On the Licensing of Innovations under Strategic Delegation

This paper uses a three-stage licensing-delegation-quantity game to study the licensing of a cost-reducing innovation by a patent-holding firm to its competitor. It is shown that licensing is less likely to occur under strategic delegation compared to no delegation

Observing Brane Inflation

Linking the slow-roll scenario and the Dirac-Born-Infeld scenario of ultra-relativistic roll (where, thanks to the warp factor, the inflaton moves slowly even with an ultra-relativistic Lorentz factor), we find that the KKLMMT D3/anti-D3 brane inflation is robust, that is, enough e-folds of inflation is quite generic in the parameter space of the model. We show that the intermediate regime of relativistic roll can be quite interesting observationally. Introducing appropriate inflationary parameters, we explore the parameter space and give the constraints and predictions for the cosmological observables in this scenario. Among other properties, this scenario allows the saturation of the present observational bound of either the tensor/scalar ratio r (in the intermediate regime) or the non-Gaussianity f_NL (in the ultra-relativistic regime), but not both.Comment: 31 pages, 12 figures; typo correcte

Is Brane Inflation Eternal?

In this paper, we show that eternal inflation of the random walk type is generically absent in the brane inflationary scenario. Depending on how the brane inflationary universe originated, eternal inflation of the false vacuum type is still quite possible. Since the inflaton is the position of the D3-brane relative to the anti-D3-brane inside the compactified bulk with finite size, its value is bounded. In DBI inflation, the warped space also restricts the amplitude of the scalar fluctuation. These upper bounds impose strong constraints on the possibility of eternal inflation. We find that eternal inflation due to the random walk of the inflaton field is absent in both the KKLMMT slow roll scenario and the DBI scenario. A more careful analysis for the slow-roll case is also presented using the Langevin equation, which gives very similar results. We discuss possible ways to obtain eternal inflation of the random walk type in brane inflation. In the multi-throat brane inflationary scenario, the branes may be generated by quantum tunneling and roll out the throat. Eternal inflation of the false vacuum type inevitably happens in this scenario due to the tunneling process. Since these scenarios have different cosmological predictions, more data from the cosmic microwave background radiation will hopefully select the specific scenario our universe has gone through.Comment: 32 pages; v2: references and comments adde

Comammox Nitrospira Clade B is the most abundant complete ammonia oxidizer in a dairy pasture soil and inhibited by dicyandiamide and high ammonium concentrations

The recent discovery of comammox Nitrospira, a complete ammonia oxidizer, capable of completing the nitrification on their own has presented tremendous challenges to our understanding of the nitrification process. There are two divergent clades of comammox Nitrospira, Clade A and B. However, their population abundance, community structure and role in ammonia and nitrite oxidation are poorly understood. We conducted a 94-day microcosm study using a grazed dairy pasture soil amended with urea fertilizers, synthetic cow urine, and the nitrification inhibitor, dicyandiamide (DCD), to investigate the growth and community structure of comammox Nitrospira spp. We discovered that comammox Nitrospira Clade B was two orders of magnitude more abundant than Clade A in this fertile dairy pasture soil and the most abundant subcluster was a distinctive phylogenetic uncultured subcluster Clade B2. We found that comammox Nitrospira Clade B might not play a major role in nitrite oxidation compared to the role of canonical Nitrospira nitrite-oxidizers, however, comammox Nitrospira Clade B is active in nitrification and the growth of comammox Nitrospira Clade B was inhibited by a high ammonium concentration (700 kg synthetic urine-N ha¯¹) and the nitrification inhibitor DCD. We concluded that comammox Nitrospira Clade B: (1) was the most abundant comammox in the dairy pasture soil; (2) had a low tolerance to ammonium and can be inhibited by DCD; and (3) was not the dominant nitrite-oxidizer in the soil. This is the first study discovering a new subcluster of comammox Nitrospira Clade B2 from an agricultural soil

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia.

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. Plasma inhibitory assay demonstrated that patients dosed with ≥3000 mg had sufficient levels of active drug in their trough plasma samples to achieve 95% inhibition of FLT3 phosphorylation in an FLT3-ITD AML cell line. Based on a plateau in drug exposure, the 3000-mg dose was chosen as the recommended phase 2 dose. The most frequently reported treatment-emergent adverse events were diarrhea (50%), fatigue (47%), and nausea (46%). Based on modified response criteria, the overall response rate to pexidartinib among all patients was 21%. Twenty-three percent of patients treated at ≥2000 mg responded. The overall composite complete response rate for the study was 11%. Six patients were successfully bridged to transplantation. Median overall survival (OS) of patients treated in dose expansion was 112 days (90% confidence interval [CI], 77-150 days), and median OS of responders with complete remission with or without recovery of blood counts was 265 days (90% CI, 170-422 days). This trial was registered at www.clinicaltrials.gov as #NCT01349049

Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease

Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation

Spontaneous Creation of Inflationary Universes and the Cosmic Landscape

We study some gravitational instanton solutions that offer a natural realization of the spontaneous creation of inflationary universes in the brane world context in string theory. Decoherence due to couplings of higher (perturbative) modes of the metric as well as matter fields modifies the Hartle-Hawking wavefunction for de Sitter space. Generalizing this new wavefunction to be used in string theory, we propose a principle in string theory that hopefully will lead us to the particular vacuum we live in, thus avoiding the anthropic principle. As an illustration of this idea, we give a phenomenological analysis of the probability of quantum tunneling to various stringy vacua. We find that the preferred tunneling is to an inflationary universe (like our early universe), not to a universe with a very small cosmological constant (i.e., like today's universe) and not to a 10-dimensional uncompactified de Sitter universe. Such preferred solutions are interesting as they offer a cosmological mechanism for the stabilization of extra dimensions during the inflationary epoch.Comment: 52 pages, 7 figures, 1 table. Added discussion on supercritical string vacua, added reference

Risk-adjusted cesarean section rates for the assessment of physician performance in Taiwan: a population-based study

BACKGROUND: Over the past decade, about one-third of all births nationwide in Taiwan were delivered by cesarean section (CS). Previous studies in the US and Europe have documented the need for risk adjustment for fairer comparisons among providers. In this study, we set out to determine the impact that adjustment for patient-specific risk factors has on CS among different physicians in Taiwan. METHODS: There were 172,511 live births which occurred in either hospitals or obstetrics/gynecology clinics between 1 January and 31 December 2003, and for whom birth certificate data could be linked with National Health Insurance (NHI) claims data, available as the sample for this study. Physicians were divided into four equivalent groups based upon the quartile distribution of their crude (actual) CS rates. Stepwise logistic regressions were conducted to develop a predictive model and to determine the expected (risk-adjusted) CS rate and 95% confidence interval (CI) for each physician. The actual rates were then compared with the expected CS rates to see the proportion of physicians whose actual rates were below, within, or above the predicted CI in each quartile. RESULTS: The proportion of physicians whose CS rates were above the predicted CI increased as the quartile moved to the higher level. However, more than half of the physicians whose actual rates were higher than the predicted CI were not in the highest quartile. Conversely, there were some physicians (40 of 258 physicians) in the highest quartile who were actually providing obstetric care that was appropriate to the risk. When a stricter standard was applied to the assessment of physician performance by excluding physicians in quartile 4 for predicting CS rates, as many as 60% of physicians were found to have higher CS rates than the predicted CI, and indeed, the CS rates of no physicians in either quartile 3 or quartile 4 were below the predicted CI. CONCLUSION: Overall, our study found that the comparison of unadjusted CS rates might not provide a valid reflection of the quality of obstetric care delivered by physicians, and may ultimately lead to biased judgments by purchasers. Our study has also shown that when we changed the standard of quality assessment, the evaluation results also changed

Estimation, planning, and mapping for autonomous flight using an RGB-D camera in GPS-denied environments

RGB-D cameras provide both color images and per-pixel depth estimates. The richness of this data and the recent development of low-cost sensors have combined to present an attractive opportunity for mobile robotics research. In this paper, we describe a system for visual odometry and mapping using an RGB-D camera, and its application to autonomous flight. By leveraging results from recent state-of-the-art algorithms and hardware, our system enables 3D flight in cluttered environments using only onboard sensor data. All computation and sensing required for local position control are performed onboard the vehicle, reducing the dependence on an unreliable wireless link to a ground station. However, even with accurate 3D sensing and position estimation, some parts of the environment have more perceptual structure than others, leading to state estimates that vary in accuracy across the environment. If the vehicle plans a path without regard to how well it can localize itself along that path, it runs the risk of becoming lost or worse. We show how the belief roadmap algorithm prentice2009belief, a belief space extension of the probabilistic roadmap algorithm, can be used to plan vehicle trajectories that incorporate the sensing model of the RGB-D camera. We evaluate the effectiveness of our system for controlling a quadrotor micro air vehicle, demonstrate its use for constructing detailed 3D maps of an indoor environment, and discuss its limitations.United States. Office of Naval Research (Grant MURI N00014-07-1-0749)United States. Office of Naval Research (Science of Autonomy Program N00014-09-1-0641)United States. Army Research Office (MAST CTA)United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N00014-09-1-1052)National Science Foundation (U.S.) (Contract IIS-0812671)United States. Army Research Office (Robotics Consortium Agreement W911NF-10-2-0016)National Science Foundation (U.S.). Division of Information, Robotics, and Intelligent Systems (Grant 0546467