysis by thermogravimetry and inductively coupled plasma mass spectroctrometry confirmed the substitution of three rhenium atoms, single-crystal X-ray diffraction as well as infra red spectroscopy showed the complete Wells–Dawson structure. The presence of all three rhenium atoms in one cap is indicated by ³¹P nuclear magnetic resonance spectroscopy and the electron spin resonance spectrum shows that the tri-rhenium(V) species with three unpaired electrons is low spin, S = ½.