Institutional changes in function of improving efficiency of the economy

Summary: Establishing of the New institutional economics as dominant institutional theoretical perspective, has contributed to the theoretical affirmation of the institution and to the recognition that institutions and institutional changes are an important part of the overall dynamics of economic reality. Therefore, the importance of defining the “new” institutional paradigm is reflected not only in the "endogenization" of the institutions as the relevant economic variables, but also in the possibilities of a broader consideration of the potential contribution of institutions to the overall macroeconomic performances. However, despite to the significant theoretical achievements in the economic recognition of the multiple institutional importances, in the observation of institutional change as a determinant of economic development, many questions remain open. For instance, it is still not known which institutions, in which specific forms required, or rather useful for economic development, or in which context. Although it is known the role that specific institutions can play in the process of the economic development, the problem is how to build such institutions. If developmental effects generally depend on the quantity and quality of institutional changes, than how to explain the fact that the establishment of the same institutional forms in the countries with approximate developmental preconditions, usually in practice does not led to the equal developmental results? This study, in form of a doctoral dissertation, is exactly driven by such issues. Therefore, as its primary goal assumes the theoretical development of the concept of institutional contributions to the development and identification of institutional criteria and mechanisms for improving economic performance. The basic assumption on which this dissertation is based implies that institutions and institutional changes are necessary, but not sufficient condition for good macroeconomic performance of the country. This additional requirement is contained precisely in the implementation of „good governance“, namely the establishment of the basic principles of this concept. The research is based on an analytical basis of the theoretical framework of the New institutional economics. Starting of the known information about the nature of institutions and institutional change, as well as on the basic assumptions of institutional sustainability and efficiency, there are theoretical elaborated concept of the institutional contributions to the development. Special attention was given to comparative institutional analysis. By combining information from different comparative economics, there are studied the relationship between institutional quality and economic efficiency. An attempt was made in order to identify main channels through which institutional quality determined economic performance, and therefore which is a possible causes of institutional inefficiency. Through the analysis of several representative cases in practice, the empirical validity of the findings is further checked. Since development issues become topical, especially during the crisis, it is clear incentives to explore the institutions and mechanisms of institutional change and use this knowledge in achieving, in a greater degree, controlled development

Probabilistic Random Walk Models for Comparative Network Analysis

Graph-based systems and data analysis methods have become critical tools in many fields as they can provide an intuitive way of representing and analyzing interactions between variables. Due to the advances in measurement techniques, a massive amount of labeled data that can be represented as nodes on a graph (or network) have been archived in databases. Additionally, novel data without label information have been gradually generated and archived. Labeling and identifying characteristics of novel data is an important first step in utilizing the valuable data in an effective and meaningful way. Comparative network analysis is an effective computational means to identify and predict the properties of the unlabeled data by comparing the similarities and differences between well-studied and less-studied networks. Comparative network analysis aims to identify the matching nodes and conserved subnetworks across multiple networks to enable a prediction of the properties of the nodes in the less-studied networks based on the properties of the matching nodes in the well-studied networks (i.e., transferring knowledge between networks). One of the fundamental and important questions in comparative network analysis is how to accurately estimate node-to-node correspondence as it can be a critical clue in analyzing the similarities and differences between networks. Node correspondence is a comprehensive similarity that integrates various types of similarity measurements in a balanced manner. However, there are several challenges in accurately estimating the node correspondence for large-scale networks. First, the scale of the networks is a critical issue. As networks generally include a large number of nodes, we have to examine an extremely large space and it can pose a computational challenge due to the combinatorial nature of the problem. Furthermore, although there are matching nodes and conserved subnetworks in different networks, structural variations such as node insertions and deletions make it difficult to integrate a topological similarity. In this dissertation, novel probabilistic random walk models are proposed to accurately estimate node-to-node correspondence between networks. First, we propose a context-sensitive random walk (CSRW) model. In the CSRW model, the random walker analyzes the context of the current position of the random walker and it can switch the random movement to either a simultaneous walk on both networks or an individual walk on one of the networks. The context-sensitive nature of the random walker enables the method to effectively integrate different types of similarities by dealing with structural variations. Second, we propose the CUFID (Comparative network analysis Using the steady-state network Flow to IDentify orthologous proteins) model. In the CUFID model, we construct an integrated network by inserting pseudo edges between potential matching nodes in different networks. Then, we design the random walk protocol to transit more frequently between potential matching nodes as their node similarity increases and they have more matching neighboring nodes. We apply the proposed random walk models to comparative network analysis problems: global network alignment and network querying. Through extensive performance evaluations, we demonstrate that the proposed random walk models can accurately estimate node correspondence and these can lead to improved and reliable network comparison results

Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

<p>Abstract</p> <p>Background</p> <p>From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs). This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs.</p> <p>Methods</p> <p>Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A-LC and Child C-LC). Immunohistochemical (IHC), Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels.</p> <p>Results</p> <p>Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue.</p> <p>Conclusion</p> <p>It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.</p

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.</p

Institutional changes in function of improving efficiency of the economy

Summary: Establishing of the New institutional economics as dominant institutional theoretical perspective, has contributed to the theoretical affirmation of the institution and to the recognition that institutions and institutional changes are an important part of the overall dynamics of economic reality. Therefore, the importance of defining the “new” institutional paradigm is reflected not only in the "endogenization" of the institutions as the relevant economic variables, but also in the possibilities of a broader consideration of the potential contribution of institutions to the overall macroeconomic performances. However, despite to the significant theoretical achievements in the economic recognition of the multiple institutional importances, in the observation of institutional change as a determinant of economic development, many questions remain open. For instance, it is still not known which institutions, in which specific forms required, or rather useful for economic development, or in which context. Although it is known the role that specific institutions can play in the process of the economic development, the problem is how to build such institutions. If developmental effects generally depend on the quantity and quality of institutional changes, than how to explain the fact that the establishment of the same institutional forms in the countries with approximate developmental preconditions, usually in practice does not led to the equal developmental results? This study, in form of a doctoral dissertation, is exactly driven by such issues. Therefore, as its primary goal assumes the theoretical development of the concept of institutional contributions to the development and identification of institutional criteria and mechanisms for improving economic performance. The basic assumption on which this dissertation is based implies that institutions and institutional changes are necessary, but not sufficient condition for good macroeconomic performance of the country. This additional requirement is contained precisely in the implementation of „good governance“, namely the establishment of the basic principles of this concept. The research is based on an analytical basis of the theoretical framework of the New institutional economics. Starting of the known information about the nature of institutions and institutional change, as well as on the basic assumptions of institutional sustainability and efficiency, there are theoretical elaborated concept of the institutional contributions to the development. Special attention was given to comparative institutional analysis. By combining information from different comparative economics, there are studied the relationship between institutional quality and economic efficiency. An attempt was made in order to identify main channels through which institutional quality determined economic performance, and therefore which is a possible causes of institutional inefficiency. Through the analysis of several representative cases in practice, the empirical validity of the findings is further checked. Since development issues become topical, especially during the crisis, it is clear incentives to explore the institutions and mechanisms of institutional change and use this knowledge in achieving, in a greater degree, controlled development

Implications of posttranslational changes of fibrinogen on its reactivity and function

