Chemical Synthesis and Biological Applications of O-GlcNAcylated Peptides and Proteins

All human cells use O-GlcNAc protein modifications (O-linked N-acetylglucosamine) to rapidly adapt to changing nutrient and stress conditions through signaling, epigenetic, and proteostasis mechanisms. A key challenge for biologists in defining precise roles for specific O-GlcNAc sites is synthetic access to homogenous isoforms of O-GlcNAc proteins, a result of the non-genetically templated, transient, and heterogeneous nature of O-GlcNAc modifications. Toward a solution, this review details the state of the art of two strategies for O-GlcNAc protein modification: advances in “bottom-up” O-GlcNAc peptide synthesis and direct “top-down” installation of O-GlcNAc on full proteins. We also describe key applications of synthetic O-GlcNAc peptide and protein tools as therapeutics, biophysical structure–function studies, biomarkers, and as disease mechanistic probes to advance translational O-GlcNAc biology.     

Entrepreneurship and the carbon market: opportunities and challenges for South African entrepreneurs

The Kyoto Protocol and its implementation brought forward issues of climate change and its mitigation strategy by national measures through the creation of market mechanisms in carbon trading. The trading of emission certificates has become an important trade commodity worldwide, and its markets have diversified. While this opportunity has created new markets for entrepreneurs and actors that range from farmers to brokers, unequal involvement in most developing countries is noted. This has been mostly observed in those countries where entrepreneurship is often regarded as the cornerstone of economic growth and social improvement. South Africa has spearheaded other African countries in its implementation of Clean Development Mechanism (CDM) projects leading to carbon trading. Based on our research on South African entrepreneurship and its involvement in the carbon market, we conclude that albeit a number of opportunities, the biggest challenge for entrepreneurial participation in the carbon market remains in the nature and processes of CDM project implementation, the lack of a clear supportive system, limited access to financing and—more importantly—general ignorance of the trading opportunities by entrepreneurs. The complex nature of CDM projects themselves limits participation due to lack of the necessary skills on the national level leading to uneven distribution of CDM projects on provincial levels in South Africa. Recommendations are provided to overcome the obstacles and to promote entrepreneurial activity in the carbon market.     

Estimating shear properties of walnut wood: a combined experimental and theoretical approach

In this study, several theoretical models to numerically estimate shear properties of orthotropic materials are introduced. These approaches are based on the combination of Hankinson’s empirically derived formula with other empirical and analytical calculations. Next to shear moduli, which are estimated from the elastic moduli and Poisson’s ratios, shear strengths are also estimated from the in-axis strengths. The models are validated by mechanical tests on walnut wood (Juglans regia L.), for which a sufficient data set can be found in literature. The Arcan test is used to estimate the shear moduli, while the shear block test is used to estimate the shear strengths. The results show that the model, which is based on a combined use of Hankinson’s formula and tensor rotation, gives the best estimation of shear moduli as evaluated by the minimum differences to the experimentally obtained results. For the shear strengths, a combination of Hankinson’s formula and Norris’ failure criterion shows the best agreement in comparison to the experimental data. The theoretical calculations may be used for a time efficient estimation of shear modulus and strength in comparison to the very time-consuming experimental estimation.     

Photoacoustic‐Guided Surgery with Indocyanine Green‐Coated Superparamagnetic Iron Oxide Nanoparticle Clusters

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real‐time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles—with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20–30% of the total weight (ICG + SPIO). The ICG–SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG–SPIO clusters, animals undergoing PA‐guided surgery demonstrate increased progression‐free survival compared to animals undergoing microscopic surgery.     

A Data‐driven Segmentation for the Shoulder Complex

The human shoulder complex is perhaps the most complicated joint in the human body being comprised of a set of three bones, muscles, tendons, and ligaments. Despite this anatomical complexity, computer graphics models for motion capture most often represent this joint as a simple ball and socket. In this paper, we present a method to determine a shoulder skeletal model that, when combined with standard skinning algorithms, generates a more visually pleasing animation that is a closer approximation to the actual skin deformations of the human body. We use a data‐driven approach and collect ground truth skin deformation data with an optical motion capture system with a large number of markers (200 markers on the shoulder complex alone). We cluster these markers during movement sequences and discover that adding one extra joint around the shoulder improves the resulting animation qualitatively and quantitatively yielding a marker set of approximately 70 markers for the complete skeleton. We demonstrate the effectiveness of our skeletal model by comparing it with ground truth data as well as with recorded video. We show its practicality by integrating it with the conventional rendering/animation pipeline.     

