Coordinating a Supply Chain With a Manufacturer-Owned Online Channel: A Dual Channel Model Under Price Competition

We consider a dual channel supply chain in which a manufacturer sells a single product to end-users through both a traditional retail channel and a manufacturer-owned direct online channel. We adopt a commonly used linear demand substitution model in which the mean demand in each channel is a function of the prices in each channel.We model each channel as a news vendor problem, with price and order quantity as decision variables. In addition, the manufacturer must choose the wholesale price to charge to the independent retailer. We analyze the optimal decisions for each channel and prove the existence of a unique equilibrium for the system. We compare this equilibrium solution to the solution for an integrated system, in which the manufacturer owns both the online store and the retailer. To enable supply chain coordination, we propose two contract schemes: a modified revenue-sharing contract and gain/loss sharing contract. We show that, in cases where the retail channel has a larger market than the online channel, such contracts enable the manufacturer to maintain price discrimination, selling the products in different channels at different prices. Finally, we perform a comprehensive numerical study to consider the impact of the model parameters on the equilibrium and to demonstrate the performance of the proposed coordination contracts. We conclude that coordination is most critical for products which are highly price sensitive and for systems in which the online and traditional retail channels are not viewed as close substitutes

Investigation of thermal breakage and heat transfer in single, insulated and laminated glazing under fire conditions

To make constructions more artistic, various new kinds of glazing are increasingly employed in building envelopes. However, when subjected to a fire, these glass façades may easily break and fall out, significantly accelerating the development of enclosure fire. Thus, it is necessary to investigate and compare their different fire performance and breakage mechanisms. In this work, a total of ten tests, including single coated, insulated and laminated glazing, were heated by a 500 × 500 mm2 pool fire. Breakage time, glass surface and air temperature, incident heat flux and crack initiation and propagation were obtained. The critical conditions of three different kinds of glazing were determined. It was established that the insulated and laminated glass can survive longer than the single glass. The air gap and fire side glass pane was found to play a key role for the thermal resistance of ambient side pane in the insulated glazing. Although both panes of the laminated glazing broke, it could be held together by the layer of gel, effectively avoiding the formation of a new vent. Numerical simulations were performed to investigate the heat transfer process through the glazing panels and the temperatures in the glazing were predicted well. Suggestions for glass fire resistance design are proposed

Sexual Dysfunction as a Marker of Cardiovascular Disease in Males With 50 or More Years of Type 1 Diabetes

OBJECTIVE Vascular dysfunction is a major contributor to diabetes complications. It is also the primary physiologic cause of erectile dysfunction and considered an independent predictor of cardiovascular disease (CVD) in males over age 40 years. A cohort of individuals with 50 or more years of type 1 diabetes, Joslin Medalists, have low rates of small but not large vessel complications. This study aims to identify the prevalence and longitudinal association of sexual dysfunction (SD) with CVD in Joslin Medalists. RESEARCH DESIGN AND METHODS Description and association of self-assessment of SD in males of the Medalist cohort by self-reported sexual problems with CVD. SD is validated through the use of the abbreviated International Index of Erectile Dysfunction (IIEF). RESULTS Of 301 males in the Medalist Study, 69.8% reported a history of SD. Unadjusted risk factors included elevated glycated hemoglobin (HbA1c) (P = 0.02), elevated BMI (P = 0.03), higher total cholesterol (P = 0.02), lower HDL (P 0.05) with SD. Current report of SD (IIEF score ≤17) in a subset of Medalists was significantly correlated with self-reported longitudinal SD. CONCLUSIONS SD in those with extreme-duration type 1 diabetes is independently associated with CVD, representing a large-vessel pattern. The findings suggest that SD may predict CVD in those with type 1 diabetes of long duration. These individuals have also been found to be relatively free of microvascular complications

NASA ExoPAG Study Analysis Group 11: Preparing for the WFIRST Microlensing Survey

NASA's proposed WFIRST-AFTA mission will discover thousands of exoplanets with separations from the habitable zone out to unbound planets, using the technique of gravitational microlensing. The Study Analysis Group 11 of the NASA Exoplanet Program Analysis Group was convened to explore scientific programs that can be undertaken now, and in the years leading up to WFIRST's launch, in order to maximize the mission's scientific return and to reduce technical and scientific risk. This report presents those findings, which include suggested precursor Hubble Space Telescope observations, a ground-based, NIR microlensing survey, and other programs to develop and deepen community scientific expertise prior to the mission.Comment: 35 pages, 5 Figures. A brief overview of the findings is presented in the Executive Summary (2 pages

Liposomal phytohemagglutinin: In vivo T-cell activator as a novel pan-cancer immunotherapy

Immunotherapy is an attractive approach for treating cancer. T-cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged by weak T-cell activation and short persistence. Therefore, alternative solutions to induce greater activation and persistence of T cells during TCE immunotherapy is needed. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA). PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. An approach to overcome the limitations of PHA while also preserving its function is needed. In this study, we report a liposomal PHA which increased PHA stability, reduced toxicity and performed as an immunotherapeutic that is able to activate T cells for the use in future cancer immunotherapies to circumvent current obstacles in immunosuppression and T-cell exhaustion

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA

Citation: Dryden, M. W., Canfield, M. S., Kalosy, K., Smith, A., Crevoiserat, L., McGrady, J. C., . . . Sun, F. (2016). Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA. Parasites & Vectors, 9, 11. doi:10.1186/s13071-016-1654-7Background: A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA. Methods: Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed. Results: Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations. Conclusions: In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral fluralaner chew completely eliminated dog and premises flea infestations and markedly reduced dermatology lesions and pruritus. Three monthly doses of the afoxolaner chewable also eliminated flea infestations in dogs, markedly reduced premises' flea populations and similarly improved dermatology lesions and pruritus