Performance Evaluation of a Statistical and a Neural Network Model for Nonrigid Shape-Based Registration

Shape-based registration methods frequently encounters in the domains of computer vision, image processing and medical imaging. The registration problem is to find an optimal transformation/mapping between sets of rigid or nonrigid objects and to automatically solve for correspondences. In this paper we present a comparison of two different probabilistic methods, the entropy and the growing neural gas network (GNG), as general feature-based registration algorithms. Using entropy shape modelling is performed by connecting the point sets with the highest probability of curvature information, while with GNG the points sets are connected using nearest-neighbour relationships derived from competitive hebbian learning. In order to compare performances we use different levels of shape deformation starting with a simple shape 2D MRI brain ventricles and moving to more complicated shapes like hands. Results both quantitatively and qualitatively are given for both sets.

Cytotoxicity Evaluation of Si-Diatom Frustules in a Mouse Model

Silica additives in bone substitute materials are topical, clinically interesting and have significant support in the Orthopaedic field. Biosilica, e.g isolated from diatoms, has many advantages over its synthetic counterparts, e.g. it is amorphous, thus will be absorbed by the body, however, issues such as purity, presence of endotoxins and cytotoxicity need to be addressed before it can be further exploited. Biosilica isolated from Cyclotella Meneghiniana was then tested in a mouse model, to test the immunological response, organ toxicity (kidney, spleen, liver) and route of metabolism/excretion of silica. Five-week-old Balb-c mice were injected subcutaneously with a single high dose (50mg/ml) of Si-frustules, Si-frustules + organic linker and vehicle only control. Animals were sacrificed at 1d and 28d. The animal studies were conducted under an ethically approved protocol at Queen’s University, Belfast. The animals showed no adverse stress during the experiment and remained healthy until sacrifice. Blood results using ICP-OES analysis suggest the frustules were metabolized between comparator groups at different rates, and clearly showed elevated levels of silicon in groups injected with frustules relative to control. The histology of organs showed no variation in morphology of mice injected frustules relative compared to the control group.
Acknowledgements: The authors would like to thank Marie Curie International Outgoing Fellowships from the EU and Beaufort Marine Biodiscovery Award as part of the Marine Biotechnology Ireland Programme for providing financial support to this project.

Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns.

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD(+) acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD(+) human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro. The resistant cells, MOLM-13-RES, harboured a new D835Y tyrosine kinase domain (TKD) mutation on the FLT3-ITD(+) allele. Acquired TKD mutations, including D835Y, have recently been identified in FLT3-ITD(+) patients relapsing after treatment with the novel FLT3 inhibitor, AC220. Consistent with this clinical pattern of resistance, MOLM-13-RES cells displayed high relative resistance to AC220 and Sorafenib. Furthermore, treatment of MOLM-13-RES cells with AC220 lead to loss of the FLT3 wild-type allele and the duplication of the FLT3-ITD-D835Y allele. Our FLT3-Aurora kinase inhibitor, CCT137690, successfully inhibited growth of FLT3-ITD-D835Y cells in vitro and in vivo, suggesting that dual FLT3-Aurora inhibition may overcome selective FLT3 inhibitor resistance, in part due to inhibition of Aurora kinase, and may benefit patients with FLT3-mutated AML.

Benchmarking a modified version of the civ3 nonrelativistic atomic-structure code within Na-like-tungsten R -matrix calculations

In this work we explore the validity of employing a modified version of the nonrelativistic structure code civ3 for heavy, highly charged systems, using Na-like tungsten as a simple benchmark. Consequently, we present radiative and subsequent collisional atomic data compared with corresponding results from a fully relativistic structure and collisional model. Our motivation for this line of study is to benchmark civ3 against the relativistic grasp0 structure code. This is an important study as civ3 wave functions in nonrelativistic R-matrix calculations are computationally less expensive than their Dirac counterparts. There are very few existing data for the W LXIV ion in the literature with which we can compare except for an incomplete set of energy levels available from the NIST database. The overall accuracy of the present results is thus determined by the comparison between the civ3 and grasp0 structure codes alongside collisional atomic data computed by the R-matrix Breit-Pauli and Dirac codes. It is found that the electron-impact collision strengths and effective collision strengths computed by these differing methods are in good general agreement for the majority of the transitions considered, across a broad range of electron temperatures.

