다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

This review is an updated and expanded version of the five prior reviews that were published in this journal in 1997, 2003, 2007, 2012, and 2016. For all approved therapeutic agents, the time frame has been extended to cover the almost 39 years from the first of January 1981 to the 30th of September 2019 for all diseases worldwide and from ∼1946 (earliest so far identified) to the 30th of September 2019 for all approved antitumor drugs worldwide. As in earlier reviews, only the first approval of any drug is counted, irrespective of how many "biosimilars" or added approvals were subsequently identified. As in the 2012 and 2016 reviews, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions, and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or synthetic variations using their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from 1946 to 1980, of the 75 small molecules, 40, or 53.3%, are N or ND. In the 1981 to date time frame the equivalent figures for the N* compounds of the 185 small molecules are 62, or 33.5%, though to these can be added the 58 S* and S*/NMs, bringing the figure to 64.9%. In other areas, the influence of natural product structures is quite marked with, as expected from prior information, the anti-infective area being dependent on natural products and their structures, though as can be seen in the review there are still disease areas (shown in Table 2) for which there are no drugs derived from natural products. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are still able to identify only two de novo combinatorial compounds (one of which is a little speculative) approved as drugs in this 39-year time frame, though there is also one drug that was developed using the "fragment-binding methodology" and approved in 2012. We have also added a discussion of candidate drug entities currently in clinical trials as "warheads" and some very interesting preliminary reports on sources of novel antibiotics from Nature due to the absolute requirement for new agents to combat plasmid-borne resistance genes now in the general populace. We continue to draw the attention of readers to the recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated"; thus we consider that this area of natural product research should be expanded significantly.

Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019.

Thank you for reading principles of optics electromagnetic theory of propagation interference and diffraction of light. As you may know, people have search hundreds times for their favorite novels like this principles of optics electromagnetic theory of propagation interference and diffraction of light, but end up in harmful downloads. Rather than enjoying a good book with a cup of coffee in the afternoon, instead they are facing with some infectious bugs inside their computer.

Principles Of Optics Electromagnetic Theory Of Propagation Interference And Diffraction Of Light

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.

Wearable biosensors for healthcare monitoring.

Infusion pumps have been widely used in clinical settings for the administration of medications and fluids. We present the digital droplet infusion (DDI) device, a low-cost, high-precision digital infusion system, utilizing a microfluidic discretization unit to convert continuous flow into precisely delivered droplet aliquots and a valving unit to control the duration and frequency of flow discretization. The DDI device relies on a distinct capillarity-dominated process of coalescence and pinch-off of droplets for flow digitization, which is monitored by a pair of conductive electrodes located before and after the junction. The digital feedback-controlled flow rate can be employed to adjust a solenoid valve for refined infusion management. With this unique digital microfluidic approach, the DDI technology enables a simple yet powerful infusion system with an ultrahigh resolution of digital droplet transfer volume, as small as 57 nL, which is three orders of magnitude lower than that of clinical standard infusion pumps, as well as a wide range of digitally adjustable infusion rates ranging from 0.1 mL h-1 to 10 mL h-1, in addition to an array of programmable infusion profiles and safety features. Its modular design enables fast assembly using only off-the-shelf and 3D-printed components. Overall, benefiting from its simple device architecture and excellent infusion performance, the DDI technology has great potential to become the next-generation clinical standard for drug delivery with its high precision and ultimate portability at a low cost.

Digital droplet infusion

Digital polymerase chain reaction (PCR) is a fast-developed technology, which makes it possible to provide absolute quantitative results. However, this technology has not been widely used in research field or clinical diagnostics. Although digital PCR has been born for two decades, the products on this subject still suffer from either high cost or cumbersome user experience, hence very few labs have the willingness or budget to routinely use such product; On the other hand, the unique sensitivity of dPCR over traditional qPCR shows great potential applications. Here, a cost-effective digital PCR method based on a microfluidic printing system was introduced, trying to overcome those shortcomings. The microfluidic droplet printing technology was utilized in this study to directly generate droplet array containing PCR reaction solution onto the simple glass substrate for the subsequent PCR and imaging, which could be done with any regular flat-panel PCR machine and microscope. With simple analysis, the data generated with this method showed reliable quality, which followed the Poisson distribution trend. Compared with other expensive digital PCR methods, this system is more affordable and simpler to integrate, especially for those biological or medical labs which are in need for the digital PCR options but short in budget. Therefore, this method is believed to have the great potential in the future market application.

/pdf/digital-polymerase-chain-reaction-in-an-array-of-3uigjiqbme.pdf

Digital polymerase chain reaction in an array of microfluidic printed droplets

This paper reports a microfluidic enabled print-to-screen (P2S) platform, which can achieve low-cost, high-throughput, high-precision printing with plug-and-play disposable cartridge, as well as parallel screening with minimized crosstalk The performance of the P2S platform is characterized and, using this platform, the cell-killing performance of 3-out-of-10 drug combinations towards ovarian cancer cell is, for the first time, studied and as a result, 15 out of 175 drug combinations are newly identified to exert potent cancer cell toxicity This demonstrates the potent applicability of P2S platform for combinatorial chemotherapy, which can greatly speed up the entire cycle of drug cocktail discovery

High-throughput print-to-screen (P2S) platform for combinatorial chemotherapy

Assembly of colloidal arrays has attracted much attention over the past decade. Surface property and topology play important roles in the assembly of colloidal patterns and layers on various substrates. In this paper, we report on a novel micropattern-assisted nanoassembly (μPAN) method to organize highly ordered nanocolloidal arrays onto a nonfouling polymer surface. Polyethylene glycol (PEG) hydrogel is used as the substrate material in the study, for its desired biological properties, low surface energy and photopatternability. A high-density array of PEG microwells is first fabricated on glass substrates with the minimal feature resolution of 1 µm using photolithography method. By simply controlling the colloidal concentration of the dipping solution, the dimensions of the microwells and pulling speed of the substrate, various well organized nanocolloidal patterns are assembled inside the PEG microwells. In addition, the effect of surface property is experimentally investigated. After oxygen plasma treatment, the nonfouling property of the PEG surface deteriorates significantly, leading to a complete surface coverage of nanocolloidal beads. The novel μPAN method allows organizing highly ordered nanocolloidal arrays in a predictable and robust fashion, and has potential applications in photonic crystal fabrication, biological sensing, analytical detection and nanoassembly.

Tingrui Pan

Papers

Digital droplet infusion

Digital polymerase chain reaction in an array of microfluidic printed droplets

High-throughput print-to-screen (P2S) platform for combinatorial chemotherapy

Micropattern-assisted nanoassembly: Ordered nanocolloidal array on PEG microstructures

Electronic Skin: Imperceptible Epidermal–Iontronic Interface for Wearable Sensing (Adv. Mater. 6/2018)