Cognitive-bias toward gaming-related words and disinhibition in World of Warcraft gamers

This study investigated cognitive biases toward gaming-related words and differences in cognitive performance among twelve World of Warcraft players (WWP) and thirty non-players (NP). We measured response to valenced common English and WoW jargon words using a computer-based go/no-go task. Sometimes positive valence words were the targets for the ‘go’ response, with negative-valence words as the distracters, sometimes the reverse. Target discrimination (d′) and response disinhibition (C) were calculated using a signal detection analysis. Based on questionnaire responses, there were no differences between groups in depression, anxiety, smoking or drinking, but WWP reported significantly more screen and gaming time (17.31 h/week versus 4.12 among NP). WWP had faster reaction time (RT) and better discrimination of targets from distracters (high d′) but also showed higher disinhibition (low C). WWP also showed cognitive-bias toward game-related words in the form of higher d′ for WoW jargon than common English and more disinhibition to positive-valence WoW jargon. Similar to past studies which have found alcoholics to have cognitive biases toward alcohol-related words, WWP who play frequently showed cognitive biases toward words related to the World of Warcraft game.     

Exploring alternatives for transition verification

When an implementation under test (IUT) is state-based, and its expected abstract behavior is given in terms of a finite state machine (FSM), a checking sequence generated from a specification FSM and applied to an IUT for testing can provide us with high-level confidence in the correct functional behavior of our implementation. One of the issues here is to generate efficient checking sequences in terms of their lengths. As a major characteristics, a checking sequence must contain all β-sequences for transition verification. In this paper, we discuss the possibility of reducing the lengths of checking sequences by making use of the invertible transitions in the specification FSM to increase the choice of β-sequences to be considered for checking sequence generation. We present a sufficient condition for adopting alternative β-sequences and illustrate typical ways of incorporating these alternative β-sequences into existing methods for checking sequence generation to reduce the lengths. Compared to the direct use of three existing methods, our experiments show that most of the time the saving gained by adopting alternative β-sequences falls in the range of 10–40%.     

Benchmarking stereo-derived DSMs to lidar by land cover and slope for resource development in northern Ontario,Canada

Topographic and elevation data are essential in the development of supporting infrastructure around mining sites. The de facto standard for acquiring elevation data is through light detection and ranging (lidar). The high labour and monetary cost of acquiring lidar has fostered more cost-effective approaches for creating elevation models that use stereo photogrammetry. To assess the accuracy of stereo-photogrammetry-derived elevation models and their potential application, we benchmark satellite (Worldview-2) and aircraft (South Central Ontario Orthoimagery Project; SCOOP) stereo-derived digital surface models (DSMs) against a lidar-derived DSM. Our results show that both stereo-derived DSMs have strong monotonic correlations with lidar across a range of land-cover types and slopes. The overall vertical accuracy of Worldview-2 and SCOOP DSMs are similar and do not meet the United States National Digital Elevation Program (NDEP) standards. However, accuracy assessment across land-cover types and slope categories show that specific land cover types (i.e. grass, row crops/pasture, sparse vegetation and marsh) on gently sloping terrain compare well to lidar data and meet NDEP accuracy standards. We situate the presented research in the context of northern resource development and discuss opportunities to improve the vertical accuracy of stereo-derived DSMs, for example, through unmanned aerial systems.     

Modeling the glucose regulatory system in extreme preterm infants

Background

Premature infants represent a significant proportion of the neonatal intensive care population. Blood glucose homeostasis in this group is often disturbed by immaturity of endogenous regulatory systems and the stress of their condition. Hypo- and hyperglycemia are frequently reported in very low birth weight infants, and more mature infants often experience low levels of glycemia. A model capturing the unique fundamental dynamics of the neonatal glucose regulatory system could be used to develop better blood glucose control methods.

Methods

A metabolic system model is adapted from adult critical care to the unique physiological case of the neonate. Integral-based fitting methods were used to identify time-varying insulin sensitivity and non-insulin mediated glucose uptake profiles. The clinically important predictive ability of the model was assessed by assuming insulin sensitivity was constant over prediction intervals of 1, 2 and 4 h forward and comparing model-simulated versus actual clinical glucose values for all recorded interventions. The clinical data included 1091 glucose measurements over 3567 total patient hours, along with all associated insulin and nutritional infusion data, for N = 25 total cases. Ethics approval was obtained from the Upper South A Regional Ethics Committee for this study.

Results

The identified model had a median absolute percentage error of 2.4% [IQR: 0.9-4.8%] between model-fitted and clinical glucose values. Median absolute prediction errors at 1-, 2- and 4-h intervals were 5.2% [IQR: 2.5-10.3%], 9.4% [IQR: 4.5-18.4%] and 13.6% [IQR: 6.3-27.6%] respectively.

Conclusions

The model accurately captures and predicts the fundamental dynamic behaviors of the neonatal metabolism well enough for effective clinical decision support in glycemic control. The adaptation from adult to a neonatal case is based on the data from the literature. Low prediction errors and very low fitting errors indicate that the fundamental dynamics of glucose metabolism in both premature neonates and critical care adults can be described by similar mathematical models.