1,720,982 research outputs found
AlphaIIbG236E causes Glanzmann thrombasthenia by impairing association with beta3
Glanzmann thrombasthenia (GT) is a recessively inherited bleeding disorder caused by the quantitative or qualitative deficiency of the platelet fibrinogen receptor, integrin αIIbβ3. The N-terminal domain of the αIIb subunit is folded in a β-propeller that plays the role of binding fibrinogen and associating with the ligand-binding region of β3. Analysing the mutations of Italian GT patients we found that a patient had a αIIb G236E missense substitution that substitutes a glycine from the highly conserved ΦΦGΦ motif of blade 4 of the β-propeller. To verify experimentally the effect of the substitution of glycine 236 human embryonic kidney (HEK) cells were transfected with normal or mutated αIIb in conjunction with normal β3. Using flow cytometry analysis we found the percentage of HEK cells transfected with αIIbG236Eβ3 that reacted with anti αIIbβ3 was very low. In HEK cells transfected with either αIIbβ3 or αIIbG236Eβ3 and lysed, when immunoblotting was done in non-reducing conditions a band reacting with an antibody against αIIb was present in both lysates, although less intense in cells transfected with αIIbG236Eβ3. In reducing condition αIIb from cells transfected with αIIbβ3 was nearly all mature, while in cells transfected with αIIbG236Eβ3 the ratio pro-αIIb: αIIb was 1 : 1, with signs of degradation of the mutated protein. Cell lysates were then immunoprecipitated with antibodies against αIIb and immunoblotted with an antibody reacting with β3. While in immunoblots from cells transfected with αIIbβ3 a band corresponding to β3 was strongly detectable, in immunoblots originating from cells transfected with αIIbG236Eβ3 no band at the same level of normal β3 was detected. Immunofluorescence studies showed accumulation of αIIbG236Eβ3 in the endoplasmic reticulum and minimal transport to the Golgi. In conclusion we demonstrated that the αIIbG236E mutation causes GT by impairing the association with β3 during biogenesis of the receptor
Learning in human neural networks on microelectrode arrays
This paper describes experiments involving the growth of human neural networks of stem cells on a MEA (microelectrode array) support.
The microelectrode arrays (MEAs) are constituted by a glass support in which a set of tungsten electrodes are inserted.
The artificial neural network (ANN) paradigm was used by stimulating the neurons in parallel with digital patterns distributed on eight channels, then by analyzing a parallel multichannel output. In particular, the microelectrodes were connected following two different architectures, one inspired by the Kohonen's SOM, the other by the Hopfield network.
The output signals have been analyzed in order to evaluate the possibility of organized reactions by the natural neurons.f
The results show that the network of human neurons reacts selectively to the subministered digital signals, i.e., it produces similar output signals referred to identical or similar patterns, and clearly differentiates the outputs coming from different stimulations.
Analyses performed with a special artificial neural network called ITSOM show the possibility to codify the neural responses to different patterns, thus to interpret the signals coming from the network of biological neurons, assigning a code to each output. It is straightforward to verify that identical codes are generated by the neural reactions to similar patterns.
Further experiments are to be designed that improve the hybrid neural networks’ capabilities and to test the possibility of utilizing the organized answers of the neurons in several ways
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Behavior of living human neural networks on microelectrode array support
Researchers of the Department of Information Technologies of the University of Milano and of the Stem Cells Research Institute of the DIBIT-S. Raffaele Milano are experimenting the growth of human neural networks of stem cells on a MEA (Microelectrode Array) support. The Microelectrode arrays (MEAs) are constituted by a glass support where a set of tungsten electrodes is inserted. The distance between the electrodes is around 20 mm. The microelectrodes are connected following the architecture of classical artificial neural networks, in particular Kohonen and Hopfield networks. The neurons are stimulated following digital patterns and the output signals are analysed to evaluate the possibility of organized reaction by the natural neurons. The neurons reply selectively to different patterns and show similar reactions in front of the presentation of identical or similar patterns. These results allow to design further experiments that improve the neural networks capabilities and to test the possibility of utilizing the organized answers of the neurons in several ways
Variations on the Author
“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
We 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
Dispelling the Myths Behind First-author Citation Counts
We 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
Non-local correlations between separated neural networks
In recent times the interest for quantum models of brain activity has rapidly grown. The Penrose-Hameroff model assumes that microtubules inside neurons are responsible for quantum computation inside brain. Several experiments seem to indicate that EPR-like correlations are possible at the biological level. In the past year a very intensive experimental work about this subject has been done at DiBit Labs in Milan. Italy by our research group. Our experimental set-up is made by two separated and completely shielded basins where two parts of a common human DNA neuronal culture are monitored by EEG. Our main experimental result is that, under stimulation of one culture by means of a 630 nm laser beam at 300 ms. the cross-correlation between the two cultures grows up at maximum levels. Despite at this level of understanding it is impossible to tell if the origin of this non-locality is a genuine quantum effect. our experimental data seem to strongly suggest that biological systems present non-local properties not explainable by classical models
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