Environmental tax reform: an assessment of social responses in Ireland

Environmental tax reform (ETR) is widely accepted to be a policy with desirable environmental, and other economic effects. The question arises then as to why its implementation has been so patchy. There is a broad literature on the economic impact of ETR, however, there have been very few research efforts devoted to understanding the roles and imperatives of the public, policy makers, businesses and other stakeholders who are addressed by ETR. This paper examines the impediments to ETR in Ireland. Focus groups were formed comprising of members of the general public and these provided a forum for detailed reactions to the ETR concept. Interviews were conducted with policy makers and key business people in an attempt to identify both the patterns of thinking behind ETR and the main obstacles to its introduction. Having presented the results, a theory of the main impediments to ETR is developed. The opinions of the members of the public, the business community and the policy makers highlight a number of issues that need to be addressed in the future design of ETR in Ireland. The principal potential impediments to ETR include: mistrust of the government, implausibility of the policy, means of hypothecation, information asymmetries, the political system, the structure of government, the macroeconomic environment, the impact on competitiveness, inequity between sectors, regressivity, elasticities and the level of the tax, terminology, and the marketing of ETR.     

The Effect of Nanotube Content and Orientation on the Mechanical Properties of Polymer–Nanotube Composite Fibers: Separating Intrinsic Reinforcement from Orientational Effects

We have measured the mechanical properties of coagulation‐spun polymer–nanotube composite fibers. Both the fiber modulus, Y, and strength, σ_B, scale linearly with volume fraction, V_f, up to V_f ～10%, after which these properties remain constant. We measured dY/dV_f = 254 GPa and dσ_B/dV_f = 2.8 GPa in the linear region. By drawing fibers with V_f < 10% to a draw ratio of ～60%, we can increase these values to dY/dV_f = 600 GPa and dσ_B/dV_f = 7 GPa. Raman measurements show the Herman's orientation parameter, S, to increase with drawing, indicating that significant nanotube alignment occurs. Raman spectroscopy also shows that the nanotube effective modulus, Y_Eff, also increases with drawing. We have calculated an empirical relationship between the nanotube orientation efficiency factor, η_o, and S. This allows us to fit the data for Y_Eff versus η_o, showing that the fiber modulus scales linearly with η_o, as predicted theoretically by Krenchel. From the fit, we estimate the nanotube modulus to be; Y_NT = 480 GPa. Finally, we show that the fiber strength also scales linearly with η_o, giving an effective interfacial stress transfer of τ = 40 MPa and a nanotube critical length of l_c=1250 nm. This work demonstrates the validity of the Cox‐Krenchel rule of mixtures and shows that continuum theory still applies at the near‐molecular level.     

A lead isotopic study of the human bioaccessibility of lead in urban soils from Glasgow, Scotland

The human bioaccessibility of lead (Pb) in Pb-contaminated soils from the Glasgow area was determined by the Unified Bioaccessibility Research Group of Europe (BARGE) Method (UBM), an in vitro physiologically based extraction scheme that mimics the chemical environment of the human gastrointestinal system and contains both stomach and intestine compartments. For 27 soils ranging in total Pb concentration from 126 to 2160 mg kg^− 1 (median 539 mg kg^− 1), bioaccessibility as determined by the ‘stomach’ simulation (pH ~ 1.5) was 46-1580 mg kg^− 1, equivalent to 23-77% (mean 52%) of soil total Pb concentration. The corresponding bioaccessibility data for the ‘stomach + intestine’ simulation (pH ~ 6.3) were 6-623 mg kg^− 1 and 2-42% (mean 22%) of soil Pb concentration. The soil ²⁰⁶Pb/²⁰⁷Pb ratios ranged from 1.057 to 1.175. Three-isotope plots of ²⁰⁸Pb/²⁰⁶Pb against ²⁰⁶Pb/²⁰⁷Pb demonstrated that ²⁰⁶Pb/²⁰⁷Pb ratios were intermediate between values for source end-member extremes of imported Australian Pb ore (1.04) - used in the manufacture of alkyl Pb compounds (1.06-1.10) formerly added to petrol - and indigenous Pb ores/coal (1.17-1.19). The ²⁰⁶Pb/²⁰⁷Pb ratios of the UBM ‘stomach’ extracts were similar (< 0.01 difference) to those of the soil for 26 of the 27 samples (r = 0.993, p < 0.001) and lower in 24 of them. A slight preference for lower ²⁰⁶Pb/²⁰⁷Pb ratio was discernible in the UBM. However, the source of Pb appeared to be less important in determining the extent of UBM-bioaccessible Pb than the overall soil total Pb concentration and the soil phases with which the Pb was associated. The significant phases identified in a subset of samples were carbonates, manganese oxides, iron-aluminium oxyhydroxides and clays.     

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.     

