The last phase of the federal OSHA standard on occupational exposure to bloodborne pathogens became effective July 6. However, compliance deadlines may vary in the 23 states and two U.S. territories that have their own OSHA offices. The states and territories have the option of adopting the federal standard or drafting their own plans. Here's a status report on the OSHA-approved state programs for bloodborne pathogens. 相似文献
Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma. 相似文献
Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters. 相似文献
Elastomer materials are used in a wide application range and subjected to different loading from which failure of the material results. Because this failure is caused by initiation and propagation of cracks, the application of fracture mechanics methods for the assessment of the material is obvious. A short summary of the methods of technical fracture mechanics including possibilities of determination of crack resistance curves is given. Vulcanizates on the basis of SBR 1500 with various sulfur and carbon black contents were investigated. For describing the crack initiation and crack propagation behavior, several fracture mechanics examination methods were applied. Tear‐analyzer results were used to assess the crack propagation behavior under fatigue‐like loading conditions. Furthermore, for the characterization of the crack resistance of the materials under impact‐like loading conditions, instrumented tensile‐impact tests were performed. To obtain information about the initiation and propagation of a stable crack, quasi‐static fracture mechanics tests were applied. The results of the several tests are discussed in dependence on sulfur and carbon black contents. We found a non‐monotonous behavior of the toughness as a function of carbon black loading. An explanation is given in connection with a percolation‐like transition in filler morphology on larger length scales.
Schematic crack propagation curve for characterizing the fatigue behavior of the vulcanizates recorded in a TFA test. 相似文献
Textile rental companies are poised on the edge of a boom in the healthcare marketplace. The detonator is outpatient care. Between 1984 and 1990, outpatient visits increased from almost 233 million to more than 310 million, or about 33 percent. The shift from traditional hospital care to outpatient or ambulatory service is creating a new market opportunity for textile rental services. Innovative medical services are cropping up in suburban malls and neighborhoods, and demand is high for high-quality linen supply or contract laundry services. 相似文献
MALDI-TOF MS profiling for microorganism detection has already been demonstrated in the 1990s, but has evolved to the first-line identification method in many laboratories just during the past five years. While this application of MALDI-TOF MS has proven its broad applicability, accuracy, robustness, and cost-effectiveness it is of particular interest to expand the capabilities of the mass spectrometric platform. Resistance detection is the most desirable further application of MALDI-TOF MS in microbiology, but maybe also the most challenging. Different approaches have been published regarding diverse antibiotic drugs and distinct microorganism classes. The current review shall give an overview about the developments of the recent years and their potential to get transformed in clinical useful assays in the future. 相似文献
Abstract In an earlier study of preservice elementary and middle school teachers’ beliefs about repeating decimals, Weller, Arnon, and Dubinsky (2009) reported on a comparison of the mathematical performance of 77 preservice teachers who completed an APOS-based instructional unit with 127 preservice teachers who completed traditional instruction. The purpose of the current study, based on 47 interviews conducted 4 months after the instruction, during which time there was no further instruction on this topic, is to determine the strength and stability (over time) of the students’ beliefs, to uncover thinking that did not arise in the earlier study, and to see whether the interviews yield similar comparative results. The interviews did uncover changes in student thinking. The students who received the APOS-based instruction developed stronger and more stable (over time) beliefs that a repeating decimal is a number; a repeating decimal has a fraction or integer to which it corresponds; a repeating decimal in general equals its corresponding fraction or integer; and, in particular, In addition, a number of indices and categories were developed that may prove useful in other studies consisting of the comparison of interview and questionnaire data involving a large number of interview subjects. 相似文献
Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration. 相似文献
A critical overview of the latest developments in the aluminum battery technologies is reported. The substitution of lithium with alternative metal anodes characterized by lower cost and higher abundance is nowadays one of the most widely explored paths to reduce the cost of electrochemical storage systems and enable long‐term sustainability. Aluminum based secondary batteries could be a viable alternative to the present Li‐ion technology because of their high volumetric capacity (8040 mAh cm?3 for Al vs 2046 mAh cm?3 for Li). Additionally, the low cost aluminum makes these batteries appealing for large‐scale electrical energy storage. Here, we describe the evolution of the various aluminum systems, starting from those based on aqueous electrolytes to, in more details, those based on non‐aqueous electrolytes. Particular attention has been dedicated to the latest development of electrolytic media characterized by low reactivity towards other cell components. The attention is then focused on electrode materials enabling the reversible aluminum intercalation‐deintercalation process. Finally, we touch on the topic of high‐capacity aluminum‐sulfur batteries, attempting to forecast their chances to reach the status of practical energy storage systems. 相似文献