Novartis AG v. Union of India: “Evergreening,” TRIPS, and “Enhanced Efficacy” Under Section 3(d)

A decision in Novartis AG v. Union of India, an Indian Supreme Court case, was announced April 1, 2013. The much anticipated decision has rocked the landscape of the pharmaceutical industry and public health in India because it concerns the application of Section 3(d) of the Indian Patents Act of 2005, a controversial provision of the Indian patent law that could limit the ability of pharmaceutical companies to obtain important “secondary patents” on life-saving drugs. My paper presents three different ways, from narrowest to broadest, that the Indian Supreme Court could have interpreted Section 3(d) and argues the legality and policy consequences of each. It is argued that the narrowest interpretation of Section 3(d), the one adopted by both the lower courts and the Supreme Court of India, is the one most inconsistent with the popularly stated rationale of the provision as a means to prevent the “evergreening” of pharmaceutical patents. It is further argued that, as a boundary-defining case, the Supreme Court should not choose the interpretation of Section 3(d) that would preclude the patenting of the drug Glivec in Novartis AG v. Union of India.Recipient of the Harvard Law School 2013 Irving Oberman Memorial Award: Intellectual Property

A morphometric approach to the comparative morphology of aedeagi shapes in net-winged beetles: A case study on the Macrolycus dotatus species group (Coleoptera: Lycidae)

Insect male genitalia show an evolutionarily variable morphology that is valuable for both species identification and phylogenetic analyses. However, we often encounter some difficulties when conducting relevant studies due to only quantitative variations exhibited in male genitalia. In this study, based on the taxonomy of the Macrolycus dotatus species group (a total of seven species, including three new species described here), we analyzed the male genitalia shapes by GM and then constructed the phenotypic relationships by UPGMA, NJ and MP analyses. The results demonstrated that the species could be well delineated by the shape of male genitalia, and the produced phenograms frequently recovered phenotypic similarity between the coupled species, including M. atronotatimimus sp. nov. + M. huoditangensis sp. nov. and M. aemulus + M. dotatus, which is useful for making comparisons in species descriptions. Meanwhile, the MP analysis of male genitalia shape using two landmark configurations is considered reliable in inferring the phylogenetic relationship among species in terms of the consistency between its topologies and the molecular phylogeny. This study sheds new light on improving the morphological taxonomy of insects in lower grades while fully utilizing the taxonomic value of male genitalia in a phylogenetic context

A morphometric approach to the comparative morphology of aedeagi shapes in net-winged beetles: A case study on the Macrolycus dotatus species group (Coleoptera: Lycidae)

Insect male genitalia show an evolutionarily variable morphology that is valuable for both species identification and phylogenetic analyses. However, we often encounter some difficulties when conducting relevant studies due to only quantitative variations exhibited in male genitalia. In this study, based on the taxonomy of the Macrolycus dotatus species group (a total of seven species, including three new species described here), we analyzed the male genitalia shapes by GM and then constructed the phenotypic relationships by UPGMA, NJ and MP analyses. The results demonstrated that the species could be well delineated by the shape of male genitalia, and the produced phenograms frequently recovered phenotypic similarity between the coupled species, including M. atronotatimimus sp. nov. + M. huoditangensis sp. nov. and M. aemulus + M. dotatus, which is useful for making comparisons in species descriptions. Meanwhile, the MP analysis of male genitalia shape using two landmark configurations is considered reliable in inferring the phylogenetic relationship among species in terms of the consistency between its topologies and the molecular phylogeny. This study sheds new light on improving the morphological taxonomy of insects in lower grades while fully utilizing the taxonomic value of male genitalia in a phylogenetic context

Accurate Calculation of Iron Loss of High-Temperature and High-Speed Permanent Magnet Synchronous Generator under the Conditions of SVPWM Modulation

The high-temperature and high-speed permanent magnet synchronous generator (HTHSPMSG) is the core component ensuring the efficient and safe operation of the high-speed aircraft power supply system. At present, the existing iron loss model fails to meet the requirements for the precise calculation of the iron loss of HTHSPMSG under high-temperature and high-frequency conditions. In this paper, a 40 kW, 18,000 rpm HTHSPMSG is used to study the accurate calculation of iron loss at an ambient temperature of 350 °C. Considering the influence of high temperature and high frequency on the loss and performance of electromagnetic materials, a test platform for the loss performance of the magnetic core materials is established. Then, according to the loss performance of the electromagnetic material, the corresponding iron loss coefficient is fitted by the variable coefficient iron loss separation model. In addition, the digital twin field-circuit co-simulation method is proposed to guarantee the accuracy of the iron loss calculation. Then, the influence of carrier frequencies and modulation ratios on the iron loss characteristics of the HTHSPMSG under the conditions of SVPWM modulation is studied. Lastly, the effectiveness of the proposed method is verified by the experimental results, which provide a reference for the accurate analysis of iron loss of the same type of HTHSPMSG

Immobilization of Nanobodies with Vapor-Deposited Polymer Encapsulation for Robust Biosensors

To produce next-generation, shelf-stable biosensors for point-of-care diagnostics, a combination of rugged biomolecular recognition elements, efficient encapsulants and innocuous deposition approaches are needed. Furthermore, to ensure that the sensitivity and specificity that is inherent to biological recognition elements is maintained in solid-state biosensing systems, site-specific immobilization chemistries must be invoked such that the function of the biomolecule remains unperturbed. In this work, we present a widely-applicable strategy to develop robust solid-state biosensors using emergent nanobody (Nb) recognition elements coupled with a vapor-deposited polymer encapsulation layer. As compared to conventional immunoglobulin G (IgG) antibodies, Nbs are smaller (12-15 kDa as opposed to ~150 kDa), have higher thermal stability and pH tolerance, boast greater ease of recombinant production, and are capable of binding antigens with high affinity and specificity. Photoinitiated chemical vapor deposition (piCVD) affords thin, protective polymer barrier layers over immobilized Nb arrays that allow for retention of Nb activity and specificity after both storage under ambient conditions and complete desiccation. Most importantly, we also demonstrate that vapor-deposited polymer encapsulation of nanobody arrays enables specific detection of target proteins in complex heterogenous samples, such as unpurified cell lysate, which is otherwise challenging to achieve with bare Nb arrays

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

[INLINE:1] Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy, neurosensory impairments, and cognitive deficits, and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy. The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored. However, the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated. In this study, we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function. Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats. Following transplantation of human placental chorionic plate-derived mesenchymal stem cells, interleukin-3 expression was downregulated. To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy, we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA. We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown. Furthermore, interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy. The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy, and this effect was mediated by interleukin-3-dependent neurological function