Piracy Accommodation and the Optimal Timing of Royalty Payments

This paper generalizes the two-period model of Watt (2000) who demonstrates the possibility of optimal accommodation of a pirate when the royalty rate applying to a creation is uniform and second-period Cournot competition applies. Admitting nonlinear contracts with period-specific royalty rates that leave total payments unchanged, simulation analysis shows that a producer of originals does better to increase the royalty rate in period 1 and decrease the rate to a negative level in period 2, thereby more than offsetting the usual cost advantage available to a pirate. Watt's illustrative examples regarding piracy accommodation (but not piracy exclusion) are overturned when a nonlinear contract is chosen optimally, although accommodation remains optimal in some other cases. Further, where exclusion is impossible under uniform royalties, cases exist where exclusion is feasible under nonlinear royalties. Even so, accommodation may be a preferable strategy.accommodating copyright piracy; nonlinear royalty contracts

Ex Ante Liability Rules in New Zealand's Health and Safety in Employment Act: A Law and Economics Analysis

In addition to penalties imposed for breaches of statutory duties in the event of workplace accidents involving physical harms, New Zealand's Health and Safety in Employment Act 1992 also provides for penalties where accidents have not occurred. Ordinary negligence rules are ex post in that both an accident and harm must occur before liability accrues, whereas ex ante liability rules create liability for deficient care per se. This paper examines whether liability for breaches of duty that do not give rise to accidents have a useful incentive-enhancing role for health and safety decisions by employers in the New Zealand context when used in conjunction with ex post liability rules. We argue that ex post rules by themselves are insufficient to induce appropriate levels of precaution due to the combined presence of weak penalties and considerable uncertainty surrounding the Courts' required standard of care. Merely augmenting ex post liability with ex ante liability, however, is unlikely to induce desirable levels of employer precautions. Further, more strict ex ante standards than socially optimal precaution levels may be desirable since inspection probabilities, prosecution rates, and penalties for breaches of ex ante standards are relatively low, providing some justification for the relatively stringent safety regulations and required standard of care observed in New Zealand. Nevetheless, a weaker but less uncertain standard may instead induce a small degree of overprecaution, removing the need for ex ante regulations from this particular perspective.ex ante and ex post liability; safety incentives, health and safety standards; uncertainty

Incentives and the Changing Structure of Penalties in New Zealand's Health and Safety in Employment Act

This article argues that it is doubtful that the fivefold increase in maximum fines under New Zealand's Health and Safety in Employment Amendment Act 2002 will be successful in providing suitable precautionary incentives. Expected penalties remain at relatively low levels, with the continued use of capped fines along with substantial margins for deterrence of the most serious cases. On average, fines were initially substantially lower in response to the introduction of the Sentencing Act 2002 for which uncapped (but insurable) reparations take precedence over fines, and must be accounted for in setting fines. The combined effects of the legislation led to average total financial penalties approximately doubling through 2004 rather than increasing at anything like the rate signalled for fines by the amendments. Subsequently, while fines have grown in absolute terms, even more rapid growth in reparations has caused relative crowding-out while total penalties remain well below those signalled by the amendments alone. The case for low caps on fines appears weak, while 'asset-testing' fines is unlikely to be an efficient practice. Absent further significant changes in workplace safety incentives, New Zealand is likely to face an ongoing (if possibly somewhat abated) stream of prosecutions for serious breaches of relatively onerous statutory health and safety duties.health and safety incentives; expected penalties; capped fines; reparations

Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine.

Children with aggressive neural tumors have poor survival rates and novel therapies are needed. Previous studies have identified nifurtimox and buthionine sulfoximine (BSO) as effective agents in children with neuroblastoma and medulloblastoma. We hypothesized that nifurtimox would be effective against other neural tumor cells and would be synergistic with BSO. We determined neural tumor cell viability before and after treatment with nifurtimox using MTT assays. Assays for DNA ladder formation and poly-ADP ribose polymerase (PARP) cleavage were performed to measure the induction of apoptosis after nifurtimox treatment. Inhibition of intracellular signaling was measured by Western blot analysis of treated and untreated cells. Tumor cells were then treated with combinations of nifurtimox and BSO and evaluated for viability using MTT assays. All neural tumor cell lines were sensitive to nifurtimox, and IC50 values ranged from approximately 20 to 210 μM. Nifurtimox treatment inhibited ERK phosphorylation and induced apoptosis in tumor cells. Furthermore, the combination of nifurtimox and BSO demonstrated significant synergistic efficacy in all tested cell lines. Additional preclinical and clinical studies of the combination of nifurtimox and BSO in patients with neural tumors are warranted

Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression.

