Seven Deadliest Network Attacks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prowell, Stacy J; Borkin, Michael; Kraus, Robert

2010-05-01

Do you need to keep up with the latest hacks, attacks, and exploits effecting networks? Then you need "Seven Deadliest Network Attacks". This book pinpoints the most dangerous hacks and exploits specific to networks, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: Denial of Service; War Dialing; Penetration 'Testing'; Protocol Tunneling; Spanning Tree Attacks; Man-in-the-Middle; and, Password Replay. Knowledge is power, findmore » out about the most dominant attacks currently waging war on computers and networks globally. Discover the best ways to defend against these vicious attacks; step-by-step instruction shows you how. Institute countermeasures, don't be caught defenseless again, learn techniques to make your computer and network impenetrable.« less

Readers of Largest U.S. History Textbooks Discover a Storehouse of Misinformation.

ERIC Educational Resources Information Center

Putka, Gary

1992-01-01

Reports that a Texas advocacy group discovered thousands of errors in U.S. history textbooks. Notes that the books underwent the review after drawing favorable reactions from Texas education officials. Identifies possible explanations for the errors and steps being taken to reduce errors in the future. (SG)

Help Seeking Behavior of Women with Self-Discovered Breast Cancer Symptoms: A Meta-Ethnographic Synthesis of Patient Delay

PubMed Central

Khakbazan, Zohreh; Taghipour, Ali; Latifnejad Roudsari, Robab; Mohammadi, Eesa

2014-01-01

Background and Objective Patient delay makes a critical contribution to late diagnosis and poor survival in cases of breast cancer. Identifying the factors that influence patient delay could provide information for adopting strategies that shorten this delay. The aim of this meta-ethnography was to synthesize existing qualitative evidence in order to gain a new understanding of help seeking behavior in women with self-discovered breast cancer symptoms and to determine the factors that influence patient delay. Methods The design was a meta-ethnography approach. A systematic search of the articles was performed in different databases including Elsevier, PubMed, ProQuest and SCOPUS. Qualitative studies with a focus on help seeking behaviors in women with self-discovered breast cancer symptoms and patient delay, published in the English language between 1990 and 2013 were included. The quality appraisal of the articles was carried out using the Critical Appraisal Skills Programme qualitative research checklist and 13 articles met the inclusion criteria. The synthesis was conducted according to Noblit and Hare’s meta-ethnographic approach (1988), through reciprocal translational analysis and lines-of-argument. Findings The synthesis led to identification of eight repeated key concepts including: symptom detection, initial symptom interpretation, symptom monitoring, social interaction, emotional reaction, priority of medical help, appraisal of health services and personal-environmental factors. Symptom interpretation is identified as the important step of the help seeking process and which changed across the process through active monitoring of their symptoms, social interactions and emotional reactions. The perceived seriousness of the situation, priority to receive medical attention, perceived inaccessibility and unacceptability of the health care system influenced women’s decision-making about utilizing health services. Conclusion Help seeking processes are influenced by multiple factors. Educational programs aimed at correcting misunderstandings, erroneous social beliefs and improving self-awareness could provide key strategies to improve health policy which would reduce patient delay. PMID:25470732

A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

PubMed Central

Yoon, Sung Ho; Turkarslan, Serdar; Reiss, David J.; Pan, Min; Burn, June A.; Costa, Kyle C.; Lie, Thomas J.; Slagel, Joseph; Moritz, Robert L.; Hackett, Murray; Leigh, John A.; Baliga, Nitin S.

2013-01-01

Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase—a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions. PMID:24089473

Molecular Regulation of the Mitosis/Meiosis Decision in Multicellular Organisms

PubMed Central

Kimble, Judith

2011-01-01

A major step in the journey from germline stem cell to differentiated gamete is the decision to leave the mitotic cell cycle and begin progression through the meiotic cell cycle. Over the past decade, molecular regulators of the mitosis/meiosis decision have been discovered in most of the major model multicellular organisms. Historically, the mitosis/meiosis decision has been closely linked with controls of germline self-renewal and the sperm/egg decision, especially in nematodes and mice. Molecular explanations of those linkages clarify our understanding of this fundamental germ cell decision, and unifying themes have begun to emerge. Although the complete circuitry of the decision is not known in any organism, the recent advances promise to impact key issues in human reproduction and agriculture. PMID:21646377

Novel aspects in diagnostic approach to respiratory patients: is it the time for a new semiotics?

PubMed

Soldati, Gino; Smargiassi, Andrea; Mariani, Alberto A; Inchingolo, Riccardo

2017-01-01

Medical approach to patients is a fundamental step to get the correct diagnosis. The aim of this paper is to analyze some aspects of the reasoning process inherent in medical diagnosis in our era. Pathologic signs (anamnestic data, symptoms, semiotics, laboratory and strumental findings) represent informative phenomena to be integrated for inferring a diagnosis. Thus, diagnosis begins with "signs" and finishes in a probability of disease. The abductive reasoning process is the generation of a hypothesis to explain one or more observations (signs) in order to decide between alternative explanations searching the best one. This process is iterative during the diagnostic activity while collecting further observations and it could be creative generating new knowledge about what has not been experienced before. In the clinical setting the abductive process is not only theoretical, conversely the physical exploitation of the patient (palpation, percussion, auscultation) is always crucial. Through this manipulative abduction, new and still unexpressed information is discovered and evaluated and physicians are able "to think through doing" to get the correct diagnosis. Abductive inferential path originates with an emotional reaction (discovery of the signs), step by step explanations are formed and it ends with another emotional reaction (diagnosis). Few bedside instruments are allowed to physicians to amplify their ability to search for signs. Stethoscope is an example. Similarities between ultrasound exploration and percussion can be found. Bedside ultrasonography can be considered an external amplifier of signs, a particular kind of percussion and represents a valid example of abductive manipulation. In this searching for signs doctors act like detectives and sometimes the discovering of a strategic, unsuspected sign during abductive manipulation could represent the key point for the correct diagnosis. This condition is called serendipity. Ultrasound is a powerful tool for detecting soft, hidden, unexpected and strategic signs.

Electride support boosts nitrogen dissociation over ruthenium catalyst and shifts the bottleneck in ammonia synthesis

DOE PAGES

Kitano, Masaaki; Kanbara, Shinji; Inoue, Yasunori; ...

2015-03-30

We actively sough novel approaches to efficient ammonia synthesis at an ambient pressure so as to reduce the cost of ammonia production and to allow for compact production facilities. It is accepted that the key is the development of a high-performance catalyst that significantly enhances dissociation of the nitrogen-nitrogen triple bond, which is generally considered a rate-determining step. Here we examine the kinetics of nitrogen and hydrogen isotope exchange and hydrogen adsorption/desorption reactions for a recently discovered efficient catalyst for ammonia synthesis --ruthenium-loaded 12CaO∙7AI 2O 3 electride (Ru/C12A7:more » $$\\bar{e}$$ )--and find that the rate controlling step of ammonia synthesis over Ru/C12A7:$$\\bar{e}$$ is not dissociation of the nitrogen-nitrogen triple bond but the subsequent formation of N-H n species. A mechanism of ammonia synthesis involving reversible storage and release of hydrogen atoms on the Ru/C12A7:$$\\bar{e}$$ surface is proposed on the basis of observed hydrogen adsorption/desorption kinetics.« less

Electride support boosts nitrogen dissociation over ruthenium catalyst and shifts the bottleneck in ammonia synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitano, Masaaki; Kanbara, Shinji; Inoue, Yasunori

We actively sough novel approaches to efficient ammonia synthesis at an ambient pressure so as to reduce the cost of ammonia production and to allow for compact production facilities. It is accepted that the key is the development of a high-performance catalyst that significantly enhances dissociation of the nitrogen-nitrogen triple bond, which is generally considered a rate-determining step. Here we examine the kinetics of nitrogen and hydrogen isotope exchange and hydrogen adsorption/desorption reactions for a recently discovered efficient catalyst for ammonia synthesis --ruthenium-loaded 12CaO∙7AI 2O 3 electride (Ru/C12A7:more » $$\\bar{e}$$ )--and find that the rate controlling step of ammonia synthesis over Ru/C12A7:$$\\bar{e}$$ is not dissociation of the nitrogen-nitrogen triple bond but the subsequent formation of N-H n species. A mechanism of ammonia synthesis involving reversible storage and release of hydrogen atoms on the Ru/C12A7:$$\\bar{e}$$ surface is proposed on the basis of observed hydrogen adsorption/desorption kinetics.« less

A crucial step in cell division identified | Center for Cancer Research

Cancer.gov

When cell division doesn’t go according to plan, the resulting daughter cells can become unstable or even cancerous. A team of CCR investigators has now discovered a crucial step required for normal cell division to occur. Read more...

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

PubMed

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

An iterative network partition algorithm for accurate identification of dense network modules

PubMed Central

Sun, Siqi; Dong, Xinran; Fu, Yao; Tian, Weidong

2012-01-01

A key step in network analysis is to partition a complex network into dense modules. Currently, modularity is one of the most popular benefit functions used to partition network modules. However, recent studies suggested that it has an inherent limitation in detecting dense network modules. In this study, we observed that despite the limitation, modularity has the advantage of preserving the primary network structure of the undetected modules. Thus, we have developed a simple iterative Network Partition (iNP) algorithm to partition a network. The iNP algorithm provides a general framework in which any modularity-based algorithm can be implemented in the network partition step. Here, we tested iNP with three modularity-based algorithms: multi-step greedy (MSG), spectral clustering and Qcut. Compared with the original three methods, iNP achieved a significant improvement in the quality of network partition in a benchmark study with simulated networks, identified more modules with significantly better enrichment of functionally related genes in both yeast protein complex network and breast cancer gene co-expression network, and discovered more cancer-specific modules in the cancer gene co-expression network. As such, iNP should have a broad application as a general method to assist in the analysis of biological networks. PMID:22121225

Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell.

PubMed

Shalev, Anath

2014-08-01

Pancreatic β-cells are responsible for insulin production, and loss of functional β-cell mass is now recognized as a critical step in the pathogenesis of both type 1 and type 2 diabetes. However, the factors controlling the life and death of the pancreatic β-cell have only started to be elucidated. Discovered as the top glucose-induced gene in a human islet microarray study 12 years ago, thioredoxin-interacting protein (TXNIP) has now emerged as such a key player in pancreatic β-cell biology. Since then, β-cell expression of TXNIP has been found to be tightly regulated by multiple factors and to be dramatically increased in diabetic islets. Elevated TXNIP levels induce β-cell apoptosis, whereas TXNIP deficiency protects against type 1 and type 2 diabetes by promoting β-cell survival. TXNIP interacts with and inhibits thioredoxin and thereby controls the cellular redox state, but it also belongs to the α-arrestin family of proteins and regulates a variety of metabolic processes. Most recently, TXNIP has been discovered to control β-cell microRNA expression, β-cell function, and insulin production. In this review, the current state of knowledge regarding regulation and function of TXNIP in the pancreatic β-cell and the implications for drug development are discussed.

History and Development of Coronal Mass Ejections as a Key Player in Solar Terrestrial Relationship

NASA Technical Reports Server (NTRS)

Gopalswamy, N.

2016-01-01

Coronal mass ejections (CMEs) are relatively a recently discovered phenomenon in 1971, some 15 years into the Space Era. It took another two decades to realize that CMEs are the most important players in solar terrestrial relationship as the root cause of severe weather in Earths space environment. CMEs are now counted among the major natural hazards because they cause large solar energetic particle (SEP) events and major geomagnetic storms, both of which pose danger to humans and their technology in space and ground. Geomagnetic storms discovered in the 1700s, solar flares discovered in the 1800s, and SEP events discovered in the 1900s are all now found to be closely related to CMEs via various physical processes occurring at various locations in and around CMEs, when they interact with the ambient medium. This article identifies a number of key developments that preceded the discovery of white-light CMEs suggesting that CMEs were waiting to be discovered. The last two decades witnessed an explosion of CME research following the launch of the Solar and Heliospheric Observatory mission in 1995, resulting in the establishment of a full picture of CMEs.

Drug Development Against Parasitic Diseases: Synthesis of the Antimalarial Agent Qinghaosu and Analogs.

DTIC Science & Technology

A stereoselective total synthesis of (+)- artemisinin has been improved from 18 steps to 13 steps with a resultant 12-fold increase in the overall...yield. A new class of tricyclic analogs of artemisinin has been discovered that possess good in vitro antimalarial activity. U.S. and foreign patents

Mathematics Games with the Alphabet

ERIC Educational Resources Information Center

Gough, John

2004-01-01

Sometimes the first step towards making a new (mathematics) game is discovering an unexpected possibility in some hitherto unplayed-with piece of equipment. At other times the first step is inventing new equipment. But rarely is any "new" idea for a game wholly original, either as a way of playing a game, or in its equipment. As…

The Young Person's Guide to Becoming a Writer.

ERIC Educational Resources Information Center

Grant, Janet E.; Espeland, Pamela, Ed.

Encouraging adolescents to envision themselves as writers, this book provides 24 step-by-step exercises to help them discover their writing style, explore new types of writing, experiment with genres, and evaluate their own work. The book also provides pragmatic information about the day-to-day realities of becoming a writer: finding the right…

Development of a standardized training course for laparoscopic procedures using Delphi methodology.

PubMed

Bethlehem, Martijn S; Kramp, Kelvin H; van Det, Marc J; ten Cate Hoedemaker, Henk O; Veeger, Nicolaas J G M; Pierie, Jean Pierre E N

2014-01-01

Content, evaluation, and certification of laparoscopic skills and procedure training lack uniformity among different hospitals in The Netherlands. Within the process of developing a new regional laparoscopic training curriculum, a uniform and transferrable curriculum was constructed for a series of laparoscopic procedures. The aim of this study was to determine regional expert consensus regarding the key steps for laparoscopic appendectomy and cholecystectomy using Delphi methodology. Lists of suggested key steps for laparoscopic appendectomy and cholecystectomy were created using surgical textbooks, available guidelines, and local practice. A total of 22 experts, working for teaching hospitals throughout the region, were asked to rate the suggested key steps for both procedures on a Likert scale from 1-5. Consensus was reached with Crohnbach's α ≥ 0.90. Of the 22 experts, 21 completed and returned the survey (95%). Data analysis already showed consensus after the first round of Delphi on the key steps for laparoscopic appendectomy (Crohnbach's α = 0.92) and laparoscopic cholecystectomy (Crohnbach's α = 0.90). After the second round, 15 proposed key steps for laparoscopic appendectomy and 30 proposed key steps for laparoscopic cholecystectomy were rated as important (≥4 by at least 80% of the expert panel). These key steps were used for the further development of the training curriculum. By using the Delphi methodology, regional consensus was reached on the key steps for laparoscopic appendectomy and cholecystectomy. These key steps are going to be used for standardized training and evaluation purposes in a new regional laparoscopic curriculum. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Ontology-guided data preparation for discovering genotype-phenotype relationships.

PubMed

Coulet, Adrien; Smaïl-Tabbone, Malika; Benlian, Pascale; Napoli, Amedeo; Devignes, Marie-Dominique

2008-04-25

Complexity and amount of post-genomic data constitute two major factors limiting the application of Knowledge Discovery in Databases (KDD) methods in life sciences. Bio-ontologies may nowadays play key roles in knowledge discovery in life science providing semantics to data and to extracted units, by taking advantage of the progress of Semantic Web technologies concerning the understanding and availability of tools for knowledge representation, extraction, and reasoning. This paper presents a method that exploits bio-ontologies for guiding data selection within the preparation step of the KDD process. We propose three scenarios in which domain knowledge and ontology elements such as subsumption, properties, class descriptions, are taken into account for data selection, before the data mining step. Each of these scenarios is illustrated within a case-study relative to the search of genotype-phenotype relationships in a familial hypercholesterolemia dataset. The guiding of data selection based on domain knowledge is analysed and shows a direct influence on the volume and significance of the data mining results. The method proposed in this paper is an efficient alternative to numerical methods for data selection based on domain knowledge. In turn, the results of this study may be reused in ontology modelling and data integration.

The Adventures of Brown Sugar; Adventures in Creative Writing.

ERIC Educational Resources Information Center

Stegall, Carrie

A teacher's experience in guiding a group of 40 fourth-graders in writing a book is reported, and the book is included. Provided are descriptions of--(1) the step-by-step process of writing each chapter of the book, (2) the development of the students'"own English book"--rules for usage, spelling, punctuation, and capitalization, discovered by the…

Non-aqueous homogenous biocatalytic conversion of polysaccharides in ionic liquids using chemically modified glucosidase.

PubMed

Brogan, Alex P S; Bui-Le, Liem; Hallett, Jason P

2018-06-25

The increasing requirement to produce platform chemicals and fuels from renewable sources means advances in biocatalysis are rapidly becoming a necessity. Biomass is widely used in nature as a source of energy and as chemical building blocks. However, recalcitrance towards traditional chemical processes and solvents provides a significant barrier to widespread utility. Here, by optimizing enzyme solubility in ionic liquids, we have discovered solvent-induced substrate promiscuity of glucosidase, demonstrating an unprecedented example of homogeneous enzyme bioprocessing of cellulose. Specifically, chemical modification of glucosidase for solubilization in ionic liquids can increase thermal stability to up to 137 °C, allowing for enzymatic activity 30 times greater than is possible in aqueous media. These results establish that through a synergistic combination of chemical biology (enzyme modification) and reaction engineering (solvent choice), the biocatalytic capability of enzymes can be intensified: a key step towards the full-scale deployment of industrial biocatalysis.

Employees' Motivation for SPI: Case Study in a Small Finnish Software Company

NASA Astrophysics Data System (ADS)

Valtanen, Anu; Sihvonen, Hanna-Miina

In small software companies the resources available for SPI are often limited. With limited resources, the motivation of the employees becomes one of the key factors for SPI. In this article, the motivational factors affecting a small company's SPI efforts are discussed. In the research, we carried out interviews and a survey in a small Finnish software company considering the motivation towards SPI. The results are presented here and compared with earlier motivation research. There were differences revealed while comparing the motivating factors of smaller companies to those of larger ones. In large companies the focus seems to be on the business related motivators and in small ones the motivators related to comfortability of work are emphasized. Motivation survey and the interviews proved to be useful tools in planning the future SPI strategy. A lot of valuable information was discovered for planning and implementing the next steps of SPI.

Forces Driving Chaperone Action

PubMed Central

Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

2016-01-01

SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

A genomic approach to identify hybrid incompatibility genes.

PubMed

Cooper, Jacob C; Phadnis, Nitin

2016-07-02

Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids.

A new species of Andean toad (Bufonidae, Osornophryne) discovered using molecular and morphological data, with a taxonomic key for the genus

PubMed Central

Páez-Moscoso, Diego J.; Guayasamin, Juan M.; Yánez-Muñoz, Mario

2011-01-01

Abstract Combining a molecular phylogeny and morphological data, we discovered a new species of Osornophryne from the Amazonian slope of the Ecuadorian Andes. Morphologically, the new taxon is distinguished from all others species in Osornophryne by having the Toes IV and V longer than Toes I–III, a short and rounded snout with a small rostral papilla, and conical pustules on flanks. The new species previously was confused with Osornophryne guacamayo. A taxonomic key is provided for all known species of Osornophryne. PMID:21852930

Template-based de novo design for type II kinase inhibitors and its extented application to acetylcholinesterase inhibitors.

PubMed

Su, Bo-Han; Huang, Yi-Syuan; Chang, Chia-Yun; Tu, Yi-Shu; Tseng, Yufeng J

2013-10-31

There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar) and nilotinib (Tasigna), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.

How to Go to College: The College and Career Planning Handbook for Grades 8 and 9

ERIC Educational Resources Information Center

Washington Higher Education Coordinating Board, 2002

2002-01-01

The College and Career Planning Handbook provides five steps and associated activities to help guide high school choices and prepare students for college and beyond. Steps include: (1) Discover Yourself (Who are you, and what do you want?); (2) Explore Your Options (What's the best job in the world?); (3) Set Goals (Specific, Measurable,…

Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin

PubMed Central

2018-01-01

Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD) simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM) to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins. PMID:29698481

Dyslexia

MedlinePlus

... help figure out what's wrong. A specialist in learning disabilities knows a lot about learning problems that kids ... good grade; it's to spot problems. Discovering a learning disability is the first step toward getting help that ...

Procedural key steps in laparoscopic colorectal surgery, consensus through Delphi methodology.

PubMed

Dijkstra, Frederieke A; Bosker, Robbert J I; Veeger, Nicolaas J G M; van Det, Marc J; Pierie, Jean Pierre E N

2015-09-01

While several procedural training curricula in laparoscopic colorectal surgery have been validated and published, none have focused on dividing surgical procedures into well-identified segments, which can be trained and assessed separately. This enables the surgeon and resident to focus on a specific segment, or combination of segments, of a procedure. Furthermore, it will provide a consistent and uniform method of training for residents rotating through different teaching hospitals. The goal of this study was to determine consensus on the key steps of laparoscopic right hemicolectomy and laparoscopic sigmoid colectomy among experts in our University Medical Center and affiliated hospitals. This will form the basis for the INVEST video-assisted side-by-side training curriculum. The Delphi method was used for determining consensus on key steps of both procedures. A list of 31 steps for laparoscopic right hemicolectomy and 37 steps for laparoscopic sigmoid colectomy was compiled from textbooks and national and international guidelines. In an online questionnaire, 22 experts in 12 hospitals within our teaching region were invited to rate all steps on a Likert scale on importance for the procedure. Consensus was reached in two rounds. Sixteen experts agreed to participate. Of these 16 experts, 14 (88%) completed the questionnaire for both procedures. Of the 14 who completed the first round, 13 (93%) completed the second round. Cronbach's alpha was 0.79 for the right hemicolectomy and 0.91 for the sigmoid colectomy, showing high internal consistency between the experts. For the right hemicolectomy, 25 key steps were established; for the sigmoid colectomy, 24 key steps were established. Expert consensus on the key steps for laparoscopic right hemicolectomy and laparoscopic sigmoid colectomy was reached. These key steps will form the basis for a video-assisted teaching curriculum.

Getting a Handle on the Role of Coenzyme M in Alkene Metabolism

PubMed Central

Krishnakumar, Arathi M.; Sliwa, Darius; Endrizzi, James A.; Boyd, Eric S.; Ensign, Scott A.; Peters, John W.

2008-01-01

Summary: Coenzyme M (2-mercaptoethanesulfonate; CoM) is one of several atypical cofactors discovered in methanogenic archaea which participate in the biological reduction of CO2 to methane. Elegantly simple, CoM, so named for its role as a methyl carrier in all methanogenic archaea, is the smallest known organic cofactor. It was thought that this cofactor was used exclusively in methanogenesis until it was recently discovered that CoM is a key cofactor in the pathway of propylene metabolism in the gram-negative soil microorganism Xanthobacter autotrophicus Py2. A four-step pathway requiring CoM converts propylene and CO2 to acetoacetate, which feeds into central metabolism. In this process, CoM is used to activate and convert highly electrophilic epoxypropane, formed from propylene epoxidation, into a nucleophilic species that undergoes carboxylation. The unique properties of CoM provide a chemical handle for orienting compounds for site-specific redox chemistry and stereospecific catalysis. The three-dimensional structures of several of the enzymes in the pathway of propylene metabolism in defined states have been determined, providing significant insights into both the enzyme mechanisms and the role of CoM in this pathway. These studies provide the structural basis for understanding the efficacy of CoM as a handle to direct organic substrate transformations at the active sites of enzymes. PMID:18772284

Discover Summer School: Evaluation Report and Executive Summary

ERIC Educational Resources Information Center

Torgerson, David; Torgerson, Carole; Jefferson, Laura; Buckley, Hannah; Ainsworth, Hannah; Heaps, Clare; Mitchell, Natasha

2014-01-01

The Discover Summer School was a four-week programme which aimed to improve the reading and writing skills of children during the summer between Year 6 and Year 7. The programme was targeted at pupils who had been predicted to achieve below Level 4b in English by the end of Key Stage 2. Pupils meeting the eligibility criteria for the study, and…

Key Relation Extraction from Biomedical Publications.

PubMed

Huang, Lan; Wang, Ye; Gong, Leiguang; Kulikowski, Casimir; Bai, Tian

2017-01-01

Within the large body of biomedical knowledge, recent findings and discoveries are most often presented as research articles. Their number has been increasing sharply since the turn of the century, presenting ever-growing challenges for search and discovery of knowledge and information related to specific topics of interest, even with the help of advanced online search tools. This is especially true when the goal of a search is to find or discover key relations between important concepts or topic words. We have developed an innovative method for extracting key relations between concepts from abstracts of articles. The method focuses on relations between keywords or topic words in the articles. Early experiments with the method on PubMed publications have shown promising results in searching and discovering keywords and their relationships that are strongly related to the main topic of an article.

The Amateur Scientist.

ERIC Educational Resources Information Center

Walker, Jearl

1986-01-01

Relates how Charles Martin Hall discovered the method of making pure aluminum metal in 1886. Retraces the events and steps that led to the process of aluminum purification. Includes diagrams of the apparatus used in the investigations. (ML)

NASA's Kepler Mission Discovers Its Smallest Habitable Zone Planets (Reporter Pkg)

NASA Image and Video Library

2013-04-18

NASA's Kepler mission has discovered two new planetary systems that include three super-Earth-size planets in the 'habitable zone,' the range of distance from a star where the surface temperature of an orbiting planet might be suitable for liquid water. Scientists do not know whether life could exist on the newfound planets, but their discovery signals we are another step closer to finding a world similar to Earth around a star like our sun. Kepler-62 and -69 systems

Automated Classification of Asteroids into Families at Work

NASA Astrophysics Data System (ADS)

Knežević, Zoran; Milani, Andrea; Cellino, Alberto; Novaković, Bojan; Spoto, Federica; Paolicchi, Paolo

2014-07-01

We have recently proposed a new approach to the asteroid family classification by combining the classical HCM method with an automated procedure to add newly discovered members to existing families. This approach is specifically intended to cope with ever increasing asteroid data sets, and consists of several steps to segment the problem and handle the very large amount of data in an efficient and accurate manner. We briefly present all these steps and show the results from three subsequent updates making use of only the automated step of attributing the newly numbered asteroids to the known families. We describe the changes of the individual families membership, as well as the evolution of the classification due to the newly added intersections between the families, resolved candidate family mergers, and emergence of the new candidates for the mergers. We thus demonstrate how by the new approach the asteroid family classification becomes stable in general terms (converging towards a permanent list of confirmed families), and in the same time evolving in details (to account for the newly discovered asteroids) at each update.

Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle.

PubMed

Smith, Johanna A; Daniel, Rene

2016-11-13

Vaginal transmission is crucial to the spread of HIV-1 around the world. It is not yet clear what type (s) of innate defenses against HIV-1 infection are present in the vagina. Here, we aimed to determine whether human vaginal fluid contains exosomes that may possess anti-HIV-1 activity. The exosomal fraction was isolated from samples of vaginal fluids. The presence of exosomes was confirmed by flow cytometry and western blotting. The newly discovered exosomes were tested for their ability to block early steps of HIV-1 infection in vitro using established cell culture systems and real time PCR-based methods. Vaginal fluid contains exosomes expressing CD9, CD63, and CD81 exosomal markers. The exosomal fraction of the fluid-reduced transmission of HIV-1 vectors by 60%, the efficiency of reverse transcription step by 58.4%, and the efficiency of integration by 47%. Exosomes had no effect on the entry of HIV-1 vectors. Human vaginal fluid exosomes are newly discovered female innate defenses that may protect women against HIV-1 infection.

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

BioEve Search: A Novel Framework to Facilitate Interactive Literature Search

PubMed Central

Ahmed, Syed Toufeeq; Davulcu, Hasan; Tikves, Sukru; Nair, Radhika; Zhao, Zhongming

2012-01-01

Background. Recent advances in computational and biological methods in last two decades have remarkably changed the scale of biomedical research and with it began the unprecedented growth in both the production of biomedical data and amount of published literature discussing it. An automated extraction system coupled with a cognitive search and navigation service over these document collections would not only save time and effort, but also pave the way to discover hitherto unknown information implicitly conveyed in the texts. Results. We developed a novel framework (named “BioEve”) that seamlessly integrates Faceted Search (Information Retrieval) with Information Extraction module to provide an interactive search experience for the researchers in life sciences. It enables guided step-by-step search query refinement, by suggesting concepts and entities (like genes, drugs, and diseases) to quickly filter and modify search direction, and thereby facilitating an enriched paradigm where user can discover related concepts and keywords to search while information seeking. Conclusions. The BioEve Search framework makes it easier to enable scalable interactive search over large collection of textual articles and to discover knowledge hidden in thousands of biomedical literature articles with ease. PMID:22693501

A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle.

PubMed

Mackinder, Luke C M; Meyer, Moritz T; Mettler-Altmann, Tabea; Chen, Vivian K; Mitchell, Madeline C; Caspari, Oliver; Freeman Rosenzweig, Elizabeth S; Pallesen, Leif; Reeves, Gregory; Itakura, Alan; Roth, Robyn; Sommer, Frederik; Geimer, Stefan; Mühlhaus, Timo; Schroda, Michael; Goodenough, Ursula; Stitt, Mark; Griffiths, Howard; Jonikas, Martin C

2016-05-24

Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

Blocking the interaction between HIV-1 integrase and human LEDGF/p75: mutational studies, virtual screening and molecular dynamics simulations.

PubMed

Reddy, Karnati Konda; Singh, Poonam; Singh, Sanjeev Kumar

2014-03-04

HIV-1 integrase (IN) mediates integration of viral cDNA into the host cell genome, an essential step in the retroviral life cycle. The human lens epithelium-derived growth factor (LEDGF/p75) is a co-factor of HIV-1 IN that plays a crucial role in viral integration. Because of its crucial role in early steps of HIV replication, the IN-LEDGF/p75 interaction represents an attractive target for anti-HIV drug discovery. In this study, the IN-LEDGF/p75 interaction was studied by in silico mutational studies and molecular dynamics simulations. The results showed that all of the key residues in the LEDGF/p75 binding pocket of IN protein are important for stabilization of the complex. Structure-based virtual screening against HIV-1 IN using the ChemBridge database was performed through three different protocols of docking simulations with varying precisions and computational intensities. Six compounds based on the docking score, binding affinity and pharmacokinetic parameters were selected and an analysis of the interactions with key amino acid residues of IN was carried out. Subsequently, molecular dynamics simulations of these compounds in the LEDGF/p75 binding site of IN were carried out in order to study the stability of complexes and their hydrogen bonding interactions. IN residues Glu170, His171, and Thr174 in chain A as well as Gln95 and Thr125 in chain B were discovered to play important roles in the binding of compounds. These findings could be helpful for blocking IN-LEDGF/p75 interaction, and provide a method for avoiding viral resistance and cross-resistance.

One Step Quantum Key Distribution Based on EPR Entanglement.

PubMed

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-06-30

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper's attack would introduce at least an error rate of 46.875%. Compared with the "Ping-pong" protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step.

Performance evaluation of different types of particle representation procedures of Particle Swarm Optimization in Job-shop Scheduling Problems

NASA Astrophysics Data System (ADS)

Izah Anuar, Nurul; Saptari, Adi

2016-02-01

This paper addresses the types of particle representation (encoding) procedures in a population-based stochastic optimization technique in solving scheduling problems known in the job-shop manufacturing environment. It intends to evaluate and compare the performance of different particle representation procedures in Particle Swarm Optimization (PSO) in the case of solving Job-shop Scheduling Problems (JSP). Particle representation procedures refer to the mapping between the particle position in PSO and the scheduling solution in JSP. It is an important step to be carried out so that each particle in PSO can represent a schedule in JSP. Three procedures such as Operation and Particle Position Sequence (OPPS), random keys representation and random-key encoding scheme are used in this study. These procedures have been tested on FT06 and FT10 benchmark problems available in the OR-Library, where the objective function is to minimize the makespan by the use of MATLAB software. Based on the experimental results, it is discovered that OPPS gives the best performance in solving both benchmark problems. The contribution of this paper is the fact that it demonstrates to the practitioners involved in complex scheduling problems that different particle representation procedures can have significant effects on the performance of PSO in solving JSP.

Copper chaperone Atox1 plays role in breast cancer cell migration.

PubMed

Blockhuys, Stéphanie; Wittung-Stafshede, Pernilla

2017-01-29

Copper (Cu) is an essential transition metal ion required as cofactor in many key enzymes. After cell uptake of Cu, the metal is transported by the cytoplasmic Cu chaperone Atox1 to P 1B -type ATPases in the Golgi network for incorporation into Cu-dependent enzymes in the secretory path. Cu is vital for many steps of cancer progression and Atox1 was recently suggested to have additional functionality as a nuclear transcription factor. We here investigated the expression level, cellular localization and role in cell migration of Atox1 in an aggressive breast cancer cell line upon combining immunostaining, microscopy and a wound healing assay. We made the unexpected discovery that Atox1 accumulates at lamellipodia borders of migrating cancer cells and Atox1 silencing resulted in migration defects as evidenced from reduced wound closure. Therefore, we have discovered an unknown role of the Cu chaperone Atox1 in breast cancer cell migration. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Butterfly proboscis: natural combination of a drinking straw with a nanosponge

NASA Astrophysics Data System (ADS)

Kornev, Kostya; Monaenkova, Daria; Adler, Peter; Lee, Wah-Keat; Lehnert, Matthew; Andrukh, Taras; Beard, Charles; Rubin, Binyamin; Tokarev, Alexander

2011-11-01

The ability of Lepidoptera, or butterflies and moths, to drink liquids from rotting fruit and wet soil, as well as nectar from floral tubes, raises the question of whether the conventional view of the proboscis as a drinking straw can account for the withdrawal of fluids from porous substrates or of films and droplets from floral tubes. We discovered that the proboscis promotes capillary pull of liquids from diverse sources due to a hierarchical pore structure spanning nano- and microscales. X-ray phase-contrast imaging reveals that Plateau instability causes liquid bridges to form in the food canal, which are transported to the gut by the muscular sucking pump in the head. The dual functionality of the proboscis represents a key innovation for exploiting a vast range of nutritional sources. A transformative two-step model of capillary intake and suctioning can be applied not only to butterflies and moths but also potentially to vast numbers of other insects such as bees and flies. NSF EFRI - 0937985.

Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R-mediated intercellular calcium waves

NASA Astrophysics Data System (ADS)

Restrepo, Simon; Basler, Konrad

2016-08-01

Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3-phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key gap junction component Inx2. The knockdown of genes required for SIDIC formation and propagation negatively affects wing disc recovery after mechanical injury. Our results reveal a role for ICWs in wing disc homoeostasis and highlight the utility of the wing disc as a model for calcium signalling studies.

Mitochondrial DNA, restoring Beethovens music.

PubMed

Merheb, Maxime; Vaiedelich, Stéphane; Maniguet, Thiérry; Hänni, Catherine

2016-01-01

Great ancient composers have endured many obstacles and constraints which are very difficult to understand unless we perform the restoration process of ancient music. Species identification in leather used during manufacturing is the key step to start such a restoration process in order to produce a facsimile of a museum piano. Our study reveals the species identification in the leather covering the hammer head in a piano created by Erard in 1802. This is the last existing piano similar to the piano that Beethoven used with its leather preserved in its original state. The leather sample was not present in a homogeneous piece, yet combined with glue. Using a DNA extraction method that avoids PCR inhibitors; we discovered that sheep and cattle are the origin of the combination. To identify the species in the leather, we focused on the amounts of mitochondrial DNA in both leather and glue and results have led us to the conclusion that the leather used to cover the hammer head in this piano was made of cattle hide.

Strigolactones: new plant hormones in action.

PubMed

Zwanenburg, Binne; Pospíšil, Tomáš; Ćavar Zeljković, Sanja

2016-06-01

The key step in the mode of action of strigolactones is the enzymatic detachment of the D-ring. The thus formed hydroxy butenolide induces conformational changes of the receptor pocket which trigger a cascade of reactions in the signal transduction. Strigolactones (SLs) constitute a new class of plant hormones which are of increasing importance in plant science. For the last 60 years, they have been known as germination stimulants for parasitic plants. Recently, several new bio-properties of SLs have been discovered such as the branching factor for arbuscular mycorrhizal fungi, regulation of plant architecture (inhibition of bud outgrowth and of shoot branching) and the response to abiotic factors, etc. To broaden horizons and encourage new ideas for identifying and synthesising new and structurally simple SLs, this review is focused on molecular aspects of this new class of plant hormones. Special attention has been given to structural features, the mode of action of these phytohormones in various biological actions, the design of SL analogs and their applications.

Aqueous enzymatic extraction of Moringa oleifera oil.

PubMed

Mat Yusoff, Masni; Gordon, Michael H; Ezeh, Onyinye; Niranjan, Keshavan

2016-11-15

This paper reports on the extraction of Moringa oleifera (MO) oil by using aqueous enzymatic extraction (AEE) method. The effect of different process parameters on the oil recovery was discovered by using statistical optimization, besides the effect of selected parameters on the formation of its oil-in-water cream emulsions. Within the pre-determined ranges, the use of pH 4.5, moisture/kernel ratio of 8:1 (w/w), and 300stroke/min shaking speed at 40°C for 1h incubation time resulted in highest oil recovery of approximately 70% (goil/g solvent-extracted oil). These optimized parameters also result in a very thin emulsion layer, indicating minute amount of emulsion formed. Zero oil recovery with thick emulsion were observed when the used aqueous phase was re-utilized for another AEE process. The findings suggest that the critical selection of AEE parameters is key to high oil recovery with minimum emulsion formation thereby lowering the load on the de-emulsification step. Copyright © 2016 Elsevier Ltd. All rights reserved.

Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research.

PubMed

Kari, Jameela A; Bockenhauer, Detlef; Stanescu, Horia; Gari, Mamdooh; Kleta, Robert; Singh, Ajay K

2014-02-01

Identification of disease-related genes is a critical step in understanding the molecular basis of disease and developing targeted therapies. The genetic study of diseases occurring in the offspring of consanguineous unions is a powerful way to discover new disease genes. Pediatric nephrology provides an excellent example because ∼70% of cases of kidney disease in childhood are congenital with a likely genetic basis. This percentage is likely to be even higher in countries with a high consanguinity rate, such as the Kingdom of Saudi Arabia. However, there are a number of challenges, such as cultural, legal, and religious restrictions, that should be appreciated before carrying out genetic research in a tradition-bound country. In this article, we discuss the background, opportunities, and challenges involved with this unique opportunity to conduct studies of such genetic disorders. Keys to success include collaboration and an understanding of local traditions and laws. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

Analysis of the proteolysis of bioactive peptides using a peptidomics approach

PubMed Central

Kim, Yun-Gon; Lone, Anna Mari; Saghatelian, Alan

2014-01-01

Identifying the peptidases that inactivate bioactive peptides (e.g. peptide hormones and neuropeptides) in mammals is an important unmet challenge. This protocol describes a recent approach that combines liquid chromatography-mass spectrometry peptidomics to identify endogenous cleavage sites of a bioactive peptide, the subsequent biochemical purification of a candidate peptidase based on these cleavage sites, and validation of the candidate peptidase’s role in the physiological regulation of the bioactive peptide by examining a peptidase knockout mouse. We highlight successful application of this protocol to discover that insulin-degrading enzyme (IDE) regulates physiological calcitonin gene-related peptide (CGRP) levels and detail the key stages and steps in this approach. This protocol requires 7 days of work; however, the total time for this protocol is highly variable because of its dependence on the availability of biological reagents, namely purified enzymes and knockout mice. The protocol is valuable because it expedites the characterization of mammalian peptidases, such as IDE, which in certain instances can be used to develop novel therapeutics. PMID:23949379

Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track Gene Expression by Both Partners during Initiation of Symbiosis.

PubMed

Nikolakakis, K; Lehnert, E; McFall-Ngai, M J; Ruby, E G

2015-07-01

The establishment of a productive symbiosis between Euprymna scolopes, the Hawaiian bobtail squid, and its luminous bacterial symbiont, Vibrio fischeri, is mediated by transcriptional changes in both partners. A key challenge to unraveling the steps required to successfully initiate this and many other symbiotic associations is characterization of the timing and location of these changes. We report on the adaptation of hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) to simultaneously probe the spatiotemporal regulation of targeted genes in both E. scolopes and V. fischeri. This method revealed localized, transcriptionally coregulated epithelial cells within the light organ that responded directly to the presence of bacterial cells while, at the same time, provided a sensitive means to directly show regulated gene expression within the symbiont population. Thus, HCR-FISH provides a new approach for characterizing habitat transition in bacteria and for discovering host tissue responses to colonization. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A genomic approach to identify hybrid incompatibility genes

PubMed Central

Cooper, Jacob C.; Phadnis, Nitin

2016-01-01

ABSTRACT Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids. PMID:27230814

Realizing the potential of the CUAHSI Water Data Center to advance Earth Science

NASA Astrophysics Data System (ADS)

Hooper, R. P.; Seul, M.; Pollak, J.; Couch, A.

2015-12-01

The CUAHSI Water Data Center has developed a cloud-based system for data publication, discovery and access. Key features of this system are a semantically enabled catalog to discover data across more than 100 different services and delivery of data and metadata in a standard format. While this represents a significant technical achievement, the purpose of this system is to support data reanalysis for advancing science. A new web-based client, HydroClient, improves access to the data from previous clients. This client is envisioned as the first step in a workflow that can involve visualization and analysis using web-processing services, followed by download to local computers for further analysis. The release of the WaterML library in the R package CRAN repository is an initial attempt at linking the WDC services in a larger analysis workflow. We are seeking community input on other resources required to make the WDC services more valuable in scientific research and education.

Graphene Oxide-Polymer Composite Langmuir Films Constructed by Interfacial Thiol-Ene Photopolymerization

NASA Astrophysics Data System (ADS)

Luo, Xiaona; Ma, Kai; Jiao, Tifeng; Xing, Ruirui; Zhang, Lexin; Zhou, Jingxin; Li, Bingbing

2017-02-01

The effective synthesis and self-assembly of graphene oxide (GO) nanocomposites are of key importance for a broad range of nanomaterial applications. In this work, a one-step chemical strategy is presented to synthesize stable GO-polymer Langmuir composite films by interfacial thiol-ene photopolymerization at room temperature, without use of any crosslinking agents and stabilizing agents. It is discovered that photopolymerization reaction between thiol groups modified GO sheets and ene in polymer molecules is critically responsible for the formation of the composite Langmuir films. The film formed by Langmuir assembly of such GO-polymer composite films shows potential to improve the mechanical and chemical properties and promotes the design of various GO-based nanocomposites. Thus, the GO-polymer composite Langmuir films synthesized by interfacial thiol-ene photopolymerization with such a straightforward and clean manner, provide new alternatives for developing chemically modified GO-based hybrid self-assembled films and nanomaterials towards a range of soft matter and graphene applications.

Controlling Oxygen Mobility in Ruddlesden–Popper Oxides

PubMed Central

Lee, Dongkyu; Lee, Ho Nyung

2017-01-01

Discovering new energy materials is a key step toward satisfying the needs for next-generation energy conversion and storage devices. Among the various types of oxides, Ruddlesden–Popper (RP) oxides (A2BO4) are promising candidates for electrochemical energy devices, such as solid oxide fuel cells, owing to their attractive physicochemical properties, including the anisotropic nature of oxygen migration and controllable stoichiometry from oxygen excess to oxygen deficiency. Thus, understanding and controlling the kinetics of oxygen transport are essential for designing optimized materials to use in electrochemical energy devices. In this review, we first discuss the basic mechanisms of oxygen migration in RP oxides depending on oxygen nonstoichiometry. We then focus on the effect of changes in the defect concentration, crystallographic orientation, and strain on the oxygen migration in RP oxides. We also briefly review their thermal and chemical stability. Finally, we conclude with a perspective on potential research directions for future investigation to facilitate controlling oxygen ion migration in RP oxides. PMID:28772732

REMOVING TRIHALOMETHANES FROM DRINKING WATER - AN OVERVIEW OF TREATMENT TECHNIQUES

EPA Science Inventory

In 1974 trihalomethanes (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) were discovered to be formed during the disinfection step of drinking water if free chlorine was the disinfectant. This, coupled with the perceived hazard to the consumer's health, led...

Measurement of interaction between antiprotons

DOE PAGES

Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; ...

2015-11-04

In this paper, one of the primary goals of nuclear physics is to understand the force between nucleons, which is a necessary step for understanding the structure of nuclei and how nuclei interact with each other. Rutherford discovered the atomic nucleus in 1911, and the large body of knowledge about the nuclear force that has since been acquired was derived from studies made on nucleons or nuclei. Although antinuclei up to antihelium-4 have been discovered and their masses measured, little is known directly about the nuclear force between antinucleons. Here, we study antiproton pair correlations among data collected by themore » STAR experiment at the Relativistic Heavy Ion Collider (RHIC), where gold ions are collided with a centre-of-mass energy of 200 gigaelectronvolts per nucleon pair. Antiprotons are abundantly produced in such collisions, thus making it feasible to study details of the antiproton–antiproton interaction. By applying a technique similar to Hanbury Brown and Twiss intensity interferometry, we show that the force between two antiprotons is attractive. In addition, we report two key parameters that characterize the corresponding strong interaction: the scattering length and the effective range of the interaction. Our measured parameters are consistent within errors with the corresponding values for proton–proton interactions. Our results provide direct information on the interaction between two antiprotons, one of the simplest systems of antinucleons, and so are fundamental to understanding the structure of more-complex antinuclei and their properties.« less

Metabolomic response of a marine bacterium to 3,6-anhydro-l-galactose, the rare sugar from red macroalgae, as the sole carbon source.

PubMed

Yun, Eun Ju; Yu, Sora; Kim, Sooah; Kim, Kyoung Heon

2018-03-20

Marine red macroalgae have received much attention as sustainable resources for producing bio-based products. Therefore, understanding the metabolic pathways of carbohydrates from red macroalgae, in fermentative microorganisms, is crucial for efficient bioconversion of the carbohydrates into bio-based products. Recently, the novel catabolic pathway of 3,6-anhydro-l-galactose (AHG), the main component of red macroalgae, was discovered in a marine bacterium, Vibrio sp. strain EJY3. However, the global metabolic network in response to AHG remains unclear. Here, the intracellular metabolites of EJY3 grown on AHG, glucose, or galactose were comparatively profiled using gas chromatography/time-of-flight mass spectrometry. The global metabolite profiling results revealed that the metabolic profile for AHG significantly differed from those for other common sugars. Specifically, the metabolic intermediate of the AHG pathway, 3,6-anhydrogalactonate, was detected during growth only in the presence of AHG; thus, the recently discovered key steps in AHG catabolism was found not to occur in the catabolism of other common sugars. Moreover, the levels of metabolic intermediates related to glycerolipid metabolism and valine biosynthesis were higher with AHG than those with other sugars. These comprehensive metabolomic analytical results for AHG in this marine bacterium can be used as the basis for having fermentative microbial strains to engineered to efficiently utilize AHG from macroalgal biomass. Copyright © 2018 Elsevier B.V. All rights reserved.

One Step Quantum Key Distribution Based on EPR Entanglement

PubMed Central

Li, Jian; Li, Na; Li, Lei-Lei; Wang, Tao

2016-01-01

A novel quantum key distribution protocol is presented, based on entanglement and dense coding and allowing asymptotically secure key distribution. Considering the storage time limit of quantum bits, a grouping quantum key distribution protocol is proposed, which overcomes the vulnerability of first protocol and improves the maneuverability. Moreover, a security analysis is given and a simple type of eavesdropper’s attack would introduce at least an error rate of 46.875%. Compared with the “Ping-pong” protocol involving two steps, the proposed protocol does not need to store the qubit and only involves one step. PMID:27357865

Assessing Socioeconomic Impacts of Cascading Infrastructure Disruptions in a Dynamic Human-Infrastructure Network

DTIC Science & Technology

2016-07-01

CAC common access card DoD Department of Defense FOUO For Official Use Only GIS geographic information systems GUI graphical user interface HISA...as per requirements of this project, is UNCLASS/For Official Use Only (FOUO), with access re- stricted to DOD common access card (CAC) users. Key...Boko Haram Fuel Dump Discovered in Maiduguru.” Available: http://saharareporters.com/2015/10/01/another-boko-haram-fuel- dump - discovered-maiduguri

48 CFR 3036.104-90 - Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Authority for one-step... General 3036.104-90 Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG). The Head of the Contracting Activity (HCA) of the U.S. Coast Guard may use one-step turn...

Using RSAT oligo-analysis and dyad-analysis tools to discover regulatory signals in nucleic sequences.

PubMed

Defrance, Matthieu; Janky, Rekin's; Sand, Olivier; van Helden, Jacques

2008-01-01

This protocol explains how to discover functional signals in genomic sequences by detecting over- or under-represented oligonucleotides (words) or spaced pairs thereof (dyads) with the Regulatory Sequence Analysis Tools (http://rsat.ulb.ac.be/rsat/). Two typical applications are presented: (i) predicting transcription factor-binding motifs in promoters of coregulated genes and (ii) discovering phylogenetic footprints in promoters of orthologous genes. The steps of this protocol include purging genomic sequences to discard redundant fragments, discovering over-represented patterns and assembling them to obtain degenerate motifs, scanning sequences and drawing feature maps. The main strength of the method is its statistical ground: the binomial significance provides an efficient control on the rate of false positives. In contrast with optimization-based pattern discovery algorithms, the method supports the detection of under- as well as over-represented motifs. Computation times vary from seconds (gene clusters) to minutes (whole genomes). The execution of the whole protocol should take approximately 1 h.

Biotin and Lipoic Acid: Synthesis, Attachment and Regulation

PubMed Central

Cronan, John E.

2014-01-01

Summary Two vitamins, biotin and lipoic acid, are essential in all three domains of life. Both coenzymes function only when covalently attached to key metabolic enzymes. There they act as “swinging arms” that shuttle intermediates between two active sites (= covalent substrate channeling) of key metabolic enzymes. Although biotin was discovered over 100 years ago and lipoic acid 60 years ago, it was not known how either coenzyme is made until recently. In Escherichia coli the synthetic pathways for both coenzymes have now been worked out for the first time. The late steps of biotin synthesis, those involved in assembling the fused rings, were well-described biochemically years ago, although recent progress has been made on the BioB reaction, the last step of the pathway in which the biotin sulfur moiety is inserted. In contrast, the early steps of biotin synthesis, assembly of the fatty acid-like “arm” of biotin were unknown. It has now been demonstrated that the arm is made by using disguised substrates to gain entry into the fatty acid synthesis pathway followed by removal of the disguise when the proper chain length is attained. The BioC methyltransferase is responsible for introducing the disguise and the BioH esterase for its removal. In contrast to biotin, which is attached to its cognate proteins as a finished molecule, lipoic acid is assembled on its cognate proteins. An octanoyl moiety is transferred from the octanoyl-ACP of fatty acid synthesis to a specific lysine residue of a cognate protein by the LipB octanoyl transferase followed by sulfur insertion at carbons C6 and C8 by the LipA lipoyl synthetase. Assembly on the cognate proteins regulates the amount of lipoic acid synthesized and thus there is no transcriptional control of the synthetic genes. In contrast transcriptional control of the biotin synthetic genes is wielded by a remarkably sophisticated, yet simple, system, exerted through BirA a dual function protein that both represses biotin operon transcription and ligates biotin to its cognate protein. PMID:26442940

Space Drive Physics: Introduction and Next Steps

NASA Astrophysics Data System (ADS)

Millis, M. G.

Research toward the visionary goal of propellantless ``space drives'' is introduced, covering key physics issues and a listing of roughly 2-dozen approaches. The targeted advantage of a space drive is to circumvent the propellant constraints of rockets and the maneuvering limits of light sails by using the interactions between the spacecraft and its surrounding space for propulsion. At present, the scientific foundations from which to engineer a space drive have not been discovered and, objectively, might be impossible. Although no propulsion breakthroughs appear imminent, the subject has matured to where the relevant questions have been broached and are beginning to be answered. The critical make-break issues include; conservation of momentum, uncertain sources of reaction mass, and the net-external thrusting requirement. Note: space drives are not necessarily faster- than-light devices. Speed limits are a separate, unanswered issue. Relevant unsolved physics includes; the sources and mechanisms of inertial frames, coupling of gravitation and electromagnetism, and the nature of the quantum vacuum. The propulsion approaches span mostly stages 1 through 3 of the scientific method (defining the problem, collecting data, and articulating hypotheses), while some have matured to stage 4 (testing hypotheses). Nonviable approaches include `stiction drives,' `gyroscopic antigravity,' and `lifters.' No attempt is made to gauge the prospects of the remaining approaches. Instead, a list of next-step research questions is derived from the examination of these goals, unknowns, and concepts.

Discovering New Variable Stars at Key Stage 3

ERIC Educational Resources Information Center

Chubb, Katy; Hood, Rosie; Wilson, Thomas; Holdship, Jonathan; Hutton, Sarah

2017-01-01

Details of the London pilot of the "Discovery Project" are presented, where university-based astronomers were given the chance to pass on some real and applied knowledge of astronomy to a group of selected secondary school pupils. It was aimed at students in Key Stage 3 of their education, allowing them to be involved in real…

A practical guide to assessing clinical decision-making skills using the key features approach.

PubMed

Farmer, Elizabeth A; Page, Gordon

2005-12-01

This paper in the series on professional assessment provides a practical guide to writing key features problems (KFPs). Key features problems test clinical decision-making skills in written or computer-based formats. They are based on the concept of critical steps or 'key features' in decision making and represent an advance on the older, less reliable patient management problem (PMP) formats. The practical steps in writing these problems are discussed and illustrated by examples. Steps include assembling problem-writing groups, selecting a suitable clinical scenario or problem and defining its key features, writing the questions, selecting question response formats, preparing scoring keys, reviewing item quality and item banking. The KFP format provides educators with a flexible approach to testing clinical decision-making skills with demonstrated validity and reliability when constructed according to the guidelines provided.

Directly Imaged Giant Planets: What Do We Hope to Learn?

NASA Technical Reports Server (NTRS)

Marley, Mark

2015-01-01

As we move into an era when GPI and SPHERE are (hopefully) discovering and characterizing new young giant planets, it is worthwhile to step back and review our science goals for young giant planets. Of course for individual planets we ideally would hope to measure mass, radius, atmospheric composition, temperature, and cloud properties, but how do these characteristics fit into our broader understanding of planetary system origin and evolution theories? In my presentation I will review both the specifics of what we hope to learn from newly discovered young worlds as well as how these characteristics inform our broader understanding of giant planets and planetary systems. Finally I will consider the limitations realistic datasets will place on our ability to understand newly discovered planets, illustrating with data from any new such worlds that are available by the conference date.

Phytophthora ramorum and sudden oak death in California: II. transmission and survival

Treesearch

Jennifer M. Davidson; David M. Rizzo; Matteo Garbelotto; Steven Tjosvold; Garey W. Slaughter

2002-01-01

The newly discovered Phytophthora ramorum canker disease of oak (Sudden Oak Death Syndrome) threatens millions of acres of California woodlands where coast live oak (Quercus agrifolia), tanoak (Lithocarpus densiflorus), or black oak (Quercus kelloggii) are dominant species. An important step in...

Discover Earth

NASA Technical Reports Server (NTRS)

Steele, Colleen

1998-01-01

Discover Earth is a NASA-sponsored project for teachers of grades 5-12, designed to: (1) enhance understanding of the Earth as an integrated system; (2) enhance the interdisciplinary approach to science instruction; and (3) provide classroom materials that focus on those goals. Discover Earth is conducted by the Institute for Global Environmental Strategies in collaboration with Dr. Eric Barron, Director, Earth System Science Center, The Pennsylvania State University; and Dr. Robert Hudson, Chair, the Department of Meteorology, University of Maryland at College Park. The enclosed materials: (1) represent only part of the Discover Earth materials; (2) were developed by classroom teachers who are participating in the Discover Earth project; (3) utilize an investigative approach and on-line data; and (4) can be effectively adjusted to classrooms with greater/without technology access. The Discover Earth classroom materials focus on the Earth system and key issues of global climate change including topics such as the greenhouse effect, clouds and Earth's radiation balance, surface hydrology and land cover, and volcanoes and climate change. All the materials developed to date are available on line at (http://www.strategies.org) You are encouraged to submit comments and recommendations about these materials to the Discover Earth project manager, contact information is listed below. You are welcome to duplicate all these materials.

Extrasolar planets: constraints for planet formation models.

PubMed

Santos, Nuno C; Benz, Willy; Mayor, Michel

2005-10-14

Since 1995, more than 150 extrasolar planets have been discovered, most of them in orbits quite different from those of the giant planets in our own solar system. The number of discovered extrasolar planets demonstrates that planetary systems are common but also that they may possess a large variety of properties. As the number of detections grows, statistical studies of the properties of exoplanets and their host stars can be conducted to unravel some of the key physical and chemical processes leading to the formation of planetary systems.

Experimental Design for the LATOR Mission

NASA Technical Reports Server (NTRS)

Turyshev, Slava G.; Shao, Michael; Nordtvedt, Kenneth, Jr.

2004-01-01

This paper discusses experimental design for the Laser Astrometric Test Of Relativity (LATOR) mission. LATOR is designed to reach unprecedented accuracy of 1 part in 10(exp 8) in measuring the curvature of the solar gravitational field as given by the value of the key Eddington post-Newtonian parameter gamma. This mission will demonstrate the accuracy needed to measure effects of the next post-Newtonian order (near infinity G2) of light deflection resulting from gravity s intrinsic non-linearity. LATOR will provide the first precise measurement of the solar quadrupole moment parameter, J(sub 2), and will improve determination of a variety of relativistic effects including Lense-Thirring precession. The mission will benefit from the recent progress in the optical communication technologies the immediate and natural step above the standard radio-metric techniques. The key element of LATOR is a geometric redundancy provided by the laser ranging and long-baseline optical interferometry. We discuss the mission and optical designs, as well as the expected performance of this proposed mission. LATOR will lead to very robust advances in the tests of Fundamental physics: this mission could discover a violation or extension of general relativity, or reveal the presence of an additional long range interaction in the physical law. There are no analogs to the LATOR experiment; it is unique and is a natural culmination of solar system gravity experiments.

Laboratory information management system for membrane protein structure initiative--from gene to crystal.

PubMed

Troshin, Petr V; Morris, Chris; Prince, Stephen M; Papiz, Miroslav Z

2008-12-01

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.

Uranium isotope separation from 1941 to the present

NASA Astrophysics Data System (ADS)

Maier-Komor, Peter

2010-02-01

Uranium isotope separation was the key development for the preparation of highly enriched isotopes in general and thus became the seed for target development and preparation for nuclear and applied physics. In 1941 (year of birth of the author) large-scale development for uranium isotope separation was started after the US authorities were warned that NAZI Germany had started its program for enrichment of uranium and might have confiscated all uranium and uranium mines in their sphere of influence. Within the framework of the Manhattan Projects the first electromagnetic mass separators (Calutrons) were installed and further developed for high throughput. The military aim of the Navy Department was to develop nuclear propulsion for submarines with practically unlimited range. Parallel to this the army worked on the development of the atomic bomb. Also in 1941 plutonium was discovered and the production of 239Pu was included into the atomic bomb program. 235U enrichment starting with natural uranium was performed in two steps with different techniques of mass separation in Oak Ridge. The first step was gas diffusion which was limited to low enrichment. The second step for high enrichment was performed with electromagnetic mass spectrometers (Calutrons). The theory for the much more effective enrichment with centrifugal separation was developed also during the Second World War, but technical problems e.g. development of high speed ball and needle bearings could not be solved before the end of the war. Spying accelerated the development of uranium separation in the Soviet Union, but also later in China, India, Pakistan, Iran and Iraq. In this paper, the physical and chemical procedures are outlined which lead to the success of the project. Some security aspects and Non-Proliferation measures are discussed.

A new approach to build VPLS with auto-discovery mechanism

NASA Astrophysics Data System (ADS)

Dong, Ximing; Yu, Shaohua

2005-11-01

VPLS is the key technology implemented to provide Layer 2 bridge-like services, connecting dispersed locations to work in a switched LAN over an MPLS backbone. However, implementing VPLS requires creating a complex matrix of services and locations that quickly becomes difficult to configure and maintain. To address this complexity, this paper proposes a new approach to automate the configuration and maintenance of VPLS networks, a node-discovery process in which each router advertises its VPLS-enabled status and capabilities to all other routers. Our approach can be summarized into four steps. (1) Discover other VPLS PE nodes with VPLS capabilities and create the VPLS capable PE routers list. We introduce a finite state machine which includes four states to illustrate the process how a VPLS peer can be discovered and the peer relations be kept alive. (2) Build MPLS LSP tunnels to all the PE routers in the list, according to the advertised VPLS protocol capabilities. (3) Use the lists to create targeted-LDP sessions for VPLS services discovery. (4) VC label assignment. The PE edge routers exchanges messages to define VC labels and bind them with each built PWE. The suggested auto-discovery mechanism is sensitive to any service provider's topology change and customer's service modification. The dynamic process for the FIB building, MAC address learning and withdrawal, is also covered as the result of VPLS auto-discovery. The suggested mechanism can be implemented as a software module and could be seamlessly integrated with currently deployed Metro Ethernet routing and switching platform.

Stuck at work? Quantitative proteomics of environmental wine yeast strains reveals the natural mechanism of overcoming stuck fermentation.

PubMed

Szopinska, Aleksandra; Christ, Eva; Planchon, Sebastien; König, Helmut; Evers, Daniele; Renaut, Jenny

2016-02-01

During fermentation oenological yeast cells are subjected to a number of different stress conditions and must respond rapidly to the continuously changing environment of this harsh ecological niche. In this study we gained more insights into the cell adaptation mechanisms by linking proteome monitoring with knowledge on physiological behaviour of different strains during fermentation under model winemaking conditions. We used 2D-DIGE technology to monitor the proteome evolution of two newly discovered environmental yeast strains Saccharomyces bayanus and triple hybrid Saccharomyces cerevisiae × Saccharomyces kudriavzevii × S. bayanus and compared them to data obtained for the commercially available S. cerevisiae strain. All strains examined showed (i) different fermentative behaviour, (ii) stress resistance as well as (iii) susceptibility to stuck fermentation which was reflected in significant differences in protein expression levels. During our research we identified differentially expressed proteins in 155 gel spots which correspond to 70 different protein functions. Differences of expression between strains were observed mainly among proteins involved in stress response, proteins degradation pathways, cell redox homeostasis and amino acids biosynthesis. Interestingly, the newly discovered triple hybrid S. cerevisiae × S. kudriavzevii × S. bayanus strain which has the ability to naturally restart stuck fermentation showed a very strong induction of expression of two proteolytic enzymes: Pep4 and Prc1 that appear as numerous isoforms on the gel image and which may be the key to its unique properties. This study is an important step towards the better understanding of wine fermentations at a molecular level. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovering functional interdependence relationship in PPI networks for protein complex identification.

PubMed

Lam, Winnie W M; Chan, Keith C C

2012-04-01

Protein molecules interact with each other in protein complexes to perform many vital functions, and different computational techniques have been developed to identify protein complexes in protein-protein interaction (PPI) networks. These techniques are developed to search for subgraphs of high connectivity in PPI networks under the assumption that the proteins in a protein complex are highly interconnected. While these techniques have been shown to be quite effective, it is also possible that the matching rate between the protein complexes they discover and those that are previously determined experimentally be relatively low and the "false-alarm" rate can be relatively high. This is especially the case when the assumption of proteins in protein complexes being more highly interconnected be relatively invalid. To increase the matching rate and reduce the false-alarm rate, we have developed a technique that can work effectively without having to make this assumption. The name of the technique called protein complex identification by discovering functional interdependence (PCIFI) searches for protein complexes in PPI networks by taking into consideration both the functional interdependence relationship between protein molecules and the network topology of the network. The PCIFI works in several steps. The first step is to construct a multiple-function protein network graph by labeling each vertex with one or more of the molecular functions it performs. The second step is to filter out protein interactions between protein pairs that are not functionally interdependent of each other in the statistical sense. The third step is to make use of an information-theoretic measure to determine the strength of the functional interdependence between all remaining interacting protein pairs. Finally, the last step is to try to form protein complexes based on the measure of the strength of functional interdependence and the connectivity between proteins. For performance evaluation, PCIFI was used to identify protein complexes in real PPI network data and the protein complexes it found were matched against those that were previously known in MIPS. The results show that PCIFI can be an effective technique for the identification of protein complexes. The protein complexes it found can match more known protein complexes with a smaller false-alarm rate and can provide useful insights into the understanding of the functional interdependence relationships between proteins in protein complexes.

Presidential Green Chemistry Challenge: 2008 Designing Greener Chemicals Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2008 award winner, Dow AgroSciences, used an artificial neural network to discover spinetoram, an improved spinosad biopesticide to replace organophosphates for key pests of fruit trees.

Human Mission to Europa and Titan - Why Not? Executive Summary

NASA Technical Reports Server (NTRS)

Finarelli, Margaret G.

2005-01-01

Outline a step-by-step Development Plan of the key barriers and their solutions to enable human exploration of the outer solar system. Secondary: Perform a case study which supports and emphasizes the key elements of the Development Plan.

HLA-G/C, miRNAs, and their role in HIV infection and replication.

PubMed

Celsi, Fulvio; Catamo, Eulalia; Kleiner, Giulio; Tricarico, Paola Maura; Vuch, Josef; Crovella, Sergio

2013-01-01

In recent years, a number of different mechanisms regulating gene expressions, either in normal or in pathological conditions, have been discovered. This review aims to highlight some of the regulatory pathways involved during the HIV-1 infection and disease progression, focusing on the novel discovered microRNAs (miRNAs) and their relation with immune system's agents. Human leukocyte antigen (HLA) family of proteins plays a key role because it is a crucial modulator of the immune response; here we will examine recent findings, centering especially on HLA-C and -G, novel players lately discovered to engage in modulation of immune system. We hope to provide novel perspectives useful to find out original therapeutic roads against HIV-1 infection and AIDS progression.

Digital Geogames to Foster Local Biodiversity

ERIC Educational Resources Information Center

Schaal, Sonja; Schaal, Steffen; Lude, Armin

2015-01-01

The valuing of biodiversity is considered to be a first step towards its conservation. Therefore, the aim of the BioDiv2Go project is to combine sensuous experiences discovering biodiversity with mobile technology and a game-based learning approach. Following the competence model for environmental education (Roczen et al, 2014), Geogames (location…

Predictable Charts: An Effective Strategy to Engage and Impact Learners

ERIC Educational Resources Information Center

McClure, Erin

2016-01-01

This article explores how to integrate reading, writing, speaking, and listening instruction by engaging students in Predictable Charts. Discover how Predictable Charts can support students with reading, writing, speaking, and listening in Kindergarten, First Grade, or Special Education classrooms. Through this article, learn the steps to…

Inreach: The Inside Step to Outreach

ERIC Educational Resources Information Center

Germain, Carol Anne

2006-01-01

After undertaking the time and energy consuming task of reference assessment, the library might discover that it needs to tweak delivery of service, weed and update the collection, upgrade workstations, or advance marketing strategies to get patrons to use reference materials and services. Like any other product or service, reference departments…

An Analysis of the Contents and Pedagogy of Al-Kashi's 1427 "Key to Arithmetic" (Miftah Al-Hisab)

ERIC Educational Resources Information Center

Ta'ani, Osama Hekmat

2011-01-01

Al-Kashi's 1427 "Key to Arithmetic" had important use over several hundred years in mathematics teaching in Medieval Islam throughout the time of the Ottoman Empire. Its pedagogical features have never been studied before. In this dissertation I have made a close pedagogical analysis of these features and discovered several teaching…

Live Cell Imaging Confocal Microscopy Analysis of HBV Myr-PreS1 Peptide Binding and Uptake in NTCP-GFP Expressing HepG2 Cells.

PubMed

König, Alexander; Glebe, Dieter

2017-01-01

To obtain basic knowledge about specific molecular mechanisms involved in the entry of pathogens into cells is the basis for establishing pharmacologic substances blocking initial viral binding, infection, and subsequent viral spread. Lack of information about key cellular factors involved in the initial steps of HBV infection has hampered the characterization of HBV binding and entry for decades. However, recently, the liver-specific sodium-dependent taurocholate cotransporting polypeptide (NTCP) has been discovered as a functional receptor for HBV and HDV, thus opening the field for new concepts of basic binding and entry of HBV and HDV. Here, we describe practical issues of a basic in vitro assay system to examine kinetics and mechanisms of receptor-dependent HBV binding, uptake, and intracellular trafficking by live-cell imaging confocal microscopy. The assay system is comprised of HepG2 cells expressing a NTCP-GFP fusion-protein and chemically synthesized, fluorophore-labeled part of HBV surface protein, spanning the first N-terminal 48 amino acids of preS1 of the large hepatitis B virus surface protein.

Marketing health educators to employers: survey findings, interpretations, and considerations for the profession.

PubMed

Gambescia, Stephen F; Cottrell, Randall R; Capwell, Ellen; Auld, M Elaine; Mullen Conley, Kathleen; Lysoby, Linda; Goldsmith, Malcolm; Smith, Becky

2009-10-01

In July 2007, a market research report was produced by Hezel Associates on behalf of five sponsoring health education profession member organizations and the National Commission for Health Education Credentialing. The purpose of the survey was to learn about current or potential employers' knowledge, attitudes, and behaviors toward health educators and the health education profession and their future hiring practices. This article presents the background leading up to the production of this report, the major findings of the survey of employers, recommendations from the market research group regarding core messages, and implications for the profession having discovered for the first time information about employers' understanding of professionally prepared health educators. The article discusses the umbrella and key messages that may be incorporated into a marketing plan and other recommendations by the firm that should assist health educators in marketing the profession. Furthermore, this article presents reactions by leaders in this field to these messages and recommendations and concludes with next steps in this project and a call for the overall need to market the profession of health education.

Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.

PubMed

Israeli, Hadar; Cohen-Dvashi, Hadas; Shulman, Anastasiya; Shimon, Amir; Diskin, Ron

2017-04-01

Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.

RAPSearch: a fast protein similarity search tool for short reads

PubMed Central

2011-01-01

Background Next Generation Sequencing (NGS) is producing enormous corpuses of short DNA reads, affecting emerging fields like metagenomics. Protein similarity search--a key step to achieve annotation of protein-coding genes in these short reads, and identification of their biological functions--faces daunting challenges because of the very sizes of the short read datasets. Results We developed a fast protein similarity search tool RAPSearch that utilizes a reduced amino acid alphabet and suffix array to detect seeds of flexible length. For short reads (translated in 6 frames) we tested, RAPSearch achieved ~20-90 times speedup as compared to BLASTX. RAPSearch missed only a small fraction (~1.3-3.2%) of BLASTX similarity hits, but it also discovered additional homologous proteins (~0.3-2.1%) that BLASTX missed. By contrast, BLAT, a tool that is even slightly faster than RAPSearch, had significant loss of sensitivity as compared to RAPSearch and BLAST. Conclusions RAPSearch is implemented as open-source software and is accessible at http://omics.informatics.indiana.edu/mg/RAPSearch. It enables faster protein similarity search. The application of RAPSearch in metageomics has also been demonstrated. PMID:21575167

A basic plasma test for gyrokinetics: GDC turbulence in LAPD

NASA Astrophysics Data System (ADS)

Pueschel, M. J.; Rossi, G.; Told, D.; Terry, P. W.; Jenko, F.; Carter, T. A.

2017-02-01

Providing an important step towards validating gyrokinetics under comparatively little-explored conditions, simulations of pressure-gradient-driven plasma turbulence in the Large Plasma Device (LAPD) are compared with experimental observations. The corresponding signatures confirm the existence of a novel regime of turbulence, based on the recently-discovered gradient-driven drift coupling (GDC) instability, which is thus confirmed as a candidate mechanism for turbulence in basic, space and astrophysical plasmas. Despite the limitations of flux-tube gyrokinetics for this scenario, when accounting for box size scaling by applying a scalar factor η =6, agreement between simulations and experiment improves to within a factor of two for key observables: compressional magnetic, density, and temperature fluctuations, both in amplitude and structure. Thus, a first, strong indication is presented that the GDC instability seen in gyrokinetics appears to operate in the experiment and that the essential instability physics is present in the numerical model. Overall, the gyrokinetic framework and its numerical implementation in the Gene code therefore perform well for LAPD plasmas very different from their brethren in fusion experiments.

Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct states responsible for multi-timescale photosynthetic photoprotection

NASA Astrophysics Data System (ADS)

Kondo, Toru; Pinnola, Alberta; Chen, Wei Jia; Dall'Osto, Luca; Bassi, Roberto; Schlau-Cohen, Gabriela S.

2017-08-01

In oxygenic photosynthesis, light harvesting is regulated to safely dissipate excess energy and prevent the formation of harmful photoproducts. Regulation is known to be necessary for fitness, but the molecular mechanisms are not understood. One challenge has been that ensemble experiments average over active and dissipative behaviours, preventing identification of distinct states. Here, we use single-molecule spectroscopy to uncover the photoprotective states and dynamics of the light-harvesting complex stress-related 1 (LHCSR1) protein, which is responsible for dissipation in green algae and moss. We discover the existence of two dissipative states. We find that one of these states is activated by pH and the other by carotenoid composition, and that distinct protein dynamics regulate these states. Together, these two states enable the organism to respond to two types of intermittency in solar intensity—step changes (clouds and shadows) and ramp changes (sunrise), respectively. Our findings reveal key control mechanisms underlying photoprotective dissipation, with implications for increasing biomass yields and developing robust solar energy devices.

Modeling perceived stress via HRV and accelerometer sensor streams.

PubMed

Wu, Min; Cao, Hong; Nguyen, Hai-Long; Surmacz, Karl; Hargrove, Caroline

2015-08-01

Discovering and modeling of stress patterns of human beings is a key step towards achieving automatic stress monitoring, stress management and healthy lifestyle. As various wearable sensors become popular, it becomes possible for individuals to acquire their own relevant sensory data and to automatically assess their stress level on the go. Previous studies for stress analysis were conducted in the controlled laboratory and clinic settings. These studies are not suitable for stress monitoring in one's daily life as various physical activities may affect the physiological signals. In this paper, we address such issue by integrating two modalities of sensors, i.e., HRV sensors and accelerometers, to monitor the perceived stress levels in daily life. We gathered both the heart and the motion data from 8 participants continuously for about 2 weeks. We then extracted features from both sensory data and compared the existing machine learning methods for learning personalized models to interpret the perceived stress levels. Experimental results showed that Bagging classifier with feature selection is able to achieve a prediction accuracy 85.7%, indicating our stress monitoring on daily basis is fairly practical.

Discovering the infectome of human endothelial cells challenged with Aspergillus fumigatus applying a mass spectrometry label-free approach.

PubMed

Curty, N; Kubitschek-Barreira, P H; Neves, G W; Gomes, D; Pizzatti, L; Abdelhay, E; Souza, G H M F; Lopes-Bezerra, L M

2014-01-31

Blood vessel invasion is a key feature of invasive aspergillosis. This angioinvasion process contributes to tissue thrombosis, which can impair the access of leukocytes and antifungal drugs to the site of infection. It has been demonstrated that human umbilical vein endothelial cells (HUVECs) are activated and assume a prothrombotic phenotype following contact with Aspergillus fumigatus hyphae or germlings, a process that is independent of fungus viability. However, the molecular mechanisms by which this pathogen can activate endothelial cells, together with the endothelial pathways that are involved in this process, remain unknown. Using a label-free approach by High Definition Mass Spectrometry (HDMS(E)), differentially expressed proteins were identified during HUVEC-A. fumigatus interaction. Among these, 89 proteins were determined to be up- or down-regulated, and another 409 proteins were exclusive to one experimental condition: the HUVEC control or HUVEC:AF interaction. The in silico predictions provided a general view of which biological processes and/or pathways were regulated during HUVEC:AF interaction, and they mainly included cell signaling, immune response and hemostasis pathways. This work describes the first global proteomic analysis of HUVECs following interaction with A. fumigatus germlings, the fungus morphotype that represents the first step of invasion and dissemination within the host. A. fumigatus causes the main opportunistic invasive fungal infection related to neutropenic hematologic patients. One of the key steps during the establishment of invasive aspergillosis is angioinvasion but the mechanism associated with the interaction of A. fumigatus with the vascular endothelium remains unknown. The identification of up- and down-regulated proteins expressed by human endothelial cells in response to the fungus infection can contribute to reveal the mechanism of endothelial response and, to understand the physiopathology of this high mortality disease. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. © 2013 Elsevier B.V. All rights reserved.

Genetic risk prediction and neurobiological understanding of alcoholism.

PubMed

Levey, D F; Le-Niculescu, H; Frank, J; Ayalew, M; Jain, N; Kirlin, B; Learman, R; Winiger, E; Rodd, Z; Shekhar, A; Schork, N; Kiefer, F; Kiefe, F; Wodarz, N; Müller-Myhsok, B; Dahmen, N; Nöthen, M; Sherva, R; Farrer, L; Smith, A H; Kranzler, H R; Rietschel, M; Gelernter, J; Niculescu, A B

2014-05-20

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n=135 genes, 713 SNPs) were used to generate a Genetic Risk Prediction Score (GRPS), which showed a trend towards significance (P=0.053) in separating alcohol-dependent individuals from controls in an independent German test cohort. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P=0.00012) and one with alcohol abuse (a less severe form of alcoholism; P=0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P=0.000013) and the alcohol abuse cohort (P=0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape.

Observation of X-rays from long laboratory negative discharge in STP air

NASA Astrophysics Data System (ADS)

Kochkin, Pavlo; van Deursen, A. P. J.; Ebert, Ute

2014-05-01

Pulses of x-rays emitted by lightning are one of the most intriguing among unsolved problem in physics of lightning. They have been detected from both - natural and rocket-triggered lightning. In natural lightning x-rays were detected during stepped leader process and later were associated with a single step. In triggered lighting x-rays were found to be originated from a tip of a dart leader that also possesses stepping propagation mechanism. Therefore, stepping mechanism is the key to understanding the x-ray pulses generated by lightning. Unfortunately, leader stepping mechanism itself is far from well understood. Negative long laboratory discharges also develop through a formation of a space stem/leader and they also generate bursts of x-ray radiation. In this study we investigate the development of a long negative laboratory spark in particular focusing on its x-ray emission. A 2 MV Marx generator delivers high-voltage standard lightning pulse with 1.2/50 microsec rise/fall time to a spark gap with conical electrodes. The distance between cone tips was varied between 1 m and 1.75 m. An upper voltage limit is set to about 1 MV level. The voltage is measured by capacitive high-voltage divider. Two Pearson 7427 current probes determine the currents through high-voltage and grounded electrodes. Two LaBr3 scintillator detectors were mounted in EMC-cabinets and recorded the x-rays. Picos4 Stanford Optics camera with intensified CCD is placed in 4 m distance from the spark gap and directed perpendicular to the spark plane. The camera allows us to make ns-fast images of pre-breakdown phenomena in controllable time. We discovered new details of space stem/leader formation and development in long laboratory sparks. The connection moment of positive part of the space stem/leader to negative high-voltage is accompanied by intense x-ray emission. Taking into account our previous study on positive discharge, we conclude that encounter between positive and negative streamers is the most likely mechanism responsible for the x-rays.

Probing the transcriptome of Aconitum carmichaelii reveals the candidate genes associated with the biosynthesis of the toxic aconitine-type C19-diterpenoid alkaloids.

PubMed

Zhao, Dake; Shen, Yong; Shi, Yana; Shi, Xingqiao; Qiao, Qin; Zi, Shuhui; Zhao, Erqiang; Yu, Diqiu; Kennelly, Edward J

2018-05-11

Aconitum carmichaelii has long been used as a traditional Chinese medicine, and its processed lateral roots are known commonly as fuzi. Aconitine-type C 19 -diterpenoid alkaloids accumulating in the lateral roots are some of the main toxicants of this species, yet their biosynthesis remains largely unresolved. As a first step towards understanding the biosynthesis of aconitine-type C 19 -diterpenoid alkaloids, we performed de novo transcriptome assembly and analysis of rootstocks and leaf tissues of Aconitum carmichaelii by next-generation sequencing. A total of 525 unigene candidates were identified as involved in the formation of C 19 -diterpenoid alkaloids, including those encoding enzymes in the early steps of diterpenoid alkaloids scaffold biosynthetic pathway, such as ent-copalyl diphosphate synthases, ent-kaurene synthases, kaurene oxidases, cyclases, and key aminotransferases. Furthermore, candidates responsible for decorating of diterpenoid alkaloid skeletons were discovered from transcriptome sequencing of fuzi, such as monooxygenases, methyltransferase, and BAHD acyltransferases. In addition, 645 differentially expressed genes encoding transcription factors potentially related to diterpenoid alkaloids accumulation underground were documented. Subsequent modular domain structure phylogenetics and differential expression analysis led to the identification of BAHD acyltransferases possibly involved in the formation of acetyl and benzoyl esters of diterpenoid alkaloids, associated with the acute toxicity of fuzi. The transcriptome data provide the foundation for future research into the molecular basis for aconitine-type C 19 -diterpenoid alkaloids biosynthesis in A. carmichaelii. Copyright © 2018. Published by Elsevier Ltd.

Post-processing techniques to enhance reliability of assignment algorithm based performance measures : [technical summary].

DOT National Transportation Integrated Search

2011-01-01

Travel demand modeling plays a key role in the transportation system planning and evaluation process. The four-step sequential travel demand model is the most widely used technique in practice. Traffic assignment is the key step in the conventional f...

Efficiency Vermont - Embedding energy efficiency into low-income programs and services

EPA Pesticide Factsheets

Discover the key features, approaches, partners, funding sources, and achievements of the Efficiency Vermont program and how it has been able to reach nearly one-half of the state’s low-income population.

Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data.

PubMed

Cui, Lu; Wang, Yu; Liu, Zhihong; Chen, Hongzhuan; Wang, Hao; Zhou, Xinxin; Xu, Jun

2015-11-23

Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed.

Investigation of Pre-Service English Language Teachers' Cognitive Structures about Some Key Concepts in Approaches and Methods in Language Teaching Course through Word Association Test

ERIC Educational Resources Information Center

Ersanli, Ceylan Yangin

2016-01-01

This study aims to map the cognitive structure of pre-service English language (EL) teachers about three key concepts related to approaches and methods in language teaching so as to discover their learning process and misconceptions. The study involves both qualitative and quantitative data. The researcher administrated a Word Association Test…

Overcoming Computer Anxiety: A Three-Step Process for Adult Learners

ERIC Educational Resources Information Center

Sivakumaran, Thillainatarajan; Lux, Allison C.

2011-01-01

Many adult learners returning to school later in life have discovered that technology is heavily embedded in the learning environment. Learning both course contents and technology in unison can be a daunting task for students who feel intimidated by technology. Computer anxiety is a term that describes resistance, fear or anxieties towards…

Stepping outside My Technology Classroom Box (My Summer RET Experience)

ERIC Educational Resources Information Center

Carter, Terry

2008-01-01

In this article, the author shares his summer RET (Research Experience for Teachers) experience. The author describes how his anxiety turned to excitement and anticipation upon entering the college campus in search of new knowledge. He discovered that working side by side with experts in a research facility was so much fun.

Every Teacher Carries a Leadership Wand

ERIC Educational Resources Information Center

Tubin, Dorit

2017-01-01

Turnaround schools require empowered teachers to discover their leadership wand. Based on a case study conducted on BART Charter School, this article highlights five steps for leaders who wish to empower their teachers and allow them to lead their schools to success: (1) Let your people know; (2) Nominate the fittest, (3) Connect teachers to a…

4 Steps to Combat Malware Enterprisewide

ERIC Educational Resources Information Center

Zeltser, Lenny

2011-01-01

Too often, organizations make the mistake of treating malware infections as a series of independent occurrences. Each time a malicious program is discovered, IT simply cleans up or rebuilds the affected host, and then moves on with routine operational tasks. Yet, this approach doesn't allow the institution to keep up with the increasingly…

Professional Learning in the Digital Age: The Educator's Guide to User-Generated Learning

ERIC Educational Resources Information Center

Swanson, Kristen

2013-01-01

Discover how to transform your professional development and become a truly connected educator with user-generated learning! This book shows educators how to enhance their professional learning using practical tools, strategies, and online resources. With beginner-friendly, real-world examples and simple steps to get started, the author shows how…

DNA sequences of Pima (Gossypium barbadense L.) cotton leaf for examining transcriptome diversity and SNP biomarker discovery

USDA-ARS?s Scientific Manuscript database

As an initial step to explore the transcriptome genetic diversity and to discover single nucleotide polymorphic (SNP)-biomarkers for marker assisted breeding within Pima (Gossypium barbadense L.) cotton, leaves from 25 day plants of three diverse genotypes were used to develop cDNA libraries. Using ...

Your 3-Step Plan to Stopping Childhood Bullying

ERIC Educational Resources Information Center

Exceptional Parent, 2007

2007-01-01

Bullying can happen to any child, especially one who is perceived as "different" or who isn't prepared to respond effectively. Children with disabilities can be especially vulnerable to bullying; in fact, sometimes children are bullied specifically because of their disability. Upon discovering that their child is being bullied, parents often feel…

Measuring the Influences That Affect Technological Literacy in Rhode Island High Schools

ERIC Educational Resources Information Center

Walach, Michael

2015-01-01

This study sampled the current state of technological literacy in Rhode Island high schools using a new instrument, the Technological Literacy Assessment, which was developed for this study. Gender inequalities in technological literacy were discovered, and possible causes and solutions are presented. This study suggests possible next steps for…

The customer-centered innovation map.

PubMed

Bettencourt, Lance A; Ulwick, Anthony W

2008-05-01

We all know that people "hire" products and services to get a job done. Surgeons hire scalpels to dissect soft tissue. Janitors hire soap dispensers and paper towels to remove grime from their hands. To find ways to innovate, it's critical to deconstruct the job the customer is trying to get done from beginning to end, to gain a complete view of all the points at which a customer might desire more help from a product or service. A methodology called job mapping helps companies analyze the biggest drawbacks of the products and services customers currently use and discover opportunities for innovation. It involves breaking down the task the customer wants to accomplish into the eight universal steps of a job: (1) defining the objectives, (2) locating the necessary inputs, (3) preparing the physical environment, (4) confirming that everything is ready, (5) executing the task, (6) monitoring its progress, (7) making modifications as necessary, and (8) concluding the job. Job mapping differs substantively from process mapping in that the goal is to identify what customers are trying to get done at every step, not what they are doing currently. For example, when an anesthesiologist checks a monitor during a surgical procedure, the action taken is just a means to the end. Detecting a change in patient vital signs is the job the doctor is trying to get done. Within each of the discrete steps lie multiple opportunities for making the job simpler, easier, or faster. By mapping out every step of the job and locating those opportunities, companies can discover new ways to differentiate their offerings.

CAN INFANTS BE “TAUGHT” TO ATTEND TO A NEW PHYSICAL VARIABLE IN AN EVENT CATEGORY? THE CASE OF HEIGHT IN COVERING EVENTS

PubMed Central

Wang, Su-hua; Baillargeon, Renée

2009-01-01

As they observe or produce events, infants identify variables that help them predict outcomes in each category of events. How do infants identify a new variable? An explanation-based learning (EBL) account suggests three essential steps: (1) observing contrastive outcomes relevant to the variable; (2) discovering the conditions associated with these outcomes; and (3) generating an explanation for the condition-outcome regularity discovered. In Experiments 1–3, 9-month-old infants watched events designed to “teach” them the variable height in covering events. After watching these events, designed in accord with the EBL account, the infants detected a height violation in a covering event, three months earlier than they ordinarily would have. In Experiments 4–6, the “teaching” events were modified to remove one of the EBL steps, and the infants no longer detected the height violation. The present findings thus support the EBL account and help specify the processes by which infants acquire their physical knowledge. PMID:18177635

Melanin fluorescence spectra by step-wise three photon excitation

NASA Astrophysics Data System (ADS)

Lai, Zhenhua; Kerimo, Josef; DiMarzio, Charles A.

2012-03-01

Melanin is the characteristic chromophore of human skin with various potential biological functions. Kerimo discovered enhanced melanin fluorescence by stepwise three-photon excitation in 2011. In this article, step-wise three-photon excited fluorescence (STPEF) spectrum between 450 nm -700 nm of melanin is reported. The melanin STPEF spectrum exhibited an exponential increase with wavelength. However, there was a probability of about 33% that another kind of step-wise multi-photon excited fluorescence (SMPEF) that peaks at 525 nm, shown by previous research, could also be generated using the same process. Using an excitation source at 920 nm as opposed to 830 nm increased the potential for generating SMPEF peaks at 525 nm. The SMPEF spectrum peaks at 525 nm photo-bleached faster than STPEF spectrum.

EPA Monthly Key Performance Indicator Dashboards 2018

EPA Pesticide Factsheets

2018 reports are added each month, which measure how well EPA web content is meeting three performance goals: increases in how much users consume content, are able to find or discover what they need, and their level of engagement.

Indoor airPLUS Videos, Podcasts, Webinars and Interviews

EPA Pesticide Factsheets

The Webinar presentations will help you discover how Indoor airPLUS homes are designed to improve indoor air quality and increase energy efficiency and learn about the key design and construction features included in Indoor airPLUS homes.

Early road location : the key to discovering historic resources?.

DOT National Transportation Integrated Search

1980-01-01

The paper describes a unique methodology used in surveying and documenting architecture along eighteenth century road systems in Virginia which could be used as a prototype in other areas. In the method described the historian geographer, and archite...

Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

PubMed

Qiao, Xue; Lin, Xiong-hao; Ji, Shuai; Zhang, Zheng-xiang; Bo, Tao; Guo, De-an; Ye, Min

2016-01-05

To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

School Climate Improvement Action Guide for District Leaders. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that district leaders--including superintendents, assistant superintendents, directors of student support services, or others--can take to support school climate improvements. Key action steps are provided for…

Finding your next core business.

PubMed

Zook, Chris

2007-04-01

How do you know when your core needs to change? And how do you determine what should replace it? From an in-depth study of 25 companies, the author, a strategy consultant, has discovered that it's possible to measure the vitality of a business's core. If it needs reinvention, he says, the best course is to mine hidden assets. Some of the 25 companies were in deep crisis when they began the process of redefining themselves. But, says Zook, management teams can learn to recognize early signs of erosion. He offers five diagnostic questions with which to evaluate the customers, key sources of differentiation, profit pools, capabilities, and organizational culture of your core business. The next step is strategic regeneration. In four-fifths of the companies Zook examined, a hidden asset was the centerpiece of the new strategy. He provides a map for identifying the hidden assets in your midst, which tend to fall into three categories: undervalued business platforms, untapped insights into customers, and underexploited capabilities. The Swedish company Dometic, for example, was manufacturing small absorption refrigerators for boats and RVs when it discovered a hidden asset: its understanding of, and access to, customers in the RV market. The company took advantage of a boom in that market to refocus on complete systems for live-in vehicles. The Danish company Novozymes, which produced relatively low-tech commodity enzymes such as those used in detergents, realized that its underutilized biochemical capability in genetic and protein engineering was a hidden asset and successfully refocused on creating bioengineered specialty enzymes. Your next core business is not likely to announce itself with fanfare. Use the author's tools to conduct an internal audit of possibilities and pinpoint your new focus.

Joint association discovery and diagnosis of Alzheimer's disease by supervised heterogeneous multiview learning.

PubMed

Zhe, Shandian; Xu, Zenglin; Qi, Yuan; Yu, Peng

2014-01-01

A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety of approaches, they are tightly coupled due to their common biological basis. We hypothesize that the two tasks can potentially benefit each other by a joint analysis, because (i) the association study discovers correlated biomarkers from different data sources, which may help improve diagnosis accuracy, and (ii) the disease status may help identify disease-sensitive associations between genetic variations and MRI features. Based on this hypothesis, we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels based on Gaussian process ordinal regression; in return, the disease status is used to guide the discovery of relationships between the data sources. The sparse projection matrices not only reveal the associations but also select groups of biomarkers related to AD. To learn the model from data, we develop an efficient variational expectation maximization algorithm. Simulation results demonstrate that our approach achieves higher accuracy in both predicting ordinal labels and discovering associations between data sources than alternative methods. We apply our approach to an imaging genetics dataset of AD. Our joint analysis approach not only identifies meaningful and interesting associations between genetic variations, brain structures, and AD status, but also achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods.

A deep learning framework for modeling structural features of RNA-binding protein targets

PubMed Central

Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang

2016-01-01

RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https://github.com/thucombio/deepnet-rbp. PMID:26467480

The Kepler Data Processing Handbook: A Field Guide to Prospecting for Habitable Worlds

NASA Technical Reports Server (NTRS)

Jenkins, Jon M.

2017-01-01

The Kepler telescope hurtled into orbit in March 2009, initiating NASA's first mission to discover Earth-size planets orbiting Sun-like stars. Kepler simultaneously collected data for approximately 165,000 target stars at a time over its four-year mission, identifying over 4700 planet candidates, over 2300 confirmed or validated planets, and over 2100 eclipsing binaries. While Kepler was designed to discover exoplanets, the long-term, ultrahigh photometric precision measurements it achieved made it a premier observational facility for stellar astrophysics, especially in the field of asteroseismology, and for variable stars, such as RR Lyrae. The Kepler Science Operations Center (SOC) was developed at NASA Ames Research Center to process the data acquired by Kepler from pixel-level calibrations all the way to identifying transiting planet signatures and subjecting them to a suite of diagnostic tests to establish or break confidence in their planetary nature. Detecting small, rocky planets transiting Sun-like stars presents a variety of daunting challenges, including achieving an unprecedented photometric precision of 20 ppm on 6.5-hour timescales, and supporting the science operations, management, processing, and repeated reprocessing of the accumulating data stream. A newly revised and expanded version of the Kepler Data Processing Handbook (KDPH) has been released to support the legacy archival products. The KDPH details the theory, design and performance of the algorithms supporting each data processing step. This paper presents an overview of the KDPH and features illustrations of several key algorithms in the Kepler Science Data Processing Pipeline. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

Sucrose synthase: A unique glycosyltransferase for biocatalytic glycosylation process development.

PubMed

Schmölzer, Katharina; Gutmann, Alexander; Diricks, Margo; Desmet, Tom; Nidetzky, Bernd

2016-01-01

Sucrose synthase (SuSy, EC 2.4.1.13) is a glycosyltransferase (GT) long known from plants and more recently discovered in bacteria. The enzyme catalyzes the reversible transfer of a glucosyl moiety between fructose and a nucleoside diphosphate (NDP) (sucrose+NDP↔NDP-glucose+fructose). The equilibrium for sucrose conversion is pH dependent, and pH values between 5.5 and 7.5 promote NDP-glucose formation. The conversion of a bulk chemical to high-priced NDP-glucose in a one-step reaction provides the key aspect for industrial interest. NDP-sugars are important as such and as key intermediates for glycosylation reactions by highly selective Leloir GTs. SuSy has gained renewed interest as industrially attractive biocatalyst, due to substantial scientific progresses achieved in the last few years. These include biochemical characterization of bacterial SuSys, overproduction of recombinant SuSys, structural information useful for design of tailor-made catalysts, and development of one-pot SuSy-GT cascade reactions for production of several relevant glycosides. These advances could pave the way for the application of Leloir GTs to be used in cost-effective processes. This review provides a framework for application requirements, focusing on catalytic properties, heterologous enzyme production and reaction engineering. The potential of SuSy biocatalysis will be presented based on various biotechnological applications: NDP-sugar synthesis; sucrose analog synthesis; glycoside synthesis by SuSy-GT cascade reactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Mathematics in Early Childhood Education: Revolution or Evolution?

ERIC Educational Resources Information Center

Stipek, Deborah

2013-01-01

Hachey (2013) aptly describes a recent surge in attention to mathematics for young children. The value of math for children as young as preschool age, however, was discovered before the 21st century. This is presently not a revolution but rather a potentially important step in an evolution of work that began at least a half century ago. Some…

The Step to Rationality: The Efficacy of Thought Experiments in Science, Ethics, and Free Will

ERIC Educational Resources Information Center

Shepard, Roger N.

2008-01-01

Examples from Archimedes, Galileo, Newton, Einstein, and others suggest that fundamental laws of physics were--or, at least, could have been--discovered by experiments performed not in the physical world but only in the mind. Although problematic for a strict empiricist, the evolutionary emergence in humans of deeply internalized implicit…

Silly Science: Strange and Startling Projects To Amaze Your Family and Friends.

ERIC Educational Resources Information Center

Levine, Shar; Johnstone, Leslie

This book is a collection of 28 experiments that are not meant to have any practical purpose. Each experiment, however, illustrates a scientific principle and enables students to discover how scientific facts and theories apply to seemingly useless experiments. Each experiment includes a list of materials, a series of steps, an explanation of the…

It Won't Happen to Me: The Role of Optimistic Bias in African-American Teens' Risky Sexual Practices.

ERIC Educational Resources Information Center

Chapin, John

Discovering why adolescents take sexual risks, despite knowledge of consequences, is a vital first step in combating the problem. Optimistic bias, the misperception that one is less likely than others to experience negative consequences from health behaviors, offers a promising explanation for adolescents' sexual risk-taking. Unfortunately,…

Discovering the Two-Step Lag Behavioral Patterns of Learners in the College SPOC Platform

ERIC Educational Resources Information Center

Liu, Zhi; Cheng, Hercy N. H.; Liu, Sanya; Sun, Jianwen

2017-01-01

Due to high retention rates, small private online course (SPOC) has become increasingly popular among universities. However, existing analyses of learning behavioral patterns in SPOC remain extremely lacking. This present study conducts an empirical analysis on the behavioral patterns of 12,517 undergraduates engaging in a college's SPOC platform,…

Sequencing Genetics Information: Integrating Data into Information Literacy for Undergraduate Biology Students

ERIC Educational Resources Information Center

MacMillan, Don

2010-01-01

This case study describes an information literacy lab for an undergraduate biology course that leads students through a range of resources to discover aspects of genetic information. The lab provides over 560 students per semester with the opportunity for hands-on exploration of resources in steps that simulate the pathways of higher-level…

Fourteen Steps to More Effective Cash Flow Management

ERIC Educational Resources Information Center

Neugebauer, Roger

2004-01-01

Managing cash flow is an incredibly important skill for a center director. Even a center with an annual budget showing a healthy surplus may experience brief periods where funds in the checkbook are insufficient to pay all the bills. To discover how successful directors manage cash flow in tight times, the author surveyed members of the "Exchange…

Screening individual hybridomas by microengraving to discover monoclonal antibodies

PubMed Central

Ogunniyi, Adebola O; Story, Craig M; Papa, Eliseo; Guillen, Eduardo; Love, J Christopher

2014-01-01

The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (~105 cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1–3 d (9–12 d including the steps for preparing arrays of microwells). PMID:19528952

Genetic risk prediction and neurobiological understanding of alcoholism

PubMed Central

Levey, D F; Le-Niculescu, H; Frank, J; Ayalew, M; Jain, N; Kirlin, B; Learman, R; Winiger, E; Rodd, Z; Shekhar, A; Schork, N; Kiefe, F; Wodarz, N; Müller-Myhsok, B; Dahmen, N; Nöthen, M; Sherva, R; Farrer, L; Smith, A H; Kranzler, H R; Rietschel, M; Gelernter, J; Niculescu, A B

2014-01-01

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P=0.00012) and one with alcohol abuse (a less severe form of alcoholism; P=0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P=0.000013) and the alcohol abuse cohort (P=0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape. PMID:24844177

RNA splicing process analysis for identifying antisense oligonucleotide inhibitors with padlock probe-based isothermal amplification.

PubMed

Ren, Xiaojun; Deng, Ruijie; Wang, Lida; Zhang, Kaixiang; Li, Jinghong

2017-08-01

RNA splicing, which mainly involves two transesterification steps, is a fundamental process of gene expression and its abnormal regulation contributes to serious genetic diseases. Antisense oligonucleotides (ASOs) are genetic control tools that can be used to specifically control genes through alteration of the RNA splicing pathway. Despite intensive research, how ASOs or various other factors influence the multiple processes of RNA splicing still remains obscure. This is largely due to an inability to analyze the splicing efficiency of each step in the RNA splicing process with high sensitivity. We addressed this limitation by introducing a padlock probe-based isothermal amplification assay to achieve quantification of the specific products in different splicing steps. With this amplified assay, the roles that ASOs play in RNA splicing inhibition in the first and second steps could be distinguished. We identified that 5'-ASO could block RNA splicing by inhibiting the first step, while 3'-ASO could block RNA splicing by inhibiting the second step. This method provides a versatile tool for assisting efficient ASO design and discovering new splicing modulators and therapeutic drugs.

School Climate Improvement Action Guide for Instructional Staff. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that instructional staff--including teachers, paraprofessionals, and others in the classroom who provide instruction or assistance--can take to support school climate improvements. Key action steps are provided…

School Climate Improvement Action Guide for School Leaders. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps that school leaders--including principals, assistant/vice principals, and building leaders--can take to support school climate improvements. Key action steps are provided for the following strategies: (1)…

School Climate Improvement Action Guide for Working with Students. School Climate Improvement Resource Package

ERIC Educational Resources Information Center

National Center on Safe Supportive Learning Environments, 2017

2017-01-01

Improving school climate takes time and commitment from a variety of people in a variety of roles. This document outlines key action steps to engage students in the school climate improvement process. Key action steps are provided for the following strategies: (1) Participate in planning for school climate improvements; (2) Engage stakeholders in…

A MOLECULAR APPROACH TO UNDERSTAND HARMFUL ALGAL BLOOMS

EPA Science Inventory

With the upcoming release of a fully sequenced genome, we have an unprecedented opportunity to discover how a HAB organism responds to nutrient loading and the cellular mechanisms underlying those responses. This project will provide key regulation data to help identify transc...

Kepler's Third Law and NASA's "Kepler Mission"

ERIC Educational Resources Information Center

Gould, Alan; Komatsu, Toshi; DeVore, Edna; Harman, Pamela; Koch, David

2015-01-01

NASA's "Kepler Mission" has been wildly successful in discovering exoplanets. This paper summarizes the mission goals, briefly explains the transit method of finding exoplanets and design of the mission, provides some key findings, and describes useful education materials available at the "Kepler" website.

Algorithmic and heuristic processing of information by the nervous system.

PubMed

Restian, A

1980-01-01

Starting from the fact that the nervous system must discover the information it needs, the author describes the way it decodes the received message. The logical circuits of the nervous system, submitting the received signals to a process by means of which information brought is discovered step by step, participates in decoding the message. The received signals, as information, can be algorithmically or heuristically processed. Algorithmic processing is done according to precise rules, which must be fulfilled step by step. By algorithmic processing, one develops somatic and vegetative reflexes as blood pressure, heart frequency or water metabolism control. When it does not dispose of precise rules of information processing or when algorithmic processing needs a very long time, the nervous system must use heuristic processing. This is the feature that differentiates the human brain from the electronic computer that can work only according to some extremely precise rules. The human brain can work according to less precise rules because it can resort to trial and error operations, and because it works according to a form of logic. Working with superior order signals which represent the class of all inferior type signals from which they begin, the human brain need not perform all the operations that it would have to perform by superior type of signals. Therefore the brain tries to submit the received signals to intensive as possible superization. All informational processing, and especially heuristical processing, is accompanied by a certain affective color and the brain cannot operate without it. Emotions, passions and sentiments usually complete the lack of precision of the heuristical programmes. Finally, the author shows that informational and especially heuristical processes study can contribute to a better understanding of the transition from neurological to psychological activity.

Roughness and uniformity improvements on self-aligned quadruple patterning technique for 10nm node and beyond by wafer stress engineering

NASA Astrophysics Data System (ADS)

Liu, Eric; Ko, Akiteru; O'Meara, David; Mohanty, Nihar; Franke, Elliott; Pillai, Karthik; Biolsi, Peter

2017-05-01

Dimension shrinkage has been a major driving force in the development of integrated circuit processing over a number of decades. The Self-Aligned Quadruple Patterning (SAQP) technique is widely adapted for sub-10nm node in order to achieve the desired feature dimensions. This technique provides theoretical feasibility of multiple pitch-halving from 193nm immersion lithography by using various pattern transferring steps. The major concept of this approach is to a create spacer defined self-aligned pattern by using single lithography print. By repeating the process steps, double, quadruple, or octuple are possible to be achieved theoretically. In these small architectures, line roughness control becomes extremely important since it may contribute to a significant portion of process and device performance variations. In addition, the complexity of SAQP in terms of processing flow makes the roughness improvement indirective and ineffective. It is necessary to discover a new approach in order to improve the roughness in the current SAQP technique. In this presentation, we demonstrate a novel method to improve line roughness performances on 30nm pitch SAQP flow. We discover that the line roughness performance is strongly related to stress management. By selecting different stress level of film to be deposited onto the substrate, we can manipulate the roughness performance in line and space patterns. In addition, the impact of curvature change by applied film stress to SAQP line roughness performance is also studied. No significant correlation is found between wafer curvature and line roughness performance. We will discuss in details the step-by-step physical performances for each processing step in terms of critical dimension (CD)/ critical dimension uniformity (CDU)/line width roughness (LWR)/line edge roughness (LER). Finally, we summarize the process needed to reach the full wafer performance targets of LWR/LER in 1.07nm/1.13nm on 30nm pitch line and space pattern.

Phosphate Tether-Mediated Approach to the Formal Total Synthesis of (-)-Salicylihalamides A and B

PubMed Central

Chegondi, Rambabu; Tan, Mary M. L.; Hanson, Paul R.

2011-01-01

A concise formal synthesis of the cytotoxic macrolides (-)-salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4-steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol. PMID:21504150

Thirty Years After: The Science of the Viking Program and the Discovery of a 'New Mars'

NASA Technical Reports Server (NTRS)

Levine, Joel S.

2006-01-01

Viking discovered a Mars that was very different from the Mars found by Mariner 4, 6 and 7. The new, exciting, more Earth-like Mars was hinted at by the Mariner 9 orbiter and confirmed by Viking. Viking discovered some very fundamental things about Mars. Viking discovered the presence of nitrogen in the atmosphere. A key ingredient needed for life. Viking made the first measurements of the isotopic composition of carbon, oxygen, nitrogen and the noble gases in the atmosphere of Mars. The ratio of 15N to 14N suggested that Mars may have lost more than 99% of the total mass of its atmosphere. The denser atmosphere in the past may explain the presence of flowing water earlier in the history of Mars first discovered by Mariner 9 with additional and higher spatial resolution examples provided by the Viking Orbiters. Viking did not measure organics or life at the surface of Mars. But, Viking did discover a surface unlike any other on the Solar System--a surface exhibiting very high chemical reactivity, most probably formed by the deposition of chemically active atmospheric gases, like hydrogen peroxide (H2O2) and ozone (O3), onto the surface of Mars.

Discovering sparse transcription factor codes for cell states and state transitions during development

PubMed Central

Furchtgott, Leon A; Melton, Samuel; Menon, Vilas; Ramanathan, Sharad

2017-01-01

Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships. We use this technique to reconstruct the early hematopoietic and intestinal developmental trees. We extend this framework to analyze single-cell RNA-seq data from early human cortical development, inferring a neocortical-hindbrain split in early progenitor cells and the key genes that could control this lineage decision. Our work allows us to simultaneously infer both the identity and lineage of cell types as well as a small set of key genes whose expression patterns reflect these relationships. DOI: http://dx.doi.org/10.7554/eLife.20488.001 PMID:28296636

Alternatives to the Fish Early Life-Stage Test: A Research Strategy for Discovering and Annotating Adverse Outcome Pathways During Fish Development

EPA Science Inventory

The OECD 210 fish early life]stage (FELS) test is the primary guideline test used to estimate chronic fish toxicity, as well as support ecological risk assessments and chemical management programs around the world. As a step toward developing alternatives to the FELS test, a HES...

Slowly but Surely: Small Steps toward Establishing Gifted Education Programs in Lebanon

ERIC Educational Resources Information Center

Sarouphim, Ketty M.

2015-01-01

The purpose of this article is to shed light on the state of gifted education in Lebanon and to describe the efforts underway to establish programs for gifted learners in the country. The article starts with a description of the Lebanese system of education followed by research conducted in Lebanon on an instrument called Discovering Intellectual…

A Chess-Like Game for Teaching Engineering Students to Solve Large System of Simultaneous Linear Equations

NASA Technical Reports Server (NTRS)

Nguyen, Duc T.; Mohammed, Ahmed Ali; Kadiam, Subhash

2010-01-01

Solving large (and sparse) system of simultaneous linear equations has been (and continues to be) a major challenging problem for many real-world engineering/science applications [1-2]. For many practical/large-scale problems, the sparse, Symmetrical and Positive Definite (SPD) system of linear equations can be conveniently represented in matrix notation as [A] {x} = {b} , where the square coefficient matrix [A] and the Right-Hand-Side (RHS) vector {b} are known. The unknown solution vector {x} can be efficiently solved by the following step-by-step procedures [1-2]: Reordering phase, Matrix Factorization phase, Forward solution phase, and Backward solution phase. In this research work, a Game-Based Learning (GBL) approach has been developed to help engineering students to understand crucial details about matrix reordering and factorization phases. A "chess-like" game has been developed and can be played by either a single player, or two players. Through this "chess-like" open-ended game, the players/learners will not only understand the key concepts involved in reordering algorithms (based on existing algorithms), but also have the opportunities to "discover new algorithms" which are better than existing algorithms. Implementing the proposed "chess-like" game for matrix reordering and factorization phases can be enhanced by FLASH [3] computer environments, where computer simulation with animated human voice, sound effects, visual/graphical/colorful displays of matrix tables, score (or monetary) awards for the best game players, etc. can all be exploited. Preliminary demonstrations of the developed GBL approach can be viewed by anyone who has access to the internet web-site [4]!

On the complexity of search for keys in quantum cryptography

NASA Astrophysics Data System (ADS)

Molotkov, S. N.

2016-03-01

The trace distance is used as a security criterion in proofs of security of keys in quantum cryptography. Some authors doubted that this criterion can be reduced to criteria used in classical cryptography. The following question has been answered in this work. Let a quantum cryptography system provide an ɛ-secure key such that ½‖ρ XE - ρ U ⊗ ρ E ‖1 < ɛ, which will be repeatedly used in classical encryption algorithms. To what extent does the ɛ-secure key reduce the number of search steps (guesswork) as compared to the use of ideal keys? A direct relation has been demonstrated between the complexity of the complete consideration of keys, which is one of the main security criteria in classical systems, and the trace distance used in quantum cryptography. Bounds for the minimum and maximum numbers of search steps for the determination of the actual key have been presented.

[Molecular mechanisms of protein biosynthesis initiation--biochemical and biomedical implications of a new model of translation enhanced by the RNA hypoxia response element (rHRE)].

PubMed

Master, Adam; Nauman, Alicja

2014-01-01

Translation initiation is a key rate-limiting step in cellular protein synthesis. A cap-dependent initiation is the most effective mechanism of the translation. However, some physiological (mitosis) and pathological (oxidative stress) processes may switch the classic mechanism to an alternative one that is regulated by an mRNA element such as IRES, uORF, IRE, CPE, DICE, AURE or CITE. A recently discovered mechanism of RNA hypoxia response element (rHRE)-dependent translation initiation, may change the view of oxygen-regulated translation and give a new insight into unexplained biochemical processes. Hypoxia is one of the better-known factors that may trigger an alternative mechanism of the translation initiation. Temporal events of oxygen deficiency within tissues and organs may activate processes such as angiogenesis, myogenesis, regeneration, wound healing, and may promote an adaptive response in cardiovascular and neurodegenerative diseases. On the other hand, growth of solid tumors may be accompanied by cyclic hypoxia, allowing for synthesis of proteins required for further progression of cancer cells. This paper provides a review of current knowledge on translational control in the context of alternative models of translation initiation.

Exo-C: A Space Mission for Direct Imaging and Spectroscopy of Extrasolar Planetary Systems

NASA Technical Reports Server (NTRS)

Stapelfeldt, Karl; Belikov, Ruslan; Marley, Mark; Bryden, Geoff; Serabyn, Eugene; Trauger, John; Cahoy, Kerri; Chakrabarti, Supriya; McElwain, Michael; Meadows, Victoria;

Considerations for optimal use of postmortem human brains for molecular psychiatry: lessons from schizophrenia.

PubMed

Weickert, Cynthia Shannon; Rothmond, Debora A; Purves-Tyson, Tertia D

2018-01-01

Schizophrenia is a disabling disease impacting millions of people around the world, for which there is no known cure. Current antipsychotic treatments for schizophrenia mainly target psychotic symptoms, do little to ameliorate social or cognitive deficits, have side-effects that cause weight gain, and diabetes and 30% of people do not respond. Thus, better therapeutics for schizophrenia aimed at the route biologic changes are needed and discovering the underlying neurobiology is key to this quest. Postmortem brain studies provide the most direct and detailed way to determine the pathophysiology of schizophrenia. This chapter outlines steps that can be taken to ensure the best-quality molecular data from postmortem brain tissue are obtained. In this chapter, we also discuss targeted and high-throughput methods for examining gene and protein expression and some of the strengths and limitations of each method. We briefly consider why gene and protein expression changes may not always concur within brain tissue. We conclude that postmortem brain research that investigates gene and protein expression in well-characterized and matched brain cohorts provides an important foundation to be considered when interpreting data obtained from studies of living schizophrenia patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Butterfly proboscis: combining a drinking straw with a nanosponge facilitated diversification of feeding habits

PubMed Central

Monaenkova, Daria; Lehnert, Matthew S.; Andrukh, Taras; Beard, Charles E.; Rubin, Binyamin; Tokarev, Alexander; Lee, Wah-Keat; Adler, Peter H.; Kornev, Konstantin G.

2012-01-01

The ability of Lepidoptera, or butterflies and moths, to drink liquids from rotting fruit and wet soil, as well as nectar from floral tubes, raises the question of whether the conventional view of the proboscis as a drinking straw can account for the withdrawal of fluids from porous substrates or of films and droplets from floral tubes. We discovered that the proboscis promotes capillary pull of liquids from diverse sources owing to a hierarchical pore structure spanning nano- and microscales. X-ray phase-contrast imaging reveals that Plateau instability causes liquid bridges to form in the food canal, which are transported to the gut by the muscular sucking pump in the head. The dual functionality of the proboscis represents a key innovation for exploiting a vast range of nutritional sources. We suggest that future studies of the adaptive radiation of the Lepidoptera take into account the role played by the structural organization of the proboscis. A transformative two-step model of capillary intake and suctioning can be applied not only to butterflies and moths but also potentially to vast numbers of other insects such as bees and flies. PMID:21849382

Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study.

PubMed

Węglarz-Tomczak, Ewelina; Burda-Grabowska, Małgorzata; Giurg, Mirosław; Mucha, Artur

2016-11-01

A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC 50 =1-12μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range. Copyright © 2016 Elsevier Ltd. All rights reserved.

g:Profiler-a web server for functional interpretation of gene lists (2016 update).

PubMed

Reimand, Jüri; Arak, Tambet; Adler, Priit; Kolberg, Liis; Reisberg, Sulev; Peterson, Hedi; Vilo, Jaak

2016-07-08

Functional enrichment analysis is a key step in interpreting gene lists discovered in diverse high-throughput experiments. g:Profiler studies flat and ranked gene lists and finds statistically significant Gene Ontology terms, pathways and other gene function related terms. Translation of hundreds of gene identifiers is another core feature of g:Profiler. Since its first publication in 2007, our web server has become a popular tool of choice among basic and translational researchers. Timeliness is a major advantage of g:Profiler as genome and pathway information is synchronized with the Ensembl database in quarterly updates. g:Profiler supports 213 species including mammals and other vertebrates, plants, insects and fungi. The 2016 update of g:Profiler introduces several novel features. We have added further functional datasets to interpret gene lists, including transcription factor binding site predictions, Mendelian disease annotations, information about protein expression and complexes and gene mappings of human genetic polymorphisms. Besides the interactive web interface, g:Profiler can be accessed in computational pipelines using our R package, Python interface and BioJS component. g:Profiler is freely available at http://biit.cs.ut.ee/gprofiler/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structure-activity relationships of 3-O-β-chacotriosyl oleanane-type triterpenoids as potential H5N1 entry inhibitors.

PubMed

Song, Gaopeng; Shen, Xintian; Li, Sumei; Li, Yibin; Si, Hongzong; Fan, Jihong; Li, Junhua; Gao, Erqiang; Liu, Shuwen

2016-08-25

A series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 1 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 1 indicated that the subtle modification of oleanolic acid as an aglycon has key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of OA or alteration of the C-3 configuration of OA from 3β-to 3α-forms can significantly improve the selective index while maintaining their antiviral activities in vitro. Compound 8 was selected for further mechanistic study because of its distinguished inhibition activity and good selective index. Molecular simulation study and surface plasmon resonance analysis confirmed that compound 8 stabilized HA2 subunit of hemagglutinin (HA) by binding with amino acid residues LYS-26, ASN-53, ASN-27 and ASN-50, therefore may prevent HA from conformational rearranging, which is a critical step for viral entry. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Artificial Mitochondria Transfer: Current Challenges, Advances, and Future Applications

PubMed Central

Aponte, Pedro M.

2017-01-01

The objective of this review is to outline existing artificial mitochondria transfer techniques and to describe the future steps necessary to develop new therapeutic applications in medicine. Inspired by the symbiotic origin of mitochondria and by the cell's capacity to transfer these organelles to damaged neighbors, many researchers have developed procedures to artificially transfer mitochondria from one cell to another. The techniques currently in use today range from simple coincubations of isolated mitochondria and recipient cells to the use of physical approaches to induce integration. These methods mimic natural mitochondria transfer. In order to use mitochondrial transfer in medicine, we must answer key questions about how to replicate aspects of natural transport processes to improve current artificial transfer methods. Another priority is to determine the optimum quantity and cell/tissue source of the mitochondria in order to induce cell reprogramming or tissue repair, in both in vitro and in vivo applications. Additionally, it is important that the field explores how artificial mitochondria transfer techniques can be used to treat different diseases and how to navigate the ethical issues in such procedures. Without a doubt, mitochondria are more than mere cell power plants, as we continue to discover their potential to be used in medicine. PMID:28751917

Process improvement for regulatory analyses of custom-blend fertilizers.

PubMed

Wegner, Keith A

2014-01-01

Chemical testing of custom-blend fertilizers is essential to ensure that the products meet the formulation requirements. For purposes of proper crop nutrition and consumer protection, regulatory oversight promotes compliance and particular attention to blending and formulation specifications. Analyses of custom-blend fertilizer products must be performed and reported within a very narrow window in order to be effective. The Colorado Department of Agriculture's Biochemistry Laboratory is an ISO 17025 accredited facility and conducts analyses of custom-blend fertilizer products primarily during the spring planting season. Using the Lean Six Sigma (LSS) process, the Biochemistry Laboratory has reduced turnaround times from as much as 45 days to as little as 3 days. The LSS methodology focuses on waste reduction through identifying: non-value-added steps, unneeded process reviews, optimization of screening and confirmatory analyses, equipment utilization, nonessential reporting requirements, and inefficient personnel deployment. Eliminating these non-value-added activities helped the laboratory significantly shorten turnaround time and reduce costs. Key improvement elements discovered during the LSS process included: focused sample tracking, equipment redundancy, strategic supply stocking, batch size optimization, critical sample paths, elimination of nonessential QC reviews, and more efficient personnel deployment.

Imparting Catalyst-Control upon Classical Palladium-Catalyzed Alkenyl C–H Bond Functionalization Reactions

PubMed Central

Sigman, Matthew S.; Werner, Erik W.

2011-01-01

Conspectus The functional group transformations carried out by the palladium-catalyzed Wacker and Heck reactions are radically different, but they are both alkenyl C-H bond functionalization reactions that have found extensive use in organic synthesis. The synthetic community depends heavily on these important reactions, but selectivity issues arising from control by the substrate, rather than control by the catalyst, have prevented the realization of their full potential. Because of important similarities in the respective selectivity-determining nucleopalladation and β-hydride elimination steps of these processes, we posit that the mechanistic insight garnered through the development of one of these catalytic reactions may be applied to the other. In this Account, we detail our efforts to develop catalyst-controlled variants of both the Wacker oxidation and the Heck reaction to address synthetic limitations and provide mechanistic insight into the underlying organometallic processes of these reactions. In contrast to previous reports, we discovered that electrophilic palladium catalysts with non-coordinating counterions allowed for the use of a Lewis basic ligand to efficiently promote TBHP-mediated Wacker oxidation reactions of styrenes. This discovery led to the mechanistically guided development of a Wacker reaction catalyzed by a palladium complex with a bidentate ligand. This ligation may prohibit coordination of allylic heteroatoms, thereby allowing for the application of the Wacker oxidation to substrates that were poorly behaved under classical conditions. Likewise, we unexpectedly discovered that electrophilic Pd-σ-alkyl intermediates are capable of distinguishing between electronically inequivalent C–H bonds during β-hydride elimination. As a result, we have developed E-styrenyl selective oxidative Heck reactions of previously unsuccessful electronically non-biased alkene substrates using arylboronic acid derivatives. The mechanistic insight gained from the development of this chemistry allowed for the rational design of a similarly E-styrenyl selective classical Heck reaction using aryldiazonium salts and a broad range of alkene substrates. The key mechanistic findings from the development of these reactions provide new insight into how to predictably impart catalyst control in organometallic processes that would otherwise afford complex product mixtures. Given our new understanding, we are optimistic that reactions that introduce increased complexity relative to simple classical processes may now be developed based on our ability to predict the selectivity-determining nucleopalladation and β-hydride elimination steps through catalyst design. PMID:22111756

Army Independent Risk Assessment Guidebook

DTIC Science & Technology

2014-04-01

17 5.4.2 Step 2: Gather relevant technology and alternative information............... 17 5.4.3 Step 3: Secure SME support for readiness...level assessment. ................... 17 5.4.4 Step 4: SMEs assess TRL, IRL, and MRL for each technology. .............. 17 5.4.5 Step 5: Identify...technical risks, risk ratings, and mitigations. .................. 20 5.4.6 Step 6: SMEs identify key technologies

Canadian patient played key role in uncovering secrets about early-onset Alzheimer's disease.

PubMed Central

Lyttle, J

1996-01-01

Last June, the University of Toronto announced that Canadian scientists and a team of international researchers had discovered the gene responsible for most cases of early-onset Alzheimer's disease. One of the key players in that discovery had died just 3 months earlier. Frances Hodge, who participated in a battery of tests for the 20 years she lived with the disease, helped lead researchers to gene S182--and an ember of hope for future generations. Images p906-a PMID:8634971

[Ocular manifestations of AIDS in Dakar].

PubMed

Ndoye, N B; Sow, P S; Ba, E A; Ndiaye, M R; Wade, A; Coll-Seck, A M

1993-01-01

In this prospective study undertaken between november 1989 and december 1991, the authors report their observations of ocular lesions seen in a cohort of 67 AIDS patients hospitalised in the Infectious Diseases department CHU Fann Dakar. Ocular lesions were discovered in 52.23%. These lesions were observed in both HIV-1 and HIV-2 positive patients, however they were much more common in the former group (77.14%). Rétinal pathology was by far the most frequently observed (63%) and yet classic retinis was not discovered in our series. We feel that the ophtalmologist should play a key role in the routine care of AIDS patients especially in surveillance of retinal changes.

The Power of Audience

ERIC Educational Resources Information Center

Levy, Steven

2008-01-01

Teachers in Expeditionary Learning schools have discovered that finding an authentic audience for a genuine product is the key to getting students to take responsibility for their own work. The author, a school designer for Expeditionary Learning Schools Outward Bound, describes three examples of projects in which students worked on curriculum…

Flexibility in Problem Solving: The Case of Equation Solving

ERIC Educational Resources Information Center

Star, Jon R.; Rittle-Johnson, Bethany

2008-01-01

A key learning outcome in problem-solving domains is the development of flexible knowledge, where learners know multiple strategies and adaptively choose efficient strategies. Two interventions hypothesized to improve flexibility in problem solving were experimentally evaluated: prompts to discover multiple strategies and direct instruction on…

48 CFR 3036.104-90 - Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Authority for one-step turn-key design-build contracting for the United States Coast Guard (USCG). 3036.104-90 Section 3036.104-90 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SPECIAL CATEGORIES OF...

Isostrychnine synthesis mediated by hypervalent iodine reagent.

PubMed

Jacquemot, Guillaume; Maertens, Gaëtan; Canesi, Sylvain

2015-05-18

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael-ether-enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Can Infants Be "Taught" to Attend to a New Physical Variable in an Event Category? The Case of Height in Covering Events

ERIC Educational Resources Information Center

Wang, Su-hua; Baillargeon, Renee

2008-01-01

As they observe or produce events, infants identify variables that help them predict outcomes in each category of events. How do infants identify a new variable? An explanation-based learning (EBL) account suggests three essential steps: (1) observing contrastive outcomes relevant to the variable; (2) discovering the conditions associated with…

Discovering the Past through Data: Promoting the Design and Analysis of Original Data-Sets in History Undergraduate Courses in Hong Kong

ERIC Educational Resources Information Center

Kim, Loretta; Wong, Shun Han Rebekah

2015-01-01

This article discusses the objectives and outcomes of a project to enhance digital humanities training at the undergraduate level in a Hong Kong university. The co-investigators re-designed a multi-source data-set as an example and then taught a multi-step curriculum about gathering, organizing, and presenting original data to an introductory…

Taking structure searches to the next dimension.

PubMed

Schafferhans, Andrea; Rost, Burkhard

2014-07-08

Structure comparisons are now the first step when a new experimental high-resolution protein structure has been determined. In this issue of Structure, Wiederstein and colleagues describe their latest tool for comparing structures, which gives us the unprecedented power to discover crucial structural connections between whole complexes of proteins in the full structural database in real time. Copyright © 2014 Elsevier Ltd. All rights reserved.

A School-Based Quality Improvement Program.

ERIC Educational Resources Information Center

Rappaport, Lewis A.

1993-01-01

As one Brooklyn high school discovered, quality improvement begins with administrator commitment and participants' immersion in the literature. Other key elements include ongoing training of personnel involved in the quality-improvement process, tools such as the Deming Cycle (plan-do-check-act), voluntary and goal-oriented teamwork, and a worthy…

Electronic Structure Theory | Materials Science | NREL

Science.gov Websites

design and discover materials for energy applications. This includes detailed studies of the physical computing. Key Research Areas Materials by Design NREL leads the U.S. Department of Energy's Center for Next Generation of Materials by Design, which incorporates metastability and synthesizability. Learn more about

Building Squares and Discovering Patterns

ERIC Educational Resources Information Center

Whitin, David J.; Whitin, Phyllis

2014-01-01

The Common Core State Standards for Mathematics (CCSSM) (CCSSI 2010) define what children should understand and be able to do in K-grade 12. This document also includes a description of key mathematical processes and proficiencies, the Standards for Mathematical Practice (SMPs), which provide an important overview for the kind of robust thinking…

Discovering regions of the bovine genome associated with variation in the immune response

USDA-ARS?s Scientific Manuscript database

Infectious disease of livestock continues to be a cause of substantial economic loss and adverse welfare. Breeding for disease resistant livestock could improve both the economic burden and animal welfare. Using genetic linkage and association methods, we aim to identify key genes and pathways that ...

Rock Art

ERIC Educational Resources Information Center

Henn, Cynthia A.

2004-01-01

There are many interpretations for the symbols that are seen in rock art, but no decoding key has ever been discovered. This article describes one classroom's experiences with a lesson on rock art--making their rock art and developing their own personal symbols. This lesson allowed for creativity, while giving an opportunity for integration…

Supplement to the knowledge of the genus Scaphidium Olivier of East China (Coleoptera: Staphylinidae: Scaphidiinae).

PubMed

Tu, Yue-Ye; Tang, Liang

2017-05-18

A new species, Scaphidium ahrensi sp. n., is described from Fujian Province and its diagnostic characters are illustrated. Scaphidium vicinum Pic, 1915 is discovered from mainland China for the first time. A modified key is given to accommodating these two species.

Discovering Design Possibilities through a Pedagogy of Multiliteracies

ERIC Educational Resources Information Center

Mills, Kathy

2006-01-01

Research and educational policies have alerted teachers to the importance of multiliteracies. Communication in society today is characterised by rapidly changing and emergent forms of meaning-making in a context of increased cultural and linguistic diversity. This paper responds to these imperatives, releasing key findings of a critical…

About the Alliance | Division of Cancer Prevention

Cancer.gov

Objectives The major objective of the Alliance is to discover and develop molecular markers for early detection of cancer by conducting innovative, translational research in the field of complex carbohydrates. An important key to biomarker discovery is to understand the biological mechanisms by which changes in glycosylation promote cancer progression. Taking this

Discover IDEA CD 2002. [CD-ROM].

ERIC Educational Resources Information Center

Council for Exceptional Children, Arlington, VA.

This Macintosh and PC compatible CD-ROM includes key resources about the Individuals with Disabilities Education Act (IDEA) amendments of 1997. It is designed as a research and training tool for administrators, professors and students in higher education, families, advocates, policy makers, and service providers who strive for quality education…

Evolution of meiotic recombination genes in maize and teosinte.

PubMed

Sidhu, Gaganpreet K; Warzecha, Tomasz; Pawlowski, Wojciech P

2017-01-25

Meiotic recombination is a major source of genetic variation in eukaryotes. The role of recombination in evolution is recognized but little is known about how evolutionary forces affect the recombination pathway itself. Although the recombination pathway is fundamentally conserved across different species, genetic variation in recombination components and outcomes has been observed. Theoretical predictions and empirical studies suggest that changes in the recombination pathway are likely to provide adaptive abilities to populations experiencing directional or strong selection pressures, such as those occurring during species domestication. We hypothesized that adaptive changes in recombination may be associated with adaptive evolution patterns of genes involved in meiotic recombination. To examine how maize evolution and domestication affected meiotic recombination genes, we studied patterns of sequence polymorphism and divergence in eleven genes controlling key steps in the meiotic recombination pathway in a diverse set of maize inbred lines and several accessions of teosinte, the wild ancestor of maize. We discovered that, even though the recombination genes generally exhibited high sequence conservation expected in a pathway controlling a key cellular process, they showed substantial levels and diverse patterns of sequence polymorphism. Among others, we found differences in sequence polymorphism patterns between tropical and temperate maize germplasms. Several recombination genes displayed patterns of polymorphism indicative of adaptive evolution. Despite their ancient origin and overall sequence conservation, meiotic recombination genes can exhibit extensive and complex patterns of molecular evolution. Changes in these genes could affect the functioning of the recombination pathway, and may have contributed to the successful domestication of maize and its expansion to new cultivation areas.

Hacking on decoy-state quantum key distribution system with partial phase randomization

NASA Astrophysics Data System (ADS)

Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

2014-04-01

Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

Hacking on decoy-state quantum key distribution system with partial phase randomization.

PubMed

Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

2014-04-23

Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

A highly sensitive and accurate gene expression analysis by sequencing ("bead-seq") for a single cell.

PubMed

Matsunaga, Hiroko; Goto, Mari; Arikawa, Koji; Shirai, Masataka; Tsunoda, Hiroyuki; Huang, Huan; Kambara, Hideki

2015-02-15

Analyses of gene expressions in single cells are important for understanding detailed biological phenomena. Here, a highly sensitive and accurate method by sequencing (called "bead-seq") to obtain a whole gene expression profile for a single cell is proposed. A key feature of the method is to use a complementary DNA (cDNA) library on magnetic beads, which enables adding washing steps to remove residual reagents in a sample preparation process. By adding the washing steps, the next steps can be carried out under the optimal conditions without losing cDNAs. Error sources were carefully evaluated to conclude that the first several steps were the key steps. It is demonstrated that bead-seq is superior to the conventional methods for single-cell gene expression analyses in terms of reproducibility, quantitative accuracy, and biases caused during sample preparation and sequencing processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Tumor image signatures and habitats: a processing pipeline of multimodality metabolic and physiological images.

PubMed

You, Daekeun; Kim, Michelle M; Aryal, Madhava P; Parmar, Hemant; Piert, Morand; Lawrence, Theodore S; Cao, Yue

2018-01-01

To create tumor "habitats" from the "signatures" discovered from multimodality metabolic and physiological images, we developed a framework of a processing pipeline. The processing pipeline consists of six major steps: (1) creating superpixels as a spatial unit in a tumor volume; (2) forming a data matrix [Formula: see text] containing all multimodality image parameters at superpixels; (3) forming and clustering a covariance or correlation matrix [Formula: see text] of the image parameters to discover major image "signatures;" (4) clustering the superpixels and organizing the parameter order of the [Formula: see text] matrix according to the one found in step 3; (5) creating "habitats" in the image space from the superpixels associated with the "signatures;" and (6) pooling and clustering a matrix consisting of correlation coefficients of each pair of image parameters from all patients to discover subgroup patterns of the tumors. The pipeline was applied to a dataset of multimodality images in glioblastoma (GBM) first, which consisted of 10 image parameters. Three major image "signatures" were identified. The three major "habitats" plus their overlaps were created. To test generalizability of the processing pipeline, a second image dataset from GBM, acquired on the scanners different from the first one, was processed. Also, to demonstrate the clinical association of image-defined "signatures" and "habitats," the patterns of recurrence of the patients were analyzed together with image parameters acquired prechemoradiation therapy. An association of the recurrence patterns with image-defined "signatures" and "habitats" was revealed. These image-defined "signatures" and "habitats" can be used to guide stereotactic tissue biopsy for genetic and mutation status analysis and to analyze for prediction of treatment outcomes, e.g., patterns of failure.

Cryptosystem based on two-step phase-shifting interferometry and the RSA public-key encryption algorithm

NASA Astrophysics Data System (ADS)

Meng, X. F.; Peng, X.; Cai, L. Z.; Li, A. M.; Gao, Z.; Wang, Y. R.

2009-08-01

A hybrid cryptosystem is proposed, in which one image is encrypted to two interferograms with the aid of double random-phase encoding (DRPE) and two-step phase-shifting interferometry (2-PSI), then three pairs of public-private keys are utilized to encode and decode the session keys (geometrical parameters, the second random-phase mask) and interferograms. In the stage of decryption, the ciphered image can be decrypted by wavefront reconstruction, inverse Fresnel diffraction, and real amplitude normalization. This approach can successfully solve the problem of key management and dispatch, resulting in increased security strength. The feasibility of the proposed cryptosystem and its robustness against some types of attack are verified and analyzed by computer simulations.

Method for exponentiating in cryptographic systems

DOEpatents

Brickell, Ernest F.; Gordon, Daniel M.; McCurley, Kevin S.

1994-01-01

An improved cryptographic method utilizing exponentiation is provided which has the advantage of reducing the number of multiplications required to determine the legitimacy of a message or user. The basic method comprises the steps of selecting a key from a preapproved group of integer keys g; exponentiating the key by an integer value e, where e represents a digital signature, to generate a value g.sup.e ; transmitting the value g.sup.e to a remote facility by a communications network; receiving the value g.sup.e at the remote facility; and verifying the digital signature as originating from the legitimate user. The exponentiating step comprises the steps of initializing a plurality of memory locations with a plurality of values g.sup.xi ; computi The United States Government has rights in this invention pursuant to Contract No. DE-AC04-76DP00789 between the Department of Energy and AT&T Company.

Quantum orbital angular momentum of elliptically symmetric light

NASA Astrophysics Data System (ADS)

Plick, William N.; Krenn, Mario; Fickler, Robert; Ramelow, Sven; Zeilinger, Anton

2013-03-01

We present a quantum-mechanical analysis of the orbital angular momentum of a class of recently discovered elliptically symmetric stable light fields—the so-called Ince-Gauss modes. We study, in a fully quantum formalism, how the orbital angular momentum of these beams varies with their ellipticity, and we discover several compelling features, including nonmonotonic behavior, stable beams with real continuous (noninteger) orbital angular momenta, and orthogonal modes with the same orbital angular momenta. We explore, and explain in detail, the reasons for this behavior. These features may have applications in quantum key distribution, atom trapping, and quantum informatics in general—as the ellipticity opens up an alternative way of navigating the spatial photonic Hilbert space.

Some Key Factors in Policy Implementation.

ERIC Educational Resources Information Center

Rowen, Henry

Business policy texts identify numerous steps that make up the policy implementation process for private firms. On the surface, these steps also appear applicable to the implementation of public policies. However, the problems of carrying out these implementing steps in the public sector are significantly different than in the private sector due…

Quantum Control of Graphene Plasmon Excitation and Propagation at Heaviside Potential Steps.

PubMed

Wang, Dongli; Fan, Xiaodong; Li, Xiaoguang; Dai, Siyuan; Wei, Laiming; Qin, Wei; Wu, Fei; Zhang, Huayang; Qi, Zeming; Zeng, Changgan; Zhang, Zhenyu; Hou, Jianguo

2018-02-14

Quantum mechanical effects of single particles can affect the collective plasmon behaviors substantially. In this work, the quantum control of plasmon excitation and propagation in graphene is demonstrated by adopting the variable quantum transmission of carriers at Heaviside potential steps as a tuning knob. First, the plasmon reflection is revealed to be tunable within a broad range by varying the ratio γ between the carrier energy and potential height, which originates from the quantum mechanical effect of carrier propagation at potential steps. Moreover, the plasmon excitation by free-space photos can be regulated from fully suppressed to fully launched in graphene potential wells also through adjusting γ, which defines the degrees of the carrier confinement in the potential wells. These discovered quantum plasmon effects offer a unified quantum-mechanical solution toward ultimate control of both plasmon launching and propagating, which are indispensable processes in building plasmon circuitry.

NASA Marshall Space Flight Center Barrel-Shaped Asymmetrical Capacitor

NASA Technical Reports Server (NTRS)

Campbell, J. W.; Carruth, M. R.; Edwards, D. L.; Finchum, A.; Maxwell, G.; Nabors, S.; Smalley, L.; Huston, D.; Ila, D.; Zimmerman, R.

2004-01-01

The NASA Barrel-Shaped Asymmetrical Capacitor (NACAP) has been extensively tested at NASA Marshall Space Flight Center and the National Space Science and Technology Center. Trichel pulse emission was first discovered here. The NACAP is a magnetohydrodynamic device for electric propulsion. In air it requires no onboard propellant nor any moving parts. No performance was observed in hard vacuum. The next step shall be optimizing the technology for future applications.

The expanding polymerase universe.

PubMed

Goodman, M F; Tippin, B

2000-11-01

Over the past year, the number of known prokaryotic and eukaryotic DNA polymerases has exploded. Many of these newly discovered enzymes copy aberrant bases in the DNA template over which 'respectable' polymerases fear to tread. The next step is to unravel their functions, which are thought to range from error-prone copying of DNA lesions, somatic hypermutation and avoidance of skin cancer, to restarting stalled replication forks and repairing double-stranded DNA breaks.

Rational drug design paradigms: the odyssey for designing better drugs.

PubMed

Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

2015-01-01

Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

Teaching Lab Report Writing through Inquiry: A Green Chemistry Stoichiometry Experiment for General Chemistry

ERIC Educational Resources Information Center

Cacciatore, Kristen L.; Sevian, Hannah

2006-01-01

We present an alternative to a traditional first-year chemistry laboratory experiment. This experiment has four key features: students utilize stoichiometry, learn and apply principles of green chemistry, engage in authentic scientific inquiry, and discover why each part of a scientific lab report is necessary. The importance and essential…

Educational Technology Research Journals: Computers & Education, 2002-2011

ERIC Educational Resources Information Center

Rackham, David D.; Hyatt, Frederick R.; Macfarlane, David C.; Nisse, Tony; Woodfield, Wendy; West, Richard E.

2013-01-01

In this study, the authors examined the journal "Computers & Education" to discover research trends in the articles published during 2002-2011. Research articles were analyzed to determine trends in the research methods and types of articles published, as well as the key topics published, top authors, and some of the most-cited…

Continuing Professional Library and Information Science Education for Advancing Equity of Access.

ERIC Educational Resources Information Center

Roy, Loriene; Lee, Seung-ah

Equity of access is one of the American Library Association's (ALA's) five key action areas. Discussions of digital divide issues sometimes sound confusing and unfocused; however, the digital divide issue provides information professionals with the opportunity to discover more about their own skills and potential, to understand more about library…

Yesterday's Conservationists: How Were They Educated about the Outdoors and the Environment?

ERIC Educational Resources Information Center

Place, Greg S.

2016-01-01

The purpose of this study was to investigate the effects of early-life educational experiences on the development of environmental attitudes among historical conservation individuals. Five key individuals who were active in conservation and environmental issues were identified in this study. Specifically, the goal was to discover what caused…

ResStock - Targeting Energy and Cost Savings for U.S. Homes | NREL

Science.gov Websites

ResStock - Targeting Energy and Cost Savings for U.S. Homes Science and Technology Highlights Highlights in Research & Development ResStock - Targeting Energy and Cost Savings for U.S. Homes Key discovered $49 billion in potential annual utility bill savings through cost-effective energy efficiency

Microfluidic platform for electrophysiological recordings from host-stage hookworm Ascaris suum larvae: a new tool for anthelmenthic research

USDA-ARS?s Scientific Manuscript database

The screening of candidate compounds and natural products for anthelmintic activity is a key component of discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device (‘chip’) that records non-invasively the tiny electrophysiologic...

Start with Service

ERIC Educational Resources Information Center

Riordan, Emily

2013-01-01

Community service has become a key part of the high school experience, with students eager to set themselves apart from one another on the path to college or to find opportunities to discover and develop new passions, creativity, and leadership skills. The author discusses The Green Apple Day of Service, an annual event that brings volunteers from…

Discovering Genres of Online Discussion Threads via Text Mining

ERIC Educational Resources Information Center

Lin, Fu-Ren; Hsieh, Lu-Shih; Chuang, Fu-Tai

2009-01-01

As course management systems (CMS) gain popularity in facilitating teaching. A forum is a key component to facilitate the interactions among students and teachers. Content analysis is the most popular way to study a discussion forum. But content analysis is a human labor intensity process; for example, the coding process relies heavily on manual…

Physiological-Cognitive-Emotional Responses to Defense-Arousing Communication: Overview and Sex Differences.

ERIC Educational Resources Information Center

Gordon, Ronald D.

A 328-item checklist, suitable for the self-reporting of responses to any stimulus event, was administered to 107 upper division college students in an attempt to investigate the physiological-cognitive-emotional responses to defense arousing communication and to discover a greater range of the key features of the phenomena of…

The Journal of Suggestive-Accelerative Learning and Teaching, Volume 5, Number 1. Proceedings of the SALT Conference (1980).

ERIC Educational Resources Information Center

Schuster, Donald, Ed.

1980-01-01

The proceedings of the 1980 Suggestive-Accelerative Learning and Teaching (SALT) conference include: "Creative Power in Action: Discovering Your 'Right' Mind" (Carole Austen and Hilary Johnson); "The Co-Creative Teacher: A Key Dimension in Accelerated Learning in the Classroom" (Susan M. Campbell); "The Application of…

Location, Location, Location!

ERIC Educational Resources Information Center

Ramsdell, Kristin

2004-01-01

Of prime importance in real estate, location is also a key element in the appeal of romances. Popular geographic settings and historical periods sell, unpopular ones do not--not always with a logical explanation, as the author discovered when she conducted a survey on this topic last year. (Why, for example, are the French Revolution and the…

A survey of single nucleotide polymorphisms identified from whole-genome sequencing and their functional effect in the porcine genome

USDA-ARS?s Scientific Manuscript database

One of the key aims of livestock genetics and genomics research is to discover the genetic variants underlying economically important traits such as reproductive performance, feed efficiency, disease susceptibility, and product quality. Next generation sequencing has recently emerged as an economica...

Understanding World Economic History

ERIC Educational Resources Information Center

Whaples, Robert

2013-01-01

One joy of studying history is discovering people living meaningful lives and behaving in unusual ways that are startling to the modern reader--young or old. Why did pre-modern people living hundreds or even thousands of years ago do things so differently than we do? Robert Whaples states that Economic historians conclude that the key difference…

[The role of branched-chain amino acids metabolism in development of cardiovascular diseases and its risk factors].

PubMed

Lyzohub, V H; Zaval's'ka, T V; Savchenko, O V; Tyravs'ka, Iu V

2013-01-01

Branched-chain amino acids play the key role in many metabolism processes in organism generally and in cardiovascular protection. It was discovered its importance in mitochondrial biogenesis, antioxidant and antiaging processes, its antihypertension and antiarrhythmic effects, its role in obesity and diabetes mellitus.

CHARACTERIZATION AND APPLICATIONS OF REDUCTIVE DEHALOGENASE GENES IN ENHANCEMENT AND MONITORING OF BIODEGRADATION OF CHLORINATED POLLUTANTS

EPA Science Inventory

Of the currently known reductive dehalogenase genes, few have functions assigned, and it seems likely that many more remain to be discovered. Very little is known of the ecology of the organisms that harbor these genes, that encode enzymes that are key to the anaerobic dechlorina...

Catch a Raindrop! Science Makes Sense Integrating across the Curriculum.

ERIC Educational Resources Information Center

Gleason, Donna; Watten, Cynthia

A thematic approach provides the best opportunity for children to discover the linkage among science, mathematics, and language arts. This document explores the water cycle. Investigations are divided into six key areas: (1) comparing the size of raindrops; (2) learning to measure rain; (3) making rainbows; (4) exploring the principles of…

Facilitating Student Experimentation with Statistical Concepts.

ERIC Educational Resources Information Center

Smith, Patricia K.

2002-01-01

Offers a Web page with seven Java applets allowing students to experiment with key concepts in an introductory statistics course. Indicates the applets can be used in three ways: to place links to the applets, to create in-class demonstrations of statistical concepts, and to lead students through experiments and discover statistical relationships.…

Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity.

PubMed

Ortega, Jose Antonio; Riccardi, Laura; Minniti, Elirosa; Borgogno, Marco; Arencibia, Jose M; Greco, Maria L; Minarini, Anna; Sissi, Claudia; De Vivo, Marco

2018-02-08

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.

Using Spreadsheets to Discover Meaning for Parameters in Nonlinear Models

ERIC Educational Resources Information Center

Green, Kris H.

2008-01-01

This paper explores the use of spreadsheets to develop an exploratory environment where mathematics students can develop their own understanding of the parameters of commonly encountered families of functions: linear, logarithmic, exponential and power. The key to this understanding involves opening up the definition of rate of change from the…

Extreme Arthropods: Exploring Evolutionary Adaptations to Polar and Temperate Deserts

ERIC Educational Resources Information Center

Sandro, Luke; Constible, Juanita M.; Lee, Richard E., Jr.

2007-01-01

In this activity, Namib and Antarctic arthropods are used to illustrate several important biological principles. Among these are the key ideas that form follows function and that the environment drives evolution. In addition, students will discover that the climates of the Namib Desert and the Antarctic Peninsula are similar in several ways, and…

New Developments in ESP Teaching and Learning Research

ERIC Educational Resources Information Center

Sarré, Cédric, Ed.; Whyte, Shona, Ed.

2017-01-01

This volume intends to address key issues related to research in English for Specific Purposes (ESP) teaching and learning by bringing together current research at the intersection of the theoretical and practical dimensions of ESP. Readers will discover a treasury of information they will find useful to their own understanding of research into…

Instructional Design in Job Skills Training for Welfare Recipients and Displaced Workers

ERIC Educational Resources Information Center

Richardson, Arline; Storberg-Walker, Julia

2006-01-01

Scully-Russ (2005) described the low-wage labor market issue and the tendency in academic literature to view the problem as "fixing" the skills of low wageworkers. However, the article does not address instructional design issues surrounding low-wage employee training interventions. This manuscript attempts to discover the key factors surrounding…

Single cell genomic study of Dehalococcoidites in deep sea sediments of Peru Margin 1230

NASA Astrophysics Data System (ADS)

Kaster, A.; Meyer-Blackwell, K.; Spormann, A. M.

2013-12-01

Dehalogenating Chloroflexi, such as Dehalococcoidites Dhc were originally discovered as the key microorganisms mediating reductive dehalogenation of the prevalent groundwater contaminants tetrachloroethene and trichloroethene. Molecular and genomic studies on their key enzymes for energy conservation, reductive dehalogenases rdh, have provided evidence for ubiquitous horizontal gene transfer. A pioneering study by Futagami et al. discovered novel putative rdh phylotypes in sediments from the Pacific, revealing an unknown and surprising abundance of rdh genes in pristine habitats. The frequent detection of Dhc-related 16S rRNA genes from these environments implied the occurrence of dissimilatory dehalorespiration in marine subsurface sediments, however, pristine Dhc could never be linked to this activity. Despite being ubiquitous in those environments, metabolic life style or ecological function of Dhc in the absence of anthropogenic contaminants is still completely unknown. We therefore analyzed a non-contaminated deep sea sediment sample of the Peru Margin 1230 site by a single cell genomic (SGC) approach. We present for the first time data on three single Dhc cells, helping to elucidate their role in the poorly understood oligotrophic marine sub-surface environment.

PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38MAPK/AKT pathways.

PubMed

Alisi, A; Spaziani, A; Anticoli, S; Ghidinelli, M; Balsano, C

2008-03-01

Myogenic differentiation is a highly orchestrated multistep process controlled by extracellular growth factors that modulate largely unknown signals into the cell affecting the muscle-transcription program. P38MAPK-dependent signalling, as well as PI3K/Akt pathway, has a key role in the control of muscle gene expression at different stages during the myogenic process. P38MAPK affects the activities of transcription factors, such as MyoD and myogenin, and contributes, together with PI3K/Akt pathway, to control the early and late steps of myogenic differentiation. The aim of our work was to better define the role of PKR, a dsRNA-activated protein kinase, as potential component in the differentiation program of C2C12 murine myogenic cells and to correlate its activity with p38MAPK and PI3K/Akt myogenic regulatory pathways. Here, we demonstrate that PKR is an essential component of the muscle development machinery and forms a functional complex with p38MAPK and/or Akt, contributing to muscle differentiation of committed myogenic cells in vitro. Inhibition of endogenous PKR activity by a specific (si)RNA and a PKR dominant-negative interferes with the myogenic program of C2C12 cells, causing a delay in activation of myogenic specific genes and inducing the formation of thinner myofibers. In addition, the construction of three PKR mutants allowed us to demonstrate that both N and C-terminal regions of PKR are critical for the interaction with p38MAPK and Akt. The novel discovered complex permits PKR to timely regulate the inhibition/activation of p38MAPK and Akt, controlling in this way the different steps characterizing skeletal muscle differentiation.

Annotating images by mining image search results.

PubMed

Wang, Xin-Jing; Zhang, Lei; Li, Xirong; Ma, Wei-Ying

2008-11-01

Although it has been studied for years by the computer vision and machine learning communities, image annotation is still far from practical. In this paper, we propose a novel attempt at model-free image annotation, which is a data-driven approach that annotates images by mining their search results. Some 2.4 million images with their surrounding text are collected from a few photo forums to support this approach. The entire process is formulated in a divide-and-conquer framework where a query keyword is provided along with the uncaptioned image to improve both the effectiveness and efficiency. This is helpful when the collected data set is not dense everywhere. In this sense, our approach contains three steps: 1) the search process to discover visually and semantically similar search results, 2) the mining process to identify salient terms from textual descriptions of the search results, and 3) the annotation rejection process to filter out noisy terms yielded by Step 2. To ensure real-time annotation, two key techniques are leveraged-one is to map the high-dimensional image visual features into hash codes, the other is to implement it as a distributed system, of which the search and mining processes are provided as Web services. As a typical result, the entire process finishes in less than 1 second. Since no training data set is required, our approach enables annotating with unlimited vocabulary and is highly scalable and robust to outliers. Experimental results on both real Web images and a benchmark image data set show the effectiveness and efficiency of the proposed algorithm. It is also worth noting that, although the entire approach is illustrated within the divide-and conquer framework, a query keyword is not crucial to our current implementation. We provide experimental results to prove this.

Stereoselective Total Synthesis of (±)-5- epi-Cyanthiwigin I via an Intramolecular Pauson-Khand Reaction as the Key Step.

PubMed

Chang, Yuanyuan; Shi, Linlin; Huang, Jun; Shi, Lili; Zhang, Zichun; Hao, Hong-Dong; Gong, Jianxian; Yang, Zhen

2018-05-09

A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.

SPLASH: structural pattern localization analysis by sequential histograms.

PubMed

Califano, A

2000-04-01

The discovery of sparse amino acid patterns that match repeatedly in a set of protein sequences is an important problem in computational biology. Statistically significant patterns, that is patterns that occur more frequently than expected, may identify regions that have been preserved by evolution and which may therefore play a key functional or structural role. Sparseness can be important because a handful of non-contiguous residues may play a key role, while others, in between, may be changed without significant loss of function or structure. Similar arguments may be applied to conserved DNA patterns. Available sparse pattern discovery algorithms are either inefficient or impose limitations on the type of patterns that can be discovered. This paper introduces a deterministic pattern discovery algorithm, called Splash, which can find sparse amino or nucleic acid patterns matching identically or similarly in a set of protein or DNA sequences. Sparse patterns of any length, up to the size of the input sequence, can be discovered without significant loss in performances. Splash is extremely efficient and embarrassingly parallel by nature. Large databases, such as a complete genome or the non-redundant SWISS-PROT database can be processed in a few hours on a typical workstation. Alternatively, a protein family or superfamily, with low overall homology, can be analyzed to discover common functional or structural signatures. Some examples of biologically interesting motifs discovered by Splash are reported for the histone I and for the G-Protein Coupled Receptor families. Due to its efficiency, Splash can be used to systematically and exhaustively identify conserved regions in protein family sets. These can then be used to build accurate and sensitive PSSM or HMM models for sequence analysis. Splash is available to non-commercial research centers upon request, conditional on the signing of a test field agreement. acal@us.ibm.com, Splash main page http://www.research.ibm.com/splash

RNA splicing process analysis for identifying antisense oligonucleotide inhibitors with padlock probe-based isothermal amplification† †Electronic supplementary information (ESI) available: Additional experimental materials, methods, DNA sequences and supplementary figures and tables. See DOI: 10.1039/c7sc01336a Click here for additional data file.

PubMed Central

Ren, Xiaojun; Deng, Ruijie; Wang, Lida; Zhang, Kaixiang

2017-01-01

RNA splicing, which mainly involves two transesterification steps, is a fundamental process of gene expression and its abnormal regulation contributes to serious genetic diseases. Antisense oligonucleotides (ASOs) are genetic control tools that can be used to specifically control genes through alteration of the RNA splicing pathway. Despite intensive research, how ASOs or various other factors influence the multiple processes of RNA splicing still remains obscure. This is largely due to an inability to analyze the splicing efficiency of each step in the RNA splicing process with high sensitivity. We addressed this limitation by introducing a padlock probe-based isothermal amplification assay to achieve quantification of the specific products in different splicing steps. With this amplified assay, the roles that ASOs play in RNA splicing inhibition in the first and second steps could be distinguished. We identified that 5′-ASO could block RNA splicing by inhibiting the first step, while 3′-ASO could block RNA splicing by inhibiting the second step. This method provides a versatile tool for assisting efficient ASO design and discovering new splicing modulators and therapeutic drugs. PMID:28989608

Prediction of drug indications based on chemical interactions and chemical similarities.

PubMed

Huang, Guohua; Lu, Yin; Lu, Changhong; Zheng, Mingyue; Cai, Yu-Dong

2015-01-01

Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs.

Cerebral Gluconeogenesis and Diseases.

PubMed

Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

2016-01-01

The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions.

Investigating the binary nature of active asteroid 288P/300163

NASA Astrophysics Data System (ADS)

Agarwal, Jessica

2016-10-01

We propose to study the suspected binary nature of active asteroid 288P/300163. We aim to confirm or disprove the existence of a binary nucleus, and - if confirmed - to measure the mutual orbital period and orbit orientation of the compoents, and their sizes. We request 5 orbits of WFC3 imaging, spaced at intervals of 8-12 days. 288P belongs to the recently discovered group of active asteroids, and is particularly remarkable as HST images obtained during its last close approach to Earth in 2011 are consistent with a barely resolved binary system. If confirmed, 288P would be the first known active binary asteroid. For the first time, we would see two important consequences of rotational break-up in a single object: binary formation and dust ejection, highlighting the importance of the YORP-effect in re-shaping the asteroid belt. Confirming 288P as a binary would be a key step towards understanding the evolutionary processes underlying asteroid activity. In order to resolve the two components we need 288P at a geocentric distance comparable to or less than we had in 2011 December (1.85 AU). This condition will be fulfilled for the first time since 2011, between mid-July and mid-November of 2016. The next opportunity to carry out such observations will be in 2021.

Prediction of Drug Indications Based on Chemical Interactions and Chemical Similarities

PubMed Central

Huang, Guohua; Lu, Yin; Lu, Changhong; Cai, Yu-Dong

2015-01-01

Discovering potential indications of novel or approved drugs is a key step in drug development. Previous computational approaches could be categorized into disease-centric and drug-centric based on the starting point of the issues or small-scaled application and large-scale application according to the diversity of the datasets. Here, a classifier has been constructed to predict the indications of a drug based on the assumption that interactive/associated drugs or drugs with similar structures are more likely to target the same diseases using a large drug indication dataset. To examine the classifier, it was conducted on a dataset with 1,573 drugs retrieved from Comprehensive Medicinal Chemistry database for five times, evaluated by 5-fold cross-validation, yielding five 1st order prediction accuracies that were all approximately 51.48%. Meanwhile, the model yielded an accuracy rate of 50.00% for the 1st order prediction by independent test on a dataset with 32 other drugs in which drug repositioning has been confirmed. Interestingly, some clinically repurposed drug indications that were not included in the datasets are successfully identified by our method. These results suggest that our method may become a useful tool to associate novel molecules with new indications or alternative indications with existing drugs. PMID:25821813

New glycyl radical enzymes catalysing key metabolic steps in anaerobic bacteria.

PubMed

Selmer, Thorsten; Pierik, Antonio J; Heider, Johann

2005-10-01

During the last decade, an increasing number of new enzymes containing glycyl radicals in their active sites have been identified and biochemically characterised. These include benzylsuccinate synthase (Bss), 4-hydroxyphenylacetate decarboxylase (Hpd) and the coenzyme B12-independent glycerol dehydratase (Gdh). These are involved in metabolic pathways as different as anaerobic toluene metabolism, fermentative production of p-cresol and glycerol fermentation. Some features of these newly discovered enzymes are described and compared with those of the previously known glycyl radical enzymes pyruvate formate-lyase (Pfl) and anaerobic ribonucleotide reductase (Nrd). Among the new enzymes, Bss and Hpd share the presence of small subunits, the function of which in the catalytic mechanisms is still enigmatic, and both enzymes contain metal centres in addition to the glycyl radical prosthetic group. The activating enzymes of the novel systems also deviate from the standard type, containing at least one additional Fe-S cluster. Finally, the available whole-genome sequences of an increasing number of strictly or facultative anaerobic bacteria revealed the presence of many more hitherto unknown glycyl radical enzyme (GRE) systems. Recent studies suggest that the particular types of these enzymes represent the ends of different evolutionary lines, which emerged early in evolution and diversified to yield remarkably versatile biocatalysts for chemical reactions that are otherwise difficult to perform in anoxic environments.

Counselling in infertility: individual, couple and group interventions.

PubMed

Van den Broeck, Uschi; Emery, Marysa; Wischmann, Tewes; Thorn, Petra

2010-12-01

Infertility is considered a biopsychosocial crisis and infertility counselling is recommended as an integral part of a multidisciplinary approach. This article will outline the theoretical background and describe common interventions used in infertility counselling for individuals, couples and in a group setting. This article summarizes the proceedings of the first campus workshop of the Special interest group of Psychology and Counselling of the European Society for Human Reproduction and Embryology (ESHRE). Infertility counselling offers the opportunity to explore, discover and clarify ways of living more satisfyingly and resourcefully when fertility impairments have been diagnosed. The Heidelberg Fertility Consultation Service is presented as a framework for individual and couples counselling and highlights important issues in counselling patients. For group work a number of steps to set up a group within an infertility framework are discussed. In recent years, infertility counselling has become a specialist form of counselling requiring professional expertise and qualification. Key issues and common interventions are presented to raise awareness for the specific counselling needs of individuals and couples experiencing infertility and undergoing medical treatment. Mental health professionals new to the field of reproductive technologies as well as those in other areas of mental health counselling clients with fertility disorders can benefit from the topics addressed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Multiple-objective evaluation of wastewater treatment plant control alternatives.

PubMed

Flores-Alsina, Xavier; Gallego, Alejandro; Feijoo, Gumersindo; Rodriguez-Roda, Ignasi

2010-05-01

Besides the evaluation of the environmental issues, the correct assessment of wastewater treatment plants (WWTP) should take into account several objectives such as: economic e.g. operation costs; technical e.g. risk of suffering microbiology-related TSS separation problems; or legal e.g. accomplishment with the effluent standards in terms of the different pollution loads. For this reason, the main objective of this paper is to show the benefits of complementing the environmental assessment carried out by life cycle assessment with economical, technical and legal criteria. Using a preliminary version of the BSM2 as a case study, different combinations of controllers are implemented, simulated and evaluated. In the following step, the resulting multi-criteria matrix is mined using multivariate statistical techniques. The results showed that the presence of an external carbon source addition, the type of aeration system and the TSS controller are the key elements creating the differences amongst the alternatives. Also, it was possible to characterize the different control strategies according to a set of aggregated criteria. Additionally, the existing synergies amongst different objectives and their consequent trade-offs were identified. Finally, it was discovered that from the initial extensive list of evaluation criteria, only a small set of five are really discriminant, being useful to differentiate within the generated alternatives. Copyright 2010 Elsevier Ltd. All rights reserved.

JCDSA: a joint covariate detection tool for survival analysis on tumor expression profiles.

PubMed

Wu, Yiming; Liu, Yanan; Wang, Yueming; Shi, Yan; Zhao, Xudong

2018-05-29

Survival analysis on tumor expression profiles has always been a key issue for subsequent biological experimental validation. It is crucial how to select features which closely correspond to survival time. Furthermore, it is important how to select features which best discriminate between low-risk and high-risk group of patients. Common features derived from the two aspects may provide variable candidates for prognosis of cancer. Based on the provided two-step feature selection strategy, we develop a joint covariate detection tool for survival analysis on tumor expression profiles. Significant features, which are not only consistent with survival time but also associated with the categories of patients with different survival risks, are chosen. Using the miRNA expression data (Level 3) of 548 patients with glioblastoma multiforme (GBM) as an example, miRNA candidates for prognosis of cancer are selected. The reliability of selected miRNAs using this tool is demonstrated by 100 simulations. Furthermore, It is discovered that significant covariates are not directly composed of individually significant variables. Joint covariate detection provides a viewpoint for selecting variables which are not individually but jointly significant. Besides, it helps to select features which are not only consistent with survival time but also associated with prognosis risk. The software is available at http://bio-nefu.com/resource/jcdsa .

Open Access Data Centers as an Essential Partner to a Data Publication Journal

NASA Astrophysics Data System (ADS)

Carlson, D.; Pfeiffenberger, H.

2016-12-01

The success of Earth System Science Data derives in part from key infrastructure: digital object identifiers (doi) and open access data centers. Our concept that a data journal should promote access and exchange through publication of reviewed data descriptions presupposed third parties to hold the data. As minimum criteria for those data centers we expected international reputation for quality of service and an active lifetime extending at least a decade into the future. We also expected modern access interfaces offering geographic, topical and parameter-based browsing - so that users could discover related holdings through an ESSD link or discover ESSD by way of links in data sets revealed through the center's browse tools - and true open access. True open access means one or two clicks from abstract in ESSD to the data itself without barriers. We started with Pangaea and CDIAC. Data providers already used these centers, the staff welcomed the ESSD initiative and all parties cooperated on doi. With this initial support ESSD proved the basic concept of data publication and demonstrated utility to a larger group of data providers, many of whom suggested additional centers. So long as those data centers met expectations for open access and quality and durability of service, ESSD agreed to collaborate. Through back-door collaborations - e.g. service on particular data sets - ESSD developed working partnerships with more than 30 data centers in 13 countries. Data centers ask to join our list. We encourage those centers to stimulate local providers to submit a data set to ESSD, thus preserving our practical data-set by data-set partnership mode. For a few data centers where national policies impose a registration step, center staff and ESSD editors created bypass access routes to facilitate anonymous reviews. For ESSD purposes, open access and doi cooperation leading to reliable curation allows a win, win, win partnership among centers, providers, and journal.

Research in action: using positive deviance to improve quality of health care

PubMed Central

Bradley, Elizabeth H; Curry, Leslie A; Ramanadhan, Shoba; Rowe, Laura; Nembhard, Ingrid M; Krumholz, Harlan M

2009-01-01

Background Despite decades of efforts to improve quality of health care, poor performance persists in many aspects of care. Less than 1% of the enormous national investment in medical research is focused on improving health care delivery. Furthermore, when effective innovations in clinical care are discovered, uptake of these innovations is often delayed and incomplete. In this paper, we build on the established principle of 'positive deviance' to propose an approach to identifying practices that improve health care quality. Methods We synthesize existing literature on positive deviance, describe major alternative approaches, propose benefits and limitations of a positive deviance approach for research directed toward improving quality of health care, and describe an application of this approach in improving hospital care for patients with acute myocardial infarction. Results The positive deviance approach, as adapted for use in health care, presumes that the knowledge about 'what works' is available in existing organizations that demonstrate consistently exceptional performance. Steps in this approach: identify 'positive deviants,' i.e., organizations that consistently demonstrate exceptionally high performance in the area of interest (e.g., proper medication use, timeliness of care); study the organizations in-depth using qualitative methods to generate hypotheses about practices that allow organizations to achieve top performance; test hypotheses statistically in larger, representative samples of organizations; and work in partnership with key stakeholders, including potential adopters, to disseminate the evidence about newly characterized best practices. The approach is particularly appropriate in situations where organizations can be ranked reliably based on valid performance measures, where there is substantial natural variation in performance within an industry, when openness about practices to achieve exceptional performance exists, and where there is an engaged constituency to promote uptake of discovered practices. Conclusion The identification and examination of health care organizations that demonstrate positive deviance provides an opportunity to characterize and disseminate strategies for improving quality. PMID:19426507

Shall We Climb on the Shoulders of the Giants to Extend the Reality Horizon of Physics?

NASA Astrophysics Data System (ADS)

Roychoudhuri, Chandrasekhar

2007-12-01

After a very successful flurry of activities for a few decades to maximize the benefits of the formalism of Quantum Mechanics to connect the micro and macro universe, the applied physics community has successfully engineered sustained technological innovations for human social advancements. However, a significant segment of the theoretical physics community put their endeavors essentially in inventing realities that are esthetically pleasing to our human logics (epistemology) rather than staying focused on discovering the actual physical realities in nature driven by cosmic logics (ontology). The purpose of this paper is an attempt to formulate a Reality Epistemology that can leverage our enormous successes in science to re-focus our attention to discovering nature's realities by understanding the physical processes behind all natural interactions that collectively make the cosmic evolution progressing forward. We underscore the deviation from seeking reality to justify the key premise of the paper. We can ``see'' (measure) the universe only through the ``eyes'' of the various sensors (detectors). None of these sensors are completely known to us as yet. All sensors also have inherently limited capabilities to respond to input signals and limited capabilities to ``report'' only a part of all that it experiences. We are thus forced to develop our mathematical theories mixing our human logics and incomplete information and hence they are all provisional and incomplete since they are predicting only correctly measured but limited report by the detector. Thus, we should be careful not to jump into conclusion that we have captured all the necessary cosmic logics behind the interactions involved. We dissect the measurement process in a generic way along with well defined steps to apply Reality Epistemology, which will jointly allow us to develop a scientific methodology of iteratively refining our ``successful'' human logics that can evolve towards our goal of capturing the cosmic logics. The core content of this paper was first presented at the 2007 QTRF-4 conference at the Vaxjo University [1].

Design and Processing of a Novel Chaos-Based Stepped Frequency Synthesized Wideband Radar Signal.

PubMed

Zeng, Tao; Chang, Shaoqiang; Fan, Huayu; Liu, Quanhua

2018-03-26

The linear stepped frequency and linear frequency shift keying (FSK) signal has been widely used in radar systems. However, such linear modulation signals suffer from the range-Doppler coupling that degrades radar multi-target resolution. Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily predicted by the interception receiver in the electronic countermeasures (ECM) environments, which limits radar anti-jamming performance. In addition, the single FSK modulation reduces the radar low probability of intercept (LPI) performance, for it cannot achieve a large time-bandwidth product. To solve such problems, we propose a novel chaos-based stepped frequency (CSF) synthesized wideband signal in this paper. The signal introduces chaotic frequency hopping between the coherent stepped frequency pulses, and adopts a chaotic frequency shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the signal has been proposed. According to our theoretical analyses and the simulations, the proposed signal and processing method achieve better multi-target resolution and LPI performance. Furthermore, flexible modulation is able to increase the robustness against identification of the interception receiver and improve the anti-jamming performance of the radar.

Did Students Get It? Self-Assessment as Key to Learning

ERIC Educational Resources Information Center

Louis, Patricia; Harada, Violet H.

2012-01-01

As the school librarian at Aliamanu Elementary School, Patty (Patricia Louis) has focused on assessment with her teachers and students as a means to improve teaching and learning. Over the years, Patty and Vi (Violet Harada) have formed a collegial mentoring relationship, and this article provides a glimpse of what both discovered about building…

Women and Careers: Issues and Challenges.

ERIC Educational Resources Information Center

Konek, Carol Wolfe, Ed.; Kitch, Sally L., Ed.

This book presents, in 11 chapters, results of a major survey to discover how women feel about the key issues surrounding their experiences in the workplace. The survey, conducted by the Research Group on Women and Work, was sent to 770 women in Wichita, Kansas; it received 494 responses, augmented by 238 responses to a follow-up survey 5 years…

Heritage Quay: What Will You Discover? Transforming the Archives of the University of Huddersfield, Yorkshire, UK

ERIC Educational Resources Information Center

Wickham, M. Sarah

2015-01-01

The University of Huddersfield presents a key case study of the transformation of its Archives Service, using the newly-developed Staff/Space/Collections dependency model for archives and the lessons of the UK's Customer Service Excellence (CSE) scheme in order to examine and illustrate service development. Heritage Lottery Fund (HLF) and…

Social and economic profile technical guide

Treesearch

David Seesholtz; Denise Wickwar; John C. Russell

2006-01-01

A social and economic profile is a key element of a social assessment. A social and economic assessment or profile is used by line officers, planning staff social scientists, and others to inform both forest planning activities and project-level work. It is important to discover how planning and management decisions made by National Forest System staff will affect...

Discovering the "-Ologies" on the Jurassic Coast

ERIC Educational Resources Information Center

Peacock, Alan

2007-01-01

The Jurassic Coast is Britain's only natural World Heritage site, a tangible time-line that takes one through 185 million years of history in 95 miles of coast. It provides individuals with a world-famous educational resource and an unrivalled outdoor classroom that has played a key role in the study of earth sciences. The author is keen to ignite…

The CLEAR[TM] Problem-Solving Model: Discovering Strengths and Solutions

ERIC Educational Resources Information Center

Koehler, Nancy; Seger, Vikki

2011-01-01

This article introduces a unique team approach to planning and positive behavior support. The young person becomes a key participant in solving problems and setting goals for growth. The CLEAR Team Problem Solving model shifts the focus from deficits to strengths and solutions. The goal is to identify how a child's private logic and interpersonal…

Discovering a Gold Mine of Strategies for At-Risk Students through Systematic Staff Development.

ERIC Educational Resources Information Center

Bernal, Jesse R.; Villarreal, Diana

This paper discusses an effective model of systematic staff development focusing on prevention and intervention strategies used with at-risk students. The following are key elements: (1) matching of the purposes of training to the goals of the school districts; (2) multiple and integrated activities; (3) participants' thorough orientation to the…

Is Anxiety in Young Boys the New Normal?

ERIC Educational Resources Information Center

Mogel, Wendy

2016-01-01

As a psychologist of 35 years, Wendy Mogel discusses what she has discovered to be the new trend behind anxiety in young boys. Through hours of probing and pondering, neither hyperparenting nor early trauma (what one might think were logical causes of a young boy's anxiety) is the key to understanding this new trend. She explains that many…

Discovering Self-Expression through Study of Harlem Renaissance Poetry.

ERIC Educational Resources Information Center

Mowery, Raymond

Self-expression is a key component that adolescents at a certain stage of development (eighth grade) need to be aware of and understand. Students are undergoing dramatic change during this time of their lives--they are moving from Erikson's Industry versus Inferiority stage to Identity versus Role Confusion stage. Poetry is a literary genre in…

Using Patent Classification to Discover Chemical Information in a Free Patent Database: Challenges and Opportunities

ERIC Educational Resources Information Center

Ha¨rtinger, Stefan; Clarke, Nigel

2016-01-01

Developing skills for searching the patent literature is an essential element of chemical information literacy programs at the university level. The present article creates awareness of patents as a rich source of chemical information. Patent classification is introduced as a key-component in comprehensive search strategies. The free Espacenet…

Connections 2015: Our History: Journeys in KF Research. Annual Newsletter

ERIC Educational Resources Information Center

Gilmore, Melinda, Ed.; Holwerk, David, Ed.

2015-01-01

Each issue of this annual newsletter focuses on a particular area of Kettering's research. The 2015 issue focuses on a yearlong review of Kettering's research over time. This issue contains the following articles that address this review: (1) How Kettering Discovered Democracy (David Mathews); (2) Key Events in KF History (Collette McDonough); (3)…

Creation of Exercises for Team-Based Learning in Business

ERIC Educational Resources Information Center

Timmerman, John E.; Morris, R. Franklin, Jr.

2015-01-01

Team-based learning (TBL) is an approach that builds on both the case method and problem-based learning and has been widely adopted in the sciences and healthcare disciplines. In recent years business disciplines have also discovered the value of this approach. One of the key characteristics of the team-based learning approach consists of…

The E-Portfolio Continuum: Discovering Variables for E-Portfolio Adoption within Music Education

ERIC Educational Resources Information Center

Taylor, John; Dunbar-Hall, Peter; Rowley, Jennifer

2012-01-01

This article presents the results of audit data compiled from a case study introducing e-portfolios into a Music Education degree program, and highlights the key challenges faced from the initial stages of student use to curricular embedding and student adoption. This article discusses the technological, social and educational impacts inherent in…

Nonlinear Penalized Estimation of True Q-Matrix in Cognitive Diagnostic Models

ERIC Educational Resources Information Center

Xiang, Rui

2013-01-01

A key issue of cognitive diagnostic models (CDMs) is the correct identification of Q-matrix which indicates the relationship between attributes and test items. Previous CDMs typically assumed a known Q-matrix provided by domain experts such as those who developed the questions. However, misspecifications of Q-matrix had been discovered in the past…

Listen to Our Salmon: Forests, Rivers and Oceans are Connected.

ERIC Educational Resources Information Center

Mueller, Andrea; Brown, Rod

1998-01-01

A university-based researcher and a grade seven teacher collaborated to plan a science curriculum that would help elementary school students discover the world of salmon and understand its life cycle. Describes key components of the salmon-enhancement program and river-health project. A student's record of hatching chum fry in the classroom is…

Discovering Synergistic Drug Combination from a Computational Perspective.

PubMed

Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen; Li, Guanghui

2018-03-30

Synergistic drug combinations play an important role in the treatment of complex diseases. The identification of effective drug combination is vital to further reduce the side effects and improve therapeutic efficiency. In previous years, in vitro method has been the main route to discover synergistic drug combinations. However, many limitations of time and resource consumption lie within the in vitro method. Therefore, with the rapid development of computational models and the explosive growth of large and phenotypic data, computational methods for discovering synergistic drug combinations are an efficient and promising tool and contribute to precision medicine. It is the key of computational methods how to construct the computational model. Different computational strategies generate different performance. In this review, the recent advancements in computational methods for predicting effective drug combination are concluded from multiple aspects. First, various datasets utilized to discover synergistic drug combinations are summarized. Second, we discussed feature-based approaches and partitioned these methods into two classes including feature-based methods in terms of similarity measure, and feature-based methods in terms of machine learning. Third, we discussed network-based approaches for uncovering synergistic drug combinations. Finally, we analyzed and prospected computational methods for predicting effective drug combinations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

PubMed

Hofler, Lisa G; Cordes, Sarah; Cwiak, Carrie A; Goedken, Peggy; Jamieson, Denise J; Kottke, Melissa

2017-01-01

To understand the most important steps required to implement immediate postpartum long-acting reversible contraception (LARC) programs in different Georgia hospitals and the barriers to implementing such a program. This was a qualitative study. We interviewed 32 key personnel from 10 Georgia hospitals working to establish immediate postpartum LARC programs. Data were analyzed using directed qualitative content analysis principles. We used the Stages of Implementation to organize participant-identified key steps for immediate postpartum LARC into an implementation guide. We compared this guide to hospitals' implementation experiences. At the completion of the study, LARC was available for immediate postpartum placement at 7 of 10 study hospitals. Participants identified common themes for the implementation experience: team member identification and ongoing communication, payer preparedness challenges, interdependent department-specific tasks, and piloting with continuing improvements. Participants expressed a need for anticipatory guidance throughout the process. Key first steps to immediate postpartum LARC program implementation were identifying project champions, creating an implementation team that included all relevant departments, obtaining financial reassurance, and ensuring hospital administration awareness of the project. Potential barriers included lack of knowledge about immediate postpartum LARC, financial concerns, and competing clinical and administrative priorities. Hospitals that were successful at implementing immediate postpartum LARC programs did so by prioritizing clear communication and multidisciplinary teamwork. Although the implementation guide reflects a comprehensive assessment of the steps to implementing immediate postpartum LARC programs, not all hospitals required every step to succeed. Hospital teams report that implementing immediate postpartum LARC programs involves multiple departments and a number of important steps to consider. A stage-based approach to implementation, and a standardized guide detailing these steps, may provide the necessary structure for the complex process of implementing immediate postpartum LARC programs in the hospital setting.

Biocatalytic conversion of methane to methanol as a key step for development of methane-based biorefineries.

PubMed

Hwang, In Yeub; Lee, Seung Hwan; Choi, Yoo Seong; Park, Si Jae; Na, Jeong Geol; Chang, In Seop; Kim, Choongik; Kim, Hyun Cheol; Kim, Yong Hwan; Lee, Jin Won; Lee, Eun Yeol

2014-12-28

Methane is considered as a next-generation carbon feedstock owing to the vast reserves of natural and shale gas. Methane can be converted to methanol by various methods, which in turn can be used as a starting chemical for the production of value-added chemicals using existing chemical conversion processes. Methane monooxygenase is the key enzyme that catalyzes the addition of oxygen to methane. Methanotrophic bacteria can transform methane to methanol by inhibiting methanol dehydrogenase. In this paper, we review the recent progress made on the biocatalytic conversion of methane to methanol as a key step for methane-based refinery systems and discuss future prospects for this technology.

Key Elements of Observing Practice: A Data Wise DVD and Facilitator's Guide

ERIC Educational Resources Information Center

Boudett, Kathryn Parker; City, Elizabeth A.; Russell, Marcia K.

2010-01-01

Based on the bestselling book "Data Wise: A Step-by-Step Guide to Using Assessment Results to Improve Teaching and Learning", and its companion volume, "Data Wise in Action", this DVD and Facilitator's Guide offer insight into one of the most challenging steps in capturing data about school performance: observing and analyzing instructional…

Key Steps in the Special Review Process

EPA Pesticide Factsheets

EPA uses this process when it has reason to believe that the use of a pesticide may result in unreasonable adverse effects on people or the environment. Steps include comprehensive risk and benefit analyses and multiple Position Documents.

Transformation and diversification in early mammal evolution.

PubMed

Luo, Zhe-Xi

2007-12-13

Evolution of the earliest mammals shows successive episodes of diversification. Lineage-splitting in Mesozoic mammals is coupled with many independent evolutionary experiments and ecological specializations. Classic scenarios of mammalian morphological evolution tend to posit an orderly acquisition of key evolutionary innovations leading to adaptive diversification, but newly discovered fossils show that evolution of such key characters as the middle ear and the tribosphenic teeth is far more labile among Mesozoic mammals. Successive diversifications of Mesozoic mammal groups multiplied the opportunities for many dead-end lineages to iteratively evolve developmental homoplasies and convergent ecological specializations, parallel to those in modern mammal groups.

A Soil Service Index: a method for quantifying the value, vulnerability, and status of soil resources

NASA Astrophysics Data System (ADS)

Harden, J. W.; Loisel, J.; Hugelius, G.; Sulman, B. N.; Bond-Lamberty, B. P.; Abramoff, R. Z.; Malhotra, A.; Gill, A. L.

2017-12-01

Soils support ecological and human systems by providing a physical and biogeochemical basis for plant growth, ecological functions, water quality, and water storage, and by providing services and functions needed for economic development, human well-being, and conservation of natural resources. Quantitative evaluation of soil services, however, is inconsistent and poorly communicated, in part because we lack a scientific, unified basis for evaluating soils and their potential for serving our needs. We introduce an index of soil service (SSI) in which multiple services are numerically or quantitatively assessed, normalized to a unit-less scale for purposes of intercomparability, and evaluated for a given site or region. Services include organic matter and/or organic carbon storage; plant productivity; CO2 or GHG exchange with the atmosphere; water storage capacity; and nutrient storage and/or availability. The status of SSI can be evaluated by individual services or by a composite index that combines multiple services. The status can be monitored over time; and key services that are more highly valued for a given soil can be weighted accordingly in comparison to other services. As a first step, existing data for each service are captured from a literature and data review in order to establish the full range of values. A site value establishes the ranking relative to the full range. Key services are weighted according to local values. A final index is the sum of the normalized, weighted products. Metrics can be updated and adapted as new data or services are discovered or recognized. Metrics can be used to compare among sites, regions, or time periods.

Gondwana Tales: an inquiry approach to plate tectonics

NASA Astrophysics Data System (ADS)

Domènech Casal, Jordi

2014-05-01

Plate tectonics and its effects on the constitution of seas and continents are key models in science education. Fossil evidences are usually taught in demostrative key when Wegener's discoverings about Pangea are introduced. In order to introduce inquiry-based science education (IBSE) approaches to this topic, we propose "Gondwana Tales", an activity where students are asked to use fossil data to reconstruct the geologic history of an imaginary planet. Grouped in independent teams, each team is furnished with stratigraphic columns from several sites containing faunistic successions of real organisms existing in the past in Earth. Students are told to reconstruct a model of the evolution of the continents, by making calculations of relative ages of the fossils, and relating each fossil to a geologic era. The different teams have incomplete and complementary information. After a first step where they have to propose a partial model based on incomplete data, each team receives a "visitor scientist" from another team, this implying an informal scientific communication event. This process is performed several times, engaging a discussion in each team and getting a final consensus model created by the whole class. Correct answer is not given to the students, even at the end of the activity, to keep the activity under the parameters of real scientific experience, where there is not a "correct answer" to compare. Instead of this, and following the IBSE standards, a reflection on the process is proposed to students. The lack of complete information and the need to collaborate are part of classroom dynamics focused to the understanding of the process of creation of the scientific knowledge. This activity is part of the C3 Project on Creation of Scientific Knowledge that is being applied in the school.

Petascale Diagnostic Assessment of the Global Portfolio Rainfall Space Missions' Ability to Support Flood Forecasting

NASA Astrophysics Data System (ADS)

Reed, P. M.; Chaney, N.; Herman, J. D.; Wood, E. F.; Ferringer, M. P.

2015-12-01

This research represents a multi-institutional collaboration between Cornell University, The Aerospace Corporation, and Princeton University that has completed a Petascale diagnostic assessment of the current 10 satellite missions providing rainfall observations. Our diagnostic assessment has required four core tasks: (1) formally linking high-resolution astrodynamics design and coordination of space assets with their global hydrological impacts within a Petascale "many-objective" global optimization framework, (2) developing a baseline diagnostic evaluation of a 1-degree resolution global implementation of the Variable Infiltration Capacity (VIC) model to establish the required satellite observation frequencies and coverage to maintain acceptable global flood forecasts, (3) evaluating the limitations and vulnerabilities of the full suite of current satellite precipitation missions including the recently approved Global Precipitation Measurement (GPM) mission, and (4) conceptualizing the next generation spaced-based platforms for water cycle observation. Our team exploited over 100 Million hours of computing access on the 700,000+ core Blue Waters machine to radically advance our ability to discover and visualize key system tradeoffs and sensitivities. This project represents to our knowledge the first attempt to develop a 10,000 member Monte Carlo global hydrologic simulation at one degree resolution that characterizes the uncertain effects of changing the available frequencies of satellite precipitation on drought and flood forecasts. The simulation—optimization components of the work have set a theoretical baseline for the best possible frequencies and coverages for global precipitation given unlimited investment, broad international coordination in reconfiguring existing assets, and new satellite constellation design objectives informed directly by key global hydrologic forecasting requirements. Our research poses a step towards realizing the integrated global water cycle observatory long sought by the World Climate Research Programme, which has to date eluded the world's space agencies.

Optimizing identification and management of COPD patients – reviewing the role of the community pharmacist

PubMed Central

van Boven, Job F. M.; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2016-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician–pharmacist collaboration. PMID:27510273

Discovering chemistry with an ab initio nanoreactor

DOE PAGES

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; ...

2014-11-02

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

Discovering chemistry with an ab initio nanoreactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

An Exploration of Latent Structure in Observational Huntington’s Disease Studies

PubMed Central

Ghosh, Soumya; Sun, Zhaonan; Li, Ying; Cheng, Yu; Mohan, Amrita; Sampaio, Cristina; Hu, Jianying

2017-01-01

Huntington’s disease (HD) is a monogenic neurodegenerative disorder characterized by the progressive decay of motor and cognitive abilities accompanied by psychiatric episodes. Tracking and modeling the progression of the multi-faceted clinical symptoms of HD is a challenging problem that has important implications for staging of HD patients and the development of improved enrollment criteria for future HD studies and trials. In this paper, we describe the first steps towards this goal. We begin by curating data from four recent observational HD studies, each containing a diverse collection of clinical assessments. The resulting dataset is unprecedented in size and contains data from 19,269 study participants. By analyzing this large dataset, we are able to discover hidden low dimensional structure in the data that correlates well with surrogate measures of HD progression. The discovered structures are promising candidates for future consumption by downstream statistical HD progression models. PMID:28815114

Mining and Utilizing Dataset Relevancy from Oceanographic Dataset (MUDROD) Metadata, Usage Metrics, and User Feedback to Improve Data Discovery and Access

NASA Astrophysics Data System (ADS)

Jiang, Y.

2015-12-01

Oceanographic resource discovery is a critical step for developing ocean science applications. With the increasing number of resources available online, many Spatial Data Infrastructure (SDI) components (e.g. catalogues and portals) have been developed to help manage and discover oceanographic resources. However, efficient and accurate resource discovery is still a big challenge because of the lack of data relevancy information. In this article, we propose a search engine framework for mining and utilizing dataset relevancy from oceanographic dataset metadata, usage metrics, and user feedback. The objective is to improve discovery accuracy of oceanographic data and reduce time for scientist to discover, download and reformat data for their projects. Experiments and a search example show that the propose engine helps both scientists and general users search for more accurate results with enhanced performance and user experience through a user-friendly interface.

Umbral moonshine and K3 surfaces

DOE PAGES

Cheng, Miranda C. N.; Harrison, Sarah

2015-06-25

Recently, 23 cases of umbral moonshine, relating mock modular forms and finite groups, have been discovered in the context of the 23 even unimodular Niemeier lattices. One of the 23 cases in fact coincides with the so-called Mathieu moonshine, discovered in the context of K3 non-linear sigma models. In this paper we establish a uniform relation between all 23 cases of umbral moonshine and K3 sigma models, and thereby take a first step in placing umbral moonshine into a geometric and physical context. In addition, this is achieved by relating the ADE root systems of the Niemeier lattices to themore » ADE du Val singularities that a K3 surface can develop, and the configuration of smooth rational curves in their resolutions. A geometric interpretation of our results is given in terms of the marking of K3 surfaces by Niemeier lattices.« less

Employing Simulation to Evaluate Designs: The APEX Approach

NASA Technical Reports Server (NTRS)

Freed, Michael A.; Shafto, Michael G.; Remington, Roger W.; Null, Cynthia H. (Technical Monitor)

1998-01-01

The key innovations of APEX are its integrated approaches to task analysis, procedure definition, and intelligent, resource-constrained multi-tasking. This paper presents a step-by-step description of how APEX is used, from scenario development through trace analysis.

