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Ultrashort pulse (USP) laser ablation is gaining popularity as a novel manufacturing technique for brittle materials, enabling the creation of complex freeform shapes that are challenging to produce with conventional optics manufacturing techniques. Freeforms have revolutionized optics manufacturing by providing designers with increased degrees of freedom using non-rotational symmetric components. However, this evolution presents new challenges for manufacturing processes, calling for innovative solutions such as USP ablation. To ensure the industrial viability of areal USP laser machining, it is crucial to not only consider material removal rates but also surface quality and subsurface damage (SSD). Especially for optical applications, harsh quality requirements must be met. This study investigates the SSD patterns of fused silica (FS) and borosilicate glass N-BK7 (BK) processed under different laser wavelengths, beam geometries and processing parameters using high-resolution optical coherence tomography (OCT). It is shown that OCT as non-destructive and 3D evaluation method is well-suited for analysing USP processes. The discovered differences in defect morphology between FS and BK emphasize the importance of selecting appropriate processes and process parameters when working with different materials. Compared to previous studies, for the parameter sets analysed here using OCT, much higher defects depths of up to 441 µm were revealed.

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.

Inhibition of fatty acid synthase (FASN) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. To investigate the potential role of FASN in the pathophysiology of human obesity, the FASN gene was sequenced in 48 German whites. Thirty-five single-nucleotide polymorphisms (SNPs) were identified. Eight SNPs representative for their linkage disequilibrium groups and the Val1483Ile (rs2228305) substitution were genotyped for subsequent association analyses in 1,311 adults from Germany. Further, the tagging SNPs were genotyped also in German childhood cohorts (738 schoolchildren, 205 obese children). Effects of genetic variation on FASN mRNA expression in visceral and subcutaneous adipose tissue from a subgroup of 172 subjects were analyzed. Several polymorphisms in the FASN (rs62078748, rs2229422, rs2229425, and rs17848939) were nominally associated with obesity in case-control studies including 446 obese subjects (BMI >or=30 kg/m(2)) and 389 lean controls (BMI

We would like to invite you to participate in the Analytical Challenge, which is a series of puzzles designed to entertain and challenge our readers. The special ABC feature 'Analytical Challenge' has established itself as a truly unique quiz series, with a new scientific puzzle published every second month. Readers can access the complete collection of published problems with their solutions on the ABC homepage at www.springeronline.com/journal/00216. Test your knowledge and tease your wits in diverse areas of analytical and bioanalytical chemistry by viewing this collection. Quality assurance is the topic of the present challenge. And please note: there is a prize to be won (a Springer book from our catalogue up to a value of euros 75,-). Please read on...

A procedure for the determination of acetaldehyde, acetone, methanol, ethanol, 1-propanol and 2-propanol in blood was developed. Separation of analytes was carried out on DB-wax capillary column (l = 30 m, I.D. = 0.32 mm, dF = 0.5 microm) at 40 degrees C, hydrogen was used as a carrier gas (at 30 kPa) and FID as a detector. Quantification was performed with the use of 2-butanol as an internal standard. Headspace solid-phase microextraction was applied as the sample preparation technique. The usefulness of most commercially available fiber coatings was checked and 65 microm Carbowax/DVB proved most effective. Microextraction was carried out from the headspace at 60 degrees C for 10 min. The sample was stirred at 750 rpm. In order to improve the extraction efficiency of analytes, salting-out agents were also applied. Potassium carbonate turned out to be the most efficient. A 1.0-g amount of this salt and 0.1 ml of I.S. were added to 0.5 ml of sample. Validation of the worked-out method was performed. For each analyte, the limits of detection and quantification, linearity, working range, accuracy and precision were determined or tested.

Comparison of the separation performance of five newly developed pH-stable HPLC columns is described for the analysis of anthocyanins in red wines. Separation of twenty anthocyanins in a single run is described using the most appropriate method.

A simple and fast HPLC method without sample pretreatment is described for the separation of anthocyanins in red wines using a new pH-stable stationary phase. The linearity between peak area and concentration and ruggedness of the method were checked. Investigations were made about the safekeeping of red wine samples concerning anthocyanins. Classification of 52 different wine samples was performed by multivariate statistical methods.

Using 1 alpha,2 alpha-oxido-cholesta-5,7-diene-3 beta,25-diol (2) as a starting material, the provitamins of calcitriol with an additional 2 beta-chloro-, 2 beta-fluoro-, and 2 beta-methoxy-substituent (3,4,5) are obtained by transdiaxial opening of the oxirane ring with nucleophiles. An efficient irradiation process is described and used for the synthesis of the 2 beta-substituted calcitriols NS2 (2 beta-Cl), NS6 (2 beta-F), and NS7 (2 beta-OCH3). The affinity of these three vitamin D3 derivatives to the vitamin D receptor (VDR) and was determined. These three A-ring derivatives of 1,25(OH)2D3 were further tested for their proliferation-inhibitory and anti-adipogenic activity and gene regulatoric activity in the vitamin D3-sensitive, murine, mesenchymal cell line C3H10T1/2. The VDR-affinity of the 2 beta-chloro derivative, NS2 (2 beta-Cl), was identical to 1,25(OH)2D3 and its vitamin D binding protein (DBP)-affinity was in the range of 1,25(OH)2D3. NS2 inhibited the proliferation of C3H10T1/2(BMP-4)-cells in the presence of fetal calf serum (FCS) 9 times, and, in the absence of FCS, 111 times lower, as compared with 1,25(OH)2D3. The ID50 dose of adipogenesis-inhibition of NS2 was 13 times higher than the ID50 dose of 1,25(OH)2D3. NS6 (2 beta-F) displayed a slightly higher affinity than 1,25(OH)2D3 to the VDR and DBP-affinity. The proliferation-inhibitory activity in the presence of FCS was 90 times higher, as compared with 1,25(OH)2D3. In the FCS-free proliferation assay NS6 displayed an inhibitory activity in the range of 1,25(OH)2D3. NS6 showed an 5 times higher potency to inhibit (pre)adipocyte-differentiation in C3H10T1/2(BMP-4)-cells than 1,25(OH)2D3. NS7 (2 beta-OCH3) showed the lowest VDR-affinity and the highest DBP-affinity of the tested substances, as compared with 1,25(OH)2D3 (11 times lower and 35 times higher respectively). Its proliferation-inhibitory activity in the FCS-free medium was 9 times and in the FCS-containing assay 67 times lower in comparison with 1,25(OH)2D3. A 1250 times higher NS7-dose was needed to reach the anti-adipogenic potency of 1,25(OH)2D3. All tested substances displayed a similar ability to activate a vitamin D responsive element-regulated reporter gene compared to 1,25(OH)2D3 (NS2 and NS6: 1.3 times higher activity; NS7: 1,4 times lower activity).

Anomalous diequatorial epoxide ring opening of 1 beta, 2 beta-oxido-cholesta-5,7-diene-3 beta, 25-diol 1 produces the 1 beta-hydroxy-2 alpha-chloro-provitamin 2 and its corresponding 1 beta-hydroxy-provitamin 3. The provitamins 2 and 3 are transformed by irradiation and thermal isomerization to 2 alpha-chloro-1-epicalcitriol NS3 (4) and 1-epicalcitriol NS8 (5), respectively. These two A-ring derivatives were tested for their in vitro biological activity in the mesenchymal, murine cell line C3H10T1/2, and their effects were compared with those of the native vitamin D3 derivatives 25(OH)D3 and 1.25(OH)2D3. NS3 and NS8 showed marked differences in their affinity for the vitamin D binding protein (DBP) and in their ability to inhibit cell proliferation. NS8 has the ability to bind to a high-affinity DBP-binding site for which 25(OH)D3 has none affinity. The 2 alpha-chloro-substitution (NS3) prevents binding to the postulated noncompetitive, NS8-specific DBP-binding site and diminishes the affinity to the vitamin D receptor (VDR) and therefore diminishing NS3's biological abilities. The elucidation of the structure-function relationships at the DBP-binding-sites could have major impact on the development of new vitamin D3 derivatives with extended serum half-life.

Starting with (20S)-20-(p-toluenesulfonyl)oxymethyl-pregna-1, 5-dien-3 alpha-ol (4), we synthesized three vitamin D analogs in 10 to 11 steps: 1 alpha, 26-dihydroxy-27-nor-vitamin D3 (1), its 3-epi analog (2), and 2 beta-methoxy-1 alpha, 26-dihydroxy-27-nor-vitamin D3 (3). We tested the derivatives in the murine mesenchymal cell line C3H1OT1/2. All substances were less potent in inhibition of cell proliferation, inhibition of adipocyte differentiation, and induction of gene activation, and had a lower affinity to the vitamin D receptor than the native vitamin D3 metabolite 1.25(OH)2D3. The affinity of 1 to the vitamin D binding protein was about three times higher than that of 1.25(OH)2D3.