A theoretical study of the C- 4So_3/2 and 2Do_{3/2,5/2} bound states and C ground configuration: fine and hyperfine structures, isotope shifts and transition probabilities

This work is an ab initio study of the 2p3 4So_3/2, and 2Do_{3/2,5/2} states of C- and 2p2 3P_{0,1,2}, 1D_2, and 1S_0 states of neutral carbon. We use the multi-configuration Hartree-Fock approach, focusing on the accuracy of the wave function itself. We obtain all C- detachment thresholds, including correlation effects to about 0.5%. Isotope shifts and hyperfine structures are calculated. The achieved accuracy of the latter is of the order of 0.1 MHz. Intra-configuration transition probabilities are also estimated.Comment: 15 pages, 2 figures, 12 table

Corticosteroid Biosynthesis Revisited: No Direct Hydroxylation of Pregnenolone by Steroid 21-Hydroxylase.

Cytochrome P450s (CYPs) are an essential family of enzymes in the human body. They play a crucial role in metabolism, especially in human steroid biosynthesis. Reactions catalyzed by these enzymes are highly stereo- and regio-specific. Lack or severe malfunctions of CYPs can cause severe diseases and even shorten life. Hence, investigations on metabolic reactions and structural requirements of substrates are crucial to gain further knowledge on the relevance of different enzymes in the human body functions and the origin of diseases. One key enzyme in the biosynthesis of gluco- and mineralocorticoids is CYP21A2, also known as steroid 21-hydroxylase. To investigate the steric and regional requirements of substrates for this enzyme, we performed whole-cell biotransformation assays using a strain of fission yeast Schizosaccharomyces pombe recombinantly expressing CYP21A2. The progestogens progesterone, pregnenolone, and their 17α-hydroxy-derivatives were used as substrates. After incubation, samples were analyzed using gas chromatography coupled to mass spectrometry. For progesterone and 17α-hydroxyprogesterone, their corresponding 21-hydroxylated metabolites 11-deoxycorticosterone and 11-deoxycortisol were detected, while after incubation of pregnenolone and 17α-hydroxypregnenolone, no hydroxylated product was observed. Findings were confirmed with authentic reference material. Molecular docking experiments agree with these results and suggest that interaction between the 3-oxo group and arginine-234 of the enzyme is a strict requirement. The presented results demonstrate once more that the presence of an oxo-group in position 3 of the steroid is indispensable, while a 3-hydroxy group prevents hydroxylation in position C-21 by CYP21A2. This knowledge may be transferred to other CYP21A2 substrates and hence help to gain essential insights into steroid metabolism

Online Demodulation and Trigger for Flux-ramp Modulated SQUID Signals

Due to the periodic characteristics of SQUIDs, a suitable linearization technique is required for SQUID-based readout. Flux-ramp modulation is a common linearization technique and is typically applied for the readout of a microwave SQUID multiplexer as well as since recently also for dc-SQUIDs. Flux-ramp modulation requires another stage in the signal processing chain to demodulate the SQUID output signal before further processing. For cryogenic microcalorimeters, the signal contains events that are given by a fast exponentially rising and slowly exponentially decaying pulses shape. The events shall be detected by a trigger engine and recorded by a storage logic. Since the data rate can be decreased significantly by demodulation and event detection, it is desirable to do both steps on the deployed fast FPGA logic during measurement before passing the data to a general-purpose processor. In this contribution, we show the implementation of efficient multi-channel flux-ramp demodulation computed at run-time on a SoC-FPGA. Furthermore, a concept and implementation for an online trigger and buffer mechanism with its theoretical trigger loss rates depending on buffer size is presented. Both FPGA modules can be operated with up to 500 MHz clock frequency and can efficiently process 32 channels. Correct functionality and data reduction capability of the modules are demonstrated in measurements utilizing magnetic microcalorimeter irradiated with an Iron-55 source for event generation and read out by a microwave SQUID multiplexer

