Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

Gene clustering using self-organizing maps and particle swarm optimization

Abstract: Gene clustering, the process of grouping related genes in the same cluster, is at the foundation of different genomic studies that aim at analyzing the function of genes. Microarray technologies have made it possible to measure gene expression levels for thousand of genes simultaneously. For knowledge to be extracted from the datasets generated by these technologies, the datasets have to be presented to a scientist in a meaningful way. Gene clustering methods serve this purpose. In this paper, a hybrid clustering approach that is based on self-organizing maps and particle swarm optimization is proposed. In the proposed algorithm, the rate of convergence is improved by adding a conscience factor to the self-organizing maps algorithm. The robustness of the result is measured by using a resampling technique. The algorithm is implemented on a cluster of workstations.

Different roles of N- and C- termini in the functional activity of FGF21.

Abstract: Fibroblast growth factor 21 is a member of endocrine FGFs subfamily, along with FGF19 and FGF23. It is emerging as a novel regulator with beneficial effects on a variety of metabolic parameters, including glucose and lipid control. FGF21 activity depends on membrane protein betaKlotho that physically complexes with various FGF receptors, thus conferring them the ability to bind FGF21 and activate downstream signaling pathways. FGF21, like other FGFs, folds to a beta-trefoil-like core region, with disordered N- and C-termini. In order to investigate their role in the activity of FGF21, we have constructed a series of deletion mutants and tested them for their ability to (1) bind betaKlotho, analyzed by surface plasmon resonance spectroscopy (2) signal through MAPK phosphorylation and inhibit apoptosis in 3T3-L1/betaKlotho fibroblasts (3) stimulate GLUT1 mRNA upregulation and glucose uptake in 3T3-L1 adipocytes. Binding studies with betaKlotho revealed that the interaction with the co-receptor involves the C-terminus, as progressive removal of amino acids from the carboxy end decreased affinity for betaKlotho. By contrast, removal of up to 17 amino acids from the N-terminus had no effect on the interaction with betaKlotho. Terminal deletions had greater effect on function, as deletions of six amino acids from the amino-terminus and only four from the carboxy-terminus each significantly impacted activity (10-fold). Of the extreme terminal truncations, with no detectable activity, DeltaN17 acted as competitive antagonist while DeltaC20 did not. Our structure/function studies show that the C-terminus is important for betaKlotho interaction whereas the N-terminus likely interacts directly with FGF receptors.

Untreated Anxiety Among Adult Primary Care Patients in a Health Maintenance Organization

Abstract: Background: Untreated anxiety may be particularly difficult for primary care physicians to recognize and diagnose because there are no reliable demographic or medical profiles for patients with this condition and because these patients present with a high rate of comorbid psychological conditions that complicate selection of treatment. Method: A prospective assessment of untreated anxiety symptoms and disorders among primary care patients. Results: Approximately 10% of eligible patients screened in clinic waiting rooms of a mixed-model health maintenance organization reported elevated symptoms and/or disorders of anxiety that were unrecognized and untreated. These patients with untreated anxiety reported significantly worse functioning on both physical and emotional measures than "not anxious" comparison patients; in fact these patients reported reduced functioning levels within ranges that would be expected for patients with chronic physical diseases, such as diabetes and congestive heart failure. The most severe reductions in functioning were reported by untreated patients whose anxiety was mixed with depression symptoms or disorders. Conclusion: Primary care physicians may benefit from screening tools and consultations by mental health specialists to assist in recognition and diagnosis of anxiety symptoms and disorders alone and mixed with depression.

Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression.

Abstract: BACKGROUND Treatment-resistant depression (TRD) is a long-term, disabling illness. We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with standard care. METHOD This 2-year prospective, multicenter, observational study (patients enrolled from January 2001 through July 2004) tracked the outcomes of 124 patients with treatment-resistant, nonpsychotic major depressive disorder (N = 109) or bipolar depressed phase disorder (N = 15) who received treatment as usual (TAU) (i.e., any therapeutic regimen agreed to by patients and psychiatrists, including medications, electroconvulsive therapy [ECT], and psychotherapy). Treatments could be adjusted, started, and stopped as necessary. The primary outcome, treatment response, was defined a priori as > or = 50% improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR-30). Remission was defined as an IDS-SR-30 score of < or = 14. The Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) was used to monitor quality-of-life changes. RESULTS The 12- and 24-month IDS-SR-30 response rates were 11.6% (13/112) and 18.4% (19/103), respectively. Of the 13 responders at 12 months, only 5 were responders at 24 months. The 12- and 24-month IDS-SR-30 remission rates were 3.6% (4/112) and 7.8% (8/103), respectively. Only 1 of the 4 12-month remitters was also a remitter at 24 months. The SF-36 indicated globally poor quality of life in this sample. CONCLUSIONS Despite the wide range of treatment options available for depression, the response rates, remission rates, and quality-of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU.