Transcription factor map alignment of promoter regions

We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments.

Monitoring of illicit pill distribution networks using an image collection exploration framework

This paper proposes a novel approach for the analysis of illicit tablets based on their visual characteristics. In particular, the paper concentrates on the problem of ecstasy pill seizure profiling and monitoring. The presented method extracts the visual information from pill images and builds a representation of it, i.e. it builds a pill profile based on the pill visual appearance. Different visual features are used to build different image similarity measures, which are the basis for a pill monitoring strategy based on both discriminative and clustering models. The discriminative model permits to infer whether two pills come from the same seizure, while the clustering models groups of pills that share similar visual characteristics. The resulting clustering structure allows to perform a visual identification of the relationships between different seizures. The proposed approach was evaluated using a data set of 621 Ecstasy pill pictures. The results demonstrate that this is a feasible and cost effective method for performing pill profiling and monitoring.

The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing

Removal of introns during pre-mRNA splicing is a critical process in gene expression, and understanding its control at both single-gene and genomic levels is one of the great challenges in Biology. Splicing takes place in a dynamic, large ribonucleoprotein complex known as the spliceosome. Combining Genetics and Biochemistry, Saccharomyces cerevisiae provides insights into its mechanisms, including its regulation by RNA-protein interactions. Recent genome-wide analyses indicate that regulated splicing is broad and biologically relevant even in organisms with a relatively simple intronic structure, such as yeast. Furthermore, the possibility of coordination in splicing regulation at genomic level is becoming clear in this model organism. This should provide a valuable system to approach the complex problem of the role of regulated splicing in genomic expression.

Splitting statistical potentials into meaningful scoring functions: testing the prediction of near-native structures from decoy conformations

Background: Recent advances on high-throughput technologies have produced a vast amount of protein sequences, while the number of high-resolution structures has seen a limited increase. This has impelled the production of many strategies to built protein structures from its sequence, generating a considerable amount of alternative models. The selection of the closest model to the native conformation has thus become crucial for structure prediction. Several methods have been developed to score protein models by energies, knowledge-based potentials and combination of both.Results: Here, we present and demonstrate a theory to split the knowledge-based potentials in scoring terms biologically meaningful and to combine them in new scores to predict near-native structures. Our strategy allows circumventing the problem of defining the reference state. In this approach we give the proof for a simple and linear application that can be further improved by optimizing the combination of Zscores. Using the simplest composite score () we obtained predictions similar to state-of-the-art methods. Besides, our approach has the advantage of identifying the most relevant terms involved in the stability of the protein structure. Finally, we also use the composite Zscores to assess the conformation of models and to detect local errors.Conclusion: We have introduced a method to split knowledge-based potentials and to solve the problem of defining a reference state. The new scores have detected near-native structures as accurately as state-of-art methods and have been successful to identify wrongly modeled regions of many near-native conformations.

An analysis of visual adaptation and contrast perception for tone mapping

Tone Mapping is the problem of compressing the range of a High-Dynamic Range image so that it can be displayed in a Low-Dynamic Range screen, without losing or introducing novel details: The final image should produce in the observer a sensation as close as possible to the perception produced by the real-world scene. We propose a tone mapping operator with two stages. The first stage is a global method that implements visual adaptation, based on experiments on human perception, in particular we point out the importance of cone saturation. The second stage performs local contrast enhancement, based on a variational model inspired by color vision phenomenology. We evaluate this method with a metric validated by psychophysical experiments and, in terms of this metric, our method compares very well with the state of the art.

Edge detection by selection of pieces of level lines

We propose an edge detector based on the selection of wellcontrasted pieces of level lines, following the proposal ofDesolneux-Moisan-Morel (DMM) [1]. The DMM edge detectorhas the problem of over-representation, that is, everyedge is detected several times in slightly different positions.In this paper we propose two modifications of the originalDMM edge detector in order to solve this problem. The firstmodification is a post-processing of the output using a generalmethod to select the best representative of a bundle of curves.The second modification is the use of Canny’s edge detectorinstead of the norm of the gradient to build the statistics. Thetwo modifications are independent and can be applied separately.Elementary reasoning and some experiments showthat the best results are obtained when both modifications areapplied together.

Goal recognition over POMDPs: inferring the intention of a POMDP agent

Plan recognition is the problem of inferring the goals and plans of an agent from partial observations of her behavior. Recently, it has been shown that the problem can be formulated and solved usingplanners, reducing plan recognition to plan generation.In this work, we extend this model-basedapproach to plan recognition to the POMDP setting, where actions are stochastic and states are partially observable. The task is to infer a probability distribution over the possible goals of an agent whose behavior results from a POMDP model. The POMDP model is shared between agent and observer except for the true goal of the agent that is hidden to the observer. The observations are action sequences O that may contain gaps as some or even most of the actions done by the agent may not be observed. We show that the posterior goal distribution P(GjO) can be computed from the value function VG(b) over beliefs b generated by the POMDPplanner for each possible goal G. Some extensionsof the basic framework are discussed, and a numberof experiments are reported.

Heritage Sporting Event : An Old Recipe for a New Problem

In the last decades, the globalized competition among cities and regions made them develop new strategies for branding and promoting their territory to attract tourists, investors, companies and residents. Major sports events - such as the Olympic Games, the FIFA World Cup or World and Continental Championships - have played an integral part in these strategies. Believing, with or without evidence, in the capacity of those events to improve the visibility and the economy of the host destination, many cities, regions and even countries have engaged in establishing sports events hosting strategies. The problem of the globalized competition in the sports events "market" is that many cities and regions do not have the resources - either financial, human or in terms of infrastructure - to compete in hosting major sports events. Consequently, many cities or regions have to turn to second-tier sports events. To organise those smaller events means less media coverage and more difficulty in finding sponsors, while the costs - both financial and in terms of services - stay high for the community. This paper analyses how Heritage Sporting Events (HSE) might be an opportunity for cities and regions engaged in sports events hosting strategies. HSE is an emerging concept that to date has been under-researched in the academic literature. Therefore, this paper aims to define the concept of HSE through an exploratory research study. A multidisciplinary literature review reveals two major characteristics of HSEs: the sustainability in the territory and the authenticity of the event constructed through a differentiation process. These characteristics, defined through multiple variables, give us the opportunity to observe the construction process of a sports event into a heritage object. This paper argues that HSEs can be seen as territorial resources that can represent a competitive advantage for host destinations. In conclusion, academics are invited to further research HSEs to better understand their construction process and their impacts on the territory, while local authorities are invited to consider HSEs for the branding and the promotion of their territory.

Sources of comparative advantage in polluting industries

We study the determinants of comparative advantage in polluting industries. We combine data on environmental policy at the country level with data on pollution intensity at the industry level to show that countries with laxer environmental regulation have a comparative advantage in polluting industries. Further, we address the potential problem of reverse causality. We propose an instrument for environmental regulation based on meteorological determinants of pollution dispersion identified by the atmospheric pollution literature. We find that the effect of environmental regulation on the pattern of trade is causal and comparable in magnitude to the effect of physical and human capital.

TECTONICS OF THE HELVETIC NAPPE SYSTEM (W SWITZERLAND): CONTROL OF STRAIN LOCALIZATION AND BASEMENT-COVER DEFORMATION. Insights from models based on continuum mechanics

The Helvetic nappe system in Western Switzerland is a stack of fold nappes and thrust sheets em-placed at low grade metamorphism. Fold nappes and thrust sheets are also some of the most common features in orogens. Fold nappes are kilometer scaled recumbent folds which feature a weakly deformed normal limb and an intensely deformed overturned limb. Thrust sheets on the other hand are characterized by the absence of overturned limb and can be defined as almost rigid blocks of crust that are displaced sub-horizontally over up to several tens of kilometers. The Morcles and Doldenhom nappe are classic examples of fold nappes and constitute the so-called infra-Helvetic complex in Western and Central Switzerland, respectively. This complex is overridden by thrust sheets such as the Diablerets and Wildhörn nappes in Western Switzerland. One of the most famous example of thrust sheets worldwide is the Glariis thrust sheet in Central Switzerland which features over 35 kilometers of thrusting which are accommodated by a ~1 m thick shear zone. Since the works of the early Alpine geologist such as Heim and Lugeon, the knowledge of these nappes has been steadily refined and today the geometry and kinematics of the Helvetic nappe system is generally agreed upon. However, despite the extensive knowledge we have today of the kinematics of fold nappes and thrust sheets, the mechanical process leading to the emplacement of these nappe is still poorly understood. For a long time geologist were facing the so-called 'mechanical paradox' which arises from the fact that a block of rock several kilometers high and tens of kilometers long (i.e. nappe) would break internally rather than start moving on a low angle plane. Several solutions were proposed to solve this apparent paradox. Certainly the most successful is the theory of critical wedges (e.g. Chappie 1978; Dahlen, 1984). In this theory the orogen is considered as a whole and this change of scale allows thrust sheet like structures to form while being consistent with mechanics. However this theoiy is intricately linked to brittle rheology and fold nappes, which are inherently ductile structures, cannot be created in these models. When considering the problem of nappe emplacement from the perspective of ductile rheology the problem of strain localization arises. The aim of this thesis was to develop and apply models based on continuum mechanics and integrating heat transfer to understand the emplacement of nappes. Models were solved either analytically or numerically. In the first two papers of this thesis we derived a simple model which describes channel flow in a homogeneous material with temperature dependent viscosity. We applied this model to the Morcles fold nappe and to several kilometer-scale shear zones worldwide. In the last paper we zoomed out and studied the tectonics of (i) ductile and (ii) visco-elasto-plastic and temperature dependent wedges. In this last paper we focused on the relationship between basement and cover deformation. We demonstrated that during the compression of a ductile passive margin both fold nappes and thrust sheets can develop and that these apparently different structures constitute two end-members of a single structure (i.e. nappe). The transition from fold nappe to thrust sheet is to first order controlled by the deformation of the basement. -- Le système des nappes helvétiques en Suisse occidentale est un empilement de nappes de plis et de nappes de charriage qui se sont mis en place à faible grade métamorphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement défor-mé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Mordes et la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glariis en Suisse centrale se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. Aujourd'hui la géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général. Malgré cela, les processus mécaniques par lesquels ces nappes se sont mises en place restent mal compris. Pendant toute la première moitié du vingtième siècle les géologues les géologues ont été confrontés au «paradoxe mécanique». Celui-ci survient du fait qu'un bloc de roche haut de plusieurs kilomètres et long de plusieurs dizaines de kilomètres (i.e., une nappe) se fracturera de l'intérieur plutôt que de se déplacer sur une surface frictionnelle. Plusieurs solutions ont été proposées pour contourner cet apparent paradoxe. La solution la plus populaire est la théorie des prismes d'accrétion critiques (par exemple Chappie, 1978 ; Dahlen, 1984). Dans le cadre de cette théorie l'orogène est considéré dans son ensemble et ce simple changement d'échelle solutionne le paradoxe mécanique (la fracturation interne de l'orogène correspond aux nappes). Cette théorie est étroitement lié à la rhéologie cassante et par conséquent des nappes de plis ne peuvent pas créer au sein d'un prisme critique. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la méca-nique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous avons dérivé un modèle d'écoulement dans un chenal d'un matériel homogène dont la viscosité dépend de la température. Nous avons appliqué ce modèle à la nappe de Mordes et à plusieurs zone de cisaillement d'échelle kilométrique provenant de différents orogènes a travers le monde. Dans le dernier article nous avons considéré le problème à l'échelle de l'orogène et avons étudié la tectonique de prismes (i) ductiles, et (ii) visco-élasto-plastiques en considérant les transferts de chaleur. Nous avons démontré que durant la compression d'une marge passive ductile, a la fois des nappes de plis et des nappes de charriages peuvent se développer. Nous avons aussi démontré que nappes de plis et de charriages sont deux cas extrêmes d'une même structure (i.e. nappe) La transition entre le développement d'une nappe de pli ou d'une nappe de charriage est contrôlé au premier ordre par la déformation du socle. -- Le système des nappes helvétiques en Suisse occidentale est un emblement de nappes de plis et de nappes de chaînage qui se sont mis en place à faible grade métamoiphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement déformé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Morcles and la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glarüs en Suisse centrale est certainement l'exemple de nappe de charriage le plus célèbre au monde. Elle se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. La géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général parmi les géologues. Au contraire les processus physiques par lesquels ces nappes sont mises en place reste mal compris. Les sédiments qui forment les nappes alpines se sont déposés à l'ère secondaire et à l'ère tertiaire sur le socle de la marge européenne qui a été étiré durant l'ouverture de l'océan Téthys. Lors de la fermeture de la Téthys, qui donnera naissance aux Alpes, le socle et les sédiments de la marge européenne ont été déformés pour former les nappes alpines. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la mécanique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous nous sommes intéressés à la localisation de la déformation à l'échelle d'une nappe. Nous avons appliqué le modèle développé à la nappe de Morcles et à plusieurs zones de cisaillement provenant de différents orogènes à travers le monde. Dans le dernier article nous avons étudié la relation entre la déformation du socle et la défonnation des sédiments. Nous avons démontré que nappe de plis et nappes de charriages constituent les cas extrêmes d'un continuum. La transition entre nappe de pli et nappe de charriage est intrinsèquement lié à la déformation du socle sur lequel les sédiments reposent.

The politics of contaminated sites management : institutional regime change and actor's mode of participation in the environmental management of the Bonfol Chemical Waste Landfill in Switzerland

By the end of the 1970s, contaminated sites had emerged as one of the most complex and urgent environmental issues affecting industrialized countries. The authors show that small and prosperous Switzerland is no exception to the pervasive problem of sites contamination, the legacy of past practices in waste management having left some 38,000 contaminated sites throughout the country. This book outlines the problem, offering evidence that open and polycentric environmental decision-making that includes civil society actors is valuable. They propose an understanding of environmental management of contaminated sites as a political process in which institutions frame interactions between strategic actors pursuing sometimes conflicting interests. In the opening chapter, the authors describe the influences of politics and the power relationships between actors involved in decision-making in contaminated sites management, which they term a "wicked problem." Chapter Two offers a theoretical framework for understanding institutions and the environmental management of contaminated sites. The next five chapters present a detailed case study on environmental management and contaminated sites in Switzerland, focused on the Bonfol Chemical Landfill. The study and analysis covers the establishment of the landfill under the first generation of environmental regulations, its closure and early remediation efforts, and the gambling on the remediation objectives, methods and funding in the first decade of the 21st Century. The concluding chapter discusses the question of whether the strength of environmental regulations, and the type of interactions between public, private, and civil society actors can explain the environmental choices in contaminated sites management. Drawing lessons from research, the authors debate the value of institutional flexibility for dealing with environmental issues such as contaminated sites.

STRATEGIES TO SURPASS THE VULNERABILITY OF THE SMALL ISLAND STATES WITH FEW RESOURCES: THE CASE OF CAPE VERDE

The problem of small Island Developing States (SIDS) is quite recent, end of the 80s and 90s, still looking for a theoretical consolidation. SIDS, as small states in development, formed by one or several islands geographically dispersed, present reduced population, market, territory, natural resources, including drinkable water, and, in great number of the cases, low level of economic activity, factors that together, hinder the gathering of scale economies. To these diseconomies they come to join the more elevated costs in transports and communications which, allies to lower productivities, to a smaller quality and diversification of its productions, which difficult its integration in the world economy. In some SIDS these factors are not dissociating of the few investments in infrastructures, in the formation of human resources and in productive investments, just as it happens in most of the developing countries. In ecological terms, many of them with shortage of natural resources, but integrating important ecosystems in national and world terms, but with great fragility relatively to the pollution action, of excessive fishing, of uncontrolled development of tourism, factors that, conjugated and associated to the stove effect, condition the climate and the slope of the medium level of the sea water and therefore could put in cause the own survival of some of them. The drive to the awareness of the international community towards its problems summed up with the accomplishment by the United Nations in the Barbados’s Conference, 1994 where the right to the development was emphasized, through the going up the appropriate strategies and the Programme of Action for the Sustainable Development of the SIDS. The orientation of the regional and international cooperation in that sense, sharing technology (namely clean technology and control and administration environmental technology), information and creation of capacity-building, supplying means, including financial resources, creating non discriminatory and just trade rules, it would drive to the establishment of a world system economically more equal, in which the production, the consumption, the pollution levels, the demographic politics were guided towards the sustainability. It constituted an important step for the recognition for the international community on the specificities of those states and it allowed the definition of a group of norms and politics to implement at the national, regional and international level and it was important that they continued in the sense of the sustainable development. But this Conference had in its origin previous summits: the Summit of Rio de Janeiro about Environment and Development, accomplished in 1992, which left an important document - the Agenda 21, in the Conference of Stockholm at 1972 and even in the Conference of Ramsar, 1971 about “Wetlands.” CENTRO DE ESTUDOS AFRICANOS Occasional Papers © CEA - Centro de Estudos Africanos 4 Later, the Valletta Declaration, Malta, 1998, the Forum of Small States, 2002, get the international community's attention for the problems of SIDS again, in the sense that they act to increase its resilience. If the definition of “vulnerability” was the inability of the countries to resist economical, ecological and socially to the external shocks and “resilience” as the potential for them to absorb and minimize the impact of those shocks, presenting a structure that allows them to be little affected by them, a part of the available studies, dated of the 90s, indicate that the SIDS are more vulnerable than the other developing countries. The vulnerability of SIDS results from the fact the they present an assemblage of characteristics that turns them less capable of resisting or they advance strategies that allow a larger resilience to the external shocks, either anthropogenic (economical, financial, environmental) or even natural, connected with the vicissitudes of the nature. If these vulnerability factors were grouped with the expansion of the economic capitalist system at world level, the economic and financial globalisation, the incessant search of growing profits on the part of the multinational enterprises, the technological accelerated evolution drives to a situation of disfavour of the more poor. The creation of the resilience to the external shocks, to the process of globalisation, demands from SIDS and of many other developing countries the endogen definition of strategies and solid but flexible programs of integrated development. These must be assumed by the instituted power, but also by the other stakeholders, including companies and organizations of the civil society and for the population in general. But that demands strong investment in the formation of human resources, in infrastructures, in investigation centres; it demands the creation capacity not only to produce, but also to produce differently and do international marketing. It demands institutional capacity. Cape Verde is on its way to this stage.

APPROACH AND TREATMENT OF SUICIDAL BEHAVIOR IN THE CLINICAL PRACTICE OF DIFFERENT GROUPS OF HEALTH PROFESSIONALS IN SPAIN: RESULTS OF THE PROJECT EUREGENA.

According to the WHO (World Health Organization) and the European Union, suicide is considered to be a health problem of prime importance and to be one of the principal causes of unnatural death. In Spain, the number of suicides has increased 12% since 2005 . The Research Project “European Regions Enforcing Actions against Suicide (EUREGENAS), funded by the Health Program 2008-2013, has as main objective the description of an integrated model of Mental Health orientated to the prevention of suicide. The differences that allow distinguishing the meaning of prevention in suicide behavior are described and explained through a qualitative methodological strategy and through the creation of discussion groups formed by different groups of health professionals. The results highlight the existing differences between the diverse health professionals who come more in contact with this problem and it shows as well the coincidence of meaning that suicide has to be considered as a priority in the field of health.

Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians

The human brainstem is a densely packed, complex but highly organised structure. It not only serves as a conduit for long projecting axons conveying motor and sensory information, but also is the location of multiple primary nuclei that control or modulate a vast array of functions, including homeostasis, consciousness, locomotion, and reflexive and emotive behaviours. Despite its importance, both in understanding normal brain function as well as neurodegenerative processes, it remains a sparsely studied structure in the neuroimaging literature. In part, this is due to the difficulties in imaging the internal architecture of the brainstem in vivo in a reliable and repeatable fashion. A modified multivariate mixture of Gaussians (mmMoG) was applied to the problem of multichannel tissue segmentation. By using quantitative magnetisation transfer and proton density maps acquired at 3 T with 0.8 mm isotropic resolution, tissue probability maps for four distinct tissue classes within the human brainstem were created. These were compared against an ex vivo fixated human brain, imaged at 0.5 mm, with excellent anatomical correspondence. These probability maps were used within SPM8 to create accurate individual subject segmentations, which were then used for further quantitative analysis. As an example, brainstem asymmetries were assessed across 34 right-handed individuals using voxel based morphometry (VBM) and tensor based morphometry (TBM), demonstrating highly significant differences within localised regions that corresponded to motor and vocalisation networks. This method may have important implications for future research into MRI biomarkers of pre-clinical neurodegenerative diseases such as Parkinson's disease.

The contributions of rare objects in correspondence analysis

Correspondence analysis, when used to visualize relationships in a table of counts(for example, abundance data in ecology), has been frequently criticized as being too sensitiveto objects (for example, species) that occur with very low frequency or in very few samples. Inthis statistical report we show that this criticism is generally unfounded. We demonstrate this inseveral data sets by calculating the actual contributions of rare objects to the results ofcorrespondence analysis and canonical correspondence analysis, both to the determination ofthe principal axes and to the chi-square distance. It is a fact that rare objects are oftenpositioned as outliers in correspondence analysis maps, which gives the impression that theyare highly influential, but their low weight offsets their distant positions and reduces their effecton the results. An alternative scaling of the correspondence analysis solution, the contributionbiplot, is proposed as a way of mapping the results in order to avoid the problem of outlying andlow contributing rare objects.