Tiebreaker: Certification and Multiple Credit Ratings

This paper explores the economic role credit rating agencies play in the corporate bond market. We consider three existing theories about multiple ratings: information production, rating shopping and regulatory certification. Using differences in rating composition, default prediction and credit spread changes, our evidence only supports regulatory certification. Marginal, additional credit ratings are more likely to occur because of, and seem to matter primarily for regulatory purposes, but do not seem to provide significant additional information related to credit quality.

Time Course of Paclitaxel-Induced Apoptosis in an Experimental Model of Virus-Induced Breast Cancer

Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. 99mTc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer. Methods: The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of 99mTc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein. Results: Baseline uptake of 99mTc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline levels at 6 h. Conclusion: These results define the time course of various biologic events taking place in this model of murine breast cancer after a proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo uptake of 99mTc-annexin V reflects the degree of apoptosis, the study also suggests that the apoptotic response to antitumor therapy may differ from tumor type to tumor type. Therefore, contradicting results previously reported may depend on an inadequate time window chosen for imaging with 99mTc-annexin V

Hierarchical Concurrent Engineering in a Multiagent Framework

Our experience indicates coordination in concurrent engineering (CE) requires support for two types of relationships among decision makers supervisor/subordinate and peer-to-peer Supervisor/subordinate relationships are created by the standard hierarchical decomposition process that is required to solve any large design problem Peer-to-peer relationships arise when teams of decision makers must interact, without direct guidance, to achieve individual and common goals In this paper, we describe a general decision-making methodology, which we call hierarchical CE The emphasis of hierarchical CE is to provide support for both supervisor/subordinate and peer-to-peer relationships In addition to the concept of hierarchical CE, we present a supporting agent-based framework in which the preferences and constraints of a design supervi sor are distributed to design subordinates, who are expected to exploit their local expertise within the context provided by this global information A distinct separation between feasibility and value facilitates optimal decision-making by design agents, since the bounds on feasibility do not include arbitrary statements about value This distinction may prove useful for other problem domains as wellPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68258/2/10.1177_1063293X9600400105.pd

Stenting of venous bypass grafts: A new treatment modality for patients who are poor candidates for reintervention

Abstract During a 2-year period, 136 self-expanding Wall-stents were implanted in saphenous vein bypass grafts in 69 patients with end-stage coronary artery disease. All patients had severe symptoms and the majority were poor candidates for either repeat surgery or conventional bypass coronary angioplasty because of unfavorable native anatomy, impaired left ventricular function, or a high-risk bypass lesion anatomy for coronary angioplasty. All procedures were technically successful without major complications and a need for emergency bypass surgery. However, during the hospital stay acute thrombotic complications occurred in seven patients (10%) resulting in one death and acute myocardial infarction in five patients and necessitating emergency repeat PTCA in two patients and repeat CABG in four. Twenty-three patients had serious hemorrhagic complications directly related to the rigorous anticoagulation schedule. Two patients died of fatal cerebral bleeding. During follow-up, another five patients died accounting for a total mortality rate of 12%. At late angiographic follow-up (4.9 ± 3.4 months, n = 53), 25 patients (47%) had a restenosis (≥50% DS) within or immediately adjacent to the stent, necessitating reintervention in 19 patients (PTCA, n = 12; repeat CABG, n = 7). In the group without stent-related restenosis (n = 28), 15 patients had progression of disease in either the native or bypass vessels leading to recurrence of major anginal symptoms within 1 to 24 months. Ten of these patients required further intervention (stent, n = 6; PTCA, n = 3; repeat CABG, n = 1). Stenting in saphenous coronary bypass grafts can be performed safely with excellent immediate angiographic and clinical results. Early occlusion, late restenosis, and bleeding complications associated with the aggressive anticoagulant treatment remain significant limitations. Reintervention as a result of restenosis or progression of disease in other lesions is common. Stenting of diseased bypass grafts in symptomatic patients with end-stage coronary artery disease (who are at high risk for conventional angioplasty or surgical reintervention) may be useful as palliative therapy

Physical Model for Plaque Action in the Tooth-Plaque-Saliva System

A physical model describing the interrelationships of demineralization, remineralization, plaque thickness, glucose levels, and plaque enzymatic activity was presented. Selection of constants and variations of the parameters were kept in the range of possible in vivo situations. The results of calculations were discussed and correlated with the results of in vivo studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66483/2/10.1177_00220345700490013001.pd

Factors determining nest-site selection of surface-nesting seabirds : a case study on the world's largest pelagic bird, the Wandering Albatross (Diomedea exulans)

Several factors may drive bird nest-site selection, including predation risk, resource avail-ability, weather conditions and interaction with other individuals. Understanding the drivers affecting where birds nest is important for conservation planning, especially where environmental change may alter the distribution of suitable nest-sites. This study investigates which environmental variables affect nest-site selection by the Wandering Albatross Diomedea exulans, the world’s largest pelagic bird. Here, wind characteristics are quantitatively investigated as a driver of nest-site selection in surface-nesting birds, in addition to several topographical variables, vegetation and geological characteristics. Nest locations from three different breeding seasons on sub-Antarctic Marion Island were modelled to assess which environmental factors affect nest-site selection. Elevation was the most important determinant of nest-site selection, with Wandering Albatrosses only nesting at low elevations. Distance from the coast and terrain roughness were also important predictors, with nests more generally found close to the coast and in flatter terrain, followed by wind velocity, which showed a hump-shaped relationship with the probability of nest occurrence. Nests occurred more frequently on coastal vegetation types, and were absent from polar desert vegetation (generally above c. 500 m elevation). Of the variables that influence Wandering Albatross nest location, both vegetation type and wind characteristics are likely to be influenced by climate change, and have already changed over the last 50 years. As a result, the availability of suitable nest-sites needs to be considered in light of future climate change, in addition to the impacts that these changes will have on foraging patterns and prey distribution. More broadly, these results provide insights into how a wide range of environmental variables, including wind, can affect nest-site selection of surface-nesting seabirds.South African National Research Foundation.https://onlinelibrary.wiley.com/journal/1474919xMechanical and Aeronautical EngineeringPlant Production and Soil Scienc

A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan

PIM-induced phosphorylation of Notch3 promotes breast cancer tumorigenicity in a CSL-independent fashion

Dysregulation of the developmentally important Notch signaling pathway is implicated in several types of cancer, including breast cancer. However, the specific roles and regulation of the four different Notch receptors have remained elusive. We have previously reported that the oncogenic PIM kinases phosphorylate Notch1 and Notch3. Phosphorylation of Notch1 within the second nuclear localization sequence of its intracellular domain (ICD) enhances its transcriptional activity and tumorigenicity. In this study, we analyzed Notch3 phosphorylation and its functional impact. Unexpectedly, we observed that the PIM target sites are not conserved between Notch1 and Notch3. Notch3 ICD (N3ICD) is phosphorylated within a domain, which is essential for formation of a transcriptionally active complex with the DNA-binding protein CSL. Through molecular modeling, X-ray crystallography, and isothermal titration calorimetry, we demonstrate that phosphorylation of N3ICD sterically hinders its interaction with CSL and thereby inhibits its CSL-dependent transcriptional activity. Surprisingly however, phosphorylated N3ICD still maintains tumorigenic potential in breast cancer cells under estrogenic conditions, which support PIM expression. Taken together, our data indicate that PIM kinases modulate the signaling output of different Notch paralogs by targeting distinct protein domains and thereby promote breast cancer tumorigenesis via both CSL-dependent and CSL-independent mechanisms.</p