Profitability, success probabilities, and incentives for cooperative R&D

As is widely conjectured, duopolists form a cost-sharing cooperative R&D alliance to develop a product - regardless of the probability of research success is either very high or very low. This study establishes that most low probabilities of research success cannot induce a financially successful cooperative R&D alliance. Incorporating the constraints in non-negative expected profits eliminates more than 95% probability of the parameter space where the probability of success is lower than 0.5. Our results further demonstrate that non-negative expected profits are attainable when the monopoly profit is not large in relation to duopoly profits, the fixed cost of R&D investment is low and the demand is large.Cooperative R&D; uncertainty; profitability

Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.</p> <p>Methods</p> <p>We measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls.</p> <p>Results</p> <p>Patients with DM had significantly lower circulating Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts, and higher Log baPWV compared with controls (all <it>P < 0.05</it>). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all <it>P < 0.05)</it>. The circulating levels of Log CD34/KDR⁺EPC (r = -0.46, <it>P < 0.001</it>) and Log CD133/KDR⁺EPC counts (r = -0.45, <it>P < 0.001</it>) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, <it>P < 0.05</it>) and negatively correlated with circulating levels of Log CD34/KDR⁺EPC (r = -0.40, <it>P < 0.001</it>) and Log CD133/KDR⁺EPC (r = -0.41, <it>P < 0.001</it>). Multivariate analysis revealed that HbA1c, Log CD34/KDR⁺and Log CD133/KDR⁺EPC counts were independent predictors of Log baPWV (<it>P < 0.05</it>).</p> <p>Conclusions</p> <p>In patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.</p

Enhanced Antifungal Bioactivity of Coptis Rhizome Prepared by Ultrafining Technology

The aim of this study was to identify and quantify the bioactive constituents in the methanol extracts of Coptis Rhizome prepared by ultrafining technology. The indicator compound was identified by spectroscopic method and its purity was determined by HPLC. Moreover, the crude extracts and indicator compound were examined for their ability to inhibit the growth of Rhizoctonia solani Kühn AG-4 on potato dextrose agar plates. The indicator compound is a potential candidate as a new plant derived pesticide to control Rhizoctonia damping-off in vegetable seedlings. In addition, the extracts of Coptis Rhizome prepared by ultrafining technology displayed higher contents of indicator compound; they not only improve their bioactivity but also reduce the amount of the pharmaceuticals required and, thereby, decrease the environmental degradation associated with the harvesting of the raw products

Tectonic erosion and crustal relamination during the India-Asian continental collision: Insights from Eocene magmatism in the southeastern Gangdese belt

Understanding the processes of tectonic erosion and crustal relamination during continental collision has important implications for the growth and differentiation of the continental crust. The discrepancy in isotopic compositions between the pre- and syn-collision magmatic rocks from the Gangdese belt in south Tibet provides an opportunity for studying these processes during the India-Asian collision. The Nyingchi granites and Confluence hornblende gabbros from the eastern Gangdese belt have zircon U-Pb ages of ca. 50 Ma. The Nyingchi granites have high Sr/Y and (Dy/Yb)N ratios, indicating that the magma was generated under eclogite-facies conditions. Their Sr-Nd-Pb-Hf isotopic compositions require significant incorporation of ancient supracrustal materials from the Gangdese belt and the Indian continent. The Confluence hornblende gabbros display arc-like trace element patterns but have enriched Sr-Nd-Pb-Hf isotopic compositions compared with those from the Jurassic-Cretaceous arc magmatic rocks, indicating significant input of ancient components into their mantle sources. The occurrence of the Cenozoic felsic metamorphic rocks in the lower crust of the Gangdese belt allows us to propose that the Nyingchi high Sr/Y granites were derived from partial melting of relaminated crustal materials which were removed from the Gangdese belt by tectonic erosion and the subducted Indian continent. The Confluence gabbros were sourced from lithospheric mantle which was metasomatized by inputs from relaminated crustal materials derived from the Gangdese belt and the subducted Indian continent. The estimated tectonic erosion rate is 150–188 km3/km/my, indicating significant crustal loss occurred during continental collision. Our study demonstrates that tectonic erosion and crustal relamination play an important role in the refinement of the composition of continental crust during continental collision

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer

AbstractThe epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell–cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl− and HCO3− conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β1-induced EMT and enhances cell migration and invasion in MCF-7. Ectopic overexpression of CFTR in a highly metastatic MDA-231 breast cancer cell line downregulates EMT markers and suppresses cell invasion and migration in vitro, as well as metastasis in vivo. The EMT-suppressing effect of CFTR is found to be associated with its ability to inhibit NFκB targeting urokinase-type plasminogen activator (uPA), known to be involved in the regulation of EMT. More importantly, CFTR expression is found significantly downregulated in primary human breast cancer samples, and is closely associated with poor prognosis in different cohorts of breast cancer patients. Taken together, the present study has demonstrated a previously undefined role of CFTR as an EMT suppressor and its potential as a prognostic indicator in breast cancer

Rapid Eocene erosion, sedimentation and burial in the eastern Himalayan syntaxis and its geodynamic significance

The lower Bomi Group of the eastern Himalayan syntaxis comprises a lithological package of sedimentary and igneous rocks that have been metamorphosed to upper amphibolite-facies conditions. The lower Bomi Group is bounded to the south by the Indus–Yarlung Suture and to the north by unmetamorphosed Paleozoic sediments of the Lhasa terrane. We report U–Pb zircon dating, geochemistry and petrography of gneiss, migmatite, mica schist and marble from the lower Bomi Group and explore their geological implications for the tectonic evolution of the eastern Himalaya. Zircons from the lower Bomi Group are composite. The inherited magmatic zircon cores display 206Pb/238U ages from ~ 74 Ma to ~ 41.5 Ma, indicating a probable source from the Gangdese magmatic arc. The metamorphic overgrowth zircons yielded 206Pb/238U ages ranging from ~ 38 Ma to ~ 23 Ma, that overlap the anatexis time (~ 37 Ma) recorded in the leucosome of the migmatites. Our data indicate that the lower Bomi Group do not represent Precambrian basement of the Lhasa terrane. Instead, the lower Bomi Group may represent sedimentary and igneous rocks of the residual forearc basin, similar to the Tsojiangding Group in the Xigaze area, derived from denudation of the hanging wall rocks during the India–Asia continental collision. We propose that following the Indian–Asian collision, the forearc basin was subducted, together with Himalayan lithologies from the Indian continental slab. The minimum age of detrital magmatic zircons from the supracrustal rocks is ~ 41.5 Ma and their metamorphism had happened at ~ 37 Ma. The short time interval (< 5 Ma) suggests that the tectonic processes associated with the eastern Himalayan syntaxis, encompassing uplift and erosion of the Gangdese terrane, followed by deposition, imbrication and subduction of the forearc basin, were extremely rapid during the Late Eocene

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice