Converging Interests: Chemoinformatics, History, and Bibliometrics.

Modern scientometric techniques, applied at scale, can provide valuable information that complements qualitative investigation of the accumulation of knowledge in a field. We discuss a trio of articles from computational chemistry selected from an analysis of 181 million tri-cited articles.

Delayed Recognition: A Co-Citation Perspective.

A Sleeping Beauty is a publication that is apparently unrecognized by citation for some period of time before experiencing a burst of recognition. Various reasons, including resistance to new ideas, have been attributed to such delayed recognition. We study this phenomenon in the special case of co-citations, which represent new ideas generated through the combination of existing ones. Using relatively stringent selection criteria derived from the work of others, we analyze a very large dataset of over 940 million unique co-cited article pairs, and identify 1,196 cases of delayed co-citations. We further classify these 1,196 cases with respect to amplitude, rate of citation, and disciplinary origin.

Viewing Computer Science through Citation Analysis: Salton and Bergmark Redux.

Computer science has experienced dramatic growth and diversification over the last twenty years. Towards a current understanding of the structure of this discipline, we analyze a large sample of the computer science literature from the DBLP database. For insight on the features of this cohort and the relationship within its components, we have constructed article level clusters based on either direct citations or co-citations, and reconciled them with major and minor subject categories in the All Science Journal Classification (ASJC). We describe complementary insights from clustering by direct citation and co-citation, and both point to the increase in computer science publications and their scope. Our analysis reveals cross-category clusters, some that interact with external fields, such as the biological sciences, while others remain inward looking. Overall, we document an increase in computer science publications and their scope.

Research synergy and drug development: Bright stars in neighboring constellations.

Drug discovery and subsequent availability of a new breakthrough therapeutic or 'cure' is a compelling example of societal benefit from research advances. These advances are invariably collaborative, involving the contributions of many scientists to a discovery network in which theory and experiment are built upon. To document and understand such scientific advances, data mining of public and commercial data sources coupled with network analysis can be used as a digital methodology to assemble and analyze component events in the history of a therapeutic. This methodology is extensible beyond the history of therapeutics and its use more generally supports (i) efficiency in exploring the scientific history of a research advance (ii) documenting and understanding collaboration (iii) portfolio analysis, planning and optimization (iv) communication of the societal value of research. Building upon prior art, we have conducted a case study of five anti-cancer therapeutics to identify the collaborations that resulted in the successful development of these therapeutics both within and across their respective networks. We have linked the work of over 235,000 authors in roughly 106,000 scientific publications that capture the research crucial for the development of these five therapeutics. Applying retrospective citation discovery, we have identified a core set of publications cited in the networks of all five therapeutics and additional intersections in combinations of networks. We have enriched the content of these networks by annotating them with information on research awards from the US National Institutes of Health (NIH). Lastly, we have mapped these awards to their cognate peer review panels, identifying another layer of collaborative scientific activity that influenced the research represented in these networks.

NIH Peer Review: Scored Review Criteria and Overall Impact.

The National Institutes of Health (NIH) is the largest source of funding for biomedical research in the world. Funding decisions are made largely based on the outcome of a peer review process that is intended to provide a fair, equitable, timely, and unbiased review of the quality, scientific merit, and potential impact of the research. There have been concerns about the criteria reviewers are using, and recent changes in review procedures at the NIH now make it possible to conduct an analysis of how reviewers evaluate applications for funding. This study examined the criteria and overall impact scores recorded by assigned reviewers for R01 grant applications. The results suggest that all the scored review criteria, including innovation, are related to the overall impact score. Further, good scores are necessary on all five scored review criteria, not just the score for research methodology, in order to achieve a good overall impact score.

Characterization of the peer review network at the Center for Scientific Review, National Institutes of Health.

The National Institutes of Health (NIH) is the largest source of funding for biomedical research in the world. This funding is largely effected through a competitive grants process. Each year the Center for Scientific Review (CSR) at NIH manages the evaluation, by peer review, of more than 55,000 grant applications. A relevant management question is how this scientific evaluation system, supported by finite resources, could be continuously evaluated and improved for maximal benefit to the scientific community and the taxpaying public. Towards this purpose, we have created the first system-level description of peer review at CSR by applying text analysis, bibliometric, and graph visualization techniques to administrative records. We identify otherwise latent relationships across scientific clusters, which in turn suggest opportunities for structural reorganization of the system based on expert evaluation. Such studies support the creation of monitoring tools and provide transparency and knowledge to stakeholders.

