Identification of N epsilon-Carboxymethyllysine as a Degradation Product of Fructoselysine in Glycated Protein

The chemistry of Maillard or browning reactionosf glycated proteins was studied using the model compound, Nu-formyl-W-fructoselysine(f FL), an analog of glycated lysine residues in protein. Incubation of fFL (15 mM) at physiological pH and temperature in 0.2 M phosphate buffer resulted in formation of lVcarboxymethyllysine (CML) in about 40% yield after 15 days. CML was formed by oxidative cleavage of fFL between C-2 and C-3 of the carbohydrate chain and erythronic acid (EA) was identified a s , the split product formed in the reaction. Neither CML nor EA was formed from fFL under a nitrogen atmosphere. The rate of formation of CML was dependent on phosphate concentration in the incubation mixture and the reaction was shown to occur by a free radical mechanism. CML was also identified by amino acid analysis in hydrolysates of both poly-L-lysine and bovine pancreatic ribonuclease glycated in phosphate buffer under air. CML was also detected in human lens proteins and tissue collagens by HPLC and the identification was confirmed by gas chromatography/mass spectroscopy. The presence of both CML and EA in human urine suggests that they are formed by degradation of glycated proteins in vivo. The browning of fFL incubation mixtures proceeded to a greater extent under a nitrogen versus an air atmosphere, suggesting that oxidative degradation of Amadori adducts to form CML may limit the browning reactions of glycated proteins. Since the reaction products, CML and EA, are relatively inert, both chemically and metabolically, oxidative cleavage of Amadori adducts may have a role in limiting the consequences of protein glycation in the body

Distance‐based time series classification approach for task recognition with application in surgical robot autonomy

BackgroundRobotic‐assisted surgery allows surgeons to perform many types of complex operations with greater precision than is possible with conventional surgery. Despite these advantages, in current systems, a surgeon should communicate with the device directly and manually. To allow the robot to adjust parameters such as camera position, the system needs to know automatically what task the surgeon is performing.MethodsA distance‐based time series classification framework has been developed which measures dynamic time warping distance between temporal trajectory data of robot arms and classifies surgical tasks and gestures using a k‐nearest neighbor algorithm.ResultsResults on real robotic surgery data show that the proposed framework outperformed state‐of‐the‐art methods by up to 9% across three tasks and by 8% across gestures.ConclusionThe proposed framework is robust and accurate. Therefore, it can be used to develop adaptive control systems that will be more responsive to surgeons’ needs by identifying next movements of the surgeon. Copyright © 2016 John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138333/1/rcs1766.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138333/2/rcs1766_am.pd

Oxidative Degradation of Glucose Adducts to Protein: Formation of 3-(N\u3csup\u3ee\u3c/sup\u3e-Lysino)-Lactic Acid from Model Compounds and Glycated Proteins

The chemistry of Maillard or browning reactions of glycated proteins is being studied in model systems in vitro in order to characterize potential reaction pathways and products in biological systems. In previous work with the Amadori rearrangement product N alpha-formyl-N epsilon-fructoselysine (fFL), an analog of glycated lysine residues in proteins, we showed that fFL was oxidatively cleaved between C-2 and C-3 of the carbohydrate chain to yield N epsilon-carboxymethyllysine (CML) and D-erythronic acid. We then detected CML in proteins glycated in vitro, as well as in human lens proteins and collagen in vivo (Ahmed, M. U., Thorpe, S. R., and Baynes, J. W. (1986) J. Biol. Chem. 261, 4889-4894). This work provided an explanation for the origin of CML in human urine and evidence for non-browning pathways of the Maillard reaction in vivo. In this report we describe the identification of a second set of products resulting from oxidative cleavage of fFL between C-3 and C-4 of the sugar chain, i.e. 3-(N epsilon-lysino)-lactic acid (LL) and D-glyceric acid. The formation of LL from fFL was increased at slightly acid pH, representing about 30% of the yield of CML at pH 6.4, compared with 4% at pH 7.4 in phosphate buffer. By gas chromatography-mass spectroscopy, LL was detected in proteins glycated in vitro and then identified as a natural product in human lens proteins and urine. Our results indicate that oxidative degradation of Amadori adducts toproteins occurs in vivo, leading to formation and excretion of CML and LL. These non-browning pathways for reaction of Amadori compounds may be physiologically relevant mechanisms for averting potentially damaging consequences of the Maillard reaction

