Taxol
, an antitumor drug with significant activity, is the first microtubule stabilizing agent described in the literature. This short review of the mechanism of action of Taxol
emphasizes the ...research done in the Horwitz' laboratory. It discusses the contribution of photoaffinity labeled analogues of Taxol
toward our understanding of the binding site of the drug on the microtubule. The importance of hydrogen/deuterium exchange experiments to further our insights into the stabilization of microtubules by Taxol
is addressed. The development of drug resistance, a major problem that arises in the clinic, is discussed. Studies describing differential drug binding to distinct β-tubulin isotypes are presented. Looking forward, it is suggested that the β-tubulin isotype content of a tumor may influence its responses to Taxol
.
•The COVID-19 emerged in Wuhan City and rapidly spread throughout China.•NLR exhibited the largest area under the curve, with the highest specificity and sensitivity.•Elevated NLR can be considered ...independent biomarkers for indicating poor clinical outcomes.
To accumulate evidence that indicated the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China.
Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte (MON) ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan–Meier curve and multivariate COX regression models.
The median age was 46.4 years old, and 37cases were females. A total of 27.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk HR 2.46, 95% confidence interval CI 1.98–4.57) and age (HR 2.52, 95% CI 1.65–4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%).
Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.
2D covalent organic frameworks (2D COFs) have been recognized as a novel class of photoactive materials owing to their extended π‐electron conjugation and high chemical stabilities. Herein, a new ...covalent organic framework (Tph‐BDP) is facilely synthesized by using a porphyrin derivative and an organic dye BODIPY derivative (5,5‐difluoro‐2,8‐diformyl‐1,3,7,9‐tetramethyl‐10‐phenyl‐5H‐dipyrrolo1,2‐c:2′,1′‐f1,3,2diazabori‐nin‐4‐ium‐5‐uide) as monomers for the first time, and their unique photosensitive properties endow them excellent simulated oxidase activity under 635 nm laser irradiation that can catalyze the oxidation of 3,3′,5,5′‐tetramethylbenzidine (TMB). Further findings demonstrate that the presence of uranium (UO22+) can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading. This research provides a preparation strategy for COFs with excellent photocatalytic properties and nanozyme activity, and broadens the applications of the simple colorimetric methods for sensitive and selective radionuclide detection.
A new covalent organic framework is facilely synthesized and its unique photosensitive property endows excellent simulated oxidase activity that can catalyze the oxidation of 3,3′,5,5′‐tetramethylbenzidine (TMB). The presence of uranium can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading.
Distributed network architecture of heterogeneous computing faces with such problems as strict performance constraints of network control, unpredictable mapping relationship between computing data ...algorithms of different mobile terminals and inconsistency between computing algorithms and link control of data networks. In order to solve the above problems, we begin with software definition network architecture and load balancing algorithm for heterogeneous computing, and gradually improve the real-time and reliability of heterogeneous computing. On the one hand, the heterogeneous computing data of fog node and cloud computing system are distributed. The centralized service of software-defined network combines with distributed computing of mobile edge terminal and its subnet. On the other hand, we define the centralized information and distributed scheduler of the network. In addition, we deploy the optimal assignment of data sharing and heterogeneous computing tasks in real time with ellipse-partitioned area as the object. A series of algorithms for classifying and assigning heterogeneous computing data streams in software-defined networks are designed to achieve the optimal balance among load balancing, minimum classification of large data streams, minimum resource occupation and time constraints. Experimental comparison compared and evaluated the Load Balancing with big data stream (LBBS), Load Balancing with Heterogeneous Computing (LBHC) and the proposed LBBHD. Compared with the other two algorithms, the proposed algorithm improves workload skewness, throughput and load balancing error respectively about 2.1%, 1.96%, 2.9%, 2.2%; 5.57%. 2.51%.
Primary lung cancer is very heterogeneous in its clinical presentation, histopathology, and treatment response; and like other diseases, the prognosis consists of two essential facets: survival and ...quality of life (QOL). Lung cancer survival is mostly determined by disease stage and treatment modality, and the 5-Year survival rate has been in a plateau of 15% for three decades. QOL is focused on life aspects that are affected by health conditions and medical interventions; the balance of physical functioning and suffering from treatment side effects has long been a concern of care providers as well as patients. Obviously needed are easily measurable biologic markers to stratify patients before treatment for optimal results in survival and QOL and to monitor treatment responses and toxicities. Targeted therapies toward the mechanisms of tumor development, growth, and metastasis are promising and actively translated into clinical practice. Long-term lung cancer (LTLC) survivors are people who are alive 5 Years after the diagnosis. Knowledge about the health and QOL in LTLC survivors is limited because outcome research in lung cancer has been focused mainly on short-term survival. The independent or combined effects of lung cancer treatment, aging, smoking and drinking, comorbid conditions, and psychosocial factors likely cause late effects, including organ malfunction, chronic fatigue, pain, or premature death among lung cancer survivors. New knowledge to be gained should help lung cancer survivors, their healthcare providers, and their caregivers by providing evidence for establishing clinical recommendations to enhance their long-term survival and health-related QOL.
Western blotting is an important technique used in cell and molecular biology. By using a western blot, researchers are able to identify specific proteins from a complex mixture of proteins extracted ...from cells. The technique uses three elements to accomplish this task: (1) separation by size, (2) transfer to a solid support, and (3) marking target protein using a proper primary and secondary antibody to visualize. This paper will attempt to explain the technique and theory behind western blot, and offer some ways to troubleshoot.
Knowledge of pore-water pressure (PWP) variation is fundamental for slope stability. A precise prediction of PWP is difficult due to complex physical mechanisms and in situ natural variability. To ...explore the applicability and advantages of recurrent neural networks (RNNs) on PWP prediction, three variants of RNNs, i.e., standard RNN, long short-term memory (LSTM) and gated recurrent unit (GRU) are adopted and compared with a traditional static artificial neural network (ANN), i.e., multi-layer perceptron (MLP). Measurements of rainfall and PWP of representative piezometers from a fully instrumented natural slope in Hong Kong are used to establish the prediction models. The coefficient of determination (R2) and root mean square error (RMSE) are used for model evaluations. The influence of input time series length on the model performance is investigated. The results reveal that MLP can provide acceptable performance but is not robust. The uncertainty bounds of RMSE of the MLP model range from 0.24 kPa to 1.12 kPa for the selected two piezometers. The standard RNN can perform better but the robustness is slightly affected when there are significant time lags between PWP changes and rainfall. The GRU and LSTM models can provide more precise and robust predictions than the standard RNN. The effects of the hidden layer structure and the dropout technique are investigated. The single-layer GRU is accurate enough for PWP prediction, whereas a double-layer GRU brings extra time cost with little accuracy improvement. The dropout technique is essential to overfitting prevention and improvement of accuracy.
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•A series of RNN variants are applied to PWP prediction for the first time.•The influence of input time series length on model performance is investigated.•RNNs are much more precise and robust than the traditional static MLP model.•RNNs can characterize the time lags between rainfall and PWP responses well.•The effects of the hidden layer structure and dropout technique are discussed.
Polarization vectors of light traveling in a coiled optical fiber rotate around its propagating axis even in the absence of birefringence. This rotation was usually explained due to the ...Pancharatnam-Berry phase of spin-1 photons. Here, we use a purely geometric method to understand this rotation. We show that similar geometric rotations also exist for twisted light carrying orbital angular momentum (OAM). The corresponding geometric phase can be applied in photonic OAM-state-based quantum computation and quantum sensing.
Black garlic is a new garlic product produced through fermentation of fresh garlic and is very popular in Asia countries due to its health benefits. Its key aroma-active compounds were characterized ...by gas chromatography–olfactometry–mass spectrometry (GC-O-MS), gas chromatography–time-of-flight mass spectrometry (GC-TOFMS), and sensory evaluation. In total 52 aroma compounds were identified, and 15 of them with high flavor dilution (FD) factors based on aroma extract dilution analysis (AEDA) were selected and quantitated. Finally, 9 key aroma-active compounds, including acetic acid (sour), allyl methyl trisulfide (cooked garlic), Furaneol (caramel), diallyldisulfide (garlic), diallyltrisulfide (sulfur), (E,Z)-2,6-nonadien-1-ol (cucumber), 3-methylbutanoic acid (sweat), 5-heptyldihydro-2(3H)-furanone (apricot), and diallyl sulfide (garlic), were determined through aroma recombination and omission experiment. In addition to the sulfur-containing compounds, heterocyclic compounds were the major aroma contributors in black garlic. Sensory evaluation revealed that the flavor profile of black garlic mainly consisted of sulfur, sour, sweet, fresh, sauce, gasoline, and roasted odors.
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