Data-driven clustering : new methods and applications

Abstract : This work is concerned with the development and application of novel unsupervised learning methods, having in mind two target applications: the analysis of forensic case data and the classification of remote sensing images. First, a method based on a symbolic optimization of the inter-sample distance measure is proposed to improve the flexibility of spectral clustering algorithms, and applied to the problem of forensic case data. This distance is optimized using a loss function related to the preservation of neighborhood structure between the input space and the space of principal components, and solutions are found using genetic programming. Results are compared to a variety of state-of--the-art clustering algorithms. Subsequently, a new large-scale clustering method based on a joint optimization of feature extraction and classification is proposed and applied to various databases, including two hyperspectral remote sensing images. The algorithm makes uses of a functional model (e.g., a neural network) for clustering which is trained by stochastic gradient descent. Results indicate that such a technique can easily scale to huge databases, can avoid the so-called out-of-sample problem, and can compete with or even outperform existing clustering algorithms on both artificial data and real remote sensing images. This is verified on small databases as well as very large problems. Résumé : Ce travail de recherche porte sur le développement et l'application de méthodes d'apprentissage dites non supervisées. Les applications visées par ces méthodes sont l'analyse de données forensiques et la classification d'images hyperspectrales en télédétection. Dans un premier temps, une méthodologie de classification non supervisée fondée sur l'optimisation symbolique d'une mesure de distance inter-échantillons est proposée. Cette mesure est obtenue en optimisant une fonction de coût reliée à la préservation de la structure de voisinage d'un point entre l'espace des variables initiales et l'espace des composantes principales. Cette méthode est appliquée à l'analyse de données forensiques et comparée à un éventail de méthodes déjà existantes. En second lieu, une méthode fondée sur une optimisation conjointe des tâches de sélection de variables et de classification est implémentée dans un réseau de neurones et appliquée à diverses bases de données, dont deux images hyperspectrales. Le réseau de neurones est entraîné à l'aide d'un algorithme de gradient stochastique, ce qui rend cette technique applicable à des images de très haute résolution. Les résultats de l'application de cette dernière montrent que l'utilisation d'une telle technique permet de classifier de très grandes bases de données sans difficulté et donne des résultats avantageusement comparables aux méthodes existantes.

Collaboration entre médecin de famille et psychiatre pour les problèmes de santé mentale [Family physicians and psychiatrists' collaborative care for mental health problems].

The burden of disease linked to mental disorders represents more than one-fifth of years lived with disability in the world. Less than half of people suffering from mental disorders are adequately treated. Three quarter of those who receive treatment are followed by primary care. Collaborative care aims to increase the efficiency of direct general practitioner's treatment. Main components are sustainable and individualized consultation-liaison relationship (1/2 day of psychiatrist by 15 days for 10-15 general practitioners), and support of a clinical case manager for complex situations. Collaboration is bidirectional: early or crisis access to specialist care and long-term followup by general practitioner. This model is a challenge for the doctor-patient dual relationship and requires incentives in a public health perspective.

Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)β(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)β(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)β(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)β(3) integrin restricted neurite outgrowth. Likewise, α(V)β(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)β(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)β(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)β(3) integrin. Binding of α(V)β(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)β(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

The parallel lives of angiogenesis and immunosuppression: cancer and other tales.

Emerging evidence indicates that angiogenesis and immunosuppression frequently occur simultaneously in response to diverse stimuli. Here, we describe a fundamental biological programme that involves the activation of both angiogenesis and immunosuppressive responses, often through the same cell types or soluble factors. We suggest that the initiation of these responses is part of a physiological and homeostatic tissue repair programme, which can be co-opted in pathological states, notably by tumours. This view can help to devise new cancer therapies and may have implications for aseptic tissue injury, pathogen-mediated tissue destruction, chronic inflammation and even reproduction.

Sensitive gene expression profiling of human T cell subsets reveals parallel post-thymic differentiation for CD4+ and CD8+ lineages.

The differentiation of CD4(+) or CD8(+) T cells following priming of naive cells is central in the establishment of the immune response against pathogens or tumors. However, our understanding of this complex process and the significance of the multiple subsets of differentiation remains controversial. Gene expression profiling has opened new directions of investigation in immunobiology. Nonetheless, the need for substantial amount of biological material often limits its application range. In this study, we have developed procedures to perform microarray analysis on amplified cDNA from low numbers of cells, including primary T lymphocytes, and applied this technology to the study of CD4 and CD8 lineage differentiation. Gene expression profiling was performed on samples of 1000 cells from 10 different subpopulations, defining the major stages of post-thymic CD4(+) or CD8(+) T cell differentiation. Surprisingly, our data revealed that while CD4(+) and CD8(+) T cell gene expression programs diverge at early stages of differentiation, they become increasingly similar as cells reach a late differentiation stage. This suggests that functional heterogeneity between Ag experienced CD4(+) and CD8(+) T cells is more likely to be located early during post-thymic differentiation, and that late stages of differentiation may represent a common end in the development of T-lymphocytes.

Full activation of the T cell receptor requires both clustering and conformational changes at CD3.

T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.

Remote collaborative multi-user informal learning experiences: design and evaluation

This paper presents a customizable system used to develop a collaborative multi-user problem solving game. It addresses the increasing demand for appealing informal learning experiences in museum-like settings. The system facilitates remote collaboration by allowing groups of learners tocommunicate through a videoconferencing system and by allowing them to simultaneously interact through a shared multi-touch interactive surface. A user study with 20 user groups indicates that the game facilitates collaboration between local and remote groups of learners. The videoconference and multitouch surface acted as communication channels, attracted students’ interest, facilitated engagement, and promoted inter- and intra-group collaboration—favoring intra-group collaboration. Our findings suggest that augmentingvideoconferencing systems with a shared multitouch space offers newpossibilities and scenarios for remote collaborative environments and collaborative learning.

Key cognitive and collaborative aptitudes in ambulance people

The aim of our study was to identify and document some key cognitive aptitudes used by ambulance people in emergency situations. Better knowing such aptitudes is necessary for a school of ambulance people in order to improve the selection and education of students. The idea was to better consider real work activity requirements and characteristics, and to develop and implement genuine educational content and selection tools. We followed the work activity of ambulance professionals involved in real emergency situations. Some interventions were filmed and post-analyzed. We completed and validated our analysis by means of interviews with ambulance personnel. We selected some video sequences and used them as a support for the interviews. We identified and documented many different key aptitudes like orientation and spatial sense, the capacity to perform complex cognitive tasks and delicate manipulations in the context of divided attention, as well as diverse aptitudes relevant in collaborative work.

Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV.

BACKGROUND: HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). METHODS: Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. RESULTS: Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR>2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. CONCLUSIONS: Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Neural networks complemented with genetic algorithms and fuzzy systems for predicting nitrogenous effluent variables in wastewater treatment plants

This work focuses on the prediction of the two main nitrogenous variables that describe the water quality at the effluent of a Wastewater Treatment Plant. We have developed two kind of Neural Networks architectures based on considering only one output or, in the other hand, the usual five effluent variables that define the water quality: suspended solids, biochemical organic matter, chemical organic matter, total nitrogen and total Kjedhal nitrogen. Two learning techniques based on a classical adaptative gradient and a Kalman filter have been implemented. In order to try to improve generalization and performance we have selected variables by means genetic algorithms and fuzzy systems. The training, testing and validation sets show that the final networks are able to learn enough well the simulated available data specially for the total nitrogen

Genetic diversity of cultivated accessions and wild species of rubber tree using EST‑SSR markers

The objective of this work was to evaluate the efficiency of EST‑SSR markers in the assessment of the genetic diversity of rubber tree genotypes (Hevea brasiliensis) and to verify the transferability of these markers for wild species of Hevea. Forty‑five rubber tree accessions from the Instituto Agronômico (Campinas, SP, Brazil) and six wild species were used. Information provided by modified Roger's genetic distance were used to analyze EST‑SSR data. UPGMA clustering divided the samples into two major groups with high genetic differentiation, while the software Structure distributed the 51 clones into eight groups. A parallel could be established between both clustering analyses. The 30 polymorphic EST‑SSRs showed from two to ten alleles and were efficient in amplifying the six wild species. Functional EST‑SSR microsatellites are efficient in evaluating the genetic diversity among rubber tree clones and can be used to translate the genetic differences among cultivars and to fingerprint closely related materials. The accessions from the Instituto Agronômico show high genetic diversity. The EST‑SSR markers, developed from Hevea brasiliensis, show transferability and are able to amplify other species of Hevea.