Evidence for Structural Variants of a- and b-Type Peptide Fragment Ions Using Combined Ion Mobility/Mass Spectrometry

Tandem mass spectrometry (MS/MS) of peptides plays a key role in the field of proteomics, and an understanding of the fragmentation mechanisms involved is vital for data interpretation. Not all the fragment ions observed by low-energy collision-induced dissociation of protonated peptides are readily explained by the generally accepted structures for a- and b-ions. The possibility of a macrocyclic structure for b-type ions has been recently proposed. In this study, we have undertaken investigations of linear protonated YAGFL-NH2, N-acetylated-YAGFL-NH2, and cyclo-(YAGFL) peptides and their fragments using a combination of ion mobility (IM) separation and mass spectrometry. The use of IM in this work both gives insight into relative structural forms of the ion species and crucial separation of isobaric species. Our study provides compelling evidence for the formation of a stable macrocyclic structure for the b5 ion generated by fragmentation of protonated linear YAGFL-NH2. Additionally we demonstrate that the a4 ion fragment of protonated YAGFL-NH2 has at least two structures; one of which is attributable to a macrocyclic structure on the basis of its subsequent fragmentation. More generally, this work emphasizes the value of combined IM-MS/MS in probing the detailed fragmentation mechanisms of peptide ions, and illustrates the use of combined ion mobility/collisional activation/mass spectrometry analysis in achieving an effective enhancement of the resolution of the mobility separator

708-4 Can the Results of SPECT Scintigraphy Safely Guide Clinical Management of Patients with Active CAD?

Myocardial perfusion scintigraphy is increasingly used to categorize risk in pts with known or a high likelihood of CAD. This strategy will only be cost-effective if: 1) cardiologists will largely reserve further testing such as angiography (angio) to high-risk subsets; and 2) it is shown that less severe patterns of abnormality can be safely managed medically. We previously reported angio rates after all 4, 162 SPECT studies (excluding those with angio within 90 days beforeSPECT) at our cardiology practice-based nuclear lab: 4% (69/1663) in pts with fixed defects only and/or no ischemia; 60% (682/1141) in pts with high-risk ischemia (2 of multivessel or LAD distribution ischemia and abnormal lung uptake); and 9% (123/1352) for pts with mild-moderate ischemia. In this study, we determined outcome of the 1229 pts with mild-moderate ischemia who did not have referral for angio. Patient characteristics: mean age 65 yrs; known CAD=1061 (86%); prior CABG=344; prior MI=575; prior PTCA=674; angina=592. Twenty-eight (2%) pts were lost to follow-up. The remainder were followed for a mean of 18 months. There were 22 hard events (MI=15; cardiac death=71) (1.8%) and 54 pts required PTCA or CABG (total event rate 6.3%). Mean time to any event was 13.2 months from SPECT. Freedom from hard events at 1 yr was 99% and at 2 yrs 97%. Freedom from any event was 97% at 1 yr and 91% at 2 yrs.Conclusions1) SPECT can be a highly effective strategy for selecting pts for angio; 2) Even in a self-referral setting angio is largely reserved for pts with high-risk scans; and 3) Pts with mildly-moderately abnormal scans can be treated safely with medical therapy and close follow-u

Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty

AbstractColchicine, an antimitogenic agent, has shown promise in preventing restenosis after coronary angioplasty in experimental animal models. A prospective trial was conducted involving 197 patients randomized in a 2:1 fashion to treatment with oral colchicine, 0.6 mg twice daily (130 patients), or placebo (67 patients) for 6 months after elective coronary angioplasty. Treatment in all patients began between 12 h before angioplasty and 24 h after angioplasty. Compliance monitoring revealed that 96% of all prescribed pills were ingested. Demographic characteristics were similar in colchicine- and placebo-treated groups. A mean of 2.7 lesions/patient were dilated. Side effects resulted in a 6.9% dropout rate in the colchicine-treated patients.Complete quantitative angiographic follow-up was obtained in 145 patients (74%) with 393 dilated lesions. Quantitative angiographic measurements were obtained in two orthogonal views at baseline before angioplasty and immediately and at 6 months after angioplasty. The quantitative mean lumen diameter stenosis before angioplasty was 67% both in the 152 lesions in the placebo-treated group and in the 241 lesions in the colchkine-treated group; this value was reduced to 24% immediately after angio-plasty in the lesions in both treatment groups.At the 6-month angiogram, lesions had restenosed to 47% lumen diameter narrowing in the placebo-treated group compared with 46% in the colchicine-treated group (p = NS). Forty-one percent of colchicine-treated patients developed restenosis in at least one lesion compared with 45% of the placebo-treated group (p = NS). In conclusion, colchicine was ineffective for preventing restenosis after coronary angioplasty

Principal forms X^2 + nY^2 representing many integers

In 1966, Shanks and Schmid investigated the asymptotic behavior of the number of positive integers less than or equal to x which are represented by the quadratic form X^2+nY^2. Based on some numerical computations, they observed that the constant occurring in the main term appears to be the largest for n=2. In this paper, we prove that in fact this constant is unbounded as n runs through positive integers with a fixed number of prime divisors.Comment: 10 pages, title has been changed, Sections 2 and 3 are new, to appear in Abh. Math. Sem. Univ. Hambur

Relationships Between Long-Range Lightning Networks and TRMM/LIS Observations

Recent advances in long-range lightning detection technologies have improved our understanding of thunderstorm evolution in the data sparse oceanic regions. Although the expansion and improvement of long-range lightning datasets have increased their applicability, these applications (e.g., data assimilation, atmospheric chemistry, and aviation weather hazards) require knowledge of the network detection capabilities. The present study intercompares long-range lightning data with observations from the Lightning Imaging Sensor (LIS) aboard the Tropical Rainfall Measurement Mission (TRMM) satellite. The study examines network detection efficiency and location accuracy relative to LIS observations, describes spatial variability in these performance metrics, and documents the characteristics of LIS flashes that are detected by the long-range networks. Improved knowledge of relationships between these datasets will allow researchers, algorithm developers, and operational users to better prepare for the spatial and temporal coverage of the upcoming GOES-R Geostationary Lightning Mapper (GLM)