Fibrinogen je vaţan protein primarne i glavni protein sekundarne hemostaze. Nakon povrede, on se dejstvom trombina pretvara u nerastvorni fibrin koji se dalje umreţava, pri čemu nastaje fibrinska mreţa koja ojačava krvni ugrušak na mestu povrede. Da bi fibrinogen obavljao svoju biohemijsku ulogu, bitni su odreĎeni faktori, u koje spadaju njegove posttranslacione modifikacije i interakcije sa drugim proteinima. Posttranslacione modifikacije fibrinogena utiču na njegovu strukturu, strukturu fibrina i interakcije sa drugim proteinima. Fibrin nije pasivna mreţa koja samo daje potporu krvnom ugrušku, već je aktivna struktura koja reguliše svoju sintezu i razgradnju interakcijom sa brojnim proteinima. Zato je vaţno otkriti nove proteine koji sa njim interaguju, a koji imaju uticaj na proces zarastanja povreda. U okviru ove diseretacije, optimizovana je procedura za izolovanje i analizu fibrinogena. Upotrebom dvostrukog taloţenja etanolom dobijen je visoko prečišćen fibrinogen, pogodan za dalju karakterizaciju. Kako je poznato da fibrinogen interaguje sa IGFBP-3 proteinom, postavilo se pitanje da li još neki protein iz grupe vezujućih proteina za IGF, pri fiziološkim uslovima, ima tu sposobnost. Upotrebom većeg broja afinitetnih metoda je pokazano da IGFBP-1 interaguje sa fibrinogenom i da je to opšta fiziološka pojava. Značaj ove interakcije treba sagledavati imajući u vidu da i IGFBP-1 podstiče zarastanje tkivnih povreda, samostalno i kao transporter IGF molekula. Brojne patologije pri kojima se javljaju i koagulopatije, kao što su dijabetes melitus tipa 2 i ciroza jetre, karakteriše izmenjena koncentracija i struktura fibrinogena, što za posledicu ima stvaranje abnormalnog, trombogenog fibrina. Detaljno izučavanje pojedinačnih proteina uključenih u koagulopatiju moţe dati bliţu sliku mehanizma odgovornog za ovu pojavu. Sa druge strane, promene na nivou posttranslacionih modifikacija i strukture fibrinogena sa starenjem mogu doprineti boljem razumevanju prisustva ili odsustva odreĎenih patologija kod starijih ljudi. Struktura fibrinogena sa starenjem se menja. Primenom lektinskog eseja uočeno je povećanje visoko-manoznih i/ili hibridnih N-glikana, tri-/tertaantenarnih kompleksnih glikana sa većim sadrţajem Gal i GlcNAc. Spektrofluorimetrijska analiza je pokazala da kod zdravih ljudi preko 60 godina starosti, fibrinogen ima kompaktniju tercijarnu strukturu...Fibrinogen is an important protein of primary and main protein of secondary hemostasis. Upon injury, fibrinogen is converted to insoluble fibrin by the action of thrombin. Fibrin further cross-links and creates fibrin network which reinforces blood clotting at the site of injury. There is a significant contribution of posttranslational modifications as well as interactions with other proteins necessary for fulfillment of fibrinogen biochemical role. Posttranslational modifications of fibrinogen influence its structure, fibrin structure and interactions with other proteins. Fibrin is not only a passive network that supports blood clot, but also an active structure that regulates its synthesis and degradation by interacting with many different proteins. For this reason, it is important to identify new proteins which interact with fibrinogen and may also have a role in wound healing. The procedure for isolation and analysis of fibrinogen was optimized in this dissertation. Application of double precipitation using ethanol resulted in highly purified fibrinogen, suitable for further characterisation. Since it is known that fibrinogen interacts with IGFBP-3 protein, the question was raised weather some other protein from the family of the IGF-binding proteins has this ability under physiological conditions. By using several affinity methods, it was shown that IGFBP-1 interacts with fibrinogen and this is a general physiological event. The significance of this interaction should be evaluated taking into consideration that IGFBP-1 itself may have beneficial effect on tissue wound healing, alone and as a transporter of the IGF molecule. Several pathologies accompanied by coagulopathies, such as diabetes mellitus type 2 and cirrhosis, are characterised by altered concentration and structure of fibrinogen, which in turn creates abnormal, thrombogenic fibrin. Detailed study of individual proteins included in coagulopathy may enable closer look at mechanisms responsible for this outcome. On the other hand, changes in posttranslational modifications and structure of fibrinogen with aging may lead to better understanding of presence or absence of certain pathologies associated with ageing. The structure of fibrinogen alteres with aging. An increase of high-mannose and/or hybrid N-glycans, tri-/tetraantennary complex glycans with greater amounts of Gal and GlcNAc was detected by lectin array..

Methodological institutionalism in the context of economic science evolution

As the achievements of the modern civilization and the result of the dominant trend of modern science, the existing methodological concepts of scientific progress analysis are incomplete and inadequate. Institutionalization of science comes to redefining the hierarchy and heterarchy in the organization of scientific research, which raises the level of cognitive effects from the individual to the collective level, leading to the establishment of a new relationship between the individual, the scientific, and ideological institutions. Contradictions between cognitive status and interests of each of the agents (operative, scientific, and ideological institutions) must be reflected in a scientific paper and thus the overall trend of progress in science. Rationality of an agent is a function that influences cognitive and institutional interests

Structure-based protein function prediction using graph convolutional networks

The rapid increase in the number of proteins in sequence databases and the diversity of their functions challenge computational approaches for automated function prediction. Here, we introduce DeepFRI, a Graph Convolutional Network for predicting protein functions by leveraging sequence features extracted from a protein language model and protein structures. It outperforms current leading methods and sequence-based Convolutional Neural Networks and scales to the size of current sequence repositories. Augmenting the training set of experimental structures with homology models allows us to significantly expand the number of predictable functions. DeepFRI has significant de-noising capability, with only a minor drop in performance when experimental structures are replaced by protein models. Class activation mapping allows function predictions at an unprecedented resolution, allowing site-specific annotations at the residue-level in an automated manner. We show the utility and high performance of our method by annotating structures from the PDB and SWISS-MODEL, making several new confident function predictions. DeepFRI is available as a webserver at https://beta.deepfri.flatironinstitute.org/