Smithkline v. Apotex: Broadening The Scope Of Inherent Anticipation And Its Impact On The Patentability Of Chemical Structures, 5 J. Marshall Rev. Intell. Prop. L. 456 (2006)

In SmithKline v. Apotex, the Court of Appeals for the Federal Circuit invalidated the main patent on Paxil as inherently anticipated. In doing so, the court over-stepped the bounds of appellate review, and broadened the scope of the inherent anticipation doctrine to include chemical structures that are not measurably produced by strict practice of the prior art. This holding does not comport with well-settled precedent and could have dire consequences for the patentability of many chemical structures. A more equitable invalidity analysis would require a chemical structure to derive directly from a disclosed reaction in order to be anticipated; in all other cases, the chemical structure must be proven obvious

PhD

dissertationThe mammalian retina is comprised of 55-60 cell types mediating transduction of photic information through visual preprocessing channels. These cell types fall into six major cell superclasses including photoreceptors, horizontal, amacrine, Muller and ganglion cells. Through computational molecular phenotyping, using amino acids as discriminands, this dissertation shows that the major cellular superclasses of the murine retina are subdivisible into the following natural classes; 1 retinal pigment epithelium class, 2 photoreceptor, 2 bipolar cell, 1 horizontal cell, 15 amacrine cell, 1 Muller cell, and 7 ganglion cell classes. Retinal degenerative diseases like retinitis pigmentosa result in loss of photoreceptors, which constitutes deafferentation of the neural retina. This deafferentation, when complete, is followed by retinal remodeling, which is the common fate of all retinal degenerations that trigger photoreceptor loss. The same strategy used to visualize cell classes in wild type murine retina was applied to examples of retinal degenerative disease in human tissues and naturally and genetically engineered models, examining all cell types in 17 human cases of retinitis pigmentosa (RP) and 85 cases of rodent retinal degenerations encompassing 13 different genetic models. Computational molecular phenotyping concurrently visualized glial transformations, neuronal translocations, and the emergence of novel synaptic complexes, achievements not possible with any other method. The fusion of phenotyping and anatomy at the ultrastructure level also enabled the modeling of synaptic connections, illustrating that the degenerating retina produces new synapses with vigor with the possibility that this phenomenon might be exploited to rescue vision. However, this circuitry is likely corruptive of visual processing and reflects, we believe, attempts by neurons to find synaptic excitation, demonstrating that even minor rewiring seriously corrupts signal processing in retinal pathways leaving many current approaches to bionic and biological retinal rescue unsustainable. The ultimate conclusion is that the sequelae of retinal degenerative disease are far more complex than previously believed, and schemes to rescue vision via bionic implants or stem/engineered cells are based on presumed beliefs in preservation of normal wiring and cell population patterning after photoreceptor death. Those beliefs are incorrect: retinal neurons die, migrate, and create new circuitries. Vision rescue strategies will need to be refined

PhD

dissertationThe mammalian retina is comprised of 55-60 cell types mediating transduction of photic information through visual preprocessing channels. These cell types fall into six major cell superclasses including photoreceptors, horizontal, amacrine, Muller and ganglion cells. Through computational molecular phenotyping, using amino acids as discriminands, this dissertation shows that the major cellular superclasses of the murine retina are subdivisible into the following natural classes; 1 retinal pigment epithelium class, 2 photoreceptor, 2 bipolar cell, 1 horizontal cell, 15 amacrine cell, 1 Muller cell, and 7 ganglion cell classes. Retinal degenerative diseases like retinitis pigmentosa result in loss of photoreceptors, which constitutes deafferentation of the neural retina. This deafferentation, when complete, is followed by retinal remodeling, which is the common fate of all retinal degenerations that trigger photoreceptor loss. The same strategy used to visualize cell classes in wild type murine retina was applied to examples of retinal degenerative disease in human tissues and naturally and genetically engineered models, examining all cell types in 17 human cases of retinitis pigmentosa (RP) and 85 cases of rodent retinal degenerations encompassing 13 different genetic models. Computational molecular phenotyping concurrently visualized glial transformations, neuronal translocations, and the emergence of novel synaptic complexes, achievements not possible with any other method. The fusion of phenotyping and anatomy at the ultrastructure level also enabled the modeling of synaptic connections, illustrating that the degenerating retina produces new synapses with vigor with the possibility that this phenomenon might be exploited to rescue vision. However, this circuitry is likely corruptive of visual processing and reflects, we believe, attempts by neurons to find synaptic excitation, demonstrating that even minor rewiring seriously corrupts signal processing in retinal pathways leaving many current approaches to bionic and biological retinal rescue unsustainable. The ultimate conclusion is that the sequelae of retinal degenerative disease are far more complex than previously believed, and schemes to rescue vision via bionic implants or stem/engineered cells are based on presumed beliefs in preservation of normal wiring and cell population patterning after photoreceptor death. Those beliefs are incorrect: retinal neurons die, migrate, and create new circuitries. Vision rescue strategies will need to be refined

