Coherent resonant interactions and slow light with molecules confined in photonic band-gap fibers

We investigate resonant nonlinear optical interactions and demonstrate induced transparency in acetylene molecules in a hollow-core photonic band-gap fiber at 1.5$\mu$m. The induced spectral transmission window is used to demonstrate slow-light effects, and we show that the observed broadening of the spectral features is due to collisions of the molecules with the inner walls of the fiber core. Our results illustrate that such fibers can be used to facilitate strong coherent light-matter interactions even when the optical response of the individual molecules is weak.Comment: 5 pages, 4 figure

Controlling the elution order of insulin and its analogs in sub-/supercritical fluid chromatography using methanesulfonic acid and 18-crown-6 as mobile phase additives

The purity analysis of therapeutic peptides can often be challenging, demanding the application of more than a single analytical technique. Supercritical fluid chromatography nowadays is a promising alternative to reversed-phase liquid chromatography, providing orthogonal and complementary information. This study investigated its applicability for the separation of human insulin, its analogs and degradation products. A previously published method development protocol for peptides up to 2000 Da was successfully applied to the higher molecular weight insulins (6 kDa). A single gradient method was optimized for all insulins using a Torus DEA column (100 × 3.0 mm, 1.7 μm), carbon dioxide and a modifier consisting of methanol/acetonitrile/water/methanesulfonic acid (65:35:2:0.1, v/v/v/v). Consecutively, the crown ether 18-crown-6, which is well known to complex charged lysine sidechains and other amino functionalities, was added to the modifier to evaluate its impact on selectivity. A decreased retention and a shift in the elution order for the insulins were observed. An inverse effect on retention was found when combined with a neutral stationary phase chemistry (Viridis BEH)

Risk assessment for nitrosated pharmaceuticals: A future perspective in drug development

Since June 2018, thousands of drug products from around the world had to be recalled due to the unexpected presence of nitrosamines (NAs). Starting with the pharmaceutical group of sartans, antidiabetic drugs, antihistamines, and antibiotics also became the subject of investigation. The occurrence of NAs has shown that pharmaceutical companies and regulatory agencies did not focus on these substances in the past during drug development. In this study, we incorporated a nitrosation assay procedure into high-resolution supercritical fluid chromatography (SFC)–mass spectrometry screening to test the potential of direct nitrosation of active pharmaceutical ingredients (APIs). The forced degradation study was performed with a four-fold molar excess of sodium nitrite, relative to the drug substance, at pH 3–4 for 4 h at 37°C. Chromatographic separation was performed on a porous graphitic carbon column by SFC. The mass analysis then focused on direct N-nitrosation or N-nitroso compounds (NOCs) formed after dealkylation. Substances (n = 67) from various pharmaceutical classes were evaluated and 49.3% of them formed NOCs, of which 21.2% have not yet been reported in the literature. In addition, for two APIs, which are known to form an unidentified NOC, the structure could be identified. A few substances also showed multiple NOCs and even N,N’-dinitroso-species. As NAs are carcinogens, they have to be eliminated or at least limited to prevent cancer in patients, who rely on these drugs. This study contributes a procedure that can be implemented in preapproval drug development and postapproval risk assessment to prevent unexpected findings in the future

Ternary eluent compositions in supercritical fluid chromatography improved fingerprinting of therapeutic peptides

Currently, little information has been published on the application of ternary eluent compositions in supercritical fluid chromatography for separating peptides. This work investigates the benefits of adding acetonitrile to methanol as the modifier. Three cyclic antibiotic peptides (bacitracin, colistin, and daptomycin) ranging between 1000 and 2000 Da were chosen as model substances. The ternary mixture of carbon dioxide, methanol, and acetonitrile is optimized to increase the resolution of the peptide's fingerprint. In addition, varying compositions of methanol and acetonitrile were found to change the elution order of the analytes, which is a valuable tool during method development. An individual gradient method using two Torus 2-PIC columns (each 100 × 3.0 mm, 1.7 μm), carbon dioxide, and a modifier consisting of acetonitrile/methanol/water/methanesulfonic acid (60:40:2:0.1, v:v:v:v) was optimized for each of the peptides. Subsequently, a generic method development protocol applicable to polypeptides is proposed

Fungi of the Bitterfeld amber forest

Volume: 249 Host publication title: III. Bitterfelder Bernsteinkolloquium Host publication sub-title: Bitterfelder Bernstein und andere fossile Harze aus Mitteldeutschland. Proceeding volume: 249 Isbn(print): 978-3-86944-094-1Peer reviewe

Prevalence of nitrosamine contaminants in drug samples: Has the crisis been overcome?

Various drug samples (N = 249; drug substances, tablets, capsules, solutions, crèmes, and more) from the European pharmaceutical market were collected since 2019 and analyzed for 16 nitrosamines (NAs). In 2.0% of the cases, NAs were detected. These findings included four active pharmaceutical ingredients already known for potential NA contamination: losartan (N-nitrosodimethylamine [NDMA] and N-nitrosodiethylamine, simultaneously), valsartan (NDMA), metformin (NDMA) and ranitidine (NDMA). The fifth new finding, which has not been reported yet, discovered contamination of a molsidomine tablet sample with N-nitrosomorpholine (NMor). The tablet contained 144% of the toxicological allowable intake for NMor. NMor was included in our screening from the beginning and is currently the focus of regulatory authorities, but was added to the guidelines only last year. Thus, it may not have been the focus of regulatory investigations for too long. Our results indicate that the majority of drug products in the market are nonhazardous in terms of patient safety and drug purity. Unfortunately, the list of individual affected products keeps growing constantly and new NA cases, such as molsidomine or nitrosated drug substances (nitrosamine drug substance-related impurities [NDSRI]), continue to emerge. We therefore expect nitrosamine screenings to remain a high priority

Simulated Greenland Surface Mass Balance in the GISS ModelE2 GCM: Role of the Ice Sheet Surface

The rate of growth or retreat of the Greenland and Antarctic ice sheets remains a highly uncertain component of future sea level change. Here we examine the simulation of Greenland ice sheet surface mass balance (GrIS SMB) in the NASA Goddard Institute for Space Studies (GISS) ModelE2 General Circulation Model (GCM). GCMs are often limited in their ability to represent SMB compared with polarregion Regional Climate Models (RCMs). We compare ModelE2 simulated GrIS SMB for presentday (19962005) simulations with fixed ocean conditions, at a spatial resolution of 2 latitude by 2.5 longitude (~200 km), with SMB simulated by the Modle Atmosphrique Rgionale (MAR) RCM (19962005 at a 25 km resolution). ModelE2 SMB agrees well with MAR SMB on the whole, but there are distinct spatial patterns of differences and large differences in some SMB components. The impact of changes to the ModelE2 surface are tested, including a subgridscale representation of SMB with surface elevation classes. This has a minimal effect on ice sheetwide SMB, but corrects local biases. Replacing fixed surface albedo with satellitederived values and an agedependent scheme has a larger impact, increasing simulated melt by 60100%. We also find that lower surface albedo can enhance the effects of elevation classes. Reducing ModelE2 surface roughness length to values closer to MAR reduces sublimation by ~50%. Further work is required to account for meltwater refreezing in ModelE2, and to understand how differences in atmospheric processes and model resolution influence simulated SMB

q-Deformed Superalgebras

The article deals with q-analogs of the three- and four-dimensional Euclidean superalgebra and the Poincare superalgebra.Comment: 38 pages, LateX, no figures, corrected typo