ASGPR‐Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes

Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes.     

Role of Scaffolds,Subchondral, Intra-Articular Injections of Fresh Autologous Bone Marrow Concentrate Regenerative Cells in Treating Human Knee Cartilage Lesions: Different Approaches and Different Results

The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review whether joint, subchondral bone, or/and scaffolds implantation of fresh autologous bone marrow aspirate concentrated (BMAC) containing mesenchymal stem cells (MSCs) would improve osteoarthritis (OA). There is in vivo evidence that suggests that all these different approaches (intra-articular injections, subchondral implantation, scaffolds loaded with BMAC) can improve the patient. This review analyzes the evidence for each different approach to treat OA. We found that the use of intra-articular injections resulted in a significant relief of pain symptoms in the short term and was maintained in 12 months. However, the clinical trials indicate that the application of autologous bone marrow concentrates in combination with scaffolds or in injection in the subchondral bone was superior to intra-articular injection for long-term results. The tendency of MSCs to differentiate into fibrocartilage affecting the outcome was a common issue faced by all the studies when biopsies were performed, except for scaffolds implantation in which some hyaline cartilage was found. The review suggests also that both implantation of subchondral BMAC and scaffolds loaded with BMAC could reduce the need for further surgery.     

Determining the Characteristics of Cosmic-Radiation Nuclei in the Sileye Experiment on Board the Mir Orbital Station

An algorithm for reconstructing the characteristics (charge, mass, and energy) of cosmic-radiation nuclei with 20- to 200-MeV/nucleon energies is described. The detector is a telescope of three two-coordinate planes with two 1-mm-thick iron filters inserted between them. Each plane is composed of two strip silicon detectors with 3.6-mm-wide orthogonally oriented strips, an effective area of 6 × 6 cm², and a thickness of 380 m. The algorithm for reconstructing the nuclei characteristics is based on the analysis of how the specific ionization losses change as the nuclei pass through the filter material. The results of the Monte Carlo simulation are presented for the energy dependence of the telescope acceptance and the energy deposited in the detectors by different nuclei in view of the detector calibration on the nuclear beams of the accelerator. The mass resolution of the telescope is 30, 12, and 5% for He, N, and Al nuclei, respectively. The energy resolution, which is 20%, is much the same for all nuclei.     

Impact of nisin producing culture and liposome-encapsulated nisin on ripening of Lactobacillus added-Cheddar cheese

This study aimed to evaluate the effects of incorporating liposome-encapsulated nisin Z, nisin Z producing Lactococcus lactis ssp. lactis biovar. diacetylactis UL719, or Lactobacillus casei-casei L2A adjunct culture into cheese milk on textural, physicochemical and sensory attributes during ripening of Cheddar cheese. For this purpose, cheeses were made using a selected nisin tolerant cheese starter culture. Proteolysis, free fatty acid production, rheological parameters and hydrophilic/hydrophobic peptides evolution were monitored over 6 mo ripening. Sensory quality of cheeses was evaluated after 6 mo. Incorporating the nisin-producing strain into cheese starter culture increased proteolysis and lipolysis but did not significantly affect cheese rheology. Liposome-encapsulated nisin did not appear to affect cheese proteolysis, rheology and sensory characteristics. The nisinogenic strain increased the formation of both hydrophilic and hydrophobic peptides present in the cheese water extract. Sensory assessment indicated that acidic and bitter tastes were enhanced in the nisinogenic strain-containing cheese compared to control cheese. Incorporating Lb. casei and the nisinogenic culture into cheese produced a debittering effect and improved cheese flavor quality. Cheeses with added Lb. casei and liposome-encapsulated nisin Z exhibited the highest flavor intensity and were ranked first for sensory characteristics.     