[18F]fluorothymidine PET imaging in the diagnosis of leptomeningeal involvement with diffuse large B-cell lymphoma.

The diagnosis of leptomeningeal carcinomatosis remains difficult despite improvement in central nervous system (CNS) imaging and cytologic examination of the cerebral spinal fluid. False-negative results are common, providing obstacles in assessing both prophylactic and therapeutic efforts. As a result of increased survival of patients with a variety of systemic neoplasms it is likely that central nervous involvement will need to be addressed more often. This article presents a patient with a diffuse large B-cell lymphoma with polymorphic features. Imaging using 18F-labeled fluorodeoxythymidine (FLT) proved useful in demonstrating both parenchymal and leptomeningeal CNS involvement. The potential for FLT to identify proliferative tissue may make it uniquely suitable for detection of CNS malignant disease.

Combinatorial library of primaryalkylammonium dicarboxylate gelators: a supramolecular synthon approach.

Following the supramolecular synthon approach, a combinatorial library comprising 35 organic salts derived from 7 dicarboxylic acids (malonic-, succinic-, adipic-, L-tartaric-, maleic-, phthalic-, and isophthalicacid) and 5 primaryalkyl amines Me-(CH2)n-NH2 (n = 11-15) was prepared and scanned for gelation. About 66% of the salts in the combinatorial library were found to show moderate to good gelling ability in various polar and nonpolar solvents including commercial fuels such as petrol. The majority of the salts having a rigid, unsaturated anionic backbone (maleate, phthalate, and isophthalate) did not show gelation; only the corresponding hexadecylammonium salts showed gelation. Some of the representative gels were characterized by rheology, small-angle neutron scattering (SANS), optical microscopy (OM), and scanning electron microscopy (SEM). Single-crystal structures of two gelator and two nongelator salts were also discussed in the context of supramolecular synthon and structure-property correlation.

PET imaging in cardiology.

The incidence of congestive heart failure (CHF) has progressively increased over the last 25 years with coronary artery disease being the aetiology in 66% of patients with CHF. Assessment of myocardial perfusion and glucose uptake using PET imaging with 18F-FDG for metabolism and 13-N-ammonia or 82-rubidium for coronary flow has proven to be the gold standard for predicting the recovery of regional and global left ventricular (LV) function following revascularization. Patients with viable ischemic myocardium identified by a flow/metabolism mismatch, represent an especially high risk subgroup for hard coronary events within one year, in the absence of myocardial revascularization. The state of the art assessment of myocardial viability in the new millennium is an optimally glucose loaded PET myocardial perfusion/metabolic study. For patients with critically depressed LV function with LVEF <20% at rest assessment of contractile reserve, in addition to 18F-FDG-PET viability imaging, may help predict a favourable surgical outcome.

Regulation of constitutive TCR internalization by the zeta-chain.

The ability of a T cell to be activated is critically regulated by the number of TCRs expressed on the plasma membrane. Cell surface TCR expression is influenced by dynamic processes such as synthesis and transport of newly assembled receptors, endocytosis of surface TCR, and recycling to the plasma membrane of internalized receptors. In this study, the internalization of fluorescently labeled anti-TCR Abs was used to analyze constitutive endocytosis of TCRs on T cells, and to investigate the role of the zeta-chain in this process. We found that cell surface TCRs lacking zeta were endocytosed more rapidly than completely assembled receptors, and that reexpression of full-length zeta led to a dose-dependent decrease in the rate of TCR internalization. Rapid TCR internalization was also observed with CD4(+)CD8(+) thymocytes from zeta-deficient mice, whereas TCR internalization on thymocytes from CD3-delta deficient animals was slow, similar to that of wild-type thymocytes. This identifies a specific role for zeta in the regulation of constitutive receptor internalization. Furthermore, chimeric zeta molecules containing non-native intracellular amino acid sequences also led to high levels of TCR expression and reduced TCR cycling. These effects were dependent solely on the length of the intracellular tail, ruling out a role for intracellular zeta-specific interactions with other molecules as a mechanism for regulating TCR internalization. Rather, these findings strongly support a model in which the zeta-chain stabilizes TCR residency on the cell surface, and functions to maintain cell surface receptor expression by sterically blocking internalization sequences in other TCR components.