177,095 research outputs found
The New ESC Guidelines for the Diagnosis and Management of Chronic Coronary Syndromes: the Good and the Not So Good
No full textDuring the annual meeting in Paris, the European Society of Cardiology released the new guidelines for the diagnosis and management of chronic coronary syndromes that will replace the 2013 guidelines on stable coronary artery disease. We intend to provide a brief commentary on what, in our opinion, is good and what is not as good. Our careful analysis shows that the 2019 guidelines contain a number of positive innovations, including a new definition, a central role of non-invasive testing for myocardial ischaemia, the most contemporary prevalence of the disease, the fact that medical therapy remains paramount despite the important advances in revascularisation and many other good issues as well as some limitations. The section on medical therapy of chronic coronary syndromes patients shows some inconsistency between text and the suggested scheme as well as contradictions with recommendations of regulatory agencies. It is not immediate to appreciate what is good and what is not so good in guidelines, which are often read in a hurry. We have provided a short commentary for the readers who usually concentrate more on the figures and flowcharts rather than on the text
La profilassi tromboembolica nei soggetti con insufficienza respiratoria cronica riacutizzata
No full textAppropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Molecular dynamics study of pathogenic mutations of SMN protein: effects on SMN-SmD1 protein complex formation and implication in Spinal Muscular Atrophy
No full textSpinal muscular atrophy (SMA) is a motor neuron disease that leads to muscle atrophy due to motor neurons degeneration. SMA is a major genetic cause of early childhood mortality and results from mutations in the Survival of Motor Neuron (SMN) gene 1. The SMN protein plays a crucial role in the assembly of spliceosomal small nuclear ribonucleoprotein complexes via binding to the spliceosomal Sm core proteins, in particular to their arginine-glycine (RG) rich C-terminal tails. SMN contains a central Tudor domain, directly involved in the SMN–Sm protein interaction by the recognition of symmetrically dimethylated arginine (DMR) residues in the RG repeats. In particular, an aromatic cage on Tudor domain seems to mediate this binding1-3.
Six of the pathogenic mutations causing SMA occur in the SMN Tudor domain. The only one that prevents the binding to the Sm proteins without a perturbation of the domain fold is E134K, that is the cause of the more severe type I SMA3.
To gain more understanding about the mechanism by which SMN interacts with the Sm proteins, and which are the structural effects on binding of its deleterious mutation E134K, we investigated the behavior of the native and mutated structure of the SMN Tudor domain in the presence of the C-terminal tail of SmD1, by means of molecular dynamics simulations.
We observed that the interaction of the SmD1 tail with the Tudor domain is electrostatic driven by the acidic residues near the entrance of the aromatic cage. In the native protein, a central DMR of the tail enters into the cage rapidly and stably, forming a network of both hydrophobic and cationic-pi interactions, both in stacking and T-shaped. The complex is stabilized also by the salt-bridges formed by the other DMRs and arginine residues wrapped around the acidic surface of the Tudor domain.
The charge inversion of E134K mutation leads to a non-correct interaction of the SmD1 tail with the acidic residues at the Tudor surface, causing the detachment the C-terminal region of the tail. In addition, the E134K mutation destabilizes the cage, not only with the disruption of the strong 134-136-127 H-bonds network, but also with the formation of new electrostatic and cationic-pi interactions. The cage collapses and expands, preventing a stable binding of the DMR.
The results are in agreement with what experimentally observed1-3 and clarify the key role of E134 in the interaction of the SmD1 tail with the Tudor domain. The loss of a strong Tudor-SmD1 interaction, if by one side causes the loss of a functional splicing machinery, by the other side causes the exposition of the detached Sm tails, that could stimulate the recognition by anti-Sm autoantibodies, as is reported for other diseases as lupus erithematosus4, giving rise to the innovative hypothesis of SMA as an autoimmune disease.
1. Selenko, P. et al., Nat. Struct. Biol. 8, 27–31 (2001).
2. Sprangers, R. et al., J. Mol. Biol. 327, 507–520 (2003).
3. Tripsianes, K. et al., Nat. Struct. Mol. Biol. 18, 1414–20 (2011).
4. Brahms, H. et al., J. Biol. Chem. 275, 17122–17129 (2000)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Letter from R. R. Zellick, Assistant Trust Officer, Anglo California National Bank of San Francisco, to Joseph R. Goodman, October 2, 1942
No full textLetter from R. R. Zellick, Assistant Trust Officer at The Anglo California National Bank of San Francisco, to Joseph R. Goodman, regarding property owned by Dave Tatsuno. Zellick mentions a dispute between current tenants and Tatsuno, and that Tatsuno has asked Goodman to help locate trustworthy tenants.Personal correspondence, organizational records, government documents, publications, and other papers created or collected by Joseph R. Goodman documenting the forced removal and incarceration of Japanese Americans during World War II, as well as organized resistance to incarceration. Included in the collection are records of the Japanese Young Men's Christian Association and the Japanese American Citizens' League in San Francisco, including papers of the Japanese YMCA's executive secretary Lincoln Kanai; Sakai family papers; Goodman's correspondence to and from Japanese American incarcerees, organizations opposing forced removal and incarceration of Japanese Americans, the War Relocation Authority, and others; publications, photographs, and ephemera from the Topaz Relocation Center, where Goodman taught high school; War Relocation Authority records and publications; and newspaper clippings, pamphlets, and reports about forced removal and incarceration created by various government, religious, and civic organizations, in California and nationwide
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Robot therapy for severely impaired stroke survivors: Toward a concurrent regulation of task difficulty and degree of assistance
No full textMany exercise protocols for robot therapy are designed to adjust their degree of difficulty in order to maintain a constant challenge level. A simple way to do this is to design exercises that consist of a variable number of sub-movements in different directions - task difficulty is determined by the number of sub-movements. But, how does recovery proceed in these tasks, and how to regulate the magnitude of the assistance provided by the robot in this case? Here we focus on a simple task in which subjects had to complete a square figure. At every trial, an adaptive regulator selects the appropriate degree of robot assistance needed to complete the entire figure. We tested this protocol with four severely impaired stroke survivors during a multisession study. Robotic training succeeded - the controller gradually reduced the degree of assistance while performance remained constant, suggesting that in fact recovery took place. We used a dynamic model of the recovery process to further analyze the effects of the assistive force and the temporal evolution of the subjects' voluntary control. The model provided an excellent fitting of the subjects' performance and revealed that magnitude and modalities of recovery are very different in the different sub-movements. These results suggest that in order to maximize the recovery the modulation of assistance should occur at the level of each sub-movement
Liftings for noncomplete probability spaces
No full textThe current state of knowledge concerning liftings for noncomplete probability spaces is discussed. This is a somewhat expanded version of the author's talk given at the 1991 Summer Conference on General Topology and Applications in Honor of Mary Ellen Rudin and Her Work.PT: S; CR: BURKE MR, IN PRESS P AM MATH S BURKE MR, 1991, ISRAEL J MATH, V73, P33 BURKE MR, 1992, ISRAEL J MATH, V79, P289 CARLSON T, THEOREM LIFTING CHRISTENSEN JPR, 1974, TOPOLOGY BOREL STRUC FREMLIN DH, 1989, HDB BOOLEAN ALGEBRAS, P877 INOESCUTULCEA A, 1966, 5TH P BERK S MATH ST, V2 IONESCUTULCEA A, 1967, CONTRIBUTIONS PROB 1, P63 IONESCUTULCEA A, 1969, TOPICS THEORY LIFTIN JECH TJ, 1978, SET THEORY JOHNSON RA, 1980, P AM MATH SOC, V80, P234 JUST W, IN PRESS T AM MATH S KUPKA J, 1983, INDIANA U MATH J, V32, P717 LOSERT V, 1983, LNM, V1080, P95 MAHARAM D, 1958, P AM MATH SOC, V9, P987 SHELAH S, 1983, ISRAEL J MATH, V45, P90 TALAGRAND M, 1982, P AM MATH SOC, V84, P379 VONNEUMANN J, 1931, CRELLES J MATH, V165, P109; NR: 18; TC: 0; J9: ANN N Y ACAD SCI; PG: 4; GA: BZ86BSource type: Electronic(1
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