Target Score—A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.     

One-Way Functions Using Algorithmic and Classical Information Theories

We prove several results relating injective one-way functions, time-bounded conditional Kolmogorov complexity, and time-bounded conditional entropy. First we establish a connection between injective, strong and weak one-way functions and the expected value of the polynomial time-bounded Kolmogorov complexity, denoted here by?E(K ^t (x|f(x))). These results are in both directions. More precisely, conditions on?E(K ^t (x|f(x))) that imply that?f is a weak one-way function, and properties of?E(K ^t (x|f(x))) that are implied by the fact that?f is a strong one-way function. In particular, we prove a separation result: based on the concept of time-bounded Kolmogorov complexity, we find an interval in which every function?f is a necessarily weak but not a strong one-way function. Then we propose an individual approach to injective one-way functions based on Kolmogorov complexity, defining Kolmogorov one-way functions and prove some relationships between the new proposal and the classical definition of one-way functions, showing that a Kolmogorov one-way function is also a deterministic one-way function. A relationship between Kolmogorov one-way functions and the conjecture of polynomial time symmetry of information is also proved. Finally, we relate?E(K ^t (x|f(x))) and two forms of time-bounded entropy, the unpredictable entropy?H ^unp, in which ??one-wayness?? of a function can be easily expressed, and the Yao⁺ entropy, a measure based on compression/decompression schema in which only the decompressor is restricted to be time-bounded.     

Complete relaxation and conformational exchange matrix (CORCEMA) analysis of NOESY spectra of interacting systems; two-dimensional transferred NOESY

A very general procedure entitled complete relaxation and conformational exchange matrix (CORCEMA) analysis has been developed to analyze the 2D-NOESY spectra of interacting systems undergoing multistate conformational exchange. This is an extension of earlier work from this laboratory on the methodological treatment of multistate conformational exchange [Krishna et al., Biopolymers 19, 2003 (1980)] and the theory of transferred NOESY for finite exchange off-rates [Lee and Krishna, J. Magn. Reson. 98, 36 (1992)]. The current theory is based on generalized rate matrices for relaxation and conformational exchange. The CORCEMA algorithm explicitly incorporates intermolecular dipolar cross relaxation between the molecules when they are complexed. It permits an analysis of NOESY intensities for the intra- as well as intermolecular contacts between the interacting molecules under a variety of binding conditions. Its application is illustrated on two examples of transferred NOESY simulations: (1) a two-state system involving a ligand and an enzyme forming a ligand-enzyme complex, and (2) a three-state system in which the ligand-enzyme complex can undergo a conformational transition from an "open state" to a "closed state," and can include conformational changes in both the complexed ligand and the complexed enzyme, such as hinge-bending motions. Simplifying expressions for generalized matrix analyses are derived for three limiting cases of the three-state system. This three-state example is illustrated using a hypothetical model of the hinge-bending motion in a thermolysin-inhibitor complex. It is shown that: (1) The neglect of cross relaxation between the interacting species in their complexed forms can lead to misleading conclusions on the "bound" conformation of the ligand. (2) If protein-mediated spin diffusion is dominant, caution is needed in analyses based on initial slopes alone due to one's inability to identify the exact range of the initial growth curve under poor signal/noise situations. (3) The neglect of conformational changes upon complexation, e.g., hinge-bending motions of the ligand-enzyme complex, can lead to erroneous results on the nature of "bound" conformations of the ligand. In this case, attempts to analyze the transferred NOESY data with a two-state model will result in a "virtual" conformation for the bound ligand. (4) When the hinge-bending rate is slower than the cross relaxation and enzyme off-rates, the bound conformation of a ligand deduced from the transferred NOESY experiment is more likely to represent nonspecific or weak binding in an open state of the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)     

Robotics in Education

Collision avoidance is essential for safe robot manipulation. Especially with humans around, robots should work only when safety can be robustly guaranteed. In this paper, we propose using virtual impedance control for reactive, smooth, and consistent collision avoidance that interferes minimally with the original task. The virtual impedance control operates in the risk space, a vector space describing the possibilities of all forthcoming collisions, and is designed to elude all risks in a consistent response in order to create assuring human-robot interaction experiences. The proposed scheme intrinsically handles kinematic singularity and the activation of avoidance using a boundary layer defined on the spectrum of Jacobian. In cooperation with the original controller, the proposed avoidance scheme provides a proof of convergence if the original controller is stable with and without projection. In simulations and experiments, we verified the characteristics of the proposed control scheme and integrated the system with Microsoft Kinect to monitor the workspace for real-time collision detection and avoidance. The results show that the proposed approach is suitable for robot operation with humans nearby.     

Frequency domain analysis of acoustic wave propagation in heterogeneous media considering iterative coupling procedures between the method of fundamental solutions and Kansa's method

Acoustic wave propagation in heterogeneous media is a topic of significant interest in many areas of science and engineering, including aeroacoustics and sound propagation in oceans. In the present work, numerical frequency domain models based on the joint use of the method of fundamental solutions and of the radial basis function collocation method (also known as Kansa's method) are discussed. In this context, the method of fundamental solutions is used to model the homogeneous part of the propagation domain, while Kansa's method is employed to model the presence of heterogeneities. The coupling between the two parts of the propagation domain is performed iteratively, allowing independent spatial discretization between the different subdomains of the model (i.e. matching collocation points at common surfaces are not necessary). Additionally, an optimised algorithm, based on the use of a varying relaxation parameter, is employed to speed up and/or to ensure the convergence of the iterative coupling process. At the end of the paper, numerical results illustrate the applicability and potentialities of the proposed formulations. Copyright © 2011 John Wiley & Sons, Ltd.     

Synapses: The Brain’s Energy-Demanding Sites

The brain is one of the most energy-consuming organs in the mammalian body, and synaptic transmission is one of the major contributors. To meet these energetic requirements, the brain primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. The relevance of these two energy production pathways in fulfilling energy at presynaptic terminals has been the subject of recent studies. In this review, we dissect the balance of glycolysis and oxidative phosphorylation to meet synaptic energy demands in both resting and stimulation conditions. Besides ATP output needs, mitochondria at synapse are also important for calcium buffering and regulation of reactive oxygen species. These two mitochondrial-associated pathways, once hampered, impact negatively on neuronal homeostasis and synaptic activity. Therefore, as mitochondria assume a critical role in synaptic homeostasis, it is becoming evident that the synaptic mitochondria population possesses a distinct functional fingerprint compared to other brain mitochondria. Ultimately, dysregulation of synaptic bioenergetics through glycolytic and mitochondrial dysfunctions is increasingly implicated in neurodegenerative disorders, as one of the first hallmarks in several of these diseases are synaptic energy deficits, followed by synapse degeneration.     

Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana

The purpose of this new study was to determine the types and levels of major phytochemicals (non-nutrients) and nutrients in the different tissues from vegetative and flowering Moringa oleifera L. an important multipurpose crop. Rhamnose and acetyl-rhamnose-substituted glucosinolates were found in all of the M. oleifera tissues with different profiles depending on the tissue. In addition the tissues of M. oleifera had a relatively complex flavonoid profile consisting of glucosides, rutinosides, malonylglucosides and traces of acetylglucosides of kaempferol, quercetin and isorhamnetin. Fatty acid profiling of the different tissues showed that leaves were rich in palmitic (16:0) and linolenic (18:3) acid whereas seeds were predominated by oleic acid (18:1). Roots were rich in palmitic and oleic acid, whereas stems and twigs predominately contained palmitic acid. Potassium, magnesium and calcium were the predominant minerals in all of the tissues. Low levels of selenium were detected only in whole seeds.     

Comparative study of the physicochemical and palynological characteristics of honey from Melipona subnitida and Apis mellifera

Twenty‐four samples of Apis mellifera honey and twenty‐four samples of Melipona subnitida (Jandaira) honey were collected in the northeast of Brazil. Moisture, hydroxymethylfurfural, free acidity, insoluble solids in water, diastase activity, ashes, electrical conductivity, proteins, lipids, total carbohydrates, energy and sugars were the parameters analysed. The efficiency of the qualitative tests (Fiehe's test, Lugol's reaction, Lund's reaction) was tested. Pollen types and the corresponding plant species were identified in all samples (3 in Apis and 1 in Melipona). Apis mellifera honey samples demonstrated parameters in accordance with the Brazilian Legislation, while the Melipona subnitida honey samples displayed moisture (24.80%) and diastase activity (null) in discordance with the established by the regulation for Apis mellifera honeys. Apis honey samples presented higher values of electric conductivity (284.00 μS cm^?1) than the obtained from the Jandaira honey samples (102.77 μS cm^?1) as well as a darker colour (26.67 mmPfund) when compared with Jandaira honey (7.00 mmPfund). The concentration of the glucose, fructose and sucrose was higher in the Apis honeys than in the Jandaira honey. The characteristics of the two types of honey were very different, highlighting the need of developing specific legislation for stingless bees' honey.