Various species of the Euphorbia genus contain diterpene ingenol and ingenol mebutate (ingenol‐3‐angelate), a substance found in the sap of the plant Euphorbia peplus and an inducer of cell death. A gel formulation of the drug has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the topical treatment of actinic keratosis.
Objective
To develop a rapid and reliable method for quantification of ingenol in various plant extracts.
Methodology
Methanolic extracts of 38 species of the Euphorbia genus were analysed via ultra‐high performance liquid chromatography with tandem mass spectrometry (UHPLC–MS/MS) after methanolysis and solid‐phase extraction (SPE) purification. The 18O–labelled ingenol analogue was prepared and used as an internal standard for ingenol content determination and method validation.
Results
The highest ingenol concentration (547 mg/kg of dry weight) was found in the lower leafless stems of E. myrsinites. The screening confirms a substantial amount of ingenol in species studied previously and furthermore, reveals some new promising candidates.
Ultra-high-resolution X-ray crystallography of macromolecules (i.e. resolution better than 0.8 Angstroms) is a rising field that promises to provide new insight into the structure-function relationships of biomacromolecules. The picture emerging from macromolecular structures at this resolution is far more complex than previously understood, requiring for its study improved tools for structure refinement, analysis and annotation. Some of these problems were highlighted during the recent High Resolution Drug Design Meeting (Bischenberg-Strasbourg, France, 13-16 May 2004). We will review here some of the results and discussions that took place during that meeting and elaborate on the trends and challenges ahead in this emerging new field of research. 相似文献
The bias in the most-probable-number (MPN) estimate of microbial densities derived from serial dilutions might be less important than it has appeared to be. For many purposes, bias in the logarithm of the MPN is more important than bias in the MPN, and the bias in the logarithm is much less. The lesser bias has been reduced by using the theorems of Salama, Koch, and Tolley. Formulas and tables are provided. 相似文献
An alteration to Woodward's methods is recommended for deriving a 1 — α confidence interval for microbial density using serial dilutions with most-probable-number (MPN) estimates. Outcomes of the serial dilution test are ordered by their MPNs. A lower limit for the confidence interval corresponding to an outcome y is the density for which y and all higher ordered outcomes have total probability α/2. An upper limit is derived in the analogous way. An alteration increases the lowest lower limits and decreases the highest upper limits. For comparison, a method that is optimal in the sense of null hypothesis rejection is described. This method ranks outcomes dependent upon the microbial density in question, using proportional first derivatives of the probabilities. These and currently used methods are compared. The recommended method is shown to be more desirable in certain respects, although resulting in slightly wider confidence intervals than De Man's (1983) method. 相似文献
Recent developments in phase contrast microscopy have enabled the label‐free visualization of certain organelles due to their distinct morphological features, making this method an attractive alternative in the study of cellular dynamics. However tubular structures such as endoplasmic reticulum (ER) networks and complex dynamics such as the fusion and fission of mitochondria, due to their low phase contrast, still need fluorescent labeling to be adequately imaged. In this article, we report a quantitative phase microscope with ultra‐oblique illumination that enables us to see those structures and their dynamics with high contrast for the first time without labeling. The imaging capability was validated through comparison to the fluorescence images with the same field‐of‐view. The high image resolution (~270 nm) was validated using both beads and cellular structures. Furthermore, we were able to record the vibration of ER networks at a frame rate of 250 Hz. We additionally show complex cellular processes such as remodeling of the mitochondria networks through fusion and fission and vesicle transportation along the ER without labels. Our high spatial and temporal resolution allowed us to observe mitochondria “spinning”, which has not been reported before, further demonstrating the advantages of the proposed method. 相似文献
There are complex considerations when planning to disclose an attenuated psychosis syndrome (APS) diagnosis. In this review, we evaluate ethical, legal, and clinical perspectives as well as caveats related to full, non‐ and partial disclosure strategies, discuss societal implications, and provide clinical suggestions. Each of the disclosure strategies is associated with benefits as well as costs/considerations. Full disclosure promotes autonomy, allows for the clearest psychoeducation about additional risk factors, helps to clarify and/or correct previous diagnoses/treatments, facilitates early intervention and bolsters communication between providers but there are important considerations involving heritability, comorbidity, culture, and stigma. Non‐disclosure advances nonmaleficence by limiting stigma and stress (which may inadvertently exacerbate the condition), and confusion (related to the rapidly evolving diagnosis) in a sensitive developmental period but is complicated by varying patient preferences and the possibility that, as new treatments without adverse effects become available, the risk with false positives no longer justifies the accompanying loss of autonomy. Partial disclosure balances ethical considerations by focusing on symptoms instead of labels, but evidence that laypersons may interpret this information as a pseudo‐diagnosis and that symptoms alone also contribute to stigma limits the efficacy of this approach. In addition, there are notable societal considerations relating to disclosure involving conservatorship, the reach of insurance companies, and discrimination. We advocate a hybrid approach to disclosure and recommend future research aimed at understanding the effects of stigma on clinical course and a renewed focus on those help‐seeking cases that do not transition but remain clinically relevant. 相似文献
The study investigates the impact of exposure to the stray magnetic field of a whole-body 7 T MRI scanner on neurobehavioral performance and cognition. Twenty seven volunteers completed four sessions, which exposed them to approximately 1600 mT (twice), 800 mT and negligible static field exposure. The order of exposure was assigned at random and was masked by placing volunteers in a tent to hide their position relative to the magnet bore. Volunteers completed a test battery assessing auditory working memory, eye-hand co-ordination, and visual perception. During three sessions the volunteers were instructed to complete a series of standardized head movements to generate additional time-varying fields ( approximately 300 and approximately 150 mT.s(-1) r.m.s.). In one session, volunteers were instructed to keep their heads as stable as possible. Performance on a visual tracking task was negatively influenced (P<.01) by 1.3% per 100 mT exposure. Furthermore, there was a trend for performance on two cognitive-motor tests to be decreased (P<.10). No effects were observed on working memory. Taken together with results of earlier studies, these results suggest that there are effects on visual perception and hand-eye co-ordination, but these are weak and variable between studies. The magnitude of these effects may depend on the magnitude of time-varying fields and not so much on the static field. While this study did not include exposure above 1.6 T, it suggests that use of strong magnetic fields is not a significant confounder in fMRI studies of cognitive function. Future work should further assess whether ultra-high field may impair performance of employees working in the vicinity of these magnets. 相似文献
The paper presents an original analysis method of corneal deformation images from the ultra‐high‐speed Scheimpflug camera (Corvis ST tonometer). Particular attention was paid to deformation frequencies exceeding 100 Hz and their reproducibility in healthy subjects examined repeatedly. A total of 4200 images with a resolution of 200 × 576 pixels were recorded. The data derived from 3 consecutive measurements from 10 volunteers with normal corneas. A new image analysis algorithm, written in Matlab with the use of the Image Processing package, adaptive image filtering, morphological analysis methods and fast Fourier transform, was proposed. The following results were obtained: (1) reproducibility of the eyeball reaction in healthy subjects with precision of 10%, (2) corneal vibrations with a frequency of 369 ± 65 Hz (3) and amplitude of 7.86 ± 1.28 µm, (4) the phase shift within two parts of the cornea of the same subject of about 150°.
The result of image sequence analysis for one subject and deformations with a corneal frequency response above 100 Hz. 相似文献
Using high definition (HD) and ultra‐high definition (UHD) of Fourier‐transform infrared (FTIR) spectroscopic imaging, we characterized spectrally pulmonary metastases in a murine model of breast cancer comparing them with histopathological results (Hematoxylin and eosin [H&E] staining). This comparison showed excellent agreement between the methods in case of localization of metastases with size below 1 mm and revealed that label‐free HD and UHD IR spectral histopathology distinguish the type of neoplastic cells. We primary focused on differentiation between metastatic foci in the pleural cavity from cancer cells present in lung parenchyma and inflamed cells present in extracellular matrix of lungs due to growing of advanced metastases. In addition, a combination of unsupervised clustering and IR imaging indicated the high sensitivity of FTIR spectroscopy to identify chemical features of small macrometastases located under the pleural cavity and during epithelial‐mesenchymal transition. FTIR‐based spectral histopathology was proved to detect not only phases of breast cancer metastasis to lungs but also to differentiate various origins of metastases seeded from breast cancer. 相似文献
Though polypyrrole (PPy) is widely used in flexible supercapacitors owing to its high electrochemical activity and intrinsic flexibility, limited capacitance and cycling stability of freestanding PPy films greatly reduce their practicality in real‐world applications. Herein, we report a new approach to enhance PPy's capacitance and cycling stability by forming a freestanding and conductive hybrid film through intercalating PPy into layered Ti3C2 (l‐Ti3C2, a MXene material). The capacitance increases from 150 (300) to 203 mF cm?2 (406 F cm?3). Moreover, almost 100% capacitance retention is achieved, even after 20 000 charging/discharging cycles. The analyses reveal that l‐Ti3C2 effectively prevents dense PPy stacking, benefiting the electrolyte infiltration. Furthermore, strong bonds, formed between the PPy backbones and surfaces of l‐Ti3C2, not only ensure good conductivity and provide precise pathways for charge‐carrier transport but also improve the structural stability of PPy backbones. The freestanding PPy/l‐Ti3C2 film is further used to fabricate an ultra‐thin all‐solid‐state supercapacitor, which shows an excellent capacitance (35 mF cm?2), stable performance at any bending state and during 10 000 charging/discharging cycles. This novel strategy provides a new way to design conductive polymer‐based freestanding flexible electrodes with greatly improved electrochemical performances. 相似文献
Expression systems capable of growing to high cell densities are now readily available and are popular due to the benefits of increased product concentration. However, such high solids density cultures pose a major challenge for bioprocess engineers as choosing the right separation equipment and operating it at optimal conditions is crucial for efficient recovery. This study proposes a methodology for the rapid determination of suitable operating conditions for the centrifugal recovery of high cell density fermentation broths. An ultra scale-down (USD) approach for the prediction of clarification and dewatering levels achieved in a range of typical high-speed centrifuges is presented. Together with a visualisation tool, a Window of Operation, this provides for the rapid analysis of separation performance and evaluation of the available operating conditions, as an aid in the selection of the centrifuge equipment most appropriate for a given process duty. A case study examining centrifuge selection for the processing of a high cell density Pichia pastoris culture demonstrates the method. The study examines semi-continuous disc-stack centrifuges and batch-operated machines such as multi-chamber bowls and Carr Powerfuges. Performance is assessed based on the variables of clarification, dewatering and product yield. Inclusion of limits imposed by the centrifuge type and design, and operation itself, serve to constrain the process and to define the Windows of Operation. The insight gained from the case study provides a useful indication of the utility of the methodology presented and illustrates the challenges of centrifuge selection for the demanding case of high solids concentration feed streams. 相似文献
The β‐lactamase Toho‐1 exhibits a strong tendency to form merohedrally twinned crystals. Here, the crystal quality of Toho‐1 was improved by using surface modification to remove a sulfate ion involved in crystal packing. The surface‐modified Toho‐1 variant (R274N/R276N) was crystallized under similar conditions to those used for wild‐type Toho‐1. R274N/R276N did not form merohedrally twinned crystals. The crystals diffracted to a significantly higher resolution (∼0.97 Å) than the wild‐type crystals (1.65 Å); they belonged to the same space group and had almost identical unit‐cell parameters to those of wild‐type Toho‐1. 相似文献
Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis. 相似文献
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