Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice

Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), perhaps with additional contributions from serotonin transporter (5-HTT) recognition, was key to its rewarding actions. We now report that knockout mice without DAT and mice without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mouse model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These results have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.

State of the art in continuous speech recognition.

In the past decade, tremendous advances in the state of the art of automatic speech recognition by machine have taken place. A reduction in the word error rate by more than a factor of 5 and an increase in recognition speeds by several orders of magnitude (brought about by a combination of faster recognition search algorithms and more powerful computers), have combined to make high-accuracy, speaker-independent, continuous speech recognition for large vocabularies possible in real time, on off-the-shelf workstations, without the aid of special hardware. These advances promise to make speech recognition technology readily available to the general public. This paper focuses on the speech recognition advances made through better speech modeling techniques, chiefly through more accurate mathematical modeling of speech sounds.

New multivalent calixarene-based ligands for protein recognition and inhibition

One of the challenges that concerns chemistry is the design of molecules able to modulate protein-protein and protein-ligand interactions, since these are involved in many physiological and pathological processes. The interactions occurring between proteins and their natural counterparts can take place through reciprocal recognition of rather large surface areas, through recognition of single contact points and single residues, through inclusion of the substrates in specific, more or less deep binding sites. In many cases, the design of synthetic molecules able to interfere with the processes involving proteins can benefit from the possibility of exploiting the multivalent effect. Multivalency, widely spread in Nature, consists in the simultaneous formation between two entities (cell-cell, cell-protein, protein-protein) of multiple equivalent ligand-recognition site complexes. In this way the whole interaction results particularly strong and specific. Calixarenes furnish a very interesting scaffold for the preparation of multivalent ligands and in the last years calixarene-based ligands demonstrated their remarkable capability to recognize and inhibit or restore the activity of different proteins, with a high efficiency and selectivity in several recognition phenomena. The relevance and versatility of these ligands is due to the different exposition geometries of the binding units that can be explored exploiting the conformational properties of these macrocycles, the wide variety of functionalities that can be linked to their structure at different distances from the aromatic units and to their intrinsic multivalent nature. With the aim of creating new multivalent systems for protein targeting, the work reported in this thesis regards the synthesis and properties of glycocalix[n]arenes and guanidino calix[4]arenes for different purposes. Firstly, a new bolaamphiphile glycocalix[4]arene in 1,3-alternate geometry, bearing cellobiose, was synthesized for the preparation of targeted drug delivery systems based on liposomes. The formed stable mixed liposomes obtained by mixing the macrocycle with DOPC were shown to be able of exploiting the sugar units emerging from the lipid bilayer to agglutinate Concanavalin A, a lectin specific for glucose. Moreover, always thanks to the presence of the glycocalixarene in the layer, the same liposomes demonstrated through preliminary experiments to be uptaken by cancer cells overexpressing glucose receptors on their exterior surface more efficiently respect to simple DOPC liposomes lacking glucose units in their structure. Then a small library of glycocalix[n]arenes having different valency and geometry was prepared, for the creation of potentially active immunostimulants against Streptococcus pneumoniae, particularly the 19F serotype, one of the most virulent. These synthesized glycocalixarenes bearing β-N-acetylmannosamine as antigenic unit were compared with the natural polysaccharide on the binding to the specific anti-19F human polyclonal antibody, to verify their inhibition potency. Among all, the glycocalixarene based on the conformationally mobile calix[4]arene resulted the more efficient ligand, probably due its major possibility to explore the antibody surface and dispose the antigenic units in a proper arrangement for the interaction process. These results pointed out the importance of how the different multivalent presentation in space of the glycosyl units can influence the recognition phenomena. At last, NMR studies, using particularly 1H-15N HSQC experiments, were performed on selected glycocalix[6]arenes and guanidino calix[4]arenes blocked in the cone geometry, in order to better understand protein-ligand interactions. The glycosylated compounds were studied with Ralstonia solanacearum lectin, in order to better understand the nature of the carbohydrate‐lectin interactions in solution. The series of cationic calixarene was employed with three different acidic proteins: GB1, Fld and alpha synuclein. Particularly GB1 and Fld were observed to interact with all five cationic calix[4]arenes but showing different behaviours and affinities.

Optimal Decision Rules in Logical Recognition Models

The task of smooth and stable decision rules construction in logical recognition models is considered. Logical regularities of classes are defined as conjunctions of one-place predicates that determine the membership of features values in an intervals of the real axis. The conjunctions are true on a special no extending subsets of reference objects of some class and are optimal. The standard approach of linear decision rules construction for given sets of logical regularities consists in realization of voting schemes. The weighting coefficients of voting procedures are done as heuristic ones or are as solutions of complex optimization task. The modifications of linear decision rules are proposed that are based on the search of maximal estimations of standard objects for their classes and use approximations of logical regularities by smooth sigmoid functions.

Tracing change in World Cultural Heritage : the recognition of intangible heritage

This thesis investigates the crossover from and intersection between tangible and intangible heritage in the context of World Heritage. Since the start of the twenty-first century, intangible heritage has become increasingly important in international cultural heritage conservation theory and practice. In heritage literature, intangible heritage has been theorized in relation to tangible or built heritage, thereby extending the definition of cultural heritage to consider a holistic perspective. New heritage conservation instruments have been created for the protection of intangible heritage, such as most prominently the 2003 UNESCO Convention for the Safeguarding of the Intangible Cultural Heritage. The changing conception of cultural heritage that goes beyond tangible heritage has also influenced existing instruments like the 1972 UNESCO Convention concerning the protection of the World Cultural and Natural Heritage. The thesis studies how intangible heritage has been recognized and interpreted in implementing the concept of cultural heritage as defined by the World Heritage Convention. It examines the historical development of the concept of World Cultural Heritage with the aim of tracing the construction of intangible heritage in this context. The thesis consists of six chapters. The introduction sets out the research problem and research question. In the literature review, international cultural heritage conservation is portrayed as the research context, the knowledge gap between World Heritage and intangible heritage is identified and an understanding of the research problem deepened, and methods from similar research in the subject area are presented. The methodology in the third chapter describes choices made concerning the research paradigm, research approach and strategy, the use of concepts and illustrative examples, as well as data collection and analysis methods. Knowledge is constructed using primarily a historical approach and related methods. Through the analysis of pertinent documents and heritage discourses, an understanding of the concept of intangible heritage is developed and the concept of World Cultural Heritage is investigated. In the fourth chapter, intangible heritage is studied by looking at specific cultural heritage discourses, that is, a scientific, a UNESCO, and an ICOMOS discourse. Intangible heritage is theorized in relation to the concepts of tangible heritage, heritage value, and cultural heritage. Knowledge gained in this chapter serves as a theoretical lens to trace the recognition of and tease out interpretations of intangible heritage in the context of implementing the concept of World Cultural Heritage. The results are presented in chapter five. A historical development is portrayed in five time periods and for the concepts of cultural heritage, Outstanding Universal Value, the criteria to assess World Heritage value, and authenticity. The conclusion summarizes the main outcomes, assesses the thesis’ contribution to scientific knowledge as well as its limitations, and outlines possible further research. The main results include the identification of the term intangible heritage as an indicator for a paradigm shift and a new approach to conceiving cultural heritage in international cultural heritage conservation. By focusing on processes and the living relationship between people and their environment or place, intangible heritage emphasizes the anthropological. In the context of this conception, intangible heritage takes on two meanings. First, value is attributed by people and hence, is inherently immaterial. Secondly, place is constituted of a tangible-intangible continuum in terms of attributes. A paradigm shift and increasing recognition of an anthropological approach to cultural heritage were identified for all discourses, that is, UNESCO, ICOMOS, the scientific field, and World Heritage. For World Heritage, intangible heritage was recognized indirectly in terms of historical associations during the 1970s and 1980s. The anthropological shift occurred in the early 1990s. The term intangible was introduced and the meaning of intangible heritage was extended to include cultural associations. The subsequent decade is characterized by a process of internalization and implementation of the new approach to cultural heritage. The 2003 Intangible Cultural Heritage Convention created momentum. By the early 2010s, while not explicitly recognizing the immaterial character of values, a holistic approach to cultural heritage was fully endorsed that considers the idea of intangible attributes as carriers of values. An understanding of the recognition of intangible heritage through the implementation of the World Heritage Convention and scientific research in general provide an important knowledge base for implementing the Convention in a more coherent, objective, and well-informed way.

