Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial enzymatic digestion of the surrounding tissue: evaluation in an in vivo rabbit model

Articular cartilage defects are a significant source of pain, have limited ability to heal, and can lead to the development of osteoarthritis. However, a surgical solution is not available. To tackle this clinical problem, non-degradable implants capable of carrying mechanical load immediately after implantation and for the duration of implantation, while integrating with the host tissue, may be viable option. But integration between articular cartilage and non-degradable implants is not well studied. Our objective was to assess the in vivo performance of a novel macroporous, nondegradable, polyvinyl alcohol construct. We hypothesized that matrix generation within the implant would be enhanced with partial digestion of the edges of articular cartilage. Our hypothesis was tested by randomizing an osteochondral defect created in the trochlea of 14 New Zealand white rabbits to treatment with: (i) collagenase or (ii) saline, prior to insertion of the implant. At 1 and 3-month post-operatively, the gross morphology and histologic appearance of the implants and the surrounding tissue were assessed. At 3 months, the mechanical properties of the implant were also quantified. Overall, the hydrogel implants performed favorably; at all time-points and in all groups the implants remained well fixed, did not cause inflammation or synovitis, and did not cause extensive damage to the opposing articular cartilage. Regardless of treatment with saline or collagenase, at 1 month post-operatively implants from both groups had a contiguous interface with adjacent cartilage and were populated with chondrocyte-like cells. At 3 months fibrous encapsulation of all implants was evident, there was no difference between area of aggrecan staining in the collagenase versus saline groups, and implant modulus was similar in both groups; leading us to reject our hypothesis. In summary, a porous PVA osteochondral implant remained well fixed in a short term in vivo osteochondral defect model; however, matrix generation within the implant was not enhanced with partial digestion of adjacent articular cartilage.     

GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract

Nutritional research is currently entering the field of personalized nutrition, to a large extent driven by major technological breakthroughs in analytical sciences and biocomputing. An efficient launching of the personalized approach depends on the ability of researchers to comprehensively monitor and characterize interindividual variability in the activity of the human gastrointestinal tract. This information is currently not available in such a form. This review therefore aims at identifying and discussing published data, providing evidence on interindividual variability in the processing of the major nutrients, i.e., protein, fat, carbohydrates, vitamins, and minerals, along the gastrointestinal tract, including oral processing, intestinal digestion, and absorption. Although interindividual variability is not a primary endpoint of most studies identified, a significant number of publications provides a wealth of information on this topic for each category of nutrients. This knowledge remains fragmented, however, and understanding the clinical relevance of most of the interindividual responses to food ingestion described in this review remains unclear. In that regard, this review has identified a gap and sets the base for future research addressing the issue of the interindividual variability in the response of the human organism to the ingestion of foods.     

Survival of Salmonella Enteritidis PT 30 on inoculated almond kernels in hot water treatments

Almonds are blanched by exposure to hot water or steam-injected water to remove the pellicle (skin) from the kernel. This study evaluated the survival of Salmonella Enteritidis PT 30, Salmonella Senftenberg 775W and Enterococcus faecalis on whole raw almond kernels exposed to hot water. Whole, inoculated (7 to 9 log CFU/g) Nonpareil almonds (40 g) were submerged in 25 L of water maintained at 60, 70, 80 and 88 °C. Almonds were heated for up to 12 min, drained for 2 s, and transferred to 80 mL of cold (4 °C) tryptic soy broth. Almonds in broth were stomached at high speed for 2 min, serially diluted, plated onto tryptic soy and bismuth sulfite agars (Salmonella) or bile esculin agar (Enterococcus) and incubated at 37 °C for 24 and 48 h, respectively. D values of 2.6, 1.2, 0.75 and 0.39 min were calculated for exposure of S. Enteritidis PT 30 to water at 60, 70, 80 and 88 °C, respectively; the calculated z value was 35 C°. D values determined for Salmonella Senftenberg 775W and E. faecalis at 88 °C were 0.37 and 0.36 min, respectively. Neither Salmonella serovar could be recovered by enrichment of 1-g samples after almonds inoculated at 5 log CFU/g were heated at 88 °C for 2 min. These data will be useful to validate almond industry blanching processes.     

Direct Determination of Energy Band Alignments of Ni/Al2O3/GaN MOS Structures Using Internal Photoemission Spectroscopy

The energy band alignments of Ni/Al₂O₃/GaN heterostructures have been explored by internal photoemission (IPE) and capacitance–voltage (CV) measurements. By performing IPE measurements at both reverse- and forward-bias conditions, the Ni/Al₂O₃ Schottky barrier is found to be 2.9 ± 0.1 eV with the presence of a strong image force lowering effect, while the Al₂O₃/GaN conduction-band offset is determined to be 2.2 ± 0.1 eV and is insensitive to oxide electrical field. CV-based flat-band voltage analysis has further been performed on samples with different oxide thicknesses, not only confirming the IPE-measured band alignment but also revealing the presence of 3.0 × 10¹² cm^-2 net positive charge at the Al₂O₃/GaN interface.     

The Flexible Rare Event Sampling Harness System (FRESHS)

We present the software package FRESHS (http://www.freshs.org) for parallel simulation of rare events using sampling techniques from the ‘splitting’ family of methods. Initially, Forward Flux Sampling (FFS) and Stochastic Process Rare Event Sampling (SPRES) have been implemented. These two methods together make rare event sampling available for both quasi-static and full non-equilibrium regimes. Our framework provides a plugin system for software implementing the underlying physics of the system of interest. At present, example plugins exist for our framework to steer the popular MD packages GROMACS, LAMMPS and ESPResSo, but due to the simple interface of our plugin system, it is also easy to attach other simulation software or self-written code. Use of our framework does not require recompilation of the simulation program. The modular structure allows the flexible implementation of further sampling methods or physics engines and creates a basis for objective comparison of different sampling algorithms.     

The Feline Josephus Problem

In the classic Josephus problem, elements 1,2,…,n are placed in order around a circle and a skip value k is chosen. The problem proceeds in n rounds, where each round consists of traveling around the circle from the current position, and selecting the kth remaining element to be eliminated from the circle. After n rounds, every element is eliminated. Special attention is given to the last surviving element, denote it by j. We generalize this popular problem by introducing a uniform number of lives ℓ, so that elements are not eliminated until they have been selected for the ℓth time. We prove two main results: 1) When n and k are fixed, then j is constant for all values of ℓ larger than the nth Fibonacci number. In other words, the last surviving element stabilizes with respect to increasing the number of lives. 2) When n and j are fixed, then there exists a value of k that allows j to be the last survivor simultaneously for all values of ℓ. In other words, certain skip values ensure that a given position is the last survivor, regardless of the number of lives. For the first result we give an algorithm for determining j (and the entire sequence of selections) that uses O(n ²) arithmetic operations.     

The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well‐known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, is described. In a previous study, replacement of the naturally occurring N‐methyl group in the 6′‐position with an N‐ethylaminocarbonyl was shown to promote cell‐cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9′‐position, regioselective O‐demethylation to reveal a free phenol in the 7‐position, and reduction of the lactone to the corresponding cyclic ether in the 1‐position. The incorporation of new aryl substituents in the 9′‐position was also investigated. The study identified interesting new compounds able to induce G2/M cell‐cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF‐7, and the human pancreatic epithelioid carcinoma cell line PANC‐1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6′‐ethylaminocarbonyl along with 9′‐chloro, 7‐hydroxy and lactone moieties exhibited the most promising biological activities, with EC₅₀ values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.