An Economic Assessment of Patent Settlements in the Pharmaceutical Industry

This article demonstrates that in recent years, patent settlements between branded and generic manufacturers involving reverse payments from branded manufacturers to generic manufacturers have received close antitrust scrutiny, driven by concerns that such settlements harm consumers by delaying the entry of lower-priced generic drugs. The authors note that such settlements will be a focus of the Obama Administration\u27s antitrust enforcement policy, yet there is a growing consensus among the courts that such settlements are anticompetitive only under narrow sets of circumstances. In this article, the authors present an analytical framework for evaluating the competitive effects of patent settlements, including those involving reverse payments, and demonstrate that these settlements can benefit consumers. Thus, the authors conclude that while continued scrutiny of such settlements is important, broad brush treatments are inappropriate and only a more individualized evaluation can correctly determine the competitive effects of a particular settlement agreement

Functional Morphology of Gliding Flight I. Modeling Reveals Distinct Performance Landscapes Based on Soaring Strategies

The physics of flight influences the morphology of bird wings through natural selection on flight performance. The connection between wing morphology and performance is unclear due to the complex relationships between various parameters of flight. In order to better understand this connection, we present a holistic analysis of gliding flight that preserves complex relationships between parameters. We use a computational model of gliding flight, along with analysis by uncertainty quantification, to 1) create performance landscapes of gliding based on output metrics (maximum lift-to-drag ratio, minimum gliding angle, minimum sinking speed, lift coefficient at minimum sinking speed); and 2) predict what parameters of flight (chordwise camber, wing aspect ratio, Reynolds number) would differ between gliding and non-gliding species of birds. We also examine performance based on soaring strategy for possible differences in morphology within gliding birds. Gliding birds likely have greater aspect ratios than non-gliding birds, due the high sensitivity of aspect ratio on most metrics of gliding performance. Furthermore, gliding birds can use two distinct soaring strategies based on performance landscapes. First, maximizing distance traveled (maximizing lift-to-drag ratio and minimizing gliding angle) should result in wings with high aspect ratios and middling-to-low wing chordwise camber. Second, maximizing lift extracted from updrafts should result in wings with middling aspect ratios and high wing chordwise camber. Following studies can test these hypotheses using morphological measurements

2006-2007 Master Class - Jonathan Coo (Piano)

https://spiral.lynn.edu/conservatory_masterclasses/1139/thumbnail.jp

Functional Morphology of Gliding Flight II. Morphology Follows Predictions of Gliding Performance

The evolution of wing morphology among birds, and its functional consequences, remains an open question, despite much attention. This is in part because the connection between form and function is difficult to test directly. To address this deficit, in prior work we used computational modeling and sensitivity analysis to interrogate the impact of altering wing aspect ratio, camber, and Reynolds number on aerodynamic performance, revealing the performance landscapes that avian evolution has explored. In the present work, we used a dataset of three-dimensionally scanned bird wings coupled with the performance landscapes to test two hypotheses regarding the evolutionary diversification of wing morphology associated with gliding flight behavior: 1) gliding birds would exhibit higher wing aspect ratio and greater chordwise camber than their non-gliding counterparts; and 2) that two strategies for gliding flight exist, with divergent morphological conformations. In support of our first hypothesis, we found evidence of morphological divergence in both wing aspect ratio and camber between gliders and non-gliders, suggesting that wing morphology of birds that utilize gliding flight is under different selective pressures than the wings of non-gliding taxa. Furthermore, we found that these morphological differences also yielded differences in coefficient of lift measured both at the maximum lift to drag ratio and at minimum sinking speed, with gliding taxa exhibiting higher coefficient of lift in both cases. Minimum sinking speed was also lower in gliders than non-gliders. However, contrary to our hypothesis, we found that the maximum ratio of the coefficient of lift to the coefficient of drag differed between gliders and non-gliders. This may point to the need for gliders to maintain high lift capability for takeoff and landing independent of gliding performance, or could be due to the divergence in flight styles among gliders, as not all gliders are predicted to optimize either quantity. However, direct evidence for the existence of two morphologically defined gliding flight strategies was equivocal, with only slightly stronger support for an evolutionary model positing separate morphological optima for these strategies than an alternative model positing a single peak. The absence of a clear result may be an artifact of low statistical power owing to a relatively small sample size of gliding flyers expected to follow the “aerial search” strategy

Performance of Queensland’s net-free zones

On 1 November 2015, three net-free zones (NFZs) were established in the Cairns, Mackay and Rockhampton regions. The objective of the NFZs is for recreational fishers to catch more and bigger fish, which will increase their enjoyment of recreational fishing in the region. If this occurs, fishers are likely to travel from further afield to fish NFZs, thereby supporting local businesses and tourism. To examine the impact of the NFZs on recreational fishing, surveys were undertaken at local boat ramps and tackle shops from 2015–18. These surveys examined: • if fishing effort has increased • whether important recreational fish species were larger and more commonly caught • if fishers travelled further to fish the NFZs • if recreational fishers’ satisfaction and expectations of fishing in NFZs have changed through time. The results of these surveys were compared to a combined set of reference areas (other areas in Queensland where NFZs were not introduced in November 2015) to assess the impacts of the NFZs relative to other trends in recreational fishing through time. The full benefits of NFZs on the number and size of fish caught by recreational fishers are likely to take time to emerge, however recreational fishers are now harvesting larger barred javelin in the Rockhampton NFZ compared to the reference areas, which have not changed. In 2016 and 2017 Barramundi kept by recreational fishers in the Rockhampton NFZ were also larger than the reference areas. The size or number of fish caught by recreational fishers has not increased in the Mackay or Cairns NFZs. More fishers are travelling further to fish the Rockhampton NFZ since it was created in November 2015. This is likely due to the high levels of community engagement and awareness in Rockhampton, with the council and local groups supporting and promoting the NFZ. The number of trailers counted at the boat ramps has remained steady at all NFZs and reference areas since the NFZs were implemented. Recreational fishers’ satisfaction with fishing in the NFZs is generally positive and appears to be increasing. Overall, fishing satisfaction over the previous 12 months was greater in 2018 than in 2015 or 2016. In Cairns and Rockhampton, satisfaction was similar between years, but in Mackay satisfaction was significantly greater in 2016 and 2018 than 2015. In 2018, recreational fishers in the NFZs were more satisfied with the following activities compared to 2015 and 2016: more exciting fights with fish; the number and size of fish caught; the quality of fishing in the area. Expectations varied depending on the NFZ and frequency of fishing. Interestingly, while catching a fish is important to recreational fishers, many people stated that it is not necessary for a satisfying fishing trip. Generally, the effects of NFZs have been positive for recreational fishing. The predicted flow-on benefits of NFZs (e.g. tourism) requires that fishers are satisfied with their fishing trips, which depends largely on them catching more targeted species. As NFZs age, they might produce stronger effects on recreational fishing catches, but these effects will vary between regions due to the area covered by the NFZ, environmental factors such as floods and drought, and the reproductive and migratory capabilities of the targeted fish and their prey. Monitoring the performance of NFZs will continue as part of Fisheries Queensland’s Fisheries Monitoring program

Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of <i>Burkholderia pseudomallei</i>

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain, and conferred resistance to the antimicrobial sphingolipid D-erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection.We thank HL Ho & K Haynes (University of Exeter) for provision of strains and relevant vectors for yeast complementation studies. This work was supported by the Defence Science 26 and Technology Laboratory under contract DSTLX-1000060221 (WP1). CJM was funded by the EASTBIO Doctoral Training Partnership. The funders had no role in study design, data collection and analysis, or preparation of the manuscript

Hadley circulation and precipitation changes control black shale deposition in the Late Jurassic Boreal Seaway

New climate simulations using the HadCM3L model with a paleogeography of the Late Jurassic [155.5 Ma], and proxy-data corroborate that warm and wet tropical-like conditions reached as far north as the UK sector of the Jurassic Boreal Seaway [~35oN]. This is associated with a northern hemisphere Jurassic Hadley cell and an intensified subtropical jet which both extend significantly polewards than in the modern (July-September). Deposition of the Kimmeridge Clay Formation [KCF] occurred in the shallow, storm-dominated, epeiric Boreal Seaway. High resolution paleo-environmental proxy data from the Kimmeridge Clay Formation [KCF; ~155–150 Ma], UK are used to test for the role of tropical atmospheric circulation on meter-scale heterogeneities in black shale deposition. Proxy and model data show that the most organic-rich section [eudoxus to mid-hudlestoni zones] is characterised by a positive δ13Corg excursion and up to 37 wt% total organic carbon [%TOC]. Orbital-modulation of organic carbon burial primarily in the long eccentricity power band combined with a clear positive correlation between %TOC carbonate-free and the kaolinite/illite ratio supports peak organic carbon burial under the influence of very humid climate conditions, similar to the modern tropics. This re-interpretation of large-scale climate relationships, supported by independent modelling and geological data, has profound implications for atmospheric circulation patterns and processes affecting marine productivity and organic carbon burial further north along the Boreal Seaway, including the Arctic

An efficient and novel technology for the extraction of parasite genomic DNA from whole blood or culture

The aim of this study was to assess pathogen DNA extraction with a new spin column-based method (DNA-XT). DNA from either whole-blood samples spiked with Plasmodium falciparum or Leishmania donovani amastigote culture was extracted with DNA-XT and compared with that produced by a commercial extraction kit (DNeasy®). Eluates from large and small sample volumes were assessed by PCR and spectroscopy. Using a small volume (5 μl) of blood, the DNA-XT and DNeasy methods produced eluates with similar DNA concentrations (0.63 vs 1.06 ng/μl, respectively). The DNA-XT method produced DNA with lower PCR inhibition than DNeasy. The new technique was also twice as fast and required fewer plastics and manipulations but had reduced total recovered DNA compared with DNeasy

Low-frequency gravitational-wave science with eLISA/NGO

We review the expected science performance of the New Gravitational-Wave Observatory (NGO, a.k.a. eLISA), a mission under study by the European Space Agency for launch in the early 2020s. eLISA will survey the low-frequency gravitational-wave sky (from 0.1 mHz to 1 Hz), detecting and characterizing a broad variety of systems and events throughout the Universe, including the coalescences of massive black holes brought together by galaxy mergers; the inspirals of stellar-mass black holes and compact stars into central galactic black holes; several millions of ultracompact binaries, both detached and mass transferring, in the Galaxy; and possibly unforeseen sources such as the relic gravitational-wave radiation from the early Universe. eLISA's high signal-to-noise measurements will provide new insight into the structure and history of the Universe, and they will test general relativity in its strong-field dynamical regime.Comment: 20 pages, 8 figures, proceedings of the 9th Amaldi Conference on Gravitational Waves. Final journal version. For a longer exposition of the eLISA science case, see http://arxiv.org/abs/1201.362

An efficient and novel technology for the extraction of parasite genomic DNA from whole blood or culture

The aim of this study was to assess pathogen DNA extraction with a new spin column-based method (DNA-XT). DNA from either whole-blood samples spiked with Plasmodium falciparum or Leishmania donovani amastigote culture was extracted with DNA-XT and compared with that produced by a commercial extraction kit (DNeasy®). Eluates from large and small sample volumes were assessed by PCR and spectroscopy. Using a small volume (5 μl) of blood, the DNA-XT and DNeasy methods produced eluates with similar DNA concentrations (0.63 vs 1.06 ng/μl, respectively). The DNA-XT method produced DNA with lower PCR inhibition than DNeasy. The new technique was also twice as fast and required fewer plastics and manipulations but had reduced total recovered DNA compared with DNeasy