1,721,073 research outputs found
COMPUTATIONAL MODELING OF PROTEINS: FROM STATISTICAL MECHANICS TO IMMUNOLOGY
Full text linkOne of the biggest revolutions occurred during the second half of the 20th century in physics was the introduction of computers in research. In particular, the use of fast computing machines opened the possibility to study complex systems by simulating their dynamics, without the need to pursue analytical solutions, otherwise impossible to tackle. The consequences of this breakthrough were huge both in the study of equilibrium and non-equilibrium many-body problems, with the strong limitation given by the number of atoms involved in the calculation.
The first technique used in biology-related problems was the Monte Carlo Method, and some years later Molecular Dynamics (MD) was formalized. In MD, for each atom of the system one can solve its Newton equations of motion, obtaining a trajectory in the phase space for the entire system, and study its behavior in equilibrium and non-equilibrium conditions. The constant rise in computational power gave the possibility to scientists to study larger and larger systems, while the advances in experimental techniques enhanced the possibility for direct comparisons between wet and in silico data at similar levels of resolution. Despite the validity of Moore’s Law (i.e., the exponential growth of the computing power due to transistors miniaturization) until now, the timescale of the events that can be simulated has an upper limit of the millisecond with tailor-made computers, which is not enough to study all the biologically-relevant phenomena. Since the birth of computational chemistry, a huge number of different statistical mechanics-based methods has been implemented to permit, given the computing power limit, an effective reliable use of MD simulations in biochemistry.
One of the most relevant problems tackled by MD is the calculation of free energy differences, both in conformational changes and in sequence mutations of a protein. The main reason of this difficulty is represented by the frustrated nature of interactions in proteins and the size of these systems: this leads to a complex energy landscape which in principle needs very long sampling times to overcome all possible energy barriers. In the present thesis, we studied and improved a path-independent and system-independent free energy calculation technique, called Simplified Confinement Method. We describe this work in Chapter 1.
Although MD has been successful in most of its applications, there are still many open problems: as mentioned before, the available parametrizations of interaction potentials (called force fields) are not completely reliable. In particular, the choice of force field parameters is performed comparing experimental data on a fixed set of (usually small) molecules with computed data on the same molecules. This raises a significant problem: large molecules can have a more complex behavior, and using these potentials can lead to a systematic error; furthermore, the timescale in which the force field is tested needs to be limited. Another strong limitation of MD depends on the equilibrium experiments used for parametrization: the kinetic properties of a system are not considered. Given the impossibility to reparametrize a general force field with non-equilibrium experimental data, we implemented a technique that uses equilibrium-based force fields, adding a potential term based on time series resulting from kinetic experiments. This approach, based on the principle of Maximum Caliber, restrains the system with an experimental-based bias, returning a more realistic behavior of the simulation in condition where the usual force fields show their limitations. We describe this work in Chapter 2.
The application of computational methods in the study of proteins confirms its efficacy in other fields of life sciences: an actual and emerging topic is represented by vaccinology. With techniques developed by Louis Pasteur at the end of the 19 th century (isolation of the pathogen, its inactivation and subsequent inoculation in the host), various scientists developed vaccines for deadly diseases like poliomyelitis, diphterite and measles. None of the mentioned was developed with molecular biology-based approaches. Almost 50 years after the birth of molecular biology, the Human Genome Project decoded human DNA and, at the same time, the genome of the most dangerous pathogen was screened. This has laid the foundation of Reverse Vaccinology (RV), where the proteins responsible for immune reaction can be identified from the pathogen DNA and tested directly on animal models, obtaining a new vaccine candidate with little or no risk for the host, having removed the pathogen itself. At the beginning of the 21st century the first vaccine against Meningococcus B, responsible for the 50% of the meningococcal meningitis, was developed using this protocol. Since then, crystallographic data was inserted in RV workflow to exploit conformational data, creating the so-called Structural Vaccinology (SV). To enhance its efficacy, SV exploits all the aspects of molecular modeling like computer-aided drug/protein design and MD to integrate information that come from experimental sources. One of the most promising technique in this field is the grafting of an immunogenic sequence (i.e., a portion of a protein recognized by the immune system) on a foreign protein; this approach could lead to a new vaccine component which have no risk for the patient. To date, the grafting technique has been carried out by human-driven workflows. Motivated by this reason, we studied immunogenic peptides from a family of pathogens involved in respiratory diseases, exploiting Structural Vaccinology principles with both computational and experimental approach. Furthermore, we developed and implemented an unsupervisionated automated tool to design grafted protein sequences. We describe this work in Chapter 3
Per una formazione umanistica. Contributo di Elena Marescotti
No full textI curatori del volume, nello stendere un "manifesto sulla formazione degli adulti", hanno interpellato docenti e ricercatori italiani che si occupano di educazione degli adulti e hanno rivolto loro tre domande: 1) Quale senso ha oggi la formazione degli adulti? Che compiti le possono essere affidati? 2) Alcuni di noi ritengono importante che alla formazione degli adulti debbano essere affidati compiti di sviluppo complessivo della persona in senso umanistico e non solo funzioni strumentali. Condividi questa impostazione? 3) Se la risposta è affermativa, quali metodologie e quali tecniche possono essere utilizzate in coerenza con tale obiettivo? Il volume raccoglie le risposte a queste domande che, nel loro insieme, rappresentano un quadro ricco e articolato delle problematiche dell'EdA in Italia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Contributo di Chiara Biasin
Full text linkIl contributo intende rispondere ad alcune domande cruciali:quale senso ha oggi l'educazione degli adulti? Che compiti le possono essere attribuiti? Esso mette in luce il compito di sviluppo complessivo della persone piuttosto che le funzioni prettamente tecniche o strumentali dell'educazione degli adult
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
