244 research outputs found

    Price determination in monopolistic markets with inventory adjustment

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    This paper presents a practical model for the analysis of the price determination mechanism in raw materials markets that are characterized by the dominance of a large firm. The model takes explicit note of the influence of inventory adjustments; it is postulated that the dominant firm?s decision on price and production levels is negatively related to the difference between actual and desired inventory levels. In a first empirical test, the model is applied to an analysis of the nickel industry. The empirical results support the hypothesized role of inventories and show the importance of inventory adjustments relative to the other factors determining price and production behavior.

    An econometric model of the world nickel industry

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    The Third United Nations Conference on the Law of the Sea has been concluded in the spring of 1982 with the adoption of a convention text. The acceptance of this text (signature and ratification) by the necessary number of states is still highly uncertain. The major disagreements relate to the convention's seabed mining regime, in particular the provisions for production controls and technology transfer. Among the four metals which can be recovered from the seabed - manganese nodules containing manganese, cobalt, copper and nickel - over half of the potential revenues would come from nickel. Conditions in the nickel market will have an impact on investment decisions in seabed mining and the nickel market itself may be significantly affected by nickel output from manganese nodules. The purpose of this paper is to present and estimate an econometric model for the world nickel industry. Furthermore, in order to quantify the impact of alternative seabed mining regimes on the future price of nickel as well as on the output of nickel from current land-based sources, a simulation analysis is provided. Such a simulation model is also helpful in estimating the revenue losses that land-based producers might incur as a result of seabed mining.

    "Familial" versus "sporadic" intellectual disability: contribution of subtelomeric rearrangements

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    <p>Abstract</p> <p>Background</p> <p>Cryptic subtelomeric rearrangements have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been studied. As positive family history of ID had been proposed as an important and significant predicting factor of subtelomeric rearrangements, it was assumed that the contribution of subtelomeric aberrations in familial ID would be much more than the sporadic ones. Three hundred and twenty two patients from 102 unrelated families with more than two ID patients in the first degree relatives have been investigated. Assessment of subtelomeric rearrangements were carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique. Detected aberrations were then confirmed by Fluorescence in Situ Hybridization (FISH) method.</p> <p>Results</p> <p>Among the families studied, 27.4% had 4-12, 36.3% had 3 and 36.3% had 2 affected individuals in the first degree relatives. One unbalanced translocation and 4 polymorphic changes were detected. The prevalence of clinically significant subtelomeric rearrangements was 0.98%.</p> <p>Conclusion</p> <p>This is the first investigation of subtelomeric aberrations in a large sample set of familial ID patients. Our results show that the contribution of subtelomeric rearrangements to familial ID is not as much as what had been determined for sporadic ones in the literature. Moreover, this study shows that the positive family history by alone, cannot be the most important and determining indicator of subtelomeric aberrations while it would be a good predicting factor when associated with dysmorphism or congenital malformations. These findings propose that other cryptic chromosomal abnormalities or even single gene disorders may be the main cause of familial ID rather than subtelomeric aberrations.</p

    C-Terminal Domain Deletion Enhances the Protective Activity of cpa/cpb Loaded Solid Lipid Nanoparticles against Leishmania major in BALB/c Mice

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    Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis with an annual incidence of approximately 2 million cases and is endemic in 88 countries, including Iran. CL's continued spread, along with rather ineffectual treatments and drug-resistant variants emergence has increased the need for advanced preventive strategies. We studied Type II cysteine proteinase (CPA) and Type I (CPB) with its C-terminal extension (CTE) as cocktail DNA vaccine against murine and canine leishmaniasis. However, adjuvants' success in enhancing immune responses to selected antigens led us to refocus our vaccine development programs. Herein, we discuss cationic solid lipid nanoparticles' (cSLN) ability to improve vaccine-induced protective efficacy against CL and subsequent lesion size and parasite load reduction in BALB/c mice. For this work, we evaluated five different conventional as well as novel parasite detection techniques, i.e., footpad imaging, footpad flowcytometry and lymph node flowcytometry for disease progression assessments. Vaccination with cSLN-cpa/cpb-CTE formulation showed highest parasite inhibition at 3-month post vaccination. Immunized mice showed reduced IL-5 level and significant IFN-ã increase, compared to control groups. We think our study represents a potential future and a major step forward in vaccine development against leishmaniasis

    "Familial" versus "Sporadic" intellectual disability: contribution of common microdeletion and microduplication syndromes

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    <p>Abstract</p> <p>Background</p> <p>Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundred and twenty eight patients from 101 unrelated Iranian families with more than two ID patients in the first-degree relatives, have been investigated. Assessment of a panel of 21 common Microdeletion and Microduplication syndromes (CMMS) was carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique.</p> <p>Results</p> <p>Among the families studied, 27.7% had 4-12, 35.6% had 3 and 36.6% had 2 affected individuals in the first-degree relatives. An autosomal dominant inheritance of Williams-Beuren syndrome (WBS) was detected in a family with no clinical suspicion of WBS. The prevalence of CMMS was therefore,0.99%.</p> <p>Conclusion</p> <p>This is the first investigation of a panel of CMMS in a large sample set of "familial ID patients". The findings of this study showed the low prevalence of CMMSs in "familial ID" patients in spite of the significant contribution of such aberrations in "sporadic ID" which has a very useful practical impact by avoiding unnecessary diagnostic tests in "familial ID" patients.</p

    Porcine Islet-Specific Tolerance Induced by the Combination of Anti-LFA-1 and Anti-CD154 mAbs is Dependent on PD-1

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    [EN]We previously demonstrated that short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) induces tolerance to neonatal porcine islet (NPI) xenografts that is mediated by regulatory T cells (Tregs) in B6 mice. In this study, we examined whether the coinhibitory molecule PD-1 is required for the induction and maintenance of tolerance to NPI xenografts. We also determined whether tolerance to NPI xenografts could be extended to allogeneic mouse or xenogeneic rat islet grafts since we previously demonstrated that tolerance to NPI xenografts could be extended to second-party NPI xenografts. Finally, we determined whether tolerance to NPI xenografts could be extended to allogeneic mouse or second-party porcine skin grafts. Diabetic B6 mice were transplanted with 2,000 NPIs under the kidney capsule and treated with short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs. Some of these mice were also treated simultaneously with anti-PD-1 mAb at >150 days posttransplantation. Spleen cells from some of the tolerant B6 mice were used for proliferation assays or were injected into B6 rag−/− mice with established islet grafts from allogeneic or xenogeneic donors. All B6 mice treated with anti-LFA-1 and anti-CD154 mAbs achieved and maintained normoglycemia until the end of the study; however, some mice that were treated with anti-PD-1 mAb became diabetic. All B6 rag−/− mouse recipients of first- and second-party NPIs maintained normoglycemia after reconstitution with spleen cells from tolerant B6 mice, while all B6 rag−/− mouse recipients of allogeneic mouse or xenogeneic rat islets rejected their grafts after cell reconstitution. Tolerant B6 mice rejected their allogeneic mouse or xenogeneic second-party porcine skin grafts while remaining normoglycemic until the end of the study. These results show that porcine islet-specific tolerance is dependent on PD-1, which could not be extended to skin grafts.SIWe acknowledge the technical assistance of Deb Dixon and Dawne Colwell and thoughtful discussions with Dr. Tsunehiro Kobayashi. We are grateful to the Canadian Diabetes Association, which provided major funding for this work as well as the Edmonton Civic Employees’ Charitable Assistance Fund, Stollery Children’s Hospital Foundation, the MacLachlan Fund University Hospital Foundation, Canadian Institutes of Health Research, Colliers International, Ken and Denise Cantor as well as Ewa and John Burton, who provided additional support. The Muttart Diabetes Research Training Centre provided scholarship for H.A. The authors declare no conflicts of interest

    Modeling the morphodynamics of coastal responses to extreme events: what shape are we in?

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    This paper is not subject to U.S. copyright. The definitive version was published in Sherwood, C. R., van Dongeren, A., Doyle, J., Hegermiller, C. A., Hsu, T.-J., Kalra, T. S., Olabarrieta, M., Penko, A. M., Rafati, Y., Roelvink, D., van der Lugt, M., Veeramony, J., & Warner, J. C. Modeling the morphodynamics of coastal responses to extreme events: what shape are we in? Annual Review of Marine Science, 14, (2022): 457–492, https://doi.org/10.1146/annurev-marine-032221-090215.This review focuses on recent advances in process-based numerical models of the impact of extreme storms on sandy coasts. Driven by larger-scale models of meteorology and hydrodynamics, these models simulate morphodynamics across the Sallenger storm-impact scale, including swash,collision, overwash, and inundation. Models are becoming both wider (as more processes are added) and deeper (as detailed physics replaces earlier parameterizations). Algorithms for wave-induced flows and sediment transport under shoaling waves are among the recent developments. Community and open-source models have become the norm. Observations of initial conditions (topography, land cover, and sediment characteristics) have become more detailed, and improvements in tropical cyclone and wave models provide forcing (winds, waves, surge, and upland flow) that is better resolved and more accurate, yielding commensurate improvements in model skill. We foresee that future storm-impact models will increasingly resolve individual waves, apply data assimilation, and be used in ensemble modeling modes to predict uncertainties.All authors except D.R. were partially supported by the IFMSIP project, funded by US Office of Naval Research grant PE 0601153N under contracts N00014-17-1-2459 (Deltares), N00014-18-1-2785 (University of Delaware), N0001419WX00733 (US Naval Research Laboratory, Monterey), N0001418WX01447 (US Naval Research Laboratory, Stennis Space Center), and N0001418IP00016 (US Geological Survey). C.R.S., C.A.H., T.S.K., and J.C.W. were supported by the US Geological Survey Coastal/Marine Hazards and Resources Program. A.v.D. and M.v.d.L. were supported by the Deltares Strategic Research project Quantifying Flood Hazards and Impacts. M.O. acknowledges support from National Science Foundation project OCE-1554892

    Physicians’ and nurses’ decision making to encounter neonates with poor prognosis in the neonatal intensive care unit

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    This is an Accepted Manuscript of an article published by Sage in Clinical Ethics on 03/06/2020. Available online: https://journals.sagepub.com/doi/abs/10.1177/1477750920927173This is an Accepted Manuscript of an article published by Sage in Clinical Ethics on 03/06/2020.Available online: https://journals.sagepub.com/doi/abs/10.1177/1477750920927173acceptedVersio

    Role of polymorphisms of the endothelial nitric oxide synthase gene in predicting slow-flow phenomenon after primary percutaneous coronary intervention

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    Objective: The aim of the present study was to examine the association between 2 polymorphisms of the endothelial nitric oxide (eNOS) gene (-786T>C and +894G>T) and the no-reflow/slow-flow phenomenon in post-primary percutaneous coronary intervention (PPCI) patients. Methods: A total of 103 post-PPCI patients were enrolled. Coronary no-reflow phenomenon was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade 0-1 and coronary slow-flow phenomenon (CSFP) was defined as a TIMI flow grade �2. Results: Due to the small number of post-PPCI patients with the no-reflow phenomenon (n=4), the primary comparison was made between CSFP (n=20) and normal flow (n=83) groups. There was a greater frequency of CSFP among carriers of the-786C allele of the eNOS-786T>C polymorphism (odds ratio OR: 3.90; 95% confidence interval CI: 0.87-17.45; p=0.07). However, no such association was detected between the +894T allele of the eNOS +894G>T and CSFP (OR: 0.92; 95% CI: 0.21-3.98; p=0.91). In the adjusted analysis, the-786T>C polymorphism did not reach statistical significance. Conclusion: There was no significant association between CSFP and 2 of the most common polymorphisms of the eNOS gene in post-PPCI patients. © 2020 Turkish Society of Cardiology
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