Stereoselectivity in the Diels‐Alder Cycloadditions of a Facially Dissymmetric Bicyclo[2.2.2]octadiene‐Grafted Maleic Anhydride with Exocyclic Butadienes. Unexpected Facial Selectivity in the Cycloaddition with 2,3,5,6‐tetramethylidenebicyclo[2.2.2]octene

The Diels‐Alder cycloadditions of facially dissymmetric maleic anhydride 1 with facially nonequivalent exocyclic 1,3‐butadienes(dimethylidenebicyclo[2.2.2]octene 3 and 2,3,5,6‐tetramethylidenebicyclo[2.2.2]‐octene ( 4 )) were investigated. In each cycloaddition, the reaction occurred via the course in which 1 added exclusively by its syn‐face (same face as the etheno‐bridge) onto either π‐face of the exocyclic 1,3‐butadiene systems to produce only two of the four possible stereoisomeric monocycloadducts ( 8a / 8b and 9a / 9b ). In the Diels‐Alder cycloaddition of 1 with bis‐exocyclic butadiene 4 , however, both monocycloadducts 9a and 9b underwent subsequent cycloaddition with distinctive facial selectivity to produce the C_s‐symmetric bis‐cyclohexanobarrelene 10a as only bis‐cycloadduct.     

Complex systems and human movement

Human movement reveals the hall mark characteristics of complex systems: namely, many interacting subsystems, multiple interactions within and between levels of analysis, emergence of movement coordination modes, and the exhibition of varying levels of the complexity of system output that continually evolve with learning and development over the life span. Here we outline how this high or infinitely dimensional complex dynamical system can be modeled by an epigenetic landscape framework—in the sense of Waddington—that captures the key features of the adaptive qualitative and quantitative properties of coordination modes (“order parameters”), the degeneracy of movement organization and the time scales of change. The framework provides some new ways to consider old problems in motor learning and development—such as an explicit and quantitative approach to exploring the concept of motor programs and developmental pathways—and yields new results and insights into the organization of learning during practice and rest times. For instance along one dimension of the landscape most of the changes occur between practice sessions. © 2006 Wiley Periodicals, Inc. Complexity 12: 40–51, 2006     

Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats

Background: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. Methods: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats’ stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity. Results: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R²Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q²Y) of −0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R²Y value of 0.726 and Q²Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. Conclusion: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.     

Designing Upconversion Nanocrystals Capable of 745 nm Sensitization and 803 nm Emission for Deep‐Tissue Imaging

A crystal design strategy is described that generates hexagonal‐phased NaYF₄:Nd/Yb@NaYF₄:Yb/Tm luminescent nanocrystals with the ability to emit light at 803 nm when illuminated at 745 nm. This is accomplished by taking advantage of the large absorption cross‐section of Nd³⁺ between 720 and 760 nm plus efficient spatial energy transfer and migration through Nd³⁺→Yb³⁺→Yb³⁺→Tm³⁺. Mechanistic investigations suggest that a cascaded two‐photon energy transfer upconversion process underlies the emission mechanism. This protocol enables deep‐tissue imaging to be achieved while mitigating the attenuation effect associated with the visible emission and the overheating constraint imposed by conventional 980 nm excitation.     

Raman endoscopy for in vivo differentiation between benign and malignant ulcers in the stomach

The aim of this study was to evaluate the clinical utility of an image-guided Raman endoscopy technique for in vivo differential diagnosis of benign and malignant ulcerous lesions in the stomach. A rapid-acquisition image-guided Raman endoscopy system with 785 nm laser excitation has been developed to acquire in vivo gastric tissue Raman spectra within 0.5 s during clinical gastroscopic examinations. A total of 1102 in vivo Raman spectra were acquired from 71 gastric patients, in which 924 Raman spectra were from normal tissue, 111 Raman spectra were from benign ulcers whereas 67 Raman spectra were from ulcerated adenocarcinoma. There were distinctive spectral differences in Raman spectra among normal mucosa, benign ulcers and malignant ulcers, particularly in the spectral ranges of 800-900, 1000-1100, 1245-1335, 1440-1450 and 1500-1800 cm(-1), which primarily contain signals related to proteins, DNA, lipids and blood. The malignant ulcerous lesions showed Raman signals to be mainly associated with abnormal nuclear activity and decrease in lipids as compared to benign ulcers. Partial least squares-discriminant analysis (PLS-DA) was employed to generate multi-class diagnostic algorithms for classification of Raman spectra of different gastric tissue types. The PLS-DA algorithms together with leave-one tissue site-out, cross validation technique yielded diagnostic sensitivities of 90.8%, 84.7%, 82.1%, and specificities of 93.8%, 94.5%, 95.3%, respectively, for classification of normal mucosa, benign and malignant ulcerous lesions in the stomach. This work demonstrates that image-guided Raman endoscopy technique associated with PLS-DA diagnostic algorithms has for the first time promising clinical potential for rapid, in vivo diagnosis and detection of malignant ulcerous gastric lesions at the molecular level.