The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity. 相似文献
The ethyl acetate-based multi-residue method for determination of pesticide residues in produce has been modified for gas
chromatographic (GC) analysis by implementation of dispersive solid-phase extraction (using primary–secondary amine and graphitized
carbon black) and large-volume (20 μL) injection. The same extract, before clean-up and after a change of solvent, was also
analyzed by liquid chromatography with tandem mass spectrometry (LC–MS–MS). All aspects related to sample preparation were
re-assessed with regard to ease and speed of the analysis. The principle of the extraction procedure (solvent, salt) was not
changed, to avoid the possibility invalidating data acquired over past decades. The modifications were made with techniques
currently commonly applied in routine laboratories, GC–MS and LC–MS–MS, in mind. The modified method enables processing (from
homogenization until final extracts for both GC and LC) of 30 samples per eight hours per person. Limits of quantification
(LOQs) of 0.01 mg kg−1 were achieved with both GC–MS (full-scan acquisition, 10 mg matrix equivalent injected) and LC–MS–MS (2 mg injected) for
most of the pesticides. Validation data for 341 pesticides and degradation products are presented. A compilation of analytical
quality-control data for pesticides routinely analyzed by GC–MS (135 compounds) and LC–MS–MS (136 compounds) in over 100 different
matrices, obtained over a period of 15 months, are also presented and discussed. At the 0.05 mg kg−1 level acceptable recoveries were obtained for 93% (GC–MS) and 92% (LC–MS–MS) of pesticide–matrix combinations. 相似文献
A new diagnostic concept based on deep Raman spectroscopy is proposed permitting the non-invasive determination of the level of carbonate substitution in type II calcifications (HAP). The carbonate substitution has shown to be directly associated with the pathology of the surrounding breast tissue and different pathology groups can therefore be separated using specific features in the Raman spectra of the calcifications. This study explores the principle of distinguishing between type II calcifications, found in proliferating lesions, by using the strongest Raman peak from calcium hydroxyapatites (the phosphate peak at 960 cm(-1)) to act as a surrogate marker for carbonate substitution levels. It is believed that carbonate ion substitution leads to a perturbation of the hydroxyapatite lattice which in turn affects the phosphate vibrational modes. By studying calcifications, with known carbonate content, buried in porcine tissue it has been possible to evaluate the feasibility of using the proposed approach to probe the composition of the calcifications in vivo and hence provide pathology specific information non-invasively, in real time. Using the proposed concept we were able to determine the level of carbonate substitutions through soft tissue phantom samples (total thickness of 5.6 mm). As the level of carbonate substitution has been previously correlated with mid-FTIR to the lesion type, i.e. whether benign or invasive or in situ carcinoma, the new findings provide a major step forward towards establishing a new capability for diagnosing benign and malignant lesions in breast tissue in a safe and non-invasive manner in vivo. 相似文献
Active but unselective : Nucleoside triphosphates possessing glucose moieties (such as those depicted) instead of the natural furanose rings are recognised by the active sites of polymerases. Polymerases therefore seem to be very unspecific in their recognition patterns.
Recent years have seen the development of powerful technologies that have provided forensic scientists with new analytical capabilities, unimaginable only a few years ago. With liquid chromatography-mass spectrometry (LC-MS) in particular, there has been an explosion in the range of new products available for solving many analytical problems, especially for those applications in which non-volatile, labile and/or high molecular weight compounds are being analysed. The aim of this article is to present an overview of some of the most recent applications of LC-MS (/MS) to forensic analysis. To this end, our survey encompasses the period from 2002 to 2005 and focuses on trace analysis (including chemical warfare agents, explosives and dyes), the use of alternative specimens for monitoring drugs of abuse, systematic toxicological analysis and high-throughput analysis. It is not the intention to provide an exhaustive review of the literature but rather to provide the reader with a 'flavour' of the versatility and utility of the technique within the forensic sciences. 相似文献
Diffusion weighted images (DWI), from which the corresponding diffusion tensor images (DTI) are estimated, are commonly acquired with anisotropic discretizations. Traditional methods to up-sample diffusion weighted images generally rely on scene-based interpolation and do not exploit structural information from the images. In this study, a DTI up-sampling framework is presented that incorporates the underlying anatomical shape information by means of non-rigid inter-slice registration. A strategy is proposed to reorient the interpolated tensor in order to maintain its proper orientation. Tests on phantom as well as on real data sets show that the proposed method is able to produce better results compared to scene based interpolation methods in terms of the accuracy of DWI/DTI interpolation, especially when diffusion tensor orientation is taken into account. 相似文献
Summary A study has been made of possible interferences upon the determination of selenium by hydride generation atomic absorption spectrometry (HGAAS), due to the presence of other hydride forming elements such as As, Ge, Bi, Te, Sn and Sb, and to a volatile element such as Hg. The interfering effects of these cations were determined at several concentration levels using sodium borohydride as the reductant and a commercially available semi-automatic system for the generation and the flameless combustion of the hydrides. It has been demonstrated that the determination of selenium by HGAAS is relatively free from interferences with regard to other elements that form volatile hydrides, except for tin and bismuth that strongly interfere.
Einfluß von flüchtige Hydride bildenden Elementen auf die Selenbestimmung als Hydrid durch AAS
Zusammenfassung Bei der AAS-Bestimmung von Selen als Hydrid wurde der Einfluß der hydridbildenden Elemente As, Ge, Bi, Te, Sn, Sb sowie auch des flüchtigen Elements Hg untersucht. Die Untersuchungen wurden bei verschiedenen Konzentrationen mit Natriumborhydrid als Reduktionsmittel durchgeführt. Dabei wurde ein handelsübliches halbautomatisches System zur Erzeugung und flammenlosen Verbrennung der Hydride benutzt. Es zeigte sich, daß die Selenbestimmung bis auf die stark störenden Elemente Sn und Bi relativ frei von Beeinflussungen ist.
The automation of test validation procedures in a routine clinical laboratory by integrating artificial intelligence with the lab information system (LIS) is the focus of this study. Test validation consists of three layers: (1) acceptance of patient results based on technical criteria (technical validation), (2) acceptance of patient results based on internal quality control (QC) results (QC validation) and (3) medical validation of the patient protocol. The emphasis here is put on QC validation. General concepts regarding the setting of performance limits for internal QC results are briefly reviewed. As a practical example, we describe how the different layers of test validation were integrated with Molis, a LIS (Sysmex, Barchon, Belgium) used in a routine clinical biochemistry lab. PGP5 software (PGP, Brussels, Belgium) is used for technical validation and is installed on a Linx work-cell (Thermo Clinical Labsystems, Vantaa, Finland). The latter integrates four different Vitros instruments (OCD, Beerse, Belgium). QC validation and medical validation are performed with QC-Today (IL, Zaventem, Belgium) and VALAB (Erim, Toulouse, France), respectively. Both programs are bi-directionally coupled with the LIS. After 2 years of experience with this integrated system, it is clear that automation of validation rules and procedures has enhanced efficiency and overall quality of patient results.Presented at the Ninth Conference on Quality in the Spotlight, 18–19 March 2004, Antwerp, Belgium. 相似文献