A new approach to segmentation based on fusing circumscribed contours, region growing and clustering

One of the major problems in machine vision is the segmentation of images of natural scenes. This paper presents a new proposal for the image segmentation problem which has been based on the integration of edge and region information. The main contours of the scene are detected and used to guide the posterior region growing process. The algorithm places a number of seeds at both sides of a contour allowing stating a set of concurrent growing processes. A previous analysis of the seeds permits to adjust the homogeneity criterion to the regions's characteristics. A new homogeneity criterion based on clustering analysis and convex hull construction is proposed

Active regions for colour texture segmentation integrating region and boundary information

In this paper a colour texture segmentation method, which unifies region and boundary information, is proposed. The algorithm uses a coarse detection of the perceptual (colour and texture) edges of the image to adequately place and initialise a set of active regions. Colour texture of regions is modelled by the conjunction of non-parametric techniques of kernel density estimation (which allow to estimate the colour behaviour) and classical co-occurrence matrix based texture features. Therefore, region information is defined and accurate boundary information can be extracted to guide the segmentation process. Regions concurrently compete for the image pixels in order to segment the whole image taking both information sources into account. Furthermore, experimental results are shown which prove the performance of the proposed method

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced diskynesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Targeting Adenoviral Gene Therapy Vectors to Head and Neck Squamous Cell Carcinoma and Heart

Gene therapy aims to treat diseases by introducing genetic material to the diseased tissue. For cancer treatment it is important to destroy cancerous cells; this can be achieved by introducing a gene, which induces cell death or by allowing viral vectors to replicate, which also results in destruction of cancerous cells. For cardiac diseases the approach is more like the former, except the gene produces beneficial effects, like angiogenesis. Adenoviruses have many beneficial qualities, which make the virus an interesting gene therapy vector; it can be produced relatively easily, its manipulation is quite easy and it has naturally broad tropism. By removing or replacing certain genes in the adenoviral genome, it can be made non-replicative. In this study, adenoviral receptor expression patterns were characterized in both head and neck squamous cell carcinoma and the human heart. Adenovirus serotype 5 receptor expression in head and neck cancer cell lines was found to be highly variable between cell lines and overall at lower levels, while Ad35 receptor expression was more uniform and at higher levels in all analyzed cell lines. It was also shown that a hybrid virus Ad5/35 is able to infect cells refractory to Ad5, which correlates with receptor expression in these cells. Furthermore, this difference in infection properties extends to cell killing efficiency in case of conditionally replicative viruses. Expression levels of adenoviral receptors CAR, CD46, CD86 and αv-integrins were found to be high both in normal and dilated cardiomyopathy heart tissue. The receptor levels also correlate with transduction efficiency after intracardiac injection. Ad5 showed superior transduction ability compared with Ad5/35, but evoked also a more profound immune reaction when administered this way. Adenoviral gene therapy vectors are the most used delivery vehicles in clinical trials to date. These vectors have proven to be well tolerated and positive results have been obtained when combined with traditional treatments, although poor transduction efficiency has often been reported due to low-level expression of viral receptors on target cells. In spite of this, the results are encouraging and merit for further research.

Speaker diarization: Segmentation and clustering of speeches

Speaker diarization is the process of sorting speeches according to the speaker. Diarization helps to search and retrieve what a certain speaker uttered in a meeting. Applications of diarization systemsextend to other domains than meetings, for example, lectures, telephone, television, and radio. Besides, diarization enhances the performance of several speech technologies such as speaker recognition, automatic transcription, and speaker tracking. Methodologies previously used in developing diarization systems are discussed. Prior results and techniques are studied and compared. Methods such as Hidden Markov Models and Gaussian Mixture Models that are used in speaker recognition and other speech technologies are also used in speaker diarization. The objective of this thesis is to develop a speaker diarization system in meeting domain. Experimental part of this work indicates that zero-crossing rate can be used effectively in breaking down the audio stream into segments, and adaptive Gaussian Models fit adequately short audio segments. Results show that 35 Gaussian Models and one second as average length of each segment are optimum values to build a diarization system for the tested data. Uniting the segments which are uttered by same speaker is done in a bottom-up clustering by a newapproach of categorizing the mixture weights.

Transition management and the sustainable nutrients economy in the Netherlands; positioning paper

In this positioning paper transition management (TM) and the sustainable nutrient economy are addressed. We discuss TM from its scholarly origins in the 1990’s to its implementation as a comprehensive sector-wide policy program on sustainability in The Netherlands during the first decade of the 2000´s. Although the program was innovative and provoked a new approach to environmental policy and governance, the program at large failed to set the right conditions under which sustainable transition take place. Lessons from the Netherlands, both successful and less successful, are addressed in this positioning paper to inform Finnish governmental and knowledge institutes on how (not) to implement TM on environmental issues. When looking at sustainable nutrient economy the paper takes a historical view at how problems with nutrients (especially phosphates) were dealt with in the Netherlands during the post World War II era. This transition did not occur easily. In the agricultural sector environmental policies to prevent nutrient problems were not easily accepted, as large agricultural economic interests were at stake and the sector’s main actors were generally opposed to (radical) environmental transition. Currently, sustainable nutrient economy initiatives are starting to receive attention on the political agenda once again. In 2011 a sector- and chain-wide covenant was signed, showing that sustainable nutrient transition goals get commitment from stakeholders throughout the nutrient chain. We judge that TM provides useful elements that are applicable to Finnish governance modes to support sustainable nutrient economy transition. However, the Finnish government should be careful when implementing TM to prevent making the same mistakes the Dutch government made in previous years.

Visual customer segmentation and behavior analysis : a SOM-based approach

Ett ämne som väckt intresse både inom industrin och forskningen är hantering av kundförhållanden (CRM, eng. Customer Relationship Management), dvs. en kundorienterad affärsstrategi där företagen från att ha varit produktorienterade väljer att bli mera kundcentrerade. Numera kan kundernas beteende och aktiviteter lätt registreras och sparas med hjälp av integrerade affärssystem (ERP, eng. Enterprise Resource Planning) och datalager (DW, eng. Data Warehousing). Kunder med olika preferenser och köpbeteende skapar sin egen ”signatur” i synnerhet via användningen av kundkort, vilket möjliggör mångsidig modellering av kundernas köpbeteende. För att få en översikt av kundernas köpbeteende och deras lönsamhet, används ofta kundsegmentering som en metod för att indela kunderna i grupper utgående från deras likheter. De mest använda metoderna för kundsegmentering är analytiska modeller konstruerade för en viss tidsperiod. Dessa modeller beaktar inte att kundernas beteende kan förändras med tiden. I föreliggande avhandling skapas en holistisk översikt av kundernas karaktär och köpbeteende som utöver de konventionella segmenteringsmodellerna även beaktar dynamiken i köpbeteendet. Dynamiken i en kundsegmenteringsmodell innefattar förändringar i segmentens struktur och innehåll, samt förändringen av individuella kunders tillhörighet i ett segment (s.k migrationsanalyser). Vardera förändringen modelleras, analyseras och exemplifieras med visuella datautvinningstekniker, främst med självorganiserande kartor (SOM, eng. Self-Organizing Maps) och självorganiserande tidskartor (SOTM), en vidareutveckling av SOM. Visualiseringen anteciperas underlätta tolkningen av identifierade mönster och göra processen med kunskapsöverföring mellan den som gör analysen och beslutsfattaren smidigare. Asiakkuudenhallinta (CRM) eli organisaation muuttaminen tuotepainotteisesta asiakaskeskeiseksi on herättänyt mielenkiintoa niin yliopisto- kuin yritysmaailmassakin. Asiakkaiden käyttäytymistä ja toimintaa pystytään nykyään helposti tallentamaan ja varastoimaan toiminnanohjausjärjestelmien ja tietovarastojen avulla; asiakkaat jättävät jatkuvasti piirteistään ja ostokäyttäytymisestään kertovia tietojälkiä, joita voidaan analysoida. On tavallista, että asiakkaat poikkeavat toisistaan eri tavoin, ja heidän mieltymyksensä kuten myös ostokäyttäytymisensä saattavat olla hyvinkin erilaisia. Asiakaskäyttäytymisen monimuotoisuuteen ja tuottavuuteen paneuduttaessa käytetäänkin laajalti asiakassegmentointia eli asiakkaiden jakamista ryhmiin samankaltaisuuden perusteella. Perinteiset asiakassegmentoinnin ratkaisut ovat usein yksittäisiä analyyttisia malleja, jotka on tehty tietyn aikajakson perusteella. Tämän vuoksi ne monesti jättävät huomioimatta sen, että asiakkaiden käyttäytyminen saattaa ajan kuluessa muuttua. Tässä väitöskirjassa pyritäänkin tarjoamaan holistinen kuva asiakkaiden ominaisuuksista ja ostokäyttäytymisestä tarkastelemalla kahta muutosvoimaa tiettyyn aikarajaukseen perustuvien perinteisten segmentointimallien lisäksi. Nämä kaksi asiakassegmentointimallin dynamiikkaa ovat muutokset segmenttien rakenteessa ja muutokset yksittäisten asiakkaiden kuulumisessa ryhmään. Ensimmäistä dynamiikkaa lähestytään ajallisen asiakassegmentoinnin avulla, jossa visualisoidaan ajan kuluessa tapahtuvat muutokset segmenttien rakenteissa ja profiileissa. Toista dynamiikkaa taas lähestytään käyttäen nk. segmenttisiirtymien analyysia, jossa visuaalisin keinoin tunnistetaan samantyyppisesti segmentistä toiseen vaihtavat asiakkaat. Visualisoinnin tehtävänä on tukea havaittujen kaavojen tulkitsemista sekä helpottaa tiedonsiirtoa analysoijan ja päättäjien välillä. Visuaalisia tiedonlouhintamenetelmiä, kuten itseorganisoivia karttoja ja niiden laajennuksia, käytetään osoittamaan näiden menetelmien hyödyllisyys sekä asiakkuudenhallinnassa yleisesti että erityisesti asiakassegmentoinnissa.