The Toll signaling pathway, first discovered in Drosophila, has a well-established role in immune responses in insects as well as in mammals. In Drosophila, the Toll-dependent induction of ...antimicrobial peptide production has been intensely studied as a model for innate immune responses in general. Besides this humoral immune response, Toll signaling is also known to activate blood cells in a reaction that is similar to the cellular immune response to parasite infections, but the mechanisms of this response are poorly understood. Here we have studied this response in detail, and found that Toll signaling in several different tissues can activate a cellular immune defense, and that this response does not require Toll signaling in the blood cells themselves. Like in the humoral immune response, we show that Toll signaling in the fat body (analogous to the liver in vertebrates) is of major importance in the Toll-dependent activation of blood cells. However, this Toll-dependent mechanism of blood cell activation contributes very little to the immune response against the parasitoid wasp, Leptopilina boulardi, probably because the wasp is able to suppress Toll induction. Other redundant pathways may be more important in the defense against this pathogen.
Since the last comprehensive review by Otto Sticher on natural product isolation in NPR (O. Sticher, Nat. Prod. Rep., 2008, 25, 517), a plethora of new reports on isolation of secondary compounds ...from higher plants, marine organisms and microorganisms has been published. Although methods described earlier like the liquid-solid chromatographic techniques (VLC, FC, MPLC, HPLC) or partition chromatographic methods are still the major tools for isolating pure compounds, some developments like hydrophilic interaction chromatography (HILIC) have not been fully covered in previous reviews. Furthermore, examples of using different preparative solid-phase extraction (SPE) columns including molecular imprinting technology have been included. Special attention is given to chiral stationary phases in isolation of natural products. Methods for proper identification of plant material, problems of post-harvest changes in plant material, extraction methods including application of ionic liquids, de-replication procedures during natural product isolation are further issues to be discussed by the review. Selected work published between 2008 and mid-2012 is covered.
Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases ...using medical imaging.
In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176.
Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0-90·2) for deep learning models and 86·4% (79·9-91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1-96·4) for deep learning models and 90·5% (80·6-95·7) for health-care professionals.
Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology.
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Novel Psychoactive Substances (NPS) represent an alternative to established illicit drugs. They are traded via the internet and exhibit small alterations in their chemical structure to circumvent ...law, however, their psychotropic effects are comparable. There is still poor knowledge about side effects and health risks. By the end of 2018, 730 NPS were reported to EMCDDA (European Monitoring Centre for Drugs and Drug Addiction). Among different compound classes, many NPS are chiral and few publications deal with the different pharmacological and toxicological properties of their pure enantiomers. Therefore, analytical method development concerning enantioseparation of NPS is of great interest. Chiral separation protocols of established illicit drugs have been transferred for NPS, selected examples are given as well. Different methods for enantioseparation of NPS comprising mainly stimulating drugs such as cathinones, pyrovalerones, amphetamines, ketamines, (2-aminopropyl) benzofuranes, phenidines, phenidates, morpholines and thiophenes are reviewed. Moreover, chiral resolution of some cannabinomimetics by HPLC is presented. Chromatographic and electrophoretic techniques such as GC, HPLC, SFC, CE and CEC are discussed and in some cases compared. Mainly, solid samples either purchased from internet vendors, seized by police or collected from patients in hospitals are subject to analysis. Chiral selectors used for HPLC are listed in a Table. It was shown that particularly stimulating drugs are traded as racemic mixtures, which is not the case with cannabinomimetics. Mainly, HPLC and CE were used for enantioseparation of NPS.
This review gives an overview of chiral separation principles and their applications in capillary electromigration techniques. The basic chiral separation principles are explained and the mechanisms ...discussed. Recent developments and new techniques in CZE and capillary electrochromatography (CEC) are highlighted. New chiral selectors among cyclodextrins, crown ethers, carbohydrates, macrocyclic antibiotics, proteins, chiral ion-pairing reagents, chiral surfactants and chiral metal ion complexes and their chiral recognition ability are discussed. Recent advances in chip technology for chiral separation and new approaches regarding improvement of detection sensitivity are presented. Due to the tremendous number of publications dealing with applications, in this review only recent applications are summarized.
The transparent conducting electrode is an essential component in many contemporary and future devices, ranging from displays to solar cells. Fabricating transparent electrodes requires a balancing ...act between sufficient electrical conductivity and high light transmittance, both affected by the involved materials, fabrication methodology, and design. While metal films possess the highest conductivity at room temperature, a decent optical transmittance can only be achieved with ultrathin films. Structuring the metal into optically invisible nanowires has been shown to be promising to complement or even substitute transparent conductive oxides as dominant transparent electrode material. Here the out‐of‐plane fabrication capability of the recently developed method of electrohydrodynamic NanoDrip printing to pattern gold and silver nanogrids with line widths from 80 to 500 nm is demonstrated. This fully additive process enables the printing of high aspect ratio nanowalls and by that significantly improves the electrical performance, while maintaining the optical transmittance at a high level. Metal grid transparent electrodes optimized for low sheet resistances (8 Ω sq−1 at a relative transmittance of 94%) as well as optimized for high transmittance (97% at a sheet resistance of 20 Ω sq−1) are reported, which can be tailored on demand for the use in various applications.
Electrohydrodynamic NanoDrip printing is used to pattern gold and silver nanowalls into high performance metal grid transparent electrodes. The out‐of‐plane capability of this additive process enables the printing of nanowall aspect ratios up to 7, greatly improving the electrical performance, while maintaining the exceptional optical transmittance.
We estimate the effects of climatic changes, as predicted by six climate models, on lake surface temperatures on a global scale, using the lake surface equilibrium temperature as a proxy. We evaluate ...interactions between different forcing variables, the sensitivity of lake surface temperatures to these variables, as well as differences between climate zones. Lake surface equilibrium temperatures are predicted to increase by 70 to 85 % of the increase in air temperatures. On average, air temperature is the main driver for changes in lake surface temperatures, and its effect is reduced by ~10 % by changes in other meteorological variables. However, the contribution of these other variables to the variance is ~40 % of that of air temperature, and their effects can be important at specific locations. The warming increases the importance of longwave radiation and evaporation for the lake surface heat balance compared to shortwave radiation and convective heat fluxes. We discuss the consequences of our findings for the design and evaluation of different types of studies on climate change effects on lakes.
Cannabis is globally by far the most widespread illicit drug of abuse. Especially since its legalization in some of the US, controversies about the legal status of cannabis for recreational and ...medical use have come up. Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), which is the major active ingredient in cannabis products, is mainly responsible for the psychoactive effects. Its inactive biosynthetic precursor tetrahydrocannabinolic acid (THCA) is present in different quantities in fresh and undried cannabis plants. Under influence of drying, temperature and UV exposure it decomposes to Δ(9)-THC. In this study, a quantification of Δ(9)-THC and THCA was carried out to check the stability of cannabis samples. The determination of the degradation of THCA to Δ(9)-THC in 29 cannabis products seized in Austria was monitored by HPLC-UV. Mobile phase consisted of a 25mM triethylammoniumphosphate buffer (pH 3.0) and acetonitrile (36:64). A common LiChrospher(®) 100 RP-18 column was utilized as stationary phase. To check the influence of low as well as high temperature on the degradation process of the cannabinoid THCA to Δ(9)-THC, samples were stored in a freezer or in a drying cabinet for a specified time period. It was shown successfully that high storage temperatures led to a more rapid and complete decomposition of THCA to Δ(9)-THC while at low temperatures only slight or no changes of the percentage distribution were determined.
Cannabis is a plant that is harmful and beneficial because it contains more than 400 bioactive compounds, and the main compounds are Δ9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Currently, ...cannabis extracts are used in medicine, but the amount of THC as a main psychoactive component is strictly regulated. Therefore, the ability to rapidly and accurately detect THC is important. Herein, we developed a sensitive electrochemical method combining a rapid lateral flow assay (LFA) to detect THC rapidly. An electrochemical LFA device was constructed by attaching a screen-printed electrode inside a lateral-flow device to exploit the remarkable binding of THC to the cannabinoid type 2 (CB2) receptor in the test zone. The ferrocene carboxylic acid attached to the monoclonal THC antibody acts as an electroactive species when it binds to the THC in the sample before it flows continuously to the CB2 receptor region on the electrode. Under optimal conditions, the detection time is within 6 min and the devise shows excellent performance with a detection limit of 1.30 ng/mL. Additionally, the device could be applied to detect THC in hemp extract samples. The results obtained from this sensor are similar to the standard method (HPLC) for detecting THC. Therefore, this proposed device is useful as an alternative device for the on-site determination of THC because it is inexpensive, portable, and exhibits high sensitivity.
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•Electrochemical-LFA was developed for the first time for the rapid detection of THC•Just 6 min was used for the automated quantitative assessment of THC•This device has a high sensitivity to detecting THC and has a LOD of 1.3 ng/mL•Electrochemical-LFA was successfully applied for the detection of THC in real samples
In recent years, cathinone derivatives have entered the global drug market and caused serious social problems in many European countries. Modification of the basic structure of cathinone leads to a ...multitude of derivatives, including the most popular representative mephedrone. All those substances contain a stereogenic center and therefore two isoforms exist. As it is the case with many chiral active pharmaceutical ingredients, even the pharmacological effect of the enantiomers of those psychoactive compounds may differ. During this research, an easy‐to‐prepare chiral capillary zone electrophoresis method for the enantioseparation of a set of 19 cathinone derivatives was developed. Testing different types of cyclodextrin (CD), including native‐β‐CD, carboxymethyl‐β‐CD, 2‐hydroxypropyl‐β‐CD, sulfated‐β‐CD, and native γ‐CD, best results were obtained with the negatively charged sulfated‐β‐CD. The effect of the CD concentration, the temperature, and the addition of ACN to the BGE on the enantioseparation is shown by three model compounds. Under optimal conditions, using 20 mg/mL sulfated‐β‐CD in 50 mM ammonium acetate buffer pH = 4.5 containing 10% v/v ACN at a cassette temperature of 40°C and with an applied voltage of 20 kV, all derivatives except methedrone were resolved in their enantiomers within 20 min.
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