BackgroundNovel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models.MethodsLevels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes.ResultsBoth primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib.ConclusionsNeuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify patients that may respond to MEK inhibition. MEK inhibition therefore represents a potential new therapeutic strategy for neuroblastoma

Barriers to Knowing and Being Known: Constructions of (In)competence in Research

In this paper, we examine the barriers to, and possibilities of, recognizing individuals labelled intellectually disabled as producers and contributors to knowledge about their experiences. Through engaging perspectives within the fields of philosophy of education and disability studies, we examine contrasting research about the use of facilitated communication, an augmentative and alternative communication technique for teaching people with disabilities to communicate through pointing, or typing with support provided by a communication partner. We examine how researchers impose demands for the scientific validation of facilitated communication and use such demands to discredit autistic people identified with intellectual disabilities in their attempts to be recognized as knowers and producers of knowledge. Our analysis calls into question whether self-imposed limitations on contemporary knowledge production render educational research (in)capable of accepting forms of evidence that will facilitate the agency of those labelled or regarded as intellectually disabled and (in)capable of providing consumers of educational research access to knowledge that reflects the wide range of communicative, neurocognitive, and intellectual diversity in schools and communities

Global MHD simulation of flux transfer events at the high-latitude magnetopause observed by the cluster spacecraft and the SuperDARN radar system

A global magnetohydrodynamic numerical simulation is used to study the large-scale structure and formation location of flux transfer events (FTEs) in synergy with in situ spacecraft and ground-based observations. During the main period of interest on the 14 February 2001 from 0930 to 1100 UT the Cluster spacecraft were approaching the Northern Hemisphere high-latitude magnetopause in the postnoon sector on an outbound trajectory. Throughout this period the magnetic field, electron, and ion sensors on board Cluster observed characteristic signatures of FTEs. A few minutes delayed to these observations the Super Dual Auroral Radar Network (SuperDARN) system indicated flow disturbances in the conjugate ionospheres. These “two-point” observations on the ground and in space were closely correlated and were caused by ongoing unsteady reconnection in the vicinity of the spacecraft. The three-dimensional structures and dynamics of the observed FTEs and the associated reconnection sites are studied by using the Block-Adaptive-Tree-Solarwind-Roe-Upwind-Scheme (BATS-R-US) MHD code in combination with a simple open flux tube motion model (Cooling). Using these two models the spatial and temporal evolution of the FTEs is estimated. The models fill the gaps left by measurements and allow a “point-to-point” mapping between the instruments in order to investigate the global structure of the phenomenon. The modeled results presented are in good correlation with previous theoretical and observational studies addressing individual features of FTEs

De-regulation of JNK and JAK/STAT signaling in ESCRT-II mutant tissues cooperatively contributes to neoplastic tumorigenesis

Multiple genes involved in endocytosis and endosomal protein trafficking in Drosophila have been shown to function as neoplastic tumor suppressor genes (nTSGs), including Endosomal Sorting Complex Required for Transport-II (ESCRT-II) components vacuolar protein sorting 22 (vps22), vps25, and vps36. However, most studies of endocytic nTSGs have been done in mosaic tissues containing both mutant and non-mutant populations of cells, and interactions among mutant and non-mutant cells greatly influence the final phenotype. Thus, the true autonomous phenotype of tissues mutant for endocytic nTSGs remains unclear. Here, we show that tissues predominantly mutant for ESCRT-II components display characteristics of neoplastic transformation and then undergo apoptosis. These neoplastic tissues show upregulation of c-Jun N-terminal Kinase (JNK), Notch, and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signaling. Significantly, while inhibition of JNK signaling in mutant tissues partially inhibits proliferation, inhibition of JAK/STAT signaling rescues other aspects of the neoplastic phenotype. This is the first rigorous study of tissues predominantly mutant for endocytic nTSGs and provides clear evidence for cooperation among de-regulated signaling pathways leading to tumorigenesis

The origin of Jupiter's outer radiation belt

The intense inner radiation belt at Jupiter (>50 MeV at 1.5 RJ) is generally accepted to be created by radial diffusion of electrons from further away from the planet. However, this requires a source with energies that exceed 1 MeV outside the orbit of the moon Io at 5.9 RJ, which has never been explained satisfactorily. Here we test the hypothesis that this source population could be formed from a very soft energy spectrum, by particle injection processes and resonant electron acceleration via whistler mode chorus waves. We use the British Antarctic Survey Radiation Belt Model to calculate the change in the electron flux between 6.5 and 15 RJ; these are the first simulations at Jupiter combining wave particle interactions and radial diffusion. The resulting electron flux at 100 keV and 1 MeV lies very close to the Galileo Interim Radiation Electron model spectrum after 1 and 10 days, respectively. The primary driver for the increase in the flux is cyclotron resonant acceleration by chorus waves. A peak in phase space density forms such that inside L≈9 radial diffusion transports electrons toward Jupiter, but outside L≈9 radial diffusion acts away from the planet. The results are insensitive to the softness of the initial energy spectrum but do depend on the value of the flux at the minimum energy boundary. We conclude by suggesting that the source population for the inner radiation belt at Jupiter could indeed be formed by wave-particle interactions

Fostering Communication Through Physical Activity

Many individuals with autism experience difficulties with reliable, meaningful communication often impacting their academic and social engagement. As the first and most frequent communication partners, parents of children with autism may struggle initiating or maintaining meaningful communicative interactions, and thus require training, tools, and support. This article describes an approach to coaching parents in fostering meaningful, reciprocal communication through recreational activities as part of a larger physical activity program for parents and families of children with autism. It describes a Cycle of Communication framework as a tool for parents to recognize opportunities to structure and support their children’s communicative attempts and are discussed herein for educators, families and practitioners to adapt and use within their local contexts