PhD

dissertationThe mammalian retina is comprised of 55-60 cell types mediating transduction of photic information through visual preprocessing channels. These cell types fall into six major cell superclasses including photoreceptors, horizontal, amacrine, Muller and ganglion cells. Through computational molecular phenotyping, using amino acids as discriminands, this dissertation shows that the major cellular superclasses of the murine retina are subdivisible into the following natural classes; 1 retinal pigment epithelium class, 2 photoreceptor, 2 bipolar cell, 1 horizontal cell, 15 amacrine cell, 1 Muller cell, and 7 ganglion cell classes. Retinal degenerative diseases like retinitis pigmentosa result in loss of photoreceptors, which constitutes deafferentation of the neural retina. This deafferentation, when complete, is followed by retinal remodeling, which is the common fate of all retinal degenerations that trigger photoreceptor loss. The same strategy used to visualize cell classes in wild type murine retina was applied to examples of retinal degenerative disease in human tissues and naturally and genetically engineered models, examining all cell types in 17 human cases of retinitis pigmentosa (RP) and 85 cases of rodent retinal degenerations encompassing 13 different genetic models. Computational molecular phenotyping concurrently visualized glial transformations, neuronal translocations, and the emergence of novel synaptic complexes, achievements not possible with any other method. The fusion of phenotyping and anatomy at the ultrastructure level also enabled the modeling of synaptic connections, illustrating that the degenerating retina produces new synapses with vigor with the possibility that this phenomenon might be exploited to rescue vision. However, this circuitry is likely corruptive of visual processing and reflects, we believe, attempts by neurons to find synaptic excitation, demonstrating that even minor rewiring seriously corrupts signal processing in retinal pathways leaving many current approaches to bionic and biological retinal rescue unsustainable. The ultimate conclusion is that the sequelae of retinal degenerative disease are far more complex than previously believed, and schemes to rescue vision via bionic implants or stem/engineered cells are based on presumed beliefs in preservation of normal wiring and cell population patterning after photoreceptor death. Those beliefs are incorrect: retinal neurons die, migrate, and create new circuitries. Vision rescue strategies will need to be refined

Parched elastohydrodynamic lubrication: Instrumentation and procedure

A counter rotating bearing rig was designed and constructed to study transient elastohydrodynamic lubrication phenomena. New instrumentation is described and test procedures are documented. Ball and race speed measurement systems and the capacitance (film thickness) measurement system were upgraded. Methods for measuring bearing torque and race temperatures were implemented

Demonstration of a switchable damping system to allow low-noise operation of high-Q low-mass suspension systems

Low mass suspension systems with high-Q pendulum stages are used to enable quantum radiation pressure noise limited experiments. Utilising multiple pendulum stages with vertical blade springs and materials with high quality factors provides attenuation of seismic and thermal noise, however damping of these high-Q pendulum systems in multiple degrees of freedom is essential for practical implementation. Viscous damping such as eddy-current damping can be employed but introduces displacement noise from force noise due to thermal fluctuations in the damping system. In this paper we demonstrate a passive damping system with adjustable damping strength as a solution for this problem that can be used for low mass suspension systems without adding additional displacement noise in science mode. We show a reduction of the damping factor by a factor of 8 on a test suspension and provide a general optimisation for this system.Comment: 5 pages, 5 figure

715-2 A Prospective, Randomized Trial Evaluating the Prophylactic Use of Balloon Pumping in High Risk Myocardial Infarction Patients: PAMI-2

Myocardial infarction (MI) patients with advanced age, multivessel disease or ventricular dysfunction continue to have a poor prognosis despite reperfusion therapy. Furthermore, the majority of deaths from MI occur within the first 48 hours, thus risk stratification and therapeutic interventions ideally should occur acutely. The PAMI-2 study has prospectively evaluated the hypotheses that 1) emergency catheterization with primary PTCA may allow acute risk stratification and 2) clinical outcome, ventricular function and infarct vessel patency will be improved by balloon pumping in patients identified to be high risk. MI patients who presented 0–12 hrs underwent emergency catheterization and PTCA and were stratified as high risk if one of the following was present: age>70 yrs, vein graft occlusion, 3 vessel disease, ejection fraction <45%, suboptimal PTCA result or if malignant arrhythmias persisted post PTCA. High risk patients were randomized to receive or not receive an intra aortic balloon pump (IABP) for 48 hrs. Catheterization was repeated at day 7 to determine infarct vessel patency and improvement in ventricular function. At 6 weeks a rest and exercise radionuclide ventriculogram was performed. To date, 320 patients have been enrolled, 175 of which have complete data available for analysis. The reasons for high risk status include: advanced age 38%, poor LV function 55%, 3 vessel disease 37%, vein graft occlusion 6%, suboptimal PTCA 9%, and arrhythmias 5%. Despite the high risk status, in-hospital outcomes have been favorable: death 2.9%, recurrent MI 5.8%, stroke 1.2%, angiographic reocclusion 5.8%, heart failure 19.1% and combined events 26.6%. Thus “high risk” patients treated with primary PTCA±balloon pumping appear to have a good prognosis. Whether the improved outcome is due to balloon pump support or simply due to aggressive mechanical revascularization will be determined in the entire cohort by March 1995

The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig