Conformations of biopolymers in the gas phase: a new mass spectrometric method

A method is developed for measuring collision cross sections of gas-phase biomolecules using a slightly modified commercial triple quadrupole instrument. The modifications allow accurate stopping potentials to be measured for ions exiting the collision region of the instrument. A simple model allows these curves to be converted to cross sections. In order to account for certain poorly defined experimental parameters (exact ion energy, absolute pressure in the collision cell, etc.) variable parameters are included in the model. These parameters are determined on a case by case basis by normalizing the results to the well known cross section of singly charged bradykinin, Two relatively large systems were studied (cytochrome c and myoglobin) so comparisons could be made to literature values. A number of new peptide systems were then studied in the 9 -14 residue range. These included singly and doubly charged ions of luteinizing hormone releasing hormone (LHRH) substance P, and bombesin in addition to bradykinin. The experimental cross sections were in very good agreement with predictions from extensive molecular dynamics modeling. One interesting result was the experimental observation that the cross section of the doubly charged ions of LHRH, substance P, and bombesin were all smaller than those of the corresponding singly charged ions. Molecular dynamics did not reproduce this result, predicting doubly charged cross sections of the same magnitude or slightly larger than for the singly charged species. The experimental results appear to be correct, however. Possible shortcomings in the modeling procedure for multiply charged ions were suggested that might account for the discrepancy

Variability in the reported management of pulmonary metastases in osteosarcoma.

Nearly 20% of patients with newly diagnosed osteosarcoma have detectable metastases at diagnosis; the majority of which occur in the lungs. There are no established recommendations for the timing and modality of metastasectomy. Members of the Connective Tissue Oncology Society (CTOS) were emailed an anonymous 10-min survey assessing their management practices for pulmonary findings at the time of an osteosarcoma diagnosis. The questionnaire presented three scenarios and discussed the choice to perform surgery, the timing of resection, and the choice of surgical procedure. Analyses were stratified by medical profession. One hundred and eighty-three physicians responded to our questionnaire. Respondents were comprised of orthopedic surgeons (37%), medical oncologists (31%), pediatric oncologists (22%), and other medical subspecialties (10%). There was variability among the respondents in the management of the pulmonary nodules. The majority of physicians chose to resect the pulmonary nodules following neoadjuvant chemotherapy (46-63%). Thoracotomy was the preferred technique for surgical resection. When only unilateral findings were present, the majority of physicians did not explore the contralateral lung. The majority of respondents did not recommend resection if the pulmonary nodule disappeared following chemotherapy. The survey demonstrated heterogeneity in the management of pulmonary metastases in osteosarcoma. Prospective trials need to evaluate whether these differences in management have implications for outcomes for patients with metastatic osteosarcoma

Stable-Matching Voronoi Diagrams: Combinatorial Complexity and Algorithms

We study algorithms and combinatorial complexity bounds for stable-matching Voronoi diagrams, where a set, S, of n point sites in the plane determines a stable matching between the points in R^2 and the sites in S such that (i) the points prefer sites closer to them and sites prefer points closer to them, and (ii) each site has a quota indicating the area of the set of points that can be matched to it. Thus, a stable-matching Voronoi diagram is a solution to the classic post office problem with the added (realistic) constraint that each post office has a limit on the size of its jurisdiction. Previous work provided existence and uniqueness proofs, but did not analyze its combinatorial or algorithmic complexity. We show that a stable-matching Voronoi diagram of n sites has O(n^{2+epsilon}) faces and edges, for any epsilon>0, and show that this bound is almost tight by giving a family of diagrams with Theta(n^2) faces and edges. We also provide a discrete algorithm for constructing it in O(n^3+n^2f(n)) time, where f(n) is the runtime of a geometric primitive that can be performed in the real-RAM model or can be approximated numerically. This is necessary, as the diagram cannot be computed exactly in an algebraic model of computation

Automating distributed workflow for electronic commerce: A model for building meta-workflow components

Business software development environments for web- based applications are at a very early stage in their potential lifecycle. The purpose of this research agenda is to develop a model for how business processes can be interpreted into primitive computer codes for web applications. We have taken a transaction perspective adapted from the distributed database approach to maintenance of integrity assuming the concepts of ACIDity (Atomicity, Consistency, Isolation, and Durability) and serializability. This perspective is consistent with emerging literature on “workflow agents” [e.g., Huhns and Singh, 1998]. In this paper, we design, develop, and show an example of a meta-level set of building blocks for a direct mapping between electronic commerce and workflow processes. To validate the sufficiency and completeness of the meta-level components proposed, a complete mapping of an electronic commerce application to meta-workflow components is proposed

Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice.

A152T-variant human tau (hTau-A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau-A152T or wild-type hTau (hTau-WT), we find age-dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in hTau-A152T mice. However, overexpression of either hTau species enhances neuronal responses to electrical stimulation of synaptic inputs and to an epileptogenic chemical. hTau-A152T mice have higher hTau protein/mRNA ratios in brain, suggesting that A152T increases production or decreases clearance of hTau protein. Despite their functional abnormalities, aging hTau-A152T mice show no evidence for accumulation of insoluble tau aggregates, suggesting that their dysfunctions are caused by soluble tau. In human amyloid precursor protein (hAPP) transgenic mice, co-expression of hTau-A152T enhances risk of early death and epileptic activity, suggesting copathogenic interactions between hTau-A152T and amyloid-β peptides or other hAPP metabolites. Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors

Warner-Bratzler shear force values and ranges of steaks from cattle of known sires

Carcass data and Warner-Bratzler shear force (WBSF) data on strip loin steaks were collected from nearly 8,500 cattle in contemporary groups of progeny from the more popular sires in 14 different beef cattle breeds in the Carcass Merit Traits project funded by Beef Checkoff dollars, the breed associations, and MMI Genomics. In addition, trained sensory panel evaluations were conducted on over 2,500 strip loin steaks from contemporary groups of progeny from five sires included in the DNA marker validation component of the project. The correlation between WBSF and tenderness scored by the trained sensory panel was -0.82, indicating that as WBSF increased, tenderness scored by the sensory panel decreased. Our results showed that a WBSF value of ≥ 11.0 lb generally results in a sensory score of slightly tough or tougher. In this study, 22.8% of the cattle had WBSF values ≥ 11.0 lb and 26.3% had sensory scores of slightly tough or tougher. The phenotypic range of WBSF means for sires within breeds ranged from 1.9 to 6.6 lb. The phenotypic range of WBSF means across breeds was 8.9 lb, whereas the range among sires across breeds was a dramatic 14.4 lb. The phenotypic range for flavor intensity scores among sires within and across breeds was much smaller than for tenderness, with juiciness scores being intermediate. The 40 widely used sires that produced progeny with steaks that were unacceptable in tenderness in this study might be expected to be sires of several thousand bulls used in commercial herds. This demonstrates that seedstock producers should aggressively utilize sires that have genetics for tender meat

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone