Business Method Patents

Good morning, it\u27s a pleasure to be here alive. We just participated in the daily road race from Washington to Richmond that many of you do every day. The first question I\u27ve been asked to deal with is why do we have patents? Of course we\u27re very proud of fact that the PTO\u27s origins date back the Constitution itself. In Article I Section 8 of the Constitution, the framers specifically gave Congress the power to grant inventors, for a limited time, the exclusive right to their inventions. So this is not a product of the industrial revolution but dates back to the Constitution

A designed protein interface that blocks fibril formation

Protein fibril formation is implicated in many diseases, and therefore much effort has been focused toward the development of inhibitors of this process. In a previous project, a monomeric protein was computationally engineered to bind itself and form a heterodimer complex following interfacial redesign. One of the protein monomers, termed monomer-B, was unintentionally destabilized and shown to form macroscopic fibrils. Interestingly, in the presence of the designed binding partner, fibril formation was blocked. Here we describe the complete characterization of the amyloid properties of monomer-B and the inhibition of fiber formation by the designed binding partner, monomer-A. Both proteins are mutants of the betal domain of streptococcal protein-G. The free monomer-B protein forms amyloid-type fibrils, as determined by transmission electron microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific dye. Fibril formation kinetics are influenced by pH, protein concentration, and seeding with preformed fibrils. Under all conditions tested, monomer-A was able to inhibit the formation of monomer-B fibrils. This inhibition is specific to the engineered interaction, as incubation of monomer-B with wild-type protein-G (a structural homologue) did not result in inhibition under the same conditions. Thus, this de novo-designed heterodimeric complex is an excellent model system for the study of protein-based fibril formation and inhibition. This system provides additional insight into the development of pharmaceuticals for amyloid disorders, as well as the potential use of amyloid fibrils for self-assembling nanostructures

Crossword: A Fully Automated Algorithm for the Segmentation and Quality Control of Protein Microarray Images

Biological assays formatted as microarrays have become a critical tool for the generation of the comprehensive data sets required for systems-level understanding of biological processes. Manual annotation of data extracted from images of microarrays, however, remains a significant bottleneck, particularly for protein microarrays due to the sensitivity of this technology to weak artifact signal. In order to automate the extraction and curation of data from protein microarrays, we describe an algorithm called Crossword that logically combines information from multiple approaches to fully automate microarray segmentation. Automated artifact removal is also accomplished by segregating structured pixels from the background noise using iterative clustering and pixel connectivity. Correlation of the location of structured pixels across image channels is used to identify and remove artifact pixels from the image prior to data extraction. This component improves the accuracy of data sets while reducing the requirement for time-consuming visual inspection of the data. Crossword enables a fully automated protocol that is robust to significant spatial and intensity aberrations. Overall, the average amount of user intervention is reduced by an order of magnitude and the data quality is increased through artifact removal and reduced user variability. The increase in throughput should aid the further implementation of microarray technologies in clinical studies.Camille and Henry Dreyfus Foundation (Camille Dreyfus Teacher-Scholar Award

Quantum and Classical Bayesian Agents

We describe a general approach to modeling rational decision-making agents who adopt either quantum or classical mechanics based on the Quantum Bayesian (QBist) approach to quantum theory. With the additional ingredient of a scheme by which the properties of one agent may influence another, we arrive at a flexible framework for treating multiple interacting quantum and classical Bayesian agents. We present simulations in several settings to illustrate our construction: quantum and classical agents receiving signals from an exogenous source, two interacting classical agents, two interacting quantum agents, and interactions between classical and quantum agents. A consistent treatment of multiple interacting users of quantum theory may allow us to properly interpret existing multi-agent protocols and could suggest new approaches in other areas such as quantum algorithm design.Comment: 45 pages, 17 figure

Reconnaissance Study of Pleistocene Lake and Fluvial Deposits In and Near Ancestral Yellowstone Lake, Wyoming

Seven sequences of Pleistocene strata, five of them predominantly lacustrine, are described from outcrops north of Yellowstone Lake. These are (1) Turbid Lake sequence, 30–50 feet of white pumiceous claystone and tuff with carbonaceous partings and a distinctive compositional pattern of excesses and deficiencies of many elements; (2) Yellowstone Falls sequence, 75 feet or more of varved white claystone and tuff containing pollen and diatoms, overlain by gray conglomerate and sandstone; (3) Hayden Valley sequence, 200 feet or more of gray and white silt and claystone containing sparse diatoms; (4) Alum Creek sequence, 30 feet or more of bedded sand and gravel with lesser amounts of clay; (5) Mudkettle sequence, 150 feet or more of light gray to white, soft clay and claystone with lesser amounts of sandstone and conglomerate, moderately lithified in part, and containing some pollen and diatoms; (6) Astringent Creek Sand (newly named), a gray, commonly unlithified sand as much as 300 feet thick and containing abundant volcanic debris; and (7) Pelican Valley sequence, 120 feet or more of light gray to white, soft clay, silt, sand, and some pumice pebble conglomerate and shard beds; finer grained beds contain diatoms, pollen, and carbonaceous debris that has a radiocarbon date of 7,550 ±350 years. Other localized deposits with radiocarbon dates and abundant diatoms consist of white carbonaceous tuffaceous clay and sand with an age of 9,440±300 years, in Gibbon Canyon, and a gray and white carbonaceous clay, silt, and sand with an age of 3,750+300 years at Bannock Ford in Yellowstone Canyon. Slight arching of the Upper Basin Member of the Plateau Rhyolite caused the Yellowstone River to develop an antecedent course across it. Uplift of the Pelican Valley area during the last 7,500 years averaged about one foot in 50 years

Reconnaissance Study of Pleistocene Lake and Fluvial Deposits In and Near Ancestral Yellowstone Lake, Wyoming

Seven sequences of Pleistocene strata, five of them predominantly lacustrine, are described from outcrops north of Yellowstone Lake. These are (1) Turbid Lake sequence, 30–50 feet of white pumiceous claystone and tuff with carbonaceous partings and a distinctive compositional pattern of excesses and deficiencies of many elements; (2) Yellowstone Falls sequence, 75 feet or more of varved white claystone and tuff containing pollen and diatoms, overlain by gray conglomerate and sandstone; (3) Hayden Valley sequence, 200 feet or more of gray and white silt and claystone containing sparse diatoms; (4) Alum Creek sequence, 30 feet or more of bedded sand and gravel with lesser amounts of clay; (5) Mudkettle sequence, 150 feet or more of light gray to white, soft clay and claystone with lesser amounts of sandstone and conglomerate, moderately lithified in part, and containing some pollen and diatoms; (6) Astringent Creek Sand (newly named), a gray, commonly unlithified sand as much as 300 feet thick and containing abundant volcanic debris; and (7) Pelican Valley sequence, 120 feet or more of light gray to white, soft clay, silt, sand, and some pumice pebble conglomerate and shard beds; finer grained beds contain diatoms, pollen, and carbonaceous debris that has a radiocarbon date of 7,550 ±350 years. Other localized deposits with radiocarbon dates and abundant diatoms consist of white carbonaceous tuffaceous clay and sand with an age of 9,440±300 years, in Gibbon Canyon, and a gray and white carbonaceous clay, silt, and sand with an age of 3,750+300 years at Bannock Ford in Yellowstone Canyon. Slight arching of the Upper Basin Member of the Plateau Rhyolite caused the Yellowstone River to develop an antecedent course across it. Uplift of the Pelican Valley area during the last 7,500 years averaged about one foot in 50 years

New talent: Americas

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Error management theory and the adaptive significance of transgenerational maternal‐stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring’s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field‐testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps.This article provides a quantitative framework as a means of generating field‐testable hypotheses regarding the adaptive potential of maternal stress under different scenario combinations. By providing a mechanistic basis for examining the adaptive potential of maternal stress effects, our overall aim is not only to provide a means for explaining patterns and testing new hypotheses, but to catalyze the study of maternal stress effects under this framework across a diversity of species, life histories, and environments.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145404/1/ece34074_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145404/2/ece34074.pd

Error management theory and the adaptive significance of transgenerational maternal-stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring\u27s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field-testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps

Error management theory and the adaptive significance of transgenerational maternal-stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring\u27s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field-testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps