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Rigg K.K.,University of South Florida | Monnat S.M.,The Pennsylvania State University
Addictive Behaviors | Year: 2015

Introduction: Prescription painkiller misuse (PPM) is a major U.S. public health concern. However, as prescribing practices have tightened and prescription painkillers have become less accessible, many users have turned to heroin as a substitute. This trend suggests the face of heroin users has likely changed over the past several years. Understanding the demographic, socioeconomic, psychosocial, and substance use characteristics of different groups of opiate users is important for properly tailoring interventions. Methods: This study used data from the 2010-2013 National Survey on Drug Use and Health to examine differences in characteristics of U.S. adults in three mutually exclusive categories of past-year opiate use: heroin-only (H-O, N. =. 179), prescription painkiller-only (PP-O, N. =. 9,516), and heroin and prescription painkiller (H-PP, N. =. 506). Results: Socioeconomic disadvantage, older age, disconnection from social institutions, criminal justice involvement, and easy access to heroin were associated with greater odds of being in the H-O group. HH-P users were more likely to be young white males with poor physical and mental health who also misuse other prescription medications and began such misuse as adolescents. PP-O users were the most economically stable, most connected to social institutions, least likely to have criminal justice involvement, and had the least access to heroin. Conclusions: Results suggest the socio-demographic characteristics of heroin users versus PP misusers vary widely, and the conditions leading to heroin use versus PPM versus both may be different. Ultimately, a one-size-fits-all approach to opiate prevention and treatment is likely to fail. Interventions must account for the unique needs of different user groups. © 2015. Source


Moratz R.,University of Maine | Wallgrun J.O.,The Pennsylvania State University
Journal of Spatial Information Science | Year: 2012

We present an approach for supplying existing qualitative direction calculi with a distance component to support fully fledged positional reasoning. The general underlying idea of augmenting points with local reference properties has already been applied in the OPRAm calculus. In this existing calculus, point objects are attached with a local reference direction to obtain oriented points and able to express relative direction using binary relations. We show how this approach can be extended to attach a granular distance concept to direction calculi such as the cardinal direction calculus or adjustable granularity calculi such as OPRAm or the Star calculus. We focus on the cardinal direction calculus and extend it to a multi-granular positional calculus called EPRAm. We provide a formal specification of EPRAm including a composition table for EPRA2 automatically determined using real algebraic geometry. We also report on an experimental performance analysis of EPRA2 in the context of a topological map-learning task proposed for benchmarking qualitative calculi. Our results confirm that our approach of adding a relative distance component to existing calculi improves the performance in realistic tasks when using algebraic closure for consistency checking. © by the author(s). Source


News Article
Site: http://phys.org/chemistry-news/

A group of researchers from Nankai University in China, the University of Pittsburgh, and The Pennsylvania State University have demonstrated, for the first time, a synthetic mechanism for N-unsubstituted benzazetidines that is high yielding and practical. Their synthetic strategy can be used to make a variety of benzazetidine-based compounds for possible drug design exploration. Their work appears in Nature Chemistry. Researchers have made headway in nitrogen-based heterocycle chemistry using a palladium-catalyzed intramolecular dehydrogenative C-H amination (IDCA) reaction. In this reaction, the oxidized palladium catalyst coordinates to the target carbon and the amine. Ideally, this would result in a reductive elimination reaction in which the palladium is reduced back to its original oxidation state and the dehydrogenated carbon and amine would form a ring-closing bond. However, in practice, this reaction is difficult to accomplish in high yields. Four-membered rings are hindered due to ring strain. This leads to side products that are more thermodynamically favored than forming the four-membered ring. Gang He, Gang Lu, Zhengwei Guo, Peng Liu, and Gong Chen have devised a synthetic scheme that results in the desired benzazetidine using N-benzyl-picolinamide (PAs) as the reactant and Pd(OAc) as the catalyst. Key to the success of their synthetic scheme is rigid ligand structures both from the N-benzyl-picolinamide and the oxidant. They developed the phenyl-iodonium dimethylmalonate (PhI(DMM)) as their oxidant after seeing that PhI(OAc) , which is known to promote C-H acetoxylation using similar starting materials, formed a small amount of their target benzazetidine. However, the C-N ring closing reaction is thermodynamically unfavored compared to forming a C-OAc bond. After looking at computational studies to see how they could prevent the carbon-oxygen bond from forming, they decided to tether the oxygen on the carbonyl of the acetate to prevent it from reacting with the target carbon atom for the reductive elimination. After trying several tethers, they landed upon PhI(DMM), which proved to enhance the yield of the desired benzazetidine (48%). The next step was to see if this reaction was generalizable by changing the R group on the N-benzyl picolinamide reactant. Even in cases where the benzazetidine product could be formed using PhI(OAc) , He, et al. saw better yields with PhI(DMM). Furthermore, their reaction worked with a variety of functional groups, although, interestingly, did not work for unsubstituted benzylamine. An additional advantage of their scheme is that the PA protecting group was easily removed with sodium hydroxide in methanol, THF, and water at room temperature. He, et al. conducted mechanistic studies in hopes of understanding the reaction better so that it may be optimized for later research,. They found that the transition state involves a bimetallic Pd(III)/Pd(III) complex instead of a monomeric Pd(IV) compound. It is this bimetallic complex with the PhI(DMM) tether that promotes the desired reductive elimination pathway and blocks the C-OAc bond from forming. This research opens the door to the possibility of finding pharmaceuticals that involve a benzazetidine. This synthetic mechanism is versatile for various functional groups and, using the PhI(DMM) oxidizing agent, produces product yields that make this reaction pathway significantly more practical than the limited reaction mechanisms that were previously used to make benzazetidines. More information: Gang He et al. Benzazetidine synthesis via palladium-catalysed intramolecular C−H amination, Nature Chemistry (2016). DOI: 10.1038/nchem.2585 Abstract Small-sized N-heterocycles are important structures in organic synthesis and medicinal chemistry. Palladium-catalysed intramolecular aminations of the C−H bonds of unfunctionalized amine precursors have recently emerged as an attractive new method for N-heterocycle synthesis. However, the way to control the reactivity of high-valent Pd intermediates to form the desired C−N cyclized products selectively remains poorly addressed. Herein we report a strategy to control the reductive elimination (RE) pathways in high-valent Pd catalysis and apply this strategy to achieve the synthesis of highly strained four-membered benzazetidines via the Pd-catalysed intramolecular C−H amination of N-benzyl picolinamides. These reactions represent the first practical synthetic method for benzazetidines and enable access to a range of complex benzazetidines from easily obtainable starting materials. The use of a newly designed phenyliodonium dimethylmalonate reagent is critical, as oxidation of Pd(II) palladacycles with this reagent favours a kinetically controlled C−N RE pathway to give strained ring-closed products.


Home > Press > Scientists take key step toward custom-made nanoscale chemical factories: Berkeley Lab researchers part of team that creates new function in tiny protein shell structures Abstract: Scientists have for the first time reengineered a building block of a geometric nanocompartment that occurs naturally in bacteria. They introduced a metal binding site to its shell that will allow electrons to be transferred to and from the compartment. This provides an entirely new functionality, greatly expanding the potential of nanocompartments to serve as custom-made chemical factories. Scientists hope to tailor this new use to produce high-value chemical products, such as medicines, on demand. The sturdy nanocompartments, which are polyhedral shells composed of triangle-shaped sides and resemble 20-sided dice, are formed by hundreds of copies of just three different types of proteins. Their natural counterparts, known as bacterial microcompartments or BMCs, encase a wide variety of enzymes that carry out highly specialized chemistry in bacteria. Researchers at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) devised synthetic shell structures derived from those found in a rod-shaped, ocean-dwelling bacterium, Haliangium ochraceum, and reengineered one of the shell proteins to serve as a scaffold for an iron-sulfur cluster found in many forms of life. The cluster is known as a "cofactor" because it can serve as a helper molecule in biochemical reactions. BMC-based shells are tiny, durable and naturally self-assemble and self-repair, which makes them better-suited for a range of applications than completely synthetic nanostructures. "This is the first time anyone has introduced functionality into a shell. We thought the most important functionality to introduce was the ability to transfer electrons into or out of the shell," said Cheryl Kerfeld, a structural biologist at Berkeley Lab and corresponding author in this study. Kerfeld's research group focuses on BMCs. Kerfeld holds joint appointments with Berkeley Lab's Molecular Biophysics and Integrated Bioimaging (MBIB) Division, UC Berkeley and the MSU-DOE Plant Research Laboratory at Michigan State University (MSU). "That greatly enhances the versatility of the types of chemistries you can encapsulate in the shell and the spectrum of products to be produced," she said. "Typically, the shells are thought of as simply passive barriers." Researchers used X-rays at Berkeley Lab's Advanced Light Source (ALS) to show, in 3-D and at the atomic scale, how the introduced iron-sulfur cluster binds to the engineered protein. The study is now online in the Journal of the American Chemical Society. Enzymes inside natural BMCs can convert carbon dioxide into organic compounds that can be used by the bacteria, isolate toxic or volatile compounds from the surrounding cell, and carry out other chemical reactions that provide energy for the cell. In this study, researchers introduced the iron-sulfur cluster into the tiny pores in the shell building block. This engineered protein serves as an electron relay across the shell, which is key to controlling the chemical reactivity of substances inside the shell. Clement Aussignargues, the lead author of the study and postdoctoral researcher in the MSU-DOE Plant Research Laboratory in Michigan, said, "The beauty of our system is that we now have all the tools, notably the crystallographic structure of the engineered protein, to modify the redox potential of the system--its ability to take in electrons (reduction) or give off electrons (oxidation). "If we can control this, we can expand the range of chemical reactions we can encapsulate in the shell. The limit of these applications will be what we put inside the shells, not the shells themselves." He added, "Creating a new microcompartment from scratch would be very, very complicated. That's why we're taking what nature put before us and trying to add to what nature can do." To design the metal binding site, Kerfeld's group first had to solve the structures of the building blocks of the nanocompartment to use as the template for design. These building blocks self-assemble into synthetic shells, which measure just 40 nanometers, or billionths of a meter, in diameter. The natural form of the shells can be up to 12 times larger. The iron-sulfur cofactor of the engineered protein, which was produced in E. coli bacteria, was very stable even when put through several redox cycles--a characteristic essential for future applications, Aussignargues said. "The engineered protein was also more stable than its natural counterpart, which was a big surprise," he said. "You can treat it with things that normally make proteins fall apart and unwind." A major challenge in the study was to prepare the engineered protein in an oxygen-free environment to form tiny crystals that best preserve their structure and their cofactor for X-ray imaging, Kerfeld said. The crystals were prepared in an air-sealed glovebox at MSU, frozen, and then shipped out for X-ray studies at Berkeley Lab's ALS and SLAC National Accelerator Laboratory's Stanford Synchrotron Radiation Lightsource (SSRL). In follow-up work, the research team is exploring how to incorporate different metal centers into BMC shells to access a different range of chemical reactivity, she said. "I'm working on incorporating a completely different metal center, which has a very positive reduction potential compared to the iron-sulfur cluster," said Jeff Plegaria, a postdoctoral researcher at the MSU-DOE Plant Research Laboratory who contributed to the latest study. "But it is the same sort of idea: To drive electrons in or out of the compartment." He added, "The next step is to encapsulate proteins that can accept electrons into the shells, and to use that as a probe to watch the electron transfer from the outside of the compartment to the inside." That will bring researchers closer to creating specific types of pharmaceuticals or other chemicals. ### Other scientists involved in the study were from MSU, The Pennsylvania State University and Brooklyn College. The work was supported by the U.S. DOE Office of Science, MSU AgBio Research and the European Union's PEPDIODE project. The ALS and SLAC's SSRL are both DOE Office of Science User Facilities. About Berkeley Lab Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit www.lbl.gov. The DOE Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article
Site: http://www.materialstoday.com/news/

Understanding and tailoring materials’ properties usually requires trial and error, and a bit of luck. But, as a special issue of Computational Materials Science [112, Part B, 405-546, Computational Materials Science in China.] shows, the latest generation of computation techniques and new algorithms can now model novel materials and explore existing ones better than ever before. China is embracing these new possibilities, making fast progress over the last decade as access to computation resources has become more widespread, according to Xingao Gong of Fudan University. The university is home to a Key Laboratory for Computational Physical Sciences, which has over the last five years successfully used computational tools to clarify long-held misunderstandings about the structure and properties of quaternary semiconductors tagged for future solar cells. “The profile of computational materials science as a discipline has been rising quickly in China over the last few years,” adds Editor-in-Chief, Professor Susan Sinnott of The Pennsylvania State University. “So this is an ideal time to highlight some of the best work in the field that is being carried out there.” Exploring the electronic and magnetic properties of materials theoretically begins with a simple model. By considering a few tens or hundreds of atoms at a time, computational methods can calculate properties that are scalable to larger dimensions. These basic models can be finely tuned to improve accuracy. At the University of Science and Technology of China, for example, Lixin He and colleagues are using atomic orbitals as the basic unit for ab initio electronic structure calculations of silicon, group IV and III-V semiconductors including technologically important GaAs and GaN, as well as alkali and 3d transition metals. Focusing on orbital physics can be a helpful tactic in unpicking the novel electronic and magnetic behavior of transition metal oxides, which are a platform for many functional devices, according to Hua Wu at Fudan University. The combination of charge, spin, and orbital degrees of freedom in these materials leads to unusual – and useful – effects such as colossal magnetoresistance and multiferroicity. First principles calculations based on density functional theory (DFT), where quantum mechanical equations determine the density of electrons, are proving effective and versatile in understanding the new generation of planar materials, such as graphene, silicene, and boron nitride. Despite being well known for decades, DFT has been refined in recent years so it can now be used to tailor the physical properties of 2D materials for applications. DFT can also help unravel the science behind exotic materials like topological insulators, which have an insulating core but surface conducting electrons. Researchers at Beijing Institute of Technology are using this approach to explore such fantastic phenomena as these in solid materials that would be difficult to comprehend by other means. Likewise, modeling is effective when it comes to identifying and assessing materials for extreme environments. A group at Beihang University is using DFT to identify materials able to withstand the extreme temperatures and irradiation levels inside thermonuclear reactors. Taking a different approach to models, meanwhile, can yield new insights. A group at Jilin University, for example, has devised a computational method based on a ‘swarm intelligence’ algorithm inspired by natural systems such as ant colonies, bee swarms, and flocks of birds. The self-improving approach works particularly well with atomic and molecular clusters, nanoparticles, and 3D bulk materials. “I am very excited to see that young scientists in China now have a strong interest in developing new algorithms and first principles approaches based on local atomic orbitals,” says Gong. The rise of computational methods to understand materials behaviors and properties, and drive new materials’ discovery, has been particularly impressive in China, agrees Baptiste Gault, senior publisher at Elsevier. “It is very timely to provide an overview of the state-of-the-art here and Computational Materials Science is the preeminent forum.” This special issue is published in Computational Materials Science- 112, Part B, 405-546 "Computational Materials Science in China". To find out more about each article included within this special issue, please follow the below links: The novel electronic and magnetic properties in 5d transition metal oxides system First-principles investigations on the Berry phase effect in spin–orbit coupling materials Recent progresses in real-time local-basis implementation of time dependent density functional theory for electron–nucleus dynamics Modeling and simulation of helium behavior in tungsten: A first-principles investigation Recent advances in computational studies of organometallic sheets: Magnetism, adsorption and catalysis Tailoring physical properties of graphene: Effects of hydrogenation, oxidation, and grain boundaries by atomistic simulations

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