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

OSAN, R. , TORT, A. B. L. , AMARAL, O. B. . A mismatch-based model for memory reconsolidation and extinction in attractor networks. Plos One, v. 6, p. e23113, 2011.

Geometric versus Model Predictive Control based guidance algorithms for fixed-wing UAVs in the presence of very strong wind fields.

The recent years have witnessed increased development of small, autonomous fixed-wing Unmanned Aerial Vehicles (UAVs). In order to unlock widespread applicability of these platforms, they need to be capable of operating under a variety of environmental conditions. Due to their small size, low weight, and low speeds, they require the capability of coping with wind speeds that are approaching or even faster than the nominal airspeed. In this thesis, a nonlinear-geometric guidance strategy is presented, addressing this problem. More broadly, a methodology is proposed for the high-level control of non-holonomic unicycle-like vehicles in the presence of strong flowfields (e.g. winds, underwater currents) which may outreach the maximum vehicle speed. The proposed strategy guarantees convergence to a safe and stable vehicle configuration with respect to the flowfield, while preserving some tracking performance with respect to the target path. As an alternative approach, an algorithm based on Model Predictive Control (MPC) is developed, and a comparison between advantages and disadvantages of both approaches is drawn. Evaluations in simulations and a challenging real-world flight experiment in very windy conditions confirm the feasibility of the proposed guidance approach.

On the modelling of fire atmosphere/sprinkler spray interacting using an Euler-Lagrange framework

An Euler-Lagrange particle tracking model, developed for simulating fire atmosphere/sprinkler spray interactions, is described. Full details of the model along with the approximations made and restrictions applying are presented. Errors commonly found in previous formulations of the source terms used in this two-phase approach are described and corrected. In order to demonstrate the capabilities of the model it is applied to the simulation of a fire in a long corridor containing a sprinkler. The simulation presented is three-dimensional and transient and considers mass, momentum and energy transfer between the gaseous atmosphere and injected liquid droplets.

Characterization of the glial scar tissue in a murine model of spinal cord compression, with focus on hyaluronan

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of people each year. Although in recent decades significant progress has been made in relation to understanding the molecular and cellular events underlying the nervous damage, spinal cord injury is still a highly disabling condition for which there is no curative therapy. People affected by spinal cord injuries manifested dysfunction or loss, temporary or permanent, of motor, sensory and / or autonomic functions depending on the spinal lesion damaged. Currently, the incidence rate of this type of injury is approximately 15-40 cases per million people worldwide. At the origin of these lesions are: road accidents, falls, interpersonal violence and the practice of sports. In this work we placed the hypothesis that HA is one of the component of the scar tissue formed after a compressive SCI, that it is likely synthetised by the perilesional glial cells and that it might support the permeation of the glial scar during the late phase of SCI. Nowadays, much focus is drawn on the recovery of CNS function, made impossible after SCI due to the high content of sulfated proteoglycans in the extracellular matrix. Counterbalancing the ratio between these proteoglycans and hyaluronic acid could be one of the experimental therapy to re-permeate the glial scar tissue formed after SCI, making possible axonal regrowth and functional recovery. Therefore, we established a model of spinal cord compression in mice and studied the glial scar tissue, particularly through the characterization of the expression of enzymes related to the metabolism of HA and the subsequent concentration thereof at different distances of the lesion epicenter. Our results show that the lesion induced in mice shows results similar to those produced in human lesions, in terms of histologic similarities and behavioral results. but these animals demonstrate an impressive spontaneous reorganization mechanism of the spinal cord tissue that occurs after injury and allows for partial recovery of the functions of the CNS. As regards the study of the glial scar, changes were recorded at the level of mRNA expression of enzymes metabolizing HA i.e., after injury there was a decreased expression of HA synthases 1-2 (HAS 1-2) and an increase of the expression HAS3 synthase mRNA, as well as the enzymes responsible for the HA catabolism, HYAL 1-2. But the amount of HA measured through the ELISA test was found unchanged after injury, it is not possible to explain this fact only with the change of expression of enzymes. At two weeks and in response to SCI, we found synthesized HA by reactive astrocytes and probably by others like microglial cells as it was advanced by the HA/GFAP+ and HA/IBA1+ cells co-location.

Toll-like receptor 9 in breast cancer

The innate immune system recognizes microbial features leading to the activation of the adaptive immune system. The role of Toll-like receptor 9 (TLR9) is to recognize microbial DNA. In addition to immune cells, TLR9 is widely expressed in breast cancer in addition to other cancers. Breast cancer is the most common cancer in women, affecting approximately one in eight in industrialized countries. In the clinical setting, breast cancer is divided into three clinical subtypes with type-specific treatments. These subtypes are estrogen receptor (ER)-positive, HER2-positive and triple-negative (TNBC) breast cancer. TNBC is the most aggressive subtype that can be further divided into several subtypes. TNBC tumors lack ER, progesterone receptor and HER2 receptor. Therefore, the current clinically used targeted therapies are not suitable for TNBC treatment as TNBC is a collection of diseases rather than one entity. Some TNBC patients are cured with standard chemotherapy, while others rapidly die due to the disease. There are no clinically used iomarkers which would help in predicting which patients respond to chemotherapy. During this thesis project, we discovered a novel good-prognosis TNBC subtype. These tumors have high TLR9 expression levels. Our findings suggest that TLR9 screening in TNBC patient populations might help to identify the patients that are at the highest risk regarding a relapse. To gain better understanding on the role of TLR9 in TNBC, we developed an animal model which mimicks this disease. We discovered that suppression of TLR9 expression in TNBC cells increases their invasive properties in hypoxia. In line with the clinical findings, TNBC cells with low TLR9 expression also formed more aggressive tumors in vivo. TLR9 expression did not, however, affect TNBC tumor responses to doxorubicin. Our results suggest that tumor TLR9 expression may affect chemotherapyrelated immune responses, however, this requires further investigation. Our other findings revealed that DNA released by chemotherapy-killed cells induces TLR9-mediated invasion in living cancer cells. Normally, extracellular self-DNA is degraded by enzymes, but during massive cell death, for example during chemotherapy, the degradation machinery may be exhausted and self-DNA is taken up into living cells activating TLR9. We also discovered that the malaria drug chloroquine, an inhibitor of autophagy and TLR9 signalling does not inhibit TNBC growth in vivo, independently of the TLR9 status. Finally, we found that ERα as well as the sex hormones estrogen and testosterone regulate TLR9 expression and activity in breast cancer cells in vitro. As a conclusion, we suggest that TLR9 is a potential biomarker in TNBC. ------- Sisäsyntyisen immuniteetin tehtävä on tunnistaa mikrobien molekyylirakenteita, mikä saa aikaan adaptiivisen immuunijärjestelmän aktivoitumisen. Tollin kaltainen reseptori 9 (TLR9) on dna:ta tunnistava sisäsyntyisen immuniteetin reseptori, jota ilmennetään myös useissa syövissä, kuten rintasyövässä. Rintasyöpä on naisten yleisin syöpä, johon joka kahdeksas nainen sairastuu elämänsä aikana. Kliinisesti rintasyöpä jaotellaan kolmeen alatyyppiin, joista kolmoisnegatiivinen rintasyöpä on aggressiivisin. Tämän tyypin syövät eivät ilmennä hormonireseptoreja (estrogeeni- ja progesteronireseptori) tai HER2-reseptoria. Tästä johtuen kolmoisnegatiivisten potilaiden hoitoon ei voida käyttää rintasyövän nykyisten hoitosuositusten mukaisia täsmähoitoja. Kolmoisnegatiivinen rintasyöpä ei kuitenkaan ole yksi sairaus, koska molekyylitasolla sen on osoitettu koostuvan lukuisista, biologialtaan erilaisista syöpämuodoista. Tällä hetkellä kliinisessä käytössä ei ole biomarkkeria, jonka avulla kolmoisnegatiivisen rintasyövän alatyypit voisi erottaa toisistaan. Löysimme uuden kolmoisnegatiivisen syövän alatyypin, joka ilmentää vain vähän TLR9-proteiinia. Tällä alatyypillä on erittäin huono ennuste ja tulostemme perusteella TRL9-tason selvittäminen voisi seuloa huonoennusteiset syövät kolmoisnegatiivisten syöpien joukosta. Kehitimme eläinmallin, jolla voidaan tutkia matalan ja korkean TLR9-tason vaikutuksia kolmoisnegatiivisten kasvainten hoitovasteeseen. Toinen löytömme oli, että kemoterapialla tapettujen syöpäsolujen dna saa aikaan elävien syöpäsolujen TLR9-välitteistä invaasiota. Normaalisti entsyymit hajoittavat yksilön oman solunulkoisen dna:n. Erikoistilanteissa, kuten syöpähoitojen yhteydessä, jolloin solukuolema on massiivista, elimistön oma koneisto ei ehdi tuhoamaan solunulkoista dna:ta ja sitä voi kertyä eläviin soluihin, joissa se aktivoi TLR9:n. Kolmanneksi havaitsimme, että malarialääke klorokiini, joka estää TLR9:n toimintaa ja jolla on syövänvastaisia vaikutuksia soluviljelyolosuhteissa, ei estänyt TLR9-positiivisten tai TLR9-negatiivisten kasvainten kasvua käyttämässämme eläinmallissa. Neljänneksi soluviljelykokeittemme tulokset osoittivat, että sukupuolihormonit estrogeeni ja testosteroni sekä estrogeenireseptori osallistuvat TLR9:n ilmentymisen ja aktiivisuuden säätelyyn. Tuloksemme osoittavat, että TLR9 potentiaalinen biomarkkeri kolmoisnegatiivisessa rintasyövässä.

Scotogenic model for co-bimaximal mixing

We present a scotogenic model, i.e. a one-loop neutrino mass model with dark right-handed neutrino gauge singlets and one inert dark scalar gauge doublet eta, which has symmetries that lead to co-bimaximal mixing, i.e. to an atmospheric mixing angle theta(23) = 45 degrees and to a CP-violating phase delta = +/-pi/2, while the mixing angle theta(13) remains arbitrary. The symmetries consist of softly broken lepton numbers L-alpha (alpha = e, mu, tau), a non-standard CP symmetry, and three L-2 symmetries. We indicate two possibilities for extending the model to the quark sector. Since the model has, besides eta, three scalar gauge doublets, we perform a thorough discussion of its scalar sector. We demonstrate that it can accommodate a Standard Model-like scalar with mass 125 GeV, with all the other charged and neutral scalars having much higher masses.

Some Like It Hot: The Influence and Implications of Climate Change on Coffee Berry Borer (Hypothenemus hampei) and Coffee Production in East Africa

The negative effects of climate change are already evident for many of the 25 million coffee farmers across the tropics and the 90 billion dollar (US) coffee industry. The coffee berry borer (Hypothenemus hampei), the most important pest of coffee worldwide, has already benefited from the temperature rise in East Africa: increased damage to coffee crops and expansion in its distribution range have been reported. In order to anticipate threats and prioritize management actions for H. hampei we present here, maps on future distributions of H. hampei in coffee producing areas of East Africa. Using the CLIMEX model we relate present-day insect distributions to current climate and then project the fitted climatic envelopes under future scenarios A2A and B2B (for HADCM3 model). In both scenarios, the situation with H. hampei is forecasted to worsen in the current Coffea arabica producing areas of Ethiopia, the Ugandan part of the Lake Victoria and Mt. Elgon regions, Mt. Kenya and the Kenyan side of Mt. Elgon, and most of Rwanda and Burundi. The calculated hypothetical number of generations per year of H. hampei is predicted to increase in all C. arabica-producing areas from five to ten. These outcomes will have serious implications for C. arabica production and livelihoods in East Africa. We suggest that the best way to adapt to a rise of temperatures in coffee plantations could be via the introduction of shade trees in sun grown plantations. The aims of this study are to fill knowledge gaps existing in the coffee industry, and to draft an outline for the development of an adaptation strategy package for climate change on coffee production. An abstract in Spanish is provided as Abstract S1.

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

OSAN, R. , TORT, A. B. L. , AMARAL, O. B. . A mismatch-based model for memory reconsolidation and extinction in attractor networks. Plos One, v. 6, p. e23113, 2011.

The Influence of Propagation Model and Sectorization over WCDMA Capacity

In this paper we use a dynamic model that we have developed for WCDMA capacity analysis using MATLAB and a GIS based planning tool, to estimate the capacity of a mobile system under different conditions like number of cells, propagation model, sectorization and handover margin.

The Role of Cannabinoids in the Neurobiology of Sensory Gating: A firing rate model study

Gating of sensory (e.g. auditory) information has been demonstrated as a reduction in the auditory-evoked potential responses recorded in the brain of both normal animals and human subjects. Auditory gating is perturbed in schizophrenic patients and pharmacologically by drugs such as amphetamine, phencyclidine or ketamine, which precipitate schizophrenic-like symptoms in normal subjects. The neurobiological basis underlying this sensory gating can be investigated using local field potential recordings from single electrodes. In this paper we use such technology to investigate the role of cannabinoids in sensory gating. Cannabinoids represent a fundamentally new class of retrograde messengers which are released postsynaptically and bind to presynaptic receptors. In this way they allow fine-tuning of neuronal response, and in particular can lead to so-called depolarization-induced suppression of inhibition (DSI). Our experimental results show that application of the exogenous cannabinoid WIN55, 212-2 can abolish sensory gating as measured by the amplitude of local field responses in rat hippocampal region CA3. Importantly we develop a simple firing rate population model of CA3 and show that gating is heavily dependent upon the presence of a slow inhibitory (GABAB) pathway. Moreover, a simple phenomenological model of cannabinoid dynamics underlying DSI is shown to abolish gating in a manner consistent with our experimental findings.

Exotic dynamics in a firing rate model of neural tissue with threshold accommodation

Many of the equations describing the dynamics of neural systems are written in terms of firing rate functions, which themselves are often taken to be threshold functions of synaptic activity. Dating back to work by Hill in 1936 it has been recognized that more realistic models of neural tissue can be obtained with the introduction of state-dependent dynamic thresholds. In this paper we treat a specific phenomenological model of threshold accommodation that mimics many of the properties originally described by Hill. Importantly we explore the consequences of this dynamic threshold at the tissue level, by modifying a standard neural field model of Wilson-Cowan type. As in the case without threshold accommodation classical Mexican-Hat connectivity is shown to allow for the existence of spatially localized states (bumps) in both one and two dimensions. Importantly an analysis of bump stability in one dimension, using recent Evans function techniques, shows that bumps may undergo instabilities leading to the emergence of both breathers and traveling waves. Moreover, a similar analysis for traveling pulses leads to the conditions necessary to observe a stable traveling breather. In the regime where a bump solution does not exist direct numerical simulations show the possibility of self-replicating bumps via a form of bump splitting. Simulations in two space dimensions show analogous localized and traveling solutions to those seen in one dimension. Indeed dynamical behavior in this neural model appears reminiscent of that seen in other dissipative systems that support localized structures, and in particular those of coupled cubic complex Ginzburg-Landau equations. Further numerical explorations illustrate that the traveling pulses in this model exhibit particle like properties, similar to those of dispersive solitons observed in some three component reaction-diffusion systems. A preliminary account of this work first appeared in S Coombes and M R Owen, Bumps, breathers, and waves in a neural network with spike frequency adaptation, Physical Review Letters 94 (2005), 148102(1-4).