Potential of digitalization within physiotherapy: a comparative survey

BACKGROUND Due to the global digitalization, implementation of digital elements into daily work can support physiotherapists' work but may also pose some challenges. Only little is known about physiotherapists' attitude towards digitalization. This study primarily aimed to analyze physiotherapists' attitude towards digitalization and to what extend digital tools have been implemented into their daily work. In second analysis, participants' characteristics such as age, working place, gender and mode of survey participation were assessed. METHODS A 12-main-item survey amongst voluntary course participants of one physiotherapeutic training center was conducted via paper-based as well as online questionnaires between July 2018 and June 2019 including questions on participants' general as well as particular attitude towards digitalization, the use of (mobile) applications and possible advantages and disadvantages of the ongoing digital transformation. Sub-analysis was performed for age (≤40 years versus > 40 years), gender, mode of participation (paper vs. online) and working place (practice vs. hospital). RESULTS Overall, 488 physiotherapists participated in the survey. In comparison of the age groups, younger participants had more concerns about data security (p = 0.042) and insufficient financial remuneration (p < 0.001). Younger participants stated higher satisfaction with data literacy than their counterparts (p = 0.0001). Physiotherapists working in the outpatient sector, rather than in hospitals, expected digitalization to increase more in relevance (p < 0.001). The online respondents (OG) indicated that they had more knowledge about key aspects of the current legal situation regarding digitalization than participants completing the paper-based survey (p = 0.002). 50.4% of the considered digitalization as useful for their job. CONCLUSIONS The majority of participants saw high potential for digitalization in the physiotherapy sector. Younger physiotherapists seem to be more concerned about data security and insufficient financial remuneration. Physiotherapists in the outpatient sector seem to see more potential in digital transformations. General concerns like missing reimbursement, lack of data security or knowledge on legal frameworks should be addressed in the future. Further studies should focus on identifying specific digital tools which can support physiotherapists

cetuximab in combination with platinum based chemotherapy or radiotherapy in patients with recurrent and or metastatic sschn in clinical routine updated interim results of the prospective soccer study

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Association of Plasma Lipids and Polar Metabolites with Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study.

The diagnosis of osteoporosis is mainly based on clinical examination and bone mineral density assessments. The present pilot study compares the plasma lipid and polar metabolite profiles in blood plasma of 95 Singaporean-Chinese (SC) menopausal women with normal and low bone mineral density (BMD) using an untargeted metabolomic approach. The primary finding of this study was the association between lipids and femoral neck BMD in SC menopausal women. Twelve lipids were identified to be associated with low BMD by the orthogonal partial least squares (OPLS) model. Plasma concentrations of eight glycerophospholipid, glycerolipid, and sphingolipid species were significantly lower in menopausal women with low BMD but higher in two glycerophospholipid species (phosphatidylinositol and phosphatidic acid). Further, this study found no significant differences in plasma amino acid metabolites. However, trends for lower 4-aminobutyric acid, turanose, proline, aminopropionitrile, threonine, and methionine were found in women with low BMD. This pilot study identified associations between lipid metabolism and femoral neck BMD in SC women. Further studies are required on larger populations for evaluating the bone health effect of these compounds and their usefulness as clinical biomarkers for osteoporosis prediction in women

Development and validation of an improved algorithm for overlaying flexible molecules

A program for overlaying multiple flexible molecules has been developed. Candidate overlays are generated by a novel fingerprint algorithm, scored on three objective functions (union volume, hydrogen-bond match, and hydrophobic match), and ranked by constrained Pareto ranking. A diverse subset of the best ranked solutions is chosen using an overlay-dissimilarity metric. If necessary, the solutions can be optimised. A multi-objective genetic algorithm can be used to find additional overlays with a given mapping of chemical features but different ligand conformations. The fingerprint algorithm may also be used to produce constrained overlays, in which user-specified chemical groups are forced to be superimposed. The program has been tested on several sets of ligands, for each of which the true overlay is known from protein–ligand crystal structures. Both objective and subjective success criteria indicate that good results are obtained on the majority of these sets

EDULISS: a small-molecule database with data-mining and pharmacophore searching capabilities

We present the relational database EDULISS (EDinburgh University Ligand Selection System), which stores structural, physicochemical and pharmacophoric properties of small molecules. The database comprises a collection of over 4 million commercially available compounds from 28 different suppliers. A user-friendly web-based interface for EDULISS (available at http://eduliss.bch.ed.ac.uk/) has been established providing a number of data-mining possibilities. For each compound a single 3D conformer is stored along with over 1600 calculated descriptor values (molecular properties). A very efficient method for unique compound recognition, especially for a large scale database, is demonstrated by making use of small subgroups of the descriptors. Many of the shape and distance descriptors are held as pre-calculated bit strings permitting fast and efficient similarity and pharmacophore searches which can be used to identify families of related compounds for biological testing. Two ligand searching applications are given to demonstrate how EDULISS can be used to extract families of molecules with selected structural and biophysical features