Tracing change in World Cultural Heritage : the recognition of intangible heritage

This thesis investigates the crossover from and intersection between tangible and intangible heritage in the context of World Heritage. Since the start of the twenty-first century, intangible heritage has become increasingly important in international cultural heritage conservation theory and practice. In heritage literature, intangible heritage has been theorized in relation to tangible or built heritage, thereby extending the definition of cultural heritage to consider a holistic perspective. New heritage conservation instruments have been created for the protection of intangible heritage, such as most prominently the 2003 UNESCO Convention for the Safeguarding of the Intangible Cultural Heritage. The changing conception of cultural heritage that goes beyond tangible heritage has also influenced existing instruments like the 1972 UNESCO Convention concerning the protection of the World Cultural and Natural Heritage. The thesis studies how intangible heritage has been recognized and interpreted in implementing the concept of cultural heritage as defined by the World Heritage Convention. It examines the historical development of the concept of World Cultural Heritage with the aim of tracing the construction of intangible heritage in this context. The thesis consists of six chapters. The introduction sets out the research problem and research question. In the literature review, international cultural heritage conservation is portrayed as the research context, the knowledge gap between World Heritage and intangible heritage is identified and an understanding of the research problem deepened, and methods from similar research in the subject area are presented. The methodology in the third chapter describes choices made concerning the research paradigm, research approach and strategy, the use of concepts and illustrative examples, as well as data collection and analysis methods. Knowledge is constructed using primarily a historical approach and related methods. Through the analysis of pertinent documents and heritage discourses, an understanding of the concept of intangible heritage is developed and the concept of World Cultural Heritage is investigated. In the fourth chapter, intangible heritage is studied by looking at specific cultural heritage discourses, that is, a scientific, a UNESCO, and an ICOMOS discourse. Intangible heritage is theorized in relation to the concepts of tangible heritage, heritage value, and cultural heritage. Knowledge gained in this chapter serves as a theoretical lens to trace the recognition of and tease out interpretations of intangible heritage in the context of implementing the concept of World Cultural Heritage. The results are presented in chapter five. A historical development is portrayed in five time periods and for the concepts of cultural heritage, Outstanding Universal Value, the criteria to assess World Heritage value, and authenticity. The conclusion summarizes the main outcomes, assesses the thesis’ contribution to scientific knowledge as well as its limitations, and outlines possible further research. The main results include the identification of the term intangible heritage as an indicator for a paradigm shift and a new approach to conceiving cultural heritage in international cultural heritage conservation. By focusing on processes and the living relationship between people and their environment or place, intangible heritage emphasizes the anthropological. In the context of this conception, intangible heritage takes on two meanings. First, value is attributed by people and hence, is inherently immaterial. Secondly, place is constituted of a tangible-intangible continuum in terms of attributes. A paradigm shift and increasing recognition of an anthropological approach to cultural heritage were identified for all discourses, that is, UNESCO, ICOMOS, the scientific field, and World Heritage. For World Heritage, intangible heritage was recognized indirectly in terms of historical associations during the 1970s and 1980s. The anthropological shift occurred in the early 1990s. The term intangible was introduced and the meaning of intangible heritage was extended to include cultural associations. The subsequent decade is characterized by a process of internalization and implementation of the new approach to cultural heritage. The 2003 Intangible Cultural Heritage Convention created momentum. By the early 2010s, while not explicitly recognizing the immaterial character of values, a holistic approach to cultural heritage was fully endorsed that considers the idea of intangible attributes as carriers of values. An understanding of the recognition of intangible heritage through the implementation of the World Heritage Convention and scientific research in general provide an important knowledge base for implementing the Convention in a more coherent, objective, and well-informed way.

Automatic Target Recognition in Synthetic Aperture Radar Imagery: A State-of-the-Art Review

The purpose of this paper is to survey and assess the state-of-the-art in automatic target recognition for synthetic aperture radar imagery (SAR-ATR). The aim is not to develop an exhaustive survey of the voluminous literature, but rather to capture in one place the various approaches for implementing the SAR-ATR system. This paper is meant to be as self-contained as possible, and it approaches the SAR-ATR problem from a holistic end-to-end perspective. A brief overview for the breadth of the SAR-ATR challenges is conducted. This is couched in terms of a single-channel SAR, and it is extendable to multi-channel SAR systems. Stages pertinent to the basic SAR-ATR system structure are defined, and the motivations of the requirements and constraints on the system constituents are addressed. For each stage in the SAR-ATR processing chain, a taxonomization methodology for surveying the numerous methods published in the open literature is proposed. Carefully selected works from the literature are presented under the taxa proposed. Novel comparisons, discussions, and comments are pinpointed throughout this paper. A two-fold benchmarking scheme for evaluating existing SAR-ATR systems and motivating new system designs is proposed. The scheme is applied to the works surveyed in this paper. Finally, a discussion is presented in which various interrelated issues, such as standard operating conditions, extended operating conditions, and target-model design, are addressed. This paper is a contribution toward fulfilling an objective of end-to-end SAR-ATR system design.

Behavioral traits predicting cocaine-conditioned place reference in mice: role of anxiety adn the basolateral amygdala

Aims. The individual susceptibility to cocaine addiction, a factor of interest in the understanding and prevention of this disorder, may be predicted by certain behavioral traits. However, these are not usually taken into account in research, making it difficult to identify whether they are a cause or a consequence of drug use. Methods. Male C57BL/6J mice underwent a battery of behavioral tests (elevated plus maze, hole-board, novelty preference in the Y maze, episodic-like object recognition memory and forced swimming test), followed by a cocaine-conditioned place preference (CPP) training to assess the reinforcing effect of the drug. In a second study, we aimed to determine the existence of neurobiological differences between the mice expressing high or low CPP by studying the number of neurons in certain addiction-related structures: the medial prefrontal cortex, the basolateral amygdala and the ventral tegmental area. Results. Anxiety-like behaviors in the elevated plus maze successfully predicted the cocaine-CPP behavior, so that the most anxious mice were also more likely to search for cocaine in a CPP paradigm. In addition, these mice exhibited an increased number of neurons in the basolateral amygdala, a key structure in emotional response including anxiety expression, without differences in the others regions analyzed. Conclusions. Our results suggest a relevant role of anxiety as a psychological risk factor for cocaine vulnerability, with the basolateral amygdala as potential common neural center for both anxiety and addiction.

Exploring the effectiveness of virtual product placement on recall and recognition of new brands

This paper investigates the effectiveness of virtual product placement as a marketing tool by examining the relationship between brand recall and recognition and virtual product placement. It also aims to address a gap in the existing academic literature by focusing on the impact of product placement on recall and recognition of new brands. The growing importance of product placement is discussed and a review of previous research on product placement and virtual product placement is provided. The research methodology used to study the recall and recognition effects of virtual product placement are described and key findings presented. Finally, implications are discussed and recommendations for future research provided.