Automated robot‐assisted surgical skill evaluation: Predictive analytics approach

BackgroundSurgical skill assessment has predominantly been a subjective task. Recently, technological advances such as robot‐assisted surgery have created great opportunities for objective surgical evaluation. In this paper, we introduce a predictive framework for objective skill assessment based on movement trajectory data. Our aim is to build a classification framework to automatically evaluate the performance of surgeons with different levels of expertise.MethodsEight global movement features are extracted from movement trajectory data captured by a da Vinci robot for surgeons with two levels of expertise – novice and expert. Three classification methods – k‐nearest neighbours, logistic regression and support vector machines – are applied.ResultsThe result shows that the proposed framework can classify surgeons’ expertise as novice or expert with an accuracy of 82.3% for knot tying and 89.9% for a suturing task.ConclusionThis study demonstrates and evaluates the ability of machine learning methods to automatically classify expert and novice surgeons using global movement features.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141457/1/rcs1850.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141457/2/rcs1850_am.pd

Ionic Liquid-Based Microemulsions in Catalysis

The design and properties of surface-active ionic liquids that are able to form stable microemulsions with heptane and water are presented, and their promise as reaction media for thermomorphic palladium-catalyzed cross-coupling reactions is demonstrated

On Research Challenges in Hybrid Medium Access Control Protocols for IEEE 802.15.6 WBANs

IEEE 802.15.6 is a Wireless Body Area Network (WBAN) standard proposed to facilitate the exponentially growing interest in the field of health monitoring. This standard is flexible and outlines multiple basic Medium Access Control (MAC) protocols that are contention based and collision free to meet the WBAN Quality of Service (QoS) challenges. Typically, current research trends in WBAN MAC focus on designing a hybrid MAC that is a combination of basic MAC protocols. In this paper, we provide a first detailed survey of existing hybrid MAC protocols based on IEEE 802.15.6 which would be useful for the related research community. Firstly, the paper lists the design challenges of a WBAN MAC. Secondly, it highlights the significance of hybrid MAC protocols in meeting the design challenges while comparing them to standard MAC protocols. Thirdly, a critical and thorough comparison of existing hybrid MAC protocols is presented in terms of network QoS and WBAN specific parameters. Lastly, we identify key open research areas that are often neglected in hybrid MAC design and further propose some possible directions for future research

Positional Isomers of Isocyanoazulenes as Axial Ligands Coordinated to Ruthenium(II) Tetraphenylporphyrin : Fine-Tuning Redox and Optical Profiles

Two isomeric ruthenium(II)/5,10,15,20-tetraphe-nylporphyrin complexes featuring axially coordinated redox-active, low-optical gap 2- or 6-isocyanoazulene ligands have been isolated and characterized by NMR, UV-vis, and magnetic circular dichroism (MCD) spectroscopic methods, high-resolution mass spectrometry, and single-crystal X-ray crystallography. The UV-vis and MCD spectra support the presence of the low-energy, azulene-centered transitions in the Q band region of the porphyrin chromophore. The first coordination sphere in new L2RuTPP complexes reflects compressed tetragonal geometry. The redox properties of the new compounds were assessed by electrochemical and spectroelectrochemical means and correlated with the electronic structures predicted by density functional theory and CASSCF calculations. Both experimental and theoretical data are consistent with the first two reduction processes involving the axial azulenic ligands, whereas the oxidation profile (in the direction of increasing potential) is exerted by the ruthenium ion, the porphyrin core, and the axial azulenic moieties.Peer reviewe

Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting'

Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as ‘quorum acting’ to distinguish it from quorum sensing—it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication