Population pharmacokinetics of nitroglycerin and of its two metabolites after a single 24-hour application of a nitroglycerin transdermal matrix delivery system

OBJECTIVES: To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs. STUDY DESIGN: Prospective controlled study. ANIMAL POPULATION: A total of 15 purpose-bred beagles and 17 client-owned dogs. METHODS: CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay. RESULTS: Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 +/- 2.0 pg/mL and 3.61 +/- 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 +/- 0.86 pg/mL and 6.80 +/- 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls (P < .005 and P < .0001 respectively). CONCLUSIONS: Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs. CLINICAL RELEVANCE: In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.     

An effective hybrid approach of desirability,fuzzy logic,ANFIS and LAPO algorithm for optimizing compliant mechanism

This paper proposes an efficient hybrid approach for solving multi-objective optimization design of a compliant mechanism. The approach is developed by integrating desirability function approach, fuzzy logic system, adaptive neuro-fuzzy inference system, and Lightning attachment procedure optimization. Box–Behnken design is used to form a numerically experimental matrix. First, a refinement of design variables is conducted through analysis of variance and Taguchi approach in terms of considerably eliminating space of design variables and computation efforts. Next, desirability of two objective functions is computed and transferred into the fuzzy logic system. The output of fuzzy logic system is regarded as single combined objective function. Subsequently, a modeling for fuzzy output is developed via adaptive neuro-fuzzy inference system. Then, LAPO algorithm is adopted for solving the optimization problem. By investigating three different numerical examples, performance of the proposed approach is validated. Numerical results revealed that the proposed approach has a computational accuracy better than that of Taguchi-based fuzzy logic reasoning. Finally, case study 1 is chosen as an optimal solution for the mechanism. Furthermore, the effectiveness of proposed approach is greater than that of the Jaya algorithm and TLBO algorithm through Wilcoxon signed rank test and Friedman test. The proposed approach can be used for related engineering fields.

     

Application of genetic algorithm-based intuitionistic fuzzy weighted c-ordered-means algorithm to cluster analysis

Knowledge and Information Systems - With the advance of information technology, many fields have begun using data clustering to reveal data structures and obtain useful information. Most of the...     

Integrating local action elements for action analysis

In this paper, we propose a framework for human action analysis from video footage. A video action sequence in our perspective is a dynamic structure of sparse local spatial–temporal patches termed action elements, so the problems of action analysis in video are carried out here based on the set of local characteristics as well as global shape of a prescribed action. We first detect a set of action elements that are the most compact entities of an action, then we extend the idea of Implicit Shape Model to space time, in order to properly integrate the spatial and temporal properties of these action elements. In particular, we consider two different recipes to construct action elements: one is to use a Sparse Bayesian Feature Classifier to choose action elements from all detected Spatial Temporal Interest Points, and is termed discriminative action elements. The other one detects affine invariant local features from the holistic Motion History Images, and picks up action elements according to their compactness scores, and is called generative action elements. Action elements detected from either way are then used to construct a voting space based on their local feature representations as well as their global configuration constraints. Our approach is evaluated in the two main contexts of current human action analysis challenges, action retrieval and action classification. Comprehensive experimental results show that our proposed framework marginally outperforms all existing state-of-the-arts techniques on a range of different datasets.     

Floral volatiles ofTanacetum vulgare L. attractive toLobesia botrana den. et schiff. females

The European grapevine moth (EGVM),Lobesia botrana, is a major pest of grapes in Europe. Females are attracted to a nonhost plant: tansy (Tanacetum vulgare L.), which is a common weed in Slovakian vineyards. A steam distillate extract of tansy flowers was analyzed by means of a GC-EAG technique to screen constituents detected by the olfactory receptors of EGVM females. From more than 200 GC peaks, nine peaks corresponding to monoterpenoids released an EAG response in more than 70% of the females (N=15):p-cymene,d-limonene,-thujene,-thujone,-thujone, thujyl alcohol, terpinene-4-ol, (Z)-verbenol, and piperitone. The steam distillate of tansy as well as a synthetic blend of identified compounds released consistent attraction in a field cage. The use of nonhost plants and host plant odors in integrated pest management is discussed.     

Na+ and/or Cl− Toxicities Determine Salt Sensitivity in Soybean (Glycine max (L.) Merr.), Mungbean (Vigna radiata (L.) R. Wilczek), Cowpea (Vigna unguiculata (L.) Walp.), and Common Bean (Phaseolus vulgaris L.)

Grain legumes are important crops, but they are salt sensitive. This research dissected the responses of four (sub)tropical grain legumes to ionic components (Na⁺ and/or Cl⁻) of salt stress. Soybean, mungbean, cowpea, and common bean were subjected to NaCl, Na⁺ salts (without Cl⁻), Cl⁻ salts (without Na⁺), and a “high cation” negative control for 57 days. Growth, leaf gas exchange, and tissue ion concentrations were assessed at different growing stages. For soybean, NaCl and Na⁺ salts impaired seed dry mass (30% of control), more so than Cl⁻ salts (60% of control). All treatments impaired mungbean growth, with NaCl and Cl⁻ salt treatments affecting seed dry mass the most (2% of control). For cowpea, NaCl had the greatest adverse impact on seed dry mass (20% of control), while Na⁺ salts and Cl⁻ salts had similar intermediate effects (~45% of control). For common bean, NaCl had the greatest adverse effect on seed dry mass (4% of control), while Na⁺ salts and Cl⁻ salts impaired seed dry mass to a lesser extent (~45% of control). NaCl and Na⁺ salts (without Cl⁻) affected the photosynthesis (P_n) of soybean more than Cl⁻ salts (without Na⁺) (50% of control), while the reverse was true for mungbean. Na⁺ salts (without Cl⁻), Cl⁻ salts (without Na⁺), and NaCl had similar adverse effects on P_n of cowpea and common bean (~70% of control). In conclusion, salt sensitivity is predominantly determined by Na⁺ toxicity in soybean, Cl⁻ toxicity in mungbean, and both Na⁺ and Cl⁻ toxicity in cowpea and common bean.     

One-Step Generation of Multiple Gene-Edited Pigs by Electroporation of the CRISPR/Cas9 System into Zygotes to Reduce Xenoantigen Biosynthesis

Xenoantigens cause hyperacute rejection and limit the success of interspecific xenografts. Therefore, genes involved in xenoantigen biosynthesis, such as GGTA1, CMAH, and B4GALNT2, are key targets to improve the outcomes of xenotransplantation. In this study, we introduced a CRISPR/Cas9 system simultaneously targeting GGTA1, CMAH, and B4GALNT2 into in vitro-fertilized zygotes using electroporation for the one-step generation of multiple gene-edited pigs without xenoantigens. First, we optimized the combination of guide RNAs (gRNAs) targeting GGTA1 and CMAH with respect to gene editing efficiency in zygotes, and transferred electroporated embryos with the optimized gRNAs and Cas9 into recipient gilts. Next, we optimized the Cas9 protein concentration with respect to the gene editing efficiency when GGTA1, CMAH, and B4GALNT2 were targeted simultaneously, and generated gene-edited pigs using the optimized conditions. We achieved the one-step generation of GGTA1/CMAH double-edited pigs and GGTA1/CMAH/B4GALNT2 triple-edited pigs. Immunohistological analyses demonstrated the downregulation of xenoantigens; however, these multiple gene-edited pigs were genetic mosaics that failed to knock out some xenoantigens. Although mosaicism should be resolved, the electroporation technique could become a primary method for the one-step generation of multiple gene modifications in pigs aimed at improving pig-to-human xenotransplantation.     

Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b′a′ Domain

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b′a′ domain of protein disulfide isomerase (PDIb′a′) greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb′a′-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC₅₀ of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells.     

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.     

A technique for extracting behavioral sequence patterns from GPS recorded data

The mobile wireless market has been attracting many customers. Technically, the paradigm of anytime-anywhere connectivity raises previously unthinkable challenges, including the management of million of mobile customers, their profiles, the profiles-based selective information dissemination, and server-side computing infrastructure design issues to support such a large pool of users automatically and intelligently. In this paper, we propose a data mining technique for discovering frequent behavioral patterns from a collection of trajectories gathered by Global Positioning System. Although the search space for spatiotemporal knowledge is extremely challenging, imposing spatial and temporal constraints on spatiotemporal sequences makes the computation feasible. Specifically, the mined patterns are incorporated with synthetic constraints, namely spatiotemporal sequence length restriction, minimum and maximum timing gap between events, time window of occurrence of the whole pattern, inclusion or exclusion event constraints, and frequent movement patterns predictive of one ore more classes. The algorithm for mining all frequent constrained patterns is named cAllMOP. Moreover, to control the density of pattern regions a clustering algorithm is exploited. The proposed method is efficient and scalable. Its efficiency is better than that of the previous algorithms AllMOP and GSP with respect to the compactness of discovered knowledge, execution time, and memory requirement.