Patent Licensing and Price Discrimination

We extend the Kamien and Tauman model of patent licensing by introducing heterogeneous licensees that differ in their marginal costs using the licensed technology. We show that price discrimination does not necessarily ensure an efficient allocation of licenses. Moreover, it is possible that more licenses are sold without rather than with price discrimination.Endogenous valuation

Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

Purpose: Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. Methods: The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). Results: In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50µg/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. Conclusion: These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma

Active Inverse Reward Design

Designers of AI agents often iterate on the reward function in a trial-and-error process until they get the desired behavior, but this only guarantees good behavior in the training environment. We propose structuring this process as a series of queries asking the user to compare between different reward functions. Thus we can actively select queries for maximum informativeness about the true reward. In contrast to approaches asking the designer for optimal behavior, this allows us to gather additional information by eliciting preferences between suboptimal behaviors. After each query, we need to update the posterior over the true reward function from observing the proxy reward function chosen by the designer. The recently proposed Inverse Reward Design (IRD) enables this. Our approach substantially outperforms IRD in test environments. In particular, it can query the designer about interpretable, linear reward functions and still infer non-linear ones

Muhammad Taqi al-Majlisi and Safavid Shi‘Ism: Akhbarism and Anti-sunni Polemic During the Reigns of Shah ‘Abbas the Great and Shah Safi

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.The rise of the Akhbari school in the Safavid period has been portrayed as a challenge to both the clerical power of the ʿulamaʾ and sometimes even as in opposition to the Safavid state. As a counter example to these characterisations of Akhbarism, one might consider the example Muhammad Taqi al-Majlisi (d.1070/1659), known as “The First Majlisi”, and father of the famous Safavid scholar Muhammad Baqir al-Majlisi (“The Second Majlisi”, d.1110/1699 or 1111/1700). He had close relations with the Safavid court, dedicating a work to Shah Abbas II, and generally accepting royal patronage when it was offered. His system of legal interpretation and the analysis of hadith in particular, is thoroughly Akhbari. In this article I analyse Taqi al-Majlisi’s ideas as found in the introductory sections to his Lawamiʿ-i Sahibqirani, a Persian language commentary on an early collection of Twelver Shiʿi reports from the Imams. As an appendix, I translate one section which demonstrates not only his thoroughly Akhbari methodology, but also his originality within the Akhbari school. He should, I argue, be particularly remembered for promoting the authority of the ʿulamaʾ from an Akhbari perspective, and here he links the rejection of ijtihad (a hallmark of the Akhbari school) to the Shiʿi rejection of the selection of Abu Bakr as caliph. In doing this, he establishes and exploits a link between the support of ijtihad (that is, the Usuli position), the heresy of Sunnism and the betrayal of fundamental Shi‘i beliefs

La eficacia legal de actos de taqiyya en la jurisprudencia imami: al-Risāla fi l-taqiyya de ‛Alī al-Karakī

The Imāmī Shī‛a are particularly associated with the doctrine of dissimulation (taqiyya). Generally speaking, Imāmi jurists allowed believers to act in contravention to the (true) Sharī‛a in circumstances of taqiyya. For these permitted transgressions there was no punishment, sinfulness or required repetition or compensation, provided the legal actors stayed within some stipulated boundaries. In the tenth/sixteenth century, the famous Arab jurist ‛Alī al-Karakī introduced an innovation in the Shī‛ī legal rules of taqiyya, devising a large category of taqiyya generated acts for which there may be no sin, but there was still a legal transgression, and hence the possible requirement to repeat or compensate for the acts’ commission. In this article I translate and provide an explanatory commentary on his “Treatise on Dissimulation”, and analyse some of the reactions to it in later Shī‛ī jurisprudence.La šī‛a imāmí está estrechamente asociada a la doctrina del disimulo (taqiyya). En general, los juristas imāmíes permitieron a los creyentes actuar contraviniendo a la «verdadera» šarī‛a en circunstancias de taqiyya. Para estas transgresiones permitidas no había castigo, no se incurría en pecado ni repetición ni compensación con tal de que los actores legales guardaran unos límites estipulados. En el siglo X/XVI el famoso jurista ‛Alī al-Karakī introdujo una innovación en las reglas šī‛íes de taqiyya según la cual habría una amplia categoría de actos generados por taqiyya que no implicaban pecado pero sí una transgresión legal y por lo tanto el posible requerimiento de repetir o compensar los actos cometidos. En este artículo se traduce y comenta su “Tratado del disimulo” y se analizan algunas de las reacciones posteriores que causó en la jurisprudencia šī‛í

A Brief Survey of Attitude Control Systems for Small Satellites using Momentum Concepts

High-accuracy pointing capabilities are desired for many three-axis stabilized small satellites. Momentum-based attitude control system actuators, initially developed for larger satellites, are being utilized by small satellites to meet these pointing requirements. This paper provides an overview of momentum devices available for small satellite applications and three-axis attitude control system (ACS) configurations using these devices. Factors affecting the selection and sizing of ACS components are also addressed. Included are suggestions for potential ACS improvements and cost-saving measures that will make momentum devices more accessible to the small satellite community