Quantitative Analysis of Tau-Microtubule Interaction Using FRET

The interaction between the microtubule associated protein, tau and the microtubules is investigated. A fluorescence resonance energy transfer (FRET) assay was used to determine the distance separating tau to the microtubule wall, as well as the binding parameters of the interaction. By using microtubules stabilized with Flutax-2 as donor and tau labeled with rhodamine as acceptor, a donor-to-acceptor distance of 54 ± 1 Å was found. A molecular model is proposed in which Flutax-2 is directly accessible to tau-rhodamine molecules for energy transfer. By titration, we calculated the stoichiometric dissociation constant to be equal to 1.0 ± 0.5 µM. The influence of the C-terminal tails of αβ-tubulin on the tau-microtubule interaction is presented once a procedure to form homogeneous solution of cleaved tubulin has been determined. The results indicate that the C-terminal tails of α- and β-tubulin by electrostatic effects and of recruitment seem to be involved in the binding mechanism of tau.     

Evaluation of Localized Semantics: Data, Methodology, and Experiments

We present a new data set of 1014 images with manual segmentations and semantic labels for each segment, together with a methodology for using this kind of data for recognition evaluation. The images and segmentations are from the UCB segmentation benchmark database (Martin et al., in International conference on computer vision, vol. II, pp. 416–421, 2001). The database is extended by manually labeling each segment with its most specific semantic concept in WordNet (Miller et al., in Int. J. Lexicogr. 3(4):235–244, 1990). The evaluation methodology establishes protocols for mapping algorithm specific localization (e.g., segmentations) to our data, handling synonyms, scoring matches at different levels of specificity, dealing with vocabularies with sense ambiguity (the usual case), and handling ground truth regions with multiple labels. Given these protocols, we develop two evaluation approaches. The first measures the range of semantics that an algorithm can recognize, and the second measures the frequency that an algorithm recognizes semantics correctly. The data, the image labeling tool, and programs implementing our evaluation strategy are all available on-line (kobus.ca//research/data/IJCV_2007). We apply this infrastructure to evaluate four algorithms which learn to label image regions from weakly labeled data. The algorithms tested include two variants of multiple instance learning (MIL), and two generative multi-modal mixture models. These experiments are on a significantly larger scale than previously reported, especially in the case of MIL methods. More specifically, we used training data sets up to 37,000 images and training vocabularies of up to 650 words. We found that one of the mixture models performed best on image annotation and the frequency correct measure, and that variants of MIL gave the best semantic range performance. We were able to substantively improve the performance of MIL methods on the other tasks (image annotation and frequency correct region labeling) by providing an appropriate prior.     

Stumbling blocks to the practice of health psychology: A Canadian perspective.

Argues that Canadian provincial legislation regulating the practice of medicine ignores the common goals of medicine and health psychology and therefore may impede the practice of health psychology in Canada. It is suggested that the contributions made by health psychology practitioners in the treatment of physical injuries or diseases be recognized. (French abstract) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Waterpipe smoking: construction and validation of the Lebanon Waterpipe Dependence Scale (LWDS-11).

Waterpipe smoking is becoming fashionable in Lebanon, but no studies have studied nicotine dependence related to waterpipe smoking. A score was constructed from 21 items and subsequently submitted to two factor analyses, which led to the extraction of four factors. Reliability and test-retest reproducibility were measured. Convergent construct validity and discriminant validity also were assessed for different smokers' samples. The Lebanon Waterpipe Dependence Scale-11 (LWDS-11) was composed of four subscales, the first representing nicotine dependence, the second negative reinforcement, the third psychological craving, and the fourth positive reinforcement. Internal consistency and test-retest reproducibility were adequate, and the subscales correlated adequately with measurements of nicotine metabolites, exhaled carbon monoxide levels, and the frequency of waterpipe smoking. The LWDS-11 discriminated between mild, moderate, and heavy waterpipe smokers, based on a threshold score of 10. Results were biologically and psychologically sound. This is the first scale to characterize waterpipe dependence. With further improvement and confirmation, it could become a useful clinical and epidemiological tool.