Interdependent pricing and markup behavior : an empirical analysis of GM, Ford and Chrysler

In this paper we show how to adapt the traditional contingent claims valuation techniques to correctly value the firm and its liabilities in the presence of agency costs. This enables us to measure the significance of the agency costs as a function of the quantity of debt outstanding and as a function of the design of the debt contract: with this we can determine the relative benefits of alternative contract design. Our work makes a contribution to the recent database about how much debt a corporation can prudently assume. It is possible to measure the agency advantages of the new debt instruments for a given firm, and therefore to determine for which firms the advantages are significant and for which firms they are not.Supported by the National Science Foundation and the MIT Center for Energy Policy Research

Downregulation of Rap1GAP contributes to Ras transformation.

Although abundant in well-differentiated rat thyroid cells, Rap1GAP expression was extinguished in a subset of human thyroid tumor-derived cell lines. Intriguingly, Rap1GAP was downregulated selectively in tumor cell lines that had acquired a mesenchymal morphology. Restoring Rap1GAP expression to these cells inhibited cell migration and invasion, effects that were correlated with the inhibition of Rap1 and Rac1 activity. The reexpression of Rap1GAP also inhibited DNA synthesis and anchorage-independent proliferation. Conversely, eliminating Rap1GAP expression in rat thyroid cells induced a transient increase in cell number. Strikingly, Rap1GAP expression was abolished by Ras transformation. The downregulation of Rap1GAP by Ras required the activation of the Raf/MEK/extracellular signal-regulated kinase cascade and was correlated with the induction of mesenchymal morphology and migratory behavior. Remarkably, the acute expression of oncogenic Ras was sufficient to downregulate Rap1GAP expression in rat thyroid cells, identifying Rap1GAP as a novel target of oncogenic Ras. Collectively, these data implicate Rap1GAP as a putative tumor/invasion suppressor in the thyroid. In support of that notion, Rap1GAP was highly expressed in normal human thyroid cells and downregulated in primary thyroid tumors

Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

Rapid dissemination of Francisella tularensis and the effect of route of infection

<p>Abstract</p> <p>Background</p> <p><it>Francisella tularensis </it>subsp. <it>tularensis </it>is classified as a Category A bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. However, the virulence mechanisms of this organism are not well characterized. <it>Francisella tularensis </it>subsp. <it>novicida</it>, which is an equally virulent subspecies in mice, was used in concert with a microPET scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such dissemination compares with other routes of infection. Adult mice were inoculated intranasally with <it>F. tularensis </it>subsp. <it>novicida </it>radiolabeled with ⁶⁴Cu and imaged by microPET at 0.25, 2 and 20 hours post-infection.</p> <p>Results</p> <p>⁶⁴Cu labeled <it>F. tularensis </it>subsp. <it>novicida </it>administered intranasally or intratracheally were visualized in the respiratory tract and stomach at 0.25 hours post infection. By 20 hours, there was significant tropism to the lung compared with other tissues. In contrast, the images of radiolabeled <it>F. tularensis </it>subsp. <it>novicida </it>when administered intragastrically, intradermally, intraperitoneally and intravenouslly were more generally limited to the gastrointestinal system, site of inoculation, liver and spleen respectively. MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.</p> <p>Conclusion</p> <p>Our findings suggest that Francisella has a differential tissue tropism depending on the route of entry and that the virulence of Francisella by the pulmonary route is associated with a rapid bacteremia and an early preferential tropism to the lung. In addition, the use of the microPET device allowed us to identify the cecum as a novel site of colonization of <it>Francisella tularensis </it>subsp. <it>novicida </it>in mice.</p

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): PartA = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W

Rapid Surface Oxidation as a Source of Surface Degradation Factor for Bi2Se3

Bi2Se3 is a topological insulator with metallic surface states residing in a large bulk bandgap. It is believed that Bi2Se3 gets additional n-type doping after exposure to atmosphere, thereby reducing the relative contribution of surface states in total conductivity. In this letter, transport measurements on Bi2Se3 nanoribbons provide additional evidence of such environmental doping process. Systematic surface composition analyses by X-ray photoelectron spectroscopy reveal fast formation and continuous growth of native oxide on Bi2Se3 under ambient conditions. In addition to n-type doping at the surface, such surface oxidation is likely the material origin of the degradation of topological surface states. Appropriate surface passivation or encapsulation may be required to probe topological surface states of Bi2Se3 by transport measurements

Axial Higgs Mode Detected by Quantum Pathway Interference in RTe3

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (e.g. dark matter) rely on further symmetry breaking calling for an undiscovered axial Higgs mode. In condensed matter the Higgs was seen in magnetic, superconducting and charge density wave(CDW) systems. Uncovering a low energy mode's vector properties is challenging, requiring going beyond typical spectroscopic or scattering techniques. Here, we discover an axial Higgs mode in the CDW system RTe3 using the interference of quantum pathways. In RTe3 (R=La,Gd), the electronic ordering couples bands of equal or different angular momenta. As such, the Raman scattering tensor associated to the Higgs mode contains both symmetric and antisymmetric components, which can be excited via two distinct, but degenerate pathways. This leads to constructive or destructive interference of these pathways, depending on the choice of the incident and Raman scattered light polarization. The qualitative behavior of the Raman spectra is well-captured by an appropriate tight-binding model including an axial Higgs mode. The elucidation of the antisymmetric component provides direct evidence that the Higgs mode contains an axial vector representation (i.e. a pseudo-angular momentum) and hints the CDW in RTe3 is unconventional. Thus we provide a means for measuring collective modes quantum properties without resorting to extreme experimental conditions