Glucose activates both K(ATP) channel-dependent and K(ATP) channel-independent signaling pathways in human islets

We investigated the effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) on intracellular Ca2+ concentration ([Ca2+]i) and cell length in isolated and field-stimulated rat cardiomyocytes. [Ca2+]i and cell length of field-stimulated cells were determined simultaneously by confocal laser scan microscopy by using the fluorescent Ca2+ dye Fluo-3. PAF (10(-12)-10(-8) M) inhibited systolic [Ca2+]i increase in a time- and concentration-dependent manner. Maximal effects were observed after an incubation time of 6-8 min, resulting in a 17% (10(-12) M), 41% (10(-10) M), and 52% (10(-8) M PAF) inhibition of systolic [Ca2+]i increase. A time- and concentration-dependent decrease in simultaneously measured cell shortening also was demonstrated. Cell shortening was inhibited by 10% (10(-12) M), 32% (10(-10) M), and 50% (10(-8) M) after an incubation time of 8 min. The effects of PAF could be antagonized by the PAF-receptor antagonist WEB 2170. These data demonstrate that PAF receptor-dependently induces a negative inotropic effect, which is correlated with a decrease in systolic [Ca2+]i and is most likely not due to a decrease in myofilament sensitivity.     

Verapamil, a phenylalkylamine Ca2+ channel blocker, inhibits ATP-sensitive K+ channels in insulin-secreting cells from rats

Radioisotopic and electrophysiological techniques were used to assess the effects of verapamil, a phenylalkylamine Ca2+ channel blocker, on K+ permeability of insulin-secreting cells. Verapamil provoked a concentration-dependent inhibition of 86Rb (42K substitute) outflow from prelabelled and perifused rat pancreatic islets. This property appears to be inherent to the phenylalkylamine Ca2+ channel blockers since gallopamil, a methoxyderivative of verapamil, but not nifedipine, a 1,4-dihydropyridine Ca2+ channel blocker, inhibited 86Rb outflow. The experimental data further revealed that verapamil interacted with a Ca2+-independent, glucose- and glibenclamide-sensitive modality of 86Rb extrusion. Moreover, verapamil prevented the increase in 86Rb outflow brought about by BPDZ 44; a potent activator of the ATP-sensitive K+ channel. Single-channel current recordings by the patch clamp technique confirmed that verapamil elicited a dose-dependent inhibition of the ATP-dependent K+ channel. Lastly, under experimental conditions in which verapamil clearly inhibited the ATP-sensitive K+ channels, the drug did not affect 45Ca outflow, the cytosolic free Ca2+ concentration or insulin release. It is concluded that the Ca2+ entry blocker verapamil inhibits ATP-sensitive K+ channels in pancreatic beta cells. This effect was not associated with stimulation of insulin release.     

JANA: A new iterative polyexponential curve stripping program

A new iterative polyexponential curve stripping technique for the provision of initial pharmacokinetic parameter estimates has been developed. Such estimates are required for nonlinear least-squares curve fitting. In contrast to conventional curve stripping, this new technique does not make any assumption about the relative magnitudes of the exponential rate constants. Hence, the parameter estimates which it provides are free of the bias which may arise in conventional curve stripping. A BASIC program called JANA has been developed to implement the new curve stripping procedure.     

Modified Goodness-of-Fit Tests for Gamma Distributions with Unknown Location and Scale Parameters

The common Kolmogorov-Smirnov, Anderson-Darling, and Cramer-von Mises goodness-of-fit tests require continuous underlying distributions with known parameters. This paper gives tables of critical values for these tests for gamma distributions with unknown location and scale parameters and known shape parameters. The powers of these tests are given for a number of alternative distributions. A relation between the critical values and the inverse square of the shape parameter is presented. For larger sample sizes, the modified CvM test is usually the most powerful of the three tests. One exception is for the alternative of a lognormal distribution where the modified AD test is most powerful. The equation, C = ao + a1(1/?2) describes the relation between critical value and shape parameter quite well.     

Clonal relationships among high-level penicillin-resistant Streptococcus pneumoniae in the United States

Emu antibody responses to avian influenza virus (AIV) infection were evaluated by the competitive enzyme-linked immunosorbent assay (C-ELISA), agar gel immunodiffusion (AGID) and hemagglutination inhibition (HI) tests. All birds infected with AIV H5N1, H5N3, or H7N7 developed antinucleoprotein (NP) antibodies as early as 7 days postinfection as detected by the C-ELISA. The responses lasted 49 days for the emus receiving H5N3 and at least 56 days for emus receiving the other two viruses. By evaluating 50 emu field serum samples, the C-ELISA was found more sensitive than the AGID test for the detection of anti-NP antibodies. This study indicates that emus experimentally infected with AIV developed antibody responses that can be detected by C-ELISA, AGID, and HI tests. The results from this and our previous studies demonstrate the use of the C-ELISA as a substitute for the AGID test in a routine serodiagnostic screening for detection of antibodies to AIV infection in multiple avian species.     

Cost-Duration Analysis with the Cut Network

A new approach is developed for conducting a cost-duration analysis (trade-off study) for a project denned with a CPM/PERT activity network. The approach utilizes a new graph theory concept, proper oriented cut-set (POCS). It also uses the cut network, a dual-type network defined in this paper for any planar activity network. The cut network implicitly enumerates all POCS's of an original network. The cost-duration problem defined for the original activity network is transformed into a minimum-cost flow problem for the cut network. This approach to cost-duration analysis, developed here for a planar network and linear activity cost-duration relations, is optimal, conceptually direct, and has potential for application to more general cost-functions.