Solution conformation of the biantennary N-linked oligosaccharide of human serotransferrin using 1H NMR nuclear Overhauser effect measurements

AbstractThe conformation in solution of the biantennary complex type oligosaccharide unit derived from human serotransferrin has been investigated using 1H—1H Nuclear Overhauser Effect (NOE) measurements at 300 MHz. From quantitation of the NOE, the α(1–3) antenna is shown to exist in a preferred solution conformation with respect to the mannosyl-chitobiose core. The flexibility of the α(1–6) arm, together with the absence of NOE data between this arm and the core, indicates that, in contrast to the α(1–3) arm the α(1–6) arm has no preferred conformation with respect to the core

Nonlinear Differential Equations Satisfied by Certain Classical Modular Forms

A unified treatment is given of low-weight modular forms on \Gamma_0(N), N=2,3,4, that have Eisenstein series representations. For each N, certain weight-1 forms are shown to satisfy a coupled system of nonlinear differential equations, which yields a single nonlinear third-order equation, called a generalized Chazy equation. As byproducts, a table of divisor function and theta identities is generated by means of q-expansions, and a transformation law under \Gamma_0(4) for the second complete elliptic integral is derived. More generally, it is shown how Picard-Fuchs equations of triangle subgroups of PSL(2,R) which are hypergeometric equations, yield systems of nonlinear equations for weight-1 forms, and generalized Chazy equations. Each triangle group commensurable with \Gamma(1) is treated.Comment: 40 pages, final version, accepted by Manuscripta Mathematic

Older-Patient-Specific Cancer Trials: A Pooled Analysis of 2,277 Patients (A151715)

Background: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials. Materials and Methods: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985–2012. Results: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65–89) years compared with 68 (65–84) years in the cohort of older patients in age-unspecified trials; p <.0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% (p <.0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9–13.7) and 13.5 years (95% CI, 12.9–14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92–1.28; p =.34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3–5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p <.0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. Conclusion: Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831). Implications for Practice: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer

Structure and dynamics in oligomannose-type oligosaccharides

Using a combination of 1H NMR nuclear Overhauser effect measurements, molecular orbital calculations, and molecular dynamics simulations, we have determined the tertiary structure and dynamic properties of the oligomannose oligosaccharide Man alpha 6(Man alpha 3)Man alpha 6(Man alpha 3)Man beta 4GlcNAc beta 4GLcNAc. While the calculated potential surfaces for the majority of the glycosidic linkages could be described by a single deep potential well, similar calculations for the Man alpha 1-6Man alpha and Man alpha 1-6Man beta linkages described a diffuse, shallow well, suggesting that a larger degree of flexibility exists about the latter. These conclusions are supported by the results of molecular dynamics simulations, which suggest that the NMR data should be interpreted in terms of a degree of flexibility about the Man alpha 1-6Man beta and Man alpha 1-6Man alpha linkages. In contrast, a similar series of investigations suggests that the conformation of the Man alpha 1-6Man beta linkage in Man alpha 2Man6(Man alpha 2Man alpha 3)Man alpha 6 (Man alpha 2Man alpha 2Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc is more restricted, resulting in an overall structure that is "restrained"