Hierarchical video summarization

NASA Astrophysics Data System (ADS)

Ratakonda, Krishna; Sezan, M. Ibrahim; Crinon, Regis J.

1998-12-01

We address the problem of key-frame summarization of vide in the absence of any a priori information about its content. This is a common problem that is encountered in home videos. We propose a hierarchical key-frame summarization algorithm where a coarse-to-fine key-frame summary is generated. A hierarchical key-frame summary facilitates multi-level browsing where the user can quickly discover the content of the video by accessing its coarsest but most compact summary and then view a desired segment of the video with increasingly more detail. At the finest level, the summary is generated on the basis of color features of video frames, using an extension of a recently proposed key-frame extraction algorithm. The finest level key-frames are recursively clustered using a novel pairwise K-means clustering approach with temporal consecutiveness constraint. We also address summarization of MPEG-2 compressed video without fully decoding the bitstream. We also propose efficient mechanisms that facilitate decoding the video when the hierarchical summary is utilized in browsing and playback of video segments starting at selected key-frames.

A First Step in Learning Analytics: Pre-Processing Low-Level Alice Logging Data of Middle School Students

ERIC Educational Resources Information Center

Werner, Linda; McDowell, Charlie; Denner, Jill

2013-01-01

Educational data mining can miss or misidentify key findings about student learning without a transparent process of analyzing the data. This paper describes the first steps in the process of using low-level logging data to understand how middle school students used Alice, an initial programming environment. We describe the steps that were…

Corruption in the Balkans: An Examination of the Ties Between Government and Crime in Several Southeast European Countries

DTIC Science & Technology

2013-12-01

Mataković, Transparency in Funding Political Parties: Croatia 2011 ( Zagreb : Transparency International Croatia, 2011), 7, 19; Stevan Dojčinović et al...compulsory measures that could have forced Zagreb to further reduce its corruption have now been removed. Despite many recent steps in the right...authorities discovered the body of Ivana Hodak, the daughter of a recognized prosecutor in Zagreb , in the stairwell outside her apartment building

Near East/South Asia Report.

DTIC Science & Technology

1983-07-25

Beirut in what was taken at the time as a sign of confidence in Lebanon’s economic future {An-Nahar Arab Report & MEMO, May lOand September 6,1982...leave Qatar after completing her tour of duty had to be treated for shock when she discovered her $10,000 savings were lost in the collapse of Doha...risks and save financial and adminis- trative costs. These steps are peaked by the central bank announcement of a new policy to nationalize foreign

Noise and Chaos in Driven Josephson Junctions

DTIC Science & Technology

1987-03-01

be physically close to some noisy equipment such as a CO2 laser containing an electric discharge and the laser power supply . So we have to try to...regions. The agreement is very good in some of the quanti- tative comparisons such as the step width dependence on the laser power . The simulations...discovered that the noisy I-V curves are caused I various nonlinear dynamic effects. There are I-V curves irradiated at certain laser power levels

Intra-procedural Path-insensitve Grams (I-GRAMS) and Disassembly Based Features for Packer Tool Classification and Detection

DTIC Science & Technology

2012-06-14

executable file is packed is a critical step in software security. This research uses machine learning methods to build the Polymorphic and Non-Polymorphic...Packer Detection (PNPD) system that detects whether an executable is packed by either ASPack, UPX, Metasploit’s polymorphic msfencode, or is packed in...detect packed executables used in experiments. Overall, it is discovered i-grams provide the best results with accuracies above 99.5%, average true

Verlet scheme non-conservativeness for simulation of spherical particles collisional dynamics and method of its compensation

NASA Astrophysics Data System (ADS)

Savin, Andrei V.; Smirnov, Petr G.

2018-05-01

Simulation of collisional dynamics of a large ensemble of monodisperse particles by the method of discrete elements is considered. Verle scheme is used for integration of the equations of motion. Non-conservativeness of the finite-difference scheme is discovered depending on the time step, which is equivalent to a pure-numerical energy source appearance in the process of collision. Compensation method for the source is proposed and tested.

A Step into an eco-Compatible Future: Iron- and Cobalt-catalyzed Borrowing Hydrogen Transformation.

PubMed

Quintard, Adrien; Rodriguez, Jean

2016-01-08

Living on borrowed hydrogen: Recent developments in iron- and cobalt-catalyzed borrowing hydrogen have shown that economically reliable catalysts can be used in this type of waste-free reactions. By using well-defined inexpensive catalysts, known reactions can now be run efficiently without the necessary use of noble metals; however, in addition new types of reactivity can also be discovered. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEY COMPARISON: Key comparison CCQM-K60: Total selenium and selenomethionine in selenised wheat flour

NASA Astrophysics Data System (ADS)

Goenaga Infante, Heidi; Sargent, Mike

2010-01-01

Key comparison CCQM-K60 was performed to assess the analytical capabilities of national metrology institutes (NMIs) to accurately quantitate the mass fraction of selenomethionine (SeMet) and total selenium (at low mg kg-1 levels) in selenised wheat flour. It was organized by the Inorganic Analysis Working Group (IAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) as a follow-up key comparison to the previous pilot study CCQM-P86 on selenised yeast tablets. LGC Limited (Teddington, UK) and the Institute for National Measurement Standards, National Research Council Canada (NRCC, Ottawa, Canada) acted as the coordinating laboratories. CCQM-K60 was organized in parallel with a pilot study (CCQM-P86.1) involving not only NMIs but also expert laboratories worldwide, thus enabling them to assess their capabilities, discover problems and learn how to modify analytical procedures accordingly. Nine results for total Se and four results for SeMet were reported by the participant NMIs. Methods used for sample preparation were microwave assisted acid digestion for total Se and multiple-step enzymatic hydrolysis and hydrolysis with methanesulfonic acid for SeMet. For total Se, detection techniques included inductively coupled plasma mass spectrometry (ICP-MS) with external calibration, standard additions or isotope dilution analysis (IDMS); instrumental neutron activation analysis (INAA); and graphite furnace atomic absorption spectrometry (GFAAS) with external calibration. For determination of SeMet in the wheat flour sample, the four NMIs relied upon measurements using species-specific IDMS (using 76Se-enriched SeMet) with HPLC-ICP-MS. Eight of the nine participating NMIs reported results for total Se within 3.5% deviation from the key comparison reference value (KCRV). For SeMet, the four participating NMIs reported results within 3.2% deviation from the KCRV. This shows that the performance of the majority of the CCQM-K60 participants was very good, illustrating their ability to obtain accurate results for such analytes in a complex food matrix containing approximately 17 mg kg-1 Se. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

English as a Medium of Instruction: Evidence for Language and Content Targets in Bilingual Education in Economics

ERIC Educational Resources Information Center

Hernandez-Nanclares, Nuria; Jimenez-Munoz, Antonio

2017-01-01

This paper contributes towards a framework for analysing the effect of teaching Economics through a foreign language, in order to discover best practices that foster key content and language skills for Higher Education institutions following language bilingual programmes. The first part of the paper deals with the benefits and problems of…

Inhabiting Culture: Spanish Anarchists' Vision of Cultural Learning through Aesthetics in the Nineteenth and Early Twentieth Centuries

ERIC Educational Resources Information Center

Collelldemont, Eulàlia; Vilanou, Conrad

2017-01-01

Revisions of textual and audio-visual materials reveal the educational vision of Spanish anarchists. Through research, we have discovered the importance of aesthetical education and art in general for this protest political party. By studying the three key historical moments of the movement (1868-1939/1901-1910/1910-1936-1939) we have traced the…

New species of Prolachesilla Mockford & Sullivan (Psocodea: 'Psocoptera': Lachesillidae: Graphocaeciliini) from Bolivia and Mexico.

PubMed

Arango, Stephania Sandoval; Obando, Ranulfo González; Aldrete, Alfonso Neri García

2017-03-20

The genus Prolachesilla Mockford & Sullivan presently includes nine species, all described when the genus was erected; since then, no other species have been discovered. Here, we describe and illustrate one Bolivian and three Mexican species. This is the first record of Prolachesilla from Bolivia. A key to the species of the genus is included.

The Views of Clients with Mild Intellectual Disabilities regarding Their Working Relationships with Caregivers

ERIC Educational Resources Information Center

Roeden, John M.; Maaskant, Marian A.; Curfs, Leopold M. G.

2011-01-01

Background: Research studies into the effect of therapies have shown that a good relationship between the client and his caregiver is a key factor in a positive treatment outcome. Methods: The nominal group technique (NGT) has been used in this study to discover what clients with intellectual disabilities feel contributes to a successful working…

Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening.

PubMed

Gunosewoyo, Hendra; Coster, Mark J; Bennett, Maxwell R; Kassiou, Michael

2009-07-15

The purinergic P2X(7) receptor is a unique member of the ATP-gated P2X family. This receptor has been implicated in numerous diseases and many structurally diverse ligands have been discovered via high throughput screening. This perspective will attempt to highlight some of the most recent key findings in both the biology and chemistry.

Parents' Experience of Feeling Socially Supported as Adolescents Come Out as Lesbian and Gay: A Phenomenological Study

ERIC Educational Resources Information Center

Saltzburg, Susan

2009-01-01

Discovering that an adolescent is lesbian or gay is often experienced as a family crisis. Feeling bereft of social support during times of such emotional upheaval and transition may precipitate states of despondency for parents, placing both children and parents at risk. While social support has been discussed as a key mediating agent for…

A Qualitative Analysis of the Self-Regulated Learning of First-Semester College Students

ERIC Educational Resources Information Center

Toms, Marcia

2016-01-01

Self-regulated learning (SRL) plays a key role in student's academic achievement. This study used a social cognitive lens and qualitative methods to discover and describe the SRL of a group of eight students during their first semester in college. Each participant was interviewed four times at strategic points between August and December 2012. In…

Key Considerations for the Success of Medical Education Research and Innovation Units in Canada: Unit Director Perceptions

ERIC Educational Resources Information Center

Varpio, Lara; Bidlake, Erin; Humphrey-Murto, Sue; Sutherland, Stephanie; Hamstra, Stanley J.

2014-01-01

Growth in the field of medical education is evidenced by the proliferation of units dedicated to advancing Medical Education Research and Innovation (MERI). While a review of the literature discovered narrative accounts of MERI unit development, we found no systematic examinations of the dimensions of and structures that facilitate the success of…

QUANTITATION OF PERCHLORATE ION BY ELECTROSPRAY IONIZATION MASS SPECTROMETRY (ESI-MS) USING STABLE ASSOCIATION COMPLEXES WITH ORGANIC CATIONS AND BASES TO ENHANCE SELECTIVITY

EPA Science Inventory

Quantitation of trace levels of perchlorate ion in water has become a key issue since this species was discovered in water supplies around the United States. Although ion chromatographic methods presently offer the lowest limit of detection, =40 nm (4ngm1-1), chromatographic ret...

Making Sense of the Yeast Sphingolipid Pathway.

PubMed

Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

2016-12-04

Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Six steps to an effective denials management program.

PubMed

Robertson, Brian; Doré, Alexander

2005-09-01

The following six steps can help you manage denials management issues in your organization: Create standard definitions of denial types. Establish a denial hierarchy. Establish a centralized denial database. Develop key performance indicators. Build responsibility matrices. Measure, monitor, and take action.

Revealing of photon-number splitting attack on quantum key distribution system by photon-number resolving devices

NASA Astrophysics Data System (ADS)

Gaidash, A. A.; Egorov, V. I.; Gleim, A. V.

2016-08-01

Quantum cryptography allows distributing secure keys between two users so that any performed eavesdropping attempt would be immediately discovered. However, in practice an eavesdropper can obtain key information from multi-photon states when attenuated laser radiation is used as a source of quantum states. In order to prevent actions of an eavesdropper, it is generally suggested to implement special cryptographic protocols, like decoy states or SARG04. In this paper, we describe an alternative method based on monitoring photon number statistics after detection. We provide a useful rule of thumb to estimate approximate order of difference of expected distribution and distribution in case of attack. Formula for calculating a minimum value of total pulses or time-gaps to resolve attack is shown. Also formulas for actual fraction of raw key known to Eve were derived. This method can therefore be used with any system and even combining with mentioned special protocols.

11-Step Total Synthesis of (−)-Maoecrystal V

PubMed Central

2016-01-01

An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (−)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product. PMID:27457680

Lean Information Management: Criteria For Selecting Key Performance Indicators At Shop Floor

NASA Astrophysics Data System (ADS)

Iuga, Maria Virginia; Kifor, Claudiu Vasile; Rosca, Liviu-Ion

2015-07-01

Most successful organizations worldwide use key performance indicators as an important part of their corporate strategy in order to forecast, measure and plan their businesses. Performance metrics vary in their purpose, definition and content. Therefore, the way organizations select what they think are the optimal indicators for their businesses varies from company to company, sometimes even from department to department. This study aims to answer the question of what is the most suitable way to define and select key performance indicators. More than that, it identifies the right criteria to select key performance indicators at shop floor level. This paper contributes to prior research by analysing and comparing previously researched selection criteria and proposes an original six-criteria-model, which caters towards choosing the most adequate KPIs. Furthermore, the authors take the research a step further by further steps to closed research gaps within this field of study.

Ionic Conductivity and its Role in Oxidation Reactions

NASA Astrophysics Data System (ADS)

Tamimi, Mazin Abdulla

In the field of solid oxide fuel cells (SOFCs), a substantial portion of research is focused on the ability of some oxide materials to conduct oxygen anions through their structure. For electrolytes, the benefits of improving bulk transport of ions are obvious: decrease the resistive losses of the electrolyte, and device efficiency goes up and higher power densities are possible. Even for cathode materials, better bulk ion transport leads to an increase in the oxygen exchange rate at the cathode surface, and the oxygen reduction reaction at the cathode surface is the rate limiting step for SOFC operation at intermediate temperatures (500-700ºC). As operation in this regime is a key step towards lowering the manufacturing cost and increasing the lifetime of devices, much effort is spent searching for new, more conductive materials, and analyzing existing materials to discover the structure-activity relationships that influence ionic conductivity. In the first part of this work, an overview is given of the neutron powder diffraction (NPD) techniques that are used to probe the structure of the materials in later parts. In the second part, NPD was used to analyze the structures of perovskite-type cathode materials, and show that increases in bulk conductivity led to increases in the surface oxygen exchange rate of these materials. In the final part, the methods used for SOFC cathode design were applied towards the design of oxide catalysts used for certain hydrocarbon partial oxidation reactions. The reactions studied follow the Mars van Krevelen mechanism, where oxygen atoms in the catalyst are consumed as part of the reaction and are subsequently replenished by oxygen in the gas phase. Similar to SOFC cathode operation, these processes include an oxygen reduction step, so it was hypothesized that increasing the ionic conductivity of the catalysts would improve their performance, just as it does for SOFC cathode materials. While the results are preliminary, the combination of a reference catalyst for the oxidative coupling of methane with a support with very high oxygen conductivity demonstrated a small increase in performance at low temperatures.

A CAD Approach to Integrating NDE With Finite Element

NASA Technical Reports Server (NTRS)

Abdul-Aziz, Ali; Downey, James; Ghosn, Louis J.; Baaklini, George Y.

2004-01-01

Nondestructive evaluation (NDE) is one of several technologies applied at NASA Glenn Research Center to determine atypical deformities, cracks, and other anomalies experienced by structural components. NDE consists of applying high-quality imaging techniques (such as x-ray imaging and computed tomography (CT)) to discover hidden manufactured flaws in a structure. Efforts are in progress to integrate NDE with the finite element (FE) computational method to perform detailed structural analysis of a given component. This report presents the core outlines for an in-house technical procedure that incorporates this combined NDE-FE interrelation. An example is presented to demonstrate the applicability of this analytical procedure. FE analysis of a test specimen is performed, and the resulting von Mises stresses and the stress concentrations near the anomalies are observed, which indicates the fidelity of the procedure. Additional information elaborating on the steps needed to perform such an analysis is clearly presented in the form of mini step-by-step guidelines.

Molecular Dynamics Simulation and Analysis of the Antimicrobial Peptide-Lipid Bilayer Interactions.

PubMed

Arasteh, Shima; Bagheri, Mojtaba

2017-01-01

A great deal of research has been undertaken in order to discover antimicrobial peptides (AMPs) with unexploited mechanisms of action to counteract the health-threatening issues associated with bacterial resistance. The intrinsic effectiveness of AMPs is strongly influenced by their initial interactions with the bacterial cell membrane. Understanding these interactions in the atomistic details is important for the design of the less prone bacteria-resistant peptides. However, these studies always require labor-intensive and difficult steps. With this regard, modeling studies of the AMPs binding to simple lipid membrane systems, e.g., lipid bilayers, is of great advantage. In this chapter, we present an applicable step-by-step protocol to run the molecular dynamics (MD) simulation of the interaction between cyclo-RRWFWR (c-WFW) (a small cyclic AMP) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer using the Groningen machine for chemical simulations (GROMACS) package. The protocol as described here may simply be optimized for other peptide-lipid systems of interest.

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2.

PubMed

Favaro, Marco; Xiao, Hai; Cheng, Tao; Goddard, William A; Yano, Junko; Crumlin, Ethan J

2017-06-27

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2

PubMed Central

Favaro, Marco; Yano, Junko; Crumlin, Ethan J.

2017-01-01

A national priority is to convert CO2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO2 in the presence of water as the first step toward CO2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts. PMID:28607092

Phase I/II study of alectinib in lung cancer with RET fusion gene: study protocol.

PubMed

Takeuchi, Shinji; Murayama, Toshinori; Yoshimura, Kenichi; Kawakami, Takahiro; Takahara, Shizuko; Imai, Yasuhito; Kuribayashi, Yoshikazu; Nagase, Katsuhiko; Goto, Koichi; Nishio, Makoto; Hasegawa, Yoshinori; Satouchi, Miyako; Kiura, Katsuyuki; Seto, Takashi; Yano, Seiji

2017-01-01

The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC. RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design. The primary endpoint is safety. In step 2, alectinib will be administered at the recommended dose (RD) defined by step 1. The primary endpoint is the response rate of RET inhibitor treatment-naïve patients. This is the first study to investigate the safety and preliminary efficacy of alectinib in RET fusion-positive NSCLC patients. If successful, alectinib treatment may lead to substantial and important changes in the management of NSCLC with RET fusion genes. J. Med. Invest. 64: 317-320, August, 2017.

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

Approaches for assessing and discovering protein interactions in cancer

PubMed Central

Mohammed, Hisham; Carroll, Jason S.

2013-01-01

Significant insight into the function of proteins, can be delineated by discovering and characterising interacting proteins. There are numerous methods for the discovery of unknown associated protein networks, with purification of the bait (the protein of interest) followed by Mass Spectrometry (MS) as a common theme. In recent years, advances have permitted the purification of endogenous proteins and methods for scaling down starting material. As such, approaches for rapid, unbiased identification of protein interactomes are becoming a standard tool in the researchers toolbox, rather than a technique that is only available to specialists. This review will highlight some of the recent technical advances in proteomic based discovery approaches, the pros and cons of various methods and some of the key findings in cancer related systems. PMID:24072816

An element through the looking glass: exploring the Au–C, Au–H and Au–O energy landscape

PubMed Central

Roşca, Dragoş-Adrian; Wright, Joseph A.

2015-01-01

Gold, the archetypal “noble metal”, used to be considered of little interest in catalysis. It is now clear that this was a misconception, and a multitude of gold-catalysed transformations has been reported. However, one consequence of the long-held view of gold as inert metal is that its organometallic chemistry contains many “unknowns”, and catalytic cycles devised to explain gold's reactivity draw largely on analogies with other transition metals. How realistic are such mechanistic assumptions? In the last few years a number of key compound classes have been discovered that can provide some answers. This Perspective attempts to summarise these developments, with particular emphasis on recently discovered gold(iii) complexes with bonds to hydrogen, oxygen, alkenes and CO ligands. PMID:26584519

Genomics of mucoepidermoid and adenoid cystic carcinomas.

PubMed

Yan, Kenneth; Yesensky, Jessica; Hasina, Rifat; Agrawal, Nishant

2018-02-01

To report on the current state of the literature on the genetics of mucoepidermoid and adenoid cystic carcinomas of the salivary glands with a focus on genomic screens and recently discovered genetic translocations. A PubMed based literature review was performed to query for genetics related basic science and preclinical studies about mucoepidermoid and adenoid cystic carcinomas of the salivary glands. Genetic translocations between CRTC1 and MAML2 in mucoepidermoid carcinoma and between MYB and NFIB in adenoid cystic carcinoma have been recently discovered and have therapeutic implications. Key signaling pathways such as the EGFR pathway in mucoepidermoid carcinoma and the Notch pathway, chromatin regulation, and c-kit mediated epithelial-mesenchymal transitions in adenoid cystic carcinoma have recently been elucidated, pointing to possible therapeutic targets in both cancers.

Genomics of mucoepidermoid and adenoid cystic carcinomas

PubMed Central

Yan, Kenneth; Yesensky, Jessica; Hasina, Rifat

2018-01-01

Objective To report on the current state of the literature on the genetics of mucoepidermoid and adenoid cystic carcinomas of the salivary glands with a focus on genomic screens and recently discovered genetic translocations. Methods A PubMed based literature review was performed to query for genetics related basic science and preclinical studies about mucoepidermoid and adenoid cystic carcinomas of the salivary glands. Results and conclusions Genetic translocations between CRTC1 and MAML2 in mucoepidermoid carcinoma and between MYB and NFIB in adenoid cystic carcinoma have been recently discovered and have therapeutic implications. Key signaling pathways such as the EGFR pathway in mucoepidermoid carcinoma and the Notch pathway, chromatin regulation, and c‐kit mediated epithelial‐mesenchymal transitions in adenoid cystic carcinoma have recently been elucidated, pointing to possible therapeutic targets in both cancers. PMID:29492469

Direct migration motion estimation and mode decision to decoder for a low-complexity decoder Wyner-Ziv video coding

NASA Astrophysics Data System (ADS)

Lei, Ted Chih-Wei; Tseng, Fan-Shuo

2017-07-01

This paper addresses the problem of high-computational complexity decoding in traditional Wyner-Ziv video coding (WZVC). The key focus is the migration of two traditionally high-computationally complex encoder algorithms, namely motion estimation and mode decision. In order to reduce the computational burden in this process, the proposed architecture adopts the partial boundary matching algorithm and four flexible types of block mode decision at the decoder. This approach does away with the need for motion estimation and mode decision at the encoder. The experimental results show that the proposed padding block-based WZVC not only decreases decoder complexity to approximately one hundredth that of the state-of-the-art DISCOVER decoding but also outperforms DISCOVER codec by up to 3 to 4 dB.

Quick and continuous improvement through kaizen blitz.

PubMed

McNichols, T; Hassinger, R; Bapst, G W

1999-05-01

It is our objective to provide you with a step-by-step approach to conducting a kaizen blitz within two days and describe how to achieve dramatic performance improvement with employee buy-in through this process. Kaizen blitz has been used dozens of times by the authors, and in some instances the same area has been blitzed as many as four times, with significant improvements each and every time. Employees have even taken it on themselves to conduct informal blitzes as a continuing improvement effort after a formal blitz has been conducted in their area. Blitzes can succeed in a variety of environments. The morning after the employees of one company attended this presentation, they self initiated a mini-blitz and discovered opportunities for improvement that they enthusiastically presented to management.

A METHOD FOR DETERMINING THE COMPATIBILITY OF HAZARDOUS WASTES

EPA Science Inventory

This report describes a method for determining the compatibility of the binary combinations of hazardous wastes. The method consists of two main parts, namely: (1) the step-by-step compatibility analysis procedures, and (2) the hazardous wastes compatibility chart. The key elemen...

Keys to a Safe, Secure School.

ERIC Educational Resources Information Center

Kennedy, Mike

2002-01-01

Outlines 10 steps that school administrators can take to make their schools safer and more secure for students and staff. These steps encompass crime prevention through environmental design, crisis planning, entrances, lighting, police presence, prevention programs, rapport with students, smaller schools, technology implementation, and staff…

Freedom of Information Act Requests: Six Keys to Handling Them

DTIC Science & Technology

2016-01-01

Defense AT&L: January–February 2016 50 Freedom of Information Act Requests Six Keys to Handling Them Michael A. Rodgers Rodgers is a professor of...crucial mission tasks. Understanding and using the six steps and keys provided above will free you from FOIA-induced distractions. The author can be contacted at michael.rodgers@dau.mil.

One-time pad, complexity of verification of keys, and practical security of quantum cryptography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molotkov, S. N., E-mail: sergei.molotkov@gmail.com

2016-11-15

A direct relation between the complexity of the complete verification of keys, which is one of the main criteria of security in classical systems, and a trace distance used in quantum cryptography is demonstrated. Bounds for the minimum and maximum numbers of verification steps required to determine the actual key are obtained.

Optimizing identification and management of COPD patients - reviewing the role of the community pharmacist.

PubMed

van der Molen, Thys; van Boven, Job F M; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2017-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self-management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow-up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

DOE PAGES

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

2016-04-08

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Permeability and kinetic coefficients for mesoscale BCF surface step dynamics: Discrete two-dimensional deposition-diffusion equation analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.

Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less

Location-Aware Dynamic Session-Key Management for Grid-Based Wireless Sensor Networks

PubMed Central

Chen, Chin-Ling; Lin, I-Hsien

2010-01-01

Security is a critical issue for sensor networks used in hostile environments. When wireless sensor nodes in a wireless sensor network are distributed in an insecure hostile environment, the sensor nodes must be protected: a secret key must be used to protect the nodes transmitting messages. If the nodes are not protected and become compromised, many types of attacks against the network may result. Such is the case with existing schemes, which are vulnerable to attacks because they mostly provide a hop-by-hop paradigm, which is insufficient to defend against known attacks. We propose a location-aware dynamic session-key management protocol for grid-based wireless sensor networks. The proposed protocol improves the security of a secret key. The proposed scheme also includes a key that is dynamically updated. This dynamic update can lower the probability of the key being guessed correctly. Thus currently known attacks can be defended. By utilizing the local information, the proposed scheme can also limit the flooding region in order to reduce the energy that is consumed in discovering routing paths. PMID:22163606

Efficient and Security Enhanced Anonymous Authentication with Key Agreement Scheme in Wireless Sensor Networks

PubMed Central

Jung, Jaewook; Moon, Jongho; Lee, Donghoon; Won, Dongho

2017-01-01

At present, users can utilize an authenticated key agreement protocol in a Wireless Sensor Network (WSN) to securely obtain desired information, and numerous studies have investigated authentication techniques to construct efficient, robust WSNs. Chang et al. recently presented an authenticated key agreement mechanism for WSNs and claimed that their authentication mechanism can both prevent various types of attacks, as well as preserve security properties. However, we have discovered that Chang et al’s method possesses some security weaknesses. First, their mechanism cannot guarantee protection against a password guessing attack, user impersonation attack or session key compromise. Second, the mechanism results in a high load on the gateway node because the gateway node should always maintain the verifier tables. Third, there is no session key verification process in the authentication phase. To this end, we describe how the previously-stated weaknesses occur and propose a security-enhanced version for WSNs. We present a detailed analysis of the security and performance of our authenticated key agreement mechanism, which not only enhances security compared to that of related schemes, but also takes efficiency into consideration. PMID:28335572

Efficient and Security Enhanced Anonymous Authentication with Key Agreement Scheme in Wireless Sensor Networks.

PubMed

Jung, Jaewook; Moon, Jongho; Lee, Donghoon; Won, Dongho

2017-03-21

At present, users can utilize an authenticated key agreement protocol in a Wireless Sensor Network (WSN) to securely obtain desired information, and numerous studies have investigated authentication techniques to construct efficient, robust WSNs. Chang et al. recently presented an authenticated key agreement mechanism for WSNs and claimed that their authentication mechanism can both prevent various types of attacks, as well as preserve security properties. However, we have discovered that Chang et al's method possesses some security weaknesses. First, their mechanism cannot guarantee protection against a password guessing attack, user impersonation attack or session key compromise. Second, the mechanism results in a high load on the gateway node because the gateway node should always maintain the verifier tables. Third, there is no session key verification process in the authentication phase. To this end, we describe how the previously-stated weaknesses occur and propose a security-enhanced version for WSNs. We present a detailed analysis of the security and performance of our authenticated key agreement mechanism, which not only enhances security compared to that of related schemes, but also takes efficiency into consideration.

Location-aware dynamic session-key management for grid-based Wireless Sensor Networks.

PubMed

Chen, Chin-Ling; Lin, I-Hsien

2010-01-01

Security is a critical issue for sensor networks used in hostile environments. When wireless sensor nodes in a wireless sensor network are distributed in an insecure hostile environment, the sensor nodes must be protected: a secret key must be used to protect the nodes transmitting messages. If the nodes are not protected and become compromised, many types of attacks against the network may result. Such is the case with existing schemes, which are vulnerable to attacks because they mostly provide a hop-by-hop paradigm, which is insufficient to defend against known attacks. We propose a location-aware dynamic session-key management protocol for grid-based wireless sensor networks. The proposed protocol improves the security of a secret key. The proposed scheme also includes a key that is dynamically updated. This dynamic update can lower the probability of the key being guessed correctly. Thus currently known attacks can be defended. By utilizing the local information, the proposed scheme can also limit the flooding region in order to reduce the energy that is consumed in discovering routing paths.

Traditional biotechnology for new foods and beverages.

PubMed

Hugenholtz, Jeroen

2013-04-01

The food and beverage industry is re-discovering fermentation as a crucial step in product innovation. Fermentation can provide various benefits such as unique flavor, health and nutrition, texture and safety (shelf life), while maintaining a 100% natural label. In this review several examples are presented on how fermentation is used to replace, modify or improve current, artificially produced, foods and beverages and how also fermentation can be used for completely novel consumer products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Integrated synthesis of poly(o-phenylenediamine)-derived carbon materials for high performance supercapacitors.

PubMed

Zhu, Hui; Wang, Xiaolei; Liu, Xuexia; Yang, Xiurong

2012-12-18

Poly(o-phenylenediamine) (POPD)-derived functional carbon materials with excellent capacitive performance are successfully synthesized by means of an integrated one-step process, in which FeCl(3) not only oxidizes the polymerization of the organic monomers but also activates the carbonization. Furthermore, extensive research has proved that this strategy to discover novel carbons is useful not only for capacitors but also for other energy storage/conversion devices. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacogenomics: where will it take us?

PubMed

Felcone, Linda Hull

2004-07-01

Until now, drug research has focused on discovering blockbusters to treat millions of patients. Pharmacogenomics, a multidisciplinary effort arising from the Human Genome Project, strives to deliver "personalized medicine." Researchers use genetic information to understand disease pathways and create drugs designed for small, likely-to-respond populations. The path from research to finished drugs is as logistically complex as landing a human on the moon, but don't expect a giant leap; progress will come throughout the next couple of decades via incremental steps.

Line width determination using a biomimetic fly eye vision system.

PubMed

Benson, John B; Wright, Cameron H G; Barrett, Steven F

2007-01-01

Developing a new vision system based on the vision of the common house fly, Musca domestica, has created many interesting design challenges. One of those problems is line width determination, which is the topic of this paper. It has been discovered that line width can be determined with a single sensor as long as either the sensor, or the object in question, has a constant, known velocity. This is an important first step for determining the width of any arbitrary object, with unknown velocity.

Modeling a Field Application of In Situ Bioremediation of Perchlorate-Contaminated Groundwater Using Horizontal Flow Treatment Wells (HFTWs)

DTIC Science & Technology

2004-03-01

the side effects of chemotherapy (Urbansky, 1998). As a result of several cases of aplastic anemia having been discovered in patients who were...Cl-) and oxygen (O2). The first two of 7 these reductive steps requires the presence of an electron donor, such as acetate, lactate , ethanol... Chile , is the only confirmed natural source of perchlorate (Bohlke et al., 1997; USEPA, 2001; Urbansky, 2002). The principal pathway by which

Protein synthesis and its regulation: a background study related to the biological effects of radiation. Progress report, July 1, 1976--August 31, 1977

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamecnik, P.C.

Results of studies are reported on delineation of the steps involved in protein synthesis and the role of transfer and messenger RNAs in the translation process. During the past year we have studied the mechanisms by which an oncogenic RNA virus modifies the growth process, and have begun to elucidate the role a novel dinucleotide, discovered in these laboratories, plays in rapidly growing cells in tissue culture.

Regio-selectivity of the Oxidative C-S Bond Formation in Ergothioneine and Ovothiol Biosyntheses

PubMed Central

Song, Heng; Leninger, Maureen; Lee, Norman

2014-01-01

Ergothioneine (5) and ovothiol (8) are two novel thiol-containing natural products. Their C-S bonds are formed by oxidative coupling reactions catalyzed by EgtB and OvoA enzymes, respectively. In this work, it was discovered that besides catalyzing the oxidative coupling between histidine and cysteine (1 → 6 conversion), OvoA can also catalyze a direct oxidative coupling between hercynine (2) and cysteine (2 → 4 conversion), which can shorten the ergothioneine biosynthetic pathway by two steps. PMID:24016264

The visual display of regulatory information and networks.

PubMed

Pirson, I; Fortemaison, N; Jacobs, C; Dremier, S; Dumont, J E; Maenhaut, C

2000-10-01

Cell regulation and signal transduction are becoming increasingly complex, with reports of new cross-signalling, feedback, and feedforward regulations between pathways and between the multiple isozymes discovered at each step of these pathways. However, this information, which requires pages of text for its description, can be summarized in very simple schemes, although there is no consensus on the drawing of such schemes. This article presents a simple set of rules that allows a lot of information to be inserted in easily understandable displays.

Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes.

PubMed

Martin, David B C; Nguyen, Lucas Q; Vanderwal, Christopher D

2012-01-06

A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.

Clinical research and the development of medical therapeutics.

PubMed

Antman, Elliott M

2014-01-01

Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.

Wobble↔Watson-Crick tautomeric transitions in the homo-purine DNA mismatches: a key to the intimate mechanisms of the spontaneous transversions.

PubMed

Brovarets', Ol'ha O; Hovorun, Dmytro M

2015-01-01

The intrinsic capability of the homo-purine DNA base mispairs to perform wobble↔Watson-Crick/Topal-Fresco tautomeric transitions via the sequential intrapair double proton transfer was discovered for the first time using QM (MP2/DFT) and QTAIM methodologies that are crucial for understanding the microstructural mechanisms of the spontaneous transversions.

Genetic Variation Linked to Lung Cancer Survival in White Smokers | Center for Cancer Research

Cancer.gov

CCR investigators have discovered evidence that links lung cancer survival with genetic variations (called single nucleotide polymorphisms) in the MBL2 gene, a key player in innate immunity. The variations in the gene, which codes for a protein called the mannose-binding lectin, occur in its promoter region, where the RNA polymerase molecule binds to start transcription, and

Iridium-Catalyzed Dynamic Kinetic Isomerization: Expedient Synthesis of Carbohydrates from Achmatowicz Rearrangement Products.

PubMed

Wang, Hao-Yuan; Yang, Ka; Bennett, Scott R; Guo, Sheng-rong; Tang, Weiping

2015-07-20

A highly stereoselective dynamic kinetic isomerization of Achmatowicz rearrangement products was discovered. This new internal redox isomerization provided ready access to key intermediates for the enantio- and diastereoselective synthesis of a series of naturally occurring sugars. The nature of the de novo synthesis also enables the preparation of both enantiomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Did You Remember to DID

DTIC Science & Technology

2010-04-01

threats (also known as a SWOT analysis) is a very useful method in identifying potential issues, hidden agendas, and competing egos. • Defining a...comprehensive communications plan uses what’s been defined and informs (the second key component to DID) government and con - tractor teams of the essential...program execution strategies. Inform Inform means communicating to internal and external stake- holders what was defined, expected, discovered, con

Usability Testing for e-Resource Discovery: How Students Find and Choose e-Resources Using Library Web Sites

ERIC Educational Resources Information Center

Fry, Amy; Rich, Linda

2011-01-01

In early 2010, library staff at Bowling Green State University (BGSU) in Ohio designed and conducted a usability study of key parts of the library web site, focusing on the web pages generated by the library's electronic resources management system (ERM) that list and describe the library's databases. The goal was to discover how users find and…

Fall of the Public Teacher--Discourse of Intimacy and the Teaching Profession in Denmark

ERIC Educational Resources Information Center

Johansen, Martin Blok

2015-01-01

This article reports on a case study conducted in a Danish municipality with 22 teachers as participants, in the context of a project focused on well-being and key educational competencies. The final aim was that of discovering how their ideal of the good teacher was verbalised. What is it that they thematise? How are thematisations created and…

Cooperative Institute for Research in the Atmosphere (CIRA) Requirements Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zurawski, Jason, W; Mace, Kathryn, P

2016-08-11

In August 2016 The Energy Sciences Network (ESnet) and Colorado State University (CSU) organized a review to characterize the networking requirements of the Cooperative Institute for Research in the Atmosphere (CIRA) located on the campus of Colorado State University. Several key findings highlighting the results from the review were discovered, with benefits to improve the overall scientific process for CIRA and CSU.

A Cross-Cultural Perspective about the Implementation and Adaptation Process of the Schoolwide Enrichment Model: The Importance of Talent Development in a Global World

ERIC Educational Resources Information Center

Hernández-Torrano, Daniel; Saranli, Adile Gulsah

2015-01-01

Gifted education and talent development are considered today as key elements for developing human capital and increasing competitiveness within education and the economy. Within this framework, a growing number of countries have begun to invest large amounts of resources to discover and nurture their most able students. As boundaries and…

Double emulsion formation through hierarchical flow-focusing microchannel

NASA Astrophysics Data System (ADS)

Azarmanesh, Milad; Farhadi, Mousa; Azizian, Pooya

2016-03-01

A microfluidic device is presented for creating double emulsions, controlling their sizes and also manipulating encapsulation processes. As a result of three immiscible liquids' interaction using dripping instability, double emulsions can be produced elegantly. Effects of dimensionless numbers are investigated which are Weber number of the inner phase (Wein), Capillary number of the inner droplet (Cain), and Capillary number of the outer droplet (Caout). They affect the formation process, inner and outer droplet size, and separation frequency. Direct numerical simulation of governing equations was done using volume of fluid method and adaptive mesh refinement technique. Two kinds of double emulsion formation, the two-step and the one-step, were simulated in which the thickness of the sheath of double emulsions can be adjusted. Altering each dimensionless number will change detachment location, outer droplet size and droplet formation period. Moreover, the decussate regime of the double-emulsion/empty-droplet is observed in low Wein. This phenomenon can be obtained by adjusting the Wein in which the maximum size of the sheath is discovered. Also, the results show that Cain has significant influence on the outer droplet size in the two-step process, while Caout affects the sheath in the one-step formation considerably.

From Diapers to Dating. A Parent's Guide to Raising Sexually Healthy Children.

ERIC Educational Resources Information Center

Haffner, Debra W.

This step-by-step program for raising sexually healthy children helps parents provide accurate information and communicate their own values to their children. Chapter 1, "The Basics"; includes "Sexually Healthy Families"; "The Key: Finding Teachable Moments"; and "Guidelines for Communication." Chapter 2,…

Nurse-led clinics: 10 essential steps to setting up a service.

PubMed

Hatchett, Richard

This article outlines 10 key steps for practitioners to consider when setting up and running a nurse-led clinic. It lays emphasis on careful planning, professional development and the need to audit and evaluate the service to ensure the clinic is measurably effective.

Post-processing procedure for industrial quantum key distribution systems

NASA Astrophysics Data System (ADS)

Kiktenko, Evgeny; Trushechkin, Anton; Kurochkin, Yury; Fedorov, Aleksey

2016-08-01

We present algorithmic solutions aimed on post-processing procedure for industrial quantum key distribution systems with hardware sifting. The main steps of the procedure are error correction, parameter estimation, and privacy amplification. Authentication of classical public communication channel is also considered.

Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.

PubMed

Takahata, Tatsuro; Takeda, Eri; Tobiume, Minoru; Tokunaga, Kenzo; Yokoyama, Masaru; Huang, Yu-Lun; Hasegawa, Atsuhiko; Shioda, Tatsuo; Sato, Hironori; Kannagi, Mari; Masuda, Takao

2017-01-01

Nonenzymatic roles for HIV-1 integrase (IN) at steps prior to the enzymatic integration step have been reported. To obtain structural and functional insights into the nonenzymatic roles of IN, we performed genetic analyses of HIV-1 IN, focusing on a highly conserved Tyr15 in the N-terminal domain (NTD), which has previously been shown to regulate an equilibrium state between two NTD dimer conformations. Replacement of Tyr15 with alanine, histidine, or tryptophan prevented HIV-1 infection and caused severe impairment of reverse transcription without apparent defects in reverse transcriptase (RT) or in capsid disassembly kinetics after entry into cells. Cross-link analyses of recombinant IN proteins demonstrated that lethal mutations of Tyr15 severely impaired IN structure for assembly. Notably, replacement of Tyr15 with phenylalanine was tolerated for all IN functions, demonstrating that a benzene ring of the aromatic side chain is a key moiety for IN assembly and functions. Additional mutagenic analyses based on previously proposed tetramer models for IN assembly suggested a key role of Tyr15 in facilitating the hydrophobic interaction among IN subunits, together with other proximal residues within the subunit interface. A rescue experiment with a mutated HIV-1 with RT and IN deleted (ΔRT ΔIN) and IN and RT supplied in trans revealed that the nonenzymatic IN function might be exerted through the IN precursor conjugated with RT (RT-IN). Importantly, the lethal mutations of Tyr15 significantly reduced the RT-IN function and assembly. Taken together, Tyr15 seems to play a key role in facilitating the proper assembly of IN and RT on viral RNA through the RT-IN precursor form. Inhibitors of the IN enzymatic strand transfer function (INSTI) have been applied in combination antiretroviral therapies to treat HIV-1-infected patients. Recently, allosteric IN inhibitors (ALLINIs) that interact with HIV-1 IN residues, the locations of which are distinct from the catalytic sites targeted by INSTI, have been discovered. Importantly, ALLINIs affect the nonenzymatic role(s) of HIV-1 IN, providing a rationale for the development of next-generation IN inhibitors with a mechanism that is distinct from that of INSTI. Here, we demonstrate that Tyr15 in the HIV-1 IN NTD plays a critical role during IN assembly by facilitating the hydrophobic interaction of the NTD with the other domains of IN. Importantly, we found that the functional assembly of IN through its fusion form with RT is critical for IN to exert its nonenzymatic function. Our results provide a novel mechanistic insight into the nonenzymatic function of HIV-1 IN and its prevention. Copyright © 2016 American Society for Microbiology.

Aldehyde-forming fatty acyl-CoA reductase from cyanobacteria: expression, purification and characterization of the recombinant enzyme.

PubMed

Lin, Fengming; Das, Debasis; Lin, Xiaoxia N; Marsh, E Neil G

2013-10-01

Long-chain acyl-CoA reductases (ACRs) catalyze a key step in the biosynthesis of hydrocarbon waxes. As such they are attractive as components in engineered metabolic pathways for 'drop in' biofuels. Most ACR enzymes are integral membrane proteins, but a cytosolic ACR was recently discovered in cyanobacteria. The ACR from Synechococcus elongatus was overexpressed in Escherichia coli, purified and characterized. The enzyme was specific for NADPH and catalyzed the reduction of fatty acyl-CoA esters to the corresponding aldehydes, rather than alcohols. Stearoyl-CoA was the most effective substrate, being reduced more rapidly than either longer or shorter chain acyl-CoAs. ACR required divalent metal ions, e.g. Mg(2+), for activity and was stimulated ~ 10-fold by K(+). The enzyme was inactivated by iodoacetamide and was acylated on incubation with stearoyl-CoA, suggesting that reduction occurs through an enzyme-thioester intermediate. Consistent with this, steady state kinetic analysis indicates that the enzyme operates by a 'ping-pong' mechanism with kcat = 0.36 ± 0.023 min(-1), K(m)(stearoyl-CoA) = 31.9 ± 4.2 μM and K(m)(NADPH) = 35.6 ± 4.9 μM. The slow turnover number measured for ACR poses a challenge for its use in biofuel applications where highly efficient enzymes are needed. © 2013 FEBS.

Cerebral Gluconeogenesis and Diseases

PubMed Central

Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

2017-01-01

The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions. PMID:28101056

Organocatalytic, Diastereo- and Enantioselective Synthesis of Nonsymmetric cis-Stilbene Diamines: A Platform for the Preparation of Single-Enantiomer cis-Imidazolines for Protein–Protein Inhibition

PubMed Central

2015-01-01

The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein–protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate–catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein–protein interactions. PMID:25017623

Exploiting Differential Gene Expression and Epistasis to Discover Candidate Genes for Drought-Associated QTLs in Arabidopsis thaliana.

PubMed

Lovell, John T; Mullen, Jack L; Lowry, David B; Awole, Kedija; Richards, James H; Sen, Saunak; Verslues, Paul E; Juenger, Thomas E; McKay, John K

2015-04-01

Soil water availability represents one of the most important selective agents for plants in nature and the single greatest abiotic determinant of agricultural productivity, yet the genetic bases of drought acclimation responses remain poorly understood. Here, we developed a systems-genetic approach to characterize quantitative trait loci (QTLs), physiological traits and genes that affect responses to soil moisture deficit in the TSUxKAS mapping population of Arabidopsis thaliana. To determine the effects of candidate genes underlying QTLs, we analyzed gene expression as a covariate within the QTL model in an effort to mechanistically link markers, RNA expression, and the phenotype. This strategy produced ranked lists of candidate genes for several drought-associated traits, including water use efficiency, growth, abscisic acid concentration (ABA), and proline concentration. As a proof of concept, we recovered known causal loci for several QTLs. For other traits, including ABA, we identified novel loci not previously associated with drought. Furthermore, we documented natural variation at two key steps in proline metabolism and demonstrated that the mitochondrial genome differentially affects genomic QTLs to influence proline accumulation. These findings demonstrate that linking genome, transcriptome, and phenotype data holds great promise to extend the utility of genetic mapping, even when QTL effects are modest or complex. © 2015 American Society of Plant Biologists. All rights reserved.

Uterine ALK3 is essential during the window of implantation

PubMed Central

Monsivais, Diana; Clementi, Caterina; Peng, Jia; Titus, Mary M.; Barrish, James P.; Creighton, Chad J.; Lydon, John P.; DeMayo, Francesco J.; Matzuk, Martin M.

2016-01-01

The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy. In this study, we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. Conditional knockout (cKO) of ALK3 in the uterus was obtained by producing Alk3flox/flox-Pgr-cre–positive females. Alk3 cKO mice are sterile and have defects in the luminal uterine epithelium, including increased microvilli density and maintenance of apical cell polarity. Moreover, Alk3 cKO mice exhibit an elevated uterine E2 response and unopposed epithelial cell proliferation during the window of implantation. We determined that dual transcriptional regulation of Kruppel-like factor 15 (Klf15), by both the transforming growth factor β (TGF-β) transcription factor SMAD family member 4 (SMAD4) and progesterone receptor (PR), is necessary to inhibit uterine epithelial cell proliferation, a key step for embryo implantation. Our findings present a convergence of BMP and steroid hormone signaling pathways in the regulation of uterine receptivity. PMID:26721398

Mesoscopic photosystems for solar light harvesting and conversion: facile and reversible transformation of metal-halide perovskites.

PubMed

Harms, Hauke Arne; Tétreault, Nicolas; Pellet, Norman; Bensimon, Michaël; Grätzel, Michael

2014-01-01

Recently, hybrid organic-inorganic metal halide perovskites have gained prominence as potent light harvesters in thin film solid-state photovoltaics. In particular the solar-to-electric power conversion efficiency (PCE) of devices using CH(3)NH(3)PbI(3) as sensitizer has increased from 3 to 20.1% within only a few years. This key material can be prepared by solution processing from PbI(2) and CH(3)NH(3)I in one step or by sequential deposition. In the latter case an electron capturing support such as TiO(2) is first covered with PbI(2), which upon exposure to a CH(3)NH(3)I solution is converted to the perovskite. Here we apply for the first time quartz crystal microbalance (QCMD) measurements in conjunction with X-ray diffraction and scanning electron microscopy to analyse the dynamics of the conversion of PbI(2) to CH(3)NH(3)PbI(3). Employing 200 nm thick PbI(2) films as substrates we discover that the CH(3)NH(3)I insertion in the PbI(2) is reversible, with the extraction into the solvent isopropanol occurring on the same time scale of seconds as the intercalation process. This offers an explanation for the strikingly rapid and facile exchange of halide ions in CH(3)NH(3)PbX(3) by solution processing at room temperature.

Analysis and improved characterization of minor antioxidants from leaves of Malus doumeri using a combination of major constituents' knockout with high-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry.

PubMed

Zhao, Huading; Hu, Xin; Chen, Xiaoqin; Shi, Shuyun; Jiang, Xinyu; Liang, Xuejuan; Chen, Wei; Zhang, Shuihan

2015-06-12

Due to the complexity of natural products, efficient identification of bioactive compounds, especially for minor compounds, would require a huge effort. Here, we developed an effective strategy based on combining major constituents' knockout with high-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS) to comprehensively identify minor antioxidants in Malus doumeri, one of the longest known and most used tonic plant in Taiwan. First, five major compounds (I-V) in M. doumeri were knocked out by two-step stepwise high-speed countercurrent chromatography (HSCCC). Second, minor antioxidants were screened by 1,1-diphenyl-2-picrylhydrazyl radical-HPLC (DPPH-HPLC) assay. Third, structures of thirty minor antioxidants, including 11 dihydrochalcones, 4 flavanones, 3 flavonols, 2 flavones, 3 aurones and 7 phenolic acids, were unambiguously or tentatively identified by matching their characteristic UV spectra, accurate mass signals and key diagnostic fragment ions with standards or previously reported compounds. Twenty-six of them, as far as was known, were discovered from M. doumeri for the first time. The results indicated that the proposed method was a useful approach to explore minor bioactive compounds from complex natural products. Copyright © 2015 Elsevier B.V. All rights reserved.

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity.

PubMed

Jana, Biman; Onuchic, José N

2016-08-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities.

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity

PubMed Central

Jana, Biman; Onuchic, José N.

2016-01-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities. PMID:27494025

The role of public-private partnerships in addressing the biomedical innovation challenge.

PubMed

Said, Maya; Zerhouni, Elias

2014-11-01

Without a step change in the productivity of pharmaceutical research and development, it will be difficult to tackle the public health challenges facing societies worldwide. Public–private partnerships could play a key role in achieving this step change, but they need to be well designed and led.

A facile synthesis of the basic steroidal skeleton using a Pauson-Khand reaction as a key step.

PubMed

Kim, Do Han; Kim, Kwang; Chung, Young Keun

2006-10-13

A high-yield synthesis of steroid-type molecules under mild reaction conditions is achieved in two steps involving nucleophilic addition of alkynyl cerium reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an intramolecular Pauson-Khand reaction.

Essentials of Millon Inventories Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Strack, Stephen

This step-by-step reference guide to the five key Millon personality inventories includes vital information about each of the tests, including information on psychometric characteristics, special populations, assets-limitations, reliability-validity, and interpretation. The tests are: the Millon Clinical Multiaxial Inventory III (MCMI-III); the…

Strategic Marketing: The President's Perspective.

ERIC Educational Resources Information Center

Pappas, Richard J.; Shaink, M. Richard

1994-01-01

Provides a step-by-step guide to developing a college marketing plan. Identifying a target market and determining an appropriate mix of promotional strategies are considered key to the process. Highlights the college president's role in the marketing process, indicating that, although the president is the chief marketer, all employees must be…

Exploration maturity key to ranking search areas

USGS Publications Warehouse

Attanasi, E.D.; Freeman, P.A.

2008-01-01

The study area of US Geological Survey Circular 1288, the world outside the US and Canada, was partitioned into 44 countries and country groups. Map figures such as Fig. 2 and graphs similar to Figs. 3 and 4 provide a visual summary of maturity of oil and gas exploration. From 1992 through 2001, exploration data show that in the study area the delineated prospective area expanded at a rate of about 50,000 sq miles/year, while the explored area grew at a rate of 11,000 sq miles/year. The delineated prospective area established by 1970 accounts for less than 40% of total delineated prospective area but contains 75% of the oil discovered to date in the study area. From 1991 through 2000, offshore discoveries accounted for 59% of the oil and 77% of the gas discovered in the study area.

Understanding 3D human torso shape via manifold clustering

NASA Astrophysics Data System (ADS)

Li, Sheng; Li, Peng; Fu, Yun

2013-05-01

Discovering the variations in human torso shape plays a key role in many design-oriented applications, such as suit designing. With recent advances in 3D surface imaging technologies, people can obtain 3D human torso data that provide more information than traditional measurements. However, how to find different human shapes from 3D torso data is still an open problem. In this paper, we propose to use spectral clustering approach on torso manifold to address this problem. We first represent high-dimensional torso data in a low-dimensional space using manifold learning algorithm. Then the spectral clustering method is performed to get several disjoint clusters. Experimental results show that the clusters discovered by our approach can describe the discrepancies in both genders and human shapes, and our approach achieves better performance than the compared clustering method.

Planet Imager Discovers Young Kuiper Belt

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2015-07-01

A debris disk just discovered around a nearby star is the closest thing yet seen to a young version of the Kuiper belt. This disk could be a key to better understanding the interactions between debris disks and planets, as well as how our solar system evolved early on in its lifetime. Hunting for an analog The best way to understand how the Kuiper belt — home to Pluto and thousands of other remnants of early icy planet formation in our solar system — developed would be to witness a similar debris disk in an earlier stage of its life. But before now, none of the disks we've discovered have been similar to our own: the rings are typically too large, the central star too massive, or the stars exist in regions very unlike what we think our Sun's birthplace was like. A collaboration led by Thayne Currie (National Astronomical Observatory of Japan) has changed this using the Gemini Planet Imager (GPI), part of a new generation of extreme adaptive-optics systems. The team discovered a debris disk of roughly the same size as the Kuiper belt orbiting the star HD 115600, located in the nearest OB association. The star is only slightly more massive than our Sun, and it lives in a star-forming region similar to the early Sun's environment. HD 115600 is different in one key way, however: it is only 15 million years old. This means that observing it gives us the perfect opportunity to observe how our solar system might have behaved when it was much younger. A promising future GPI's spatially-resolved spectroscopy, combined with measurements of the reflectivity of the disk, have led the team to suspect that the disk might be composed partly of water ice, just as the Kuiper belt is. The disk also shows evidence of having been sculpted by the motions of giant planets orbiting the central star, in much the same way as the outer planets of our solar system may have shaped the Kuiper belt. The observations of HD 115600 are some of the very first to emerge from GPI and the new generation of planet-hunting instruments. The detection of this disk provides a promising outlook on what we can expect to discover in the future with these systems. Citation: Thayne Currie et al. 2015 ApJ 807 L7 doi:10.1088/2041-8205/807/1/L7

NASA Applied Sciences Program. Overview Presentation; Discovering and Demonstrating Innovative and Practical Applications of Earth Science

NASA Technical Reports Server (NTRS)

Irwin, Daniel

2010-01-01

Goal 1: Enhance Applications Research Advance the use of NASA Earth science in policy making, resource management and planning, and disaster response. Key Actions: Identify priority needs, conduct applied research to generate innovative applications, and support projects that demonstrate uses of NASA Earth science. Goal 2: Increase Collaboration Establish a flexible program structure to meet diverse partner needs and applications objectives. Key Actions: Pursue partnerships to leverage resources and risks and extend the program s reach and impact. Goal 3:Accelerate Applications Ensure that NASA s flight missions plan for and support applications goals in conjunction with their science goals, starting with mission planning and extending through the mission life cycle. Key Actions: Enable identification of applications early in satellite mission lifecycle and facilitate effective ways to integrate end-user needs into satellite mission planning

Nanocarbon materials fabricated using plasmas

NASA Astrophysics Data System (ADS)

Hatakeyama, Rikizo

2017-12-01

Since the discovery of fullerenes more than three decades ago, new kinds of nanoscale materials of carbon allotropes called "nanocarbons" have so far been discovered or synthesized at successive intervals as cases such as carbon nanotubes, carbon nanohorns, graphene, carbon nanowalls, and a carbon nanobelt, while nanodiamonds were actually discovered before then. Their attractively excellent mechanical, physical, and chemical properties have driven researchers to continuously create one of the hottest frontiers in materials science and technology. While plasma states have often been involved in their discovery, on the other hand, plasma-based approaches to this exciting field originally hold promising and enormous potentials for advancing and expanding industrial/biomedical applications of nanocarbons of great diversity. This article provides an extensive overview on plasma-fabricated nanocarbon materials, where the term "fabrication" is defined as synthesis, functionalization, and assembly of devices to cover a wide range of issues associated with the step-by-step plasma processes. Specific attention has been paid to the comparative examination between plasma-based and non-plasma methods for fabricating the nanocarobons with an emphasis on the advantages of plasma processing, such as low-temperature/large-scale fabrication and diversity-carrying structure controllability. The review ends with current challenges and prospects including a ripple effect of the nanocarbon studies on the development of related novel nanomaterials such as transition metal dichalcogenides. It contains not only the latest progress in the field for cutting-edge scientists and engineers, but also the introductory guidance to non-specialists such as lower-class graduate students.

Tracker Toolkit

NASA Technical Reports Server (NTRS)

Lewis, Steven J.; Palacios, David M.

2013-01-01

This software can track multiple moving objects within a video stream simultaneously, use visual features to aid in the tracking, and initiate tracks based on object detection in a subregion. A simple programmatic interface allows plugging into larger image chain modeling suites. It extracts unique visual features for aid in tracking and later analysis, and includes sub-functionality for extracting visual features about an object identified within an image frame. Tracker Toolkit utilizes a feature extraction algorithm to tag each object with metadata features about its size, shape, color, and movement. Its functionality is independent of the scale of objects within a scene. The only assumption made on the tracked objects is that they move. There are no constraints on size within the scene, shape, or type of movement. The Tracker Toolkit is also capable of following an arbitrary number of objects in the same scene, identifying and propagating the track of each object from frame to frame. Target objects may be specified for tracking beforehand, or may be dynamically discovered within a tripwire region. Initialization of the Tracker Toolkit algorithm includes two steps: Initializing the data structures for tracked target objects, including targets preselected for tracking; and initializing the tripwire region. If no tripwire region is desired, this step is skipped. The tripwire region is an area within the frames that is always checked for new objects, and all new objects discovered within the region will be tracked until lost (by leaving the frame, stopping, or blending in to the background).

Interactions between Melanin Enzymes and Their Atypical Recruitment to the Secretory Pathway by Palmitoylation

PubMed Central

Upadhyay, Srijana; Xu, Xinping

2016-01-01

ABSTRACT Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered “atypical” secretory proteins. In this work, we found interactions among melanin enzymes and all melanin enzymes formed protein complexes. Surprisingly, the formation of protein complexes by melanin enzymes was not critical for their trafficking to the endosomal system. By palmitoylation profiling and biochemical analyses, we discovered that all four early melanin enzymes were strongly palmitoylated during conidiation. However, only the polyketide synthase (PKS) Alb1 was strongly palmitoylated during both vegetative hyphal growth and conidiation when constitutively expressed alone. This posttranslational lipid modification correlates the endosomal localization of all early melanin enzymes. Intriguingly, bioinformatic analyses predict that palmitoylation is a common mechanism for potential membrane association of polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) in A. fumigatus. Our findings indicate that protein-protein interactions facilitate melanization by metabolic channeling, while posttranslational lipid modifications help recruit the atypical enzymes to the secretory pathway, which is critical for compartmentalization of secondary metabolism. PMID:27879337

Application of Mössbauer spectroscopy for: (1) characterization of Egyptian Maghara coal; (2) evaluating the efficiency of different methods for coal desulphurization

NASA Astrophysics Data System (ADS)

Eissa, N. A.; Sheta, N. H.; Ahmed, M. A.

1992-04-01

Coal has been recently discovered in Maghara mine at Northern Sinai, Egypt. Coal samples have been collected from different depths and were measured by XRD, XRF, and MS, in order to characterize this type of coal. It has been found that the iron bearing minerals are mainly pyrite and different sulphates depending on the depth of the sample. The second part contains the application of desulphurization techniques to Egyptian coal which are: floatation (one step and two steps) chemical [(HCl+HNO3), and Fe2(SO4)3] and bacterial methods (Chromatium and Chlorobium species). The efficiency of each technique was calculated. A comparative discussion is given of each desulphurization method, from which the bacterial method has proved to be the most efficient one.

Strategic Planning for Health Care Cost Controls in a Constantly Changing Environment.

PubMed

Hembree, William E

2015-01-01

Health care cost increases are showing a resurgence. Despite recent years' comparatively modest increases, the projections for 2015 cost increases range from 6.6% to 7%--three to four times larger than 2015's expected underlying inflation. This resurgence is just one of many rapidly changing external and internal challenges health plan sponsors must overcome (and this resurgence advances the date when the majority of employers will trigger the "Cadillac tax"). What's needed is a planning approach that is effective in overcoming all known and yet-to-be-discovered challenges, not just affordability. This article provides detailed guidance in adopting six proven strategic planning steps. Following these steps will proactively and effectively create a flexible strategic plan for the present and future of employers' health plans that will withstand all internal and external challenges.

A qualitative meta-synthesis and theory of postpartum depression.

PubMed

Mollard, Elizabeth K

2014-09-01

To synthesize existing qualitative literature on the first-hand experiences of women suffering from postpartum depression (PPD), to uncover potential common themes, a meta-synthesis of 12 qualitative studies using Noblit and Hare's 7-phase model of meta-ethnography was used. Four themes were discovered: crushed maternal role expectation, going into hiding, loss of sense of self, intense feelings of vulnerability, plus practical life concerns. A preliminary theory of PPD as a 4-step process is proposed, based on the relationships between the themes in this meta-synthesis. This 4-step process is compared and contrasted with Cheryl Tatano Beck's 4-stage theory of PPD "Teetering on the Edge". This meta-synthesis and theory offers a significant contribution to the literature in helping identify PPD distinctly from depression outside of the postpartum period, and deserves further study.

The Mentor Kit. A Step-by-Step Guide To Creating an Effective Mentor Program in Your School [and] Reproducible Forms To Accompany the Mentor Program in Your School.

ERIC Educational Resources Information Center

Nash, Diane; Treffinger, Don

Mentorships, the art of a creatively productive person teaching, counseling, and inspiring a student with similar interests, can be the result of circumstance or they can be the result of mentorship programs engineered in the academic world. Data collected from over 25 different academic models of mentorship have been distilled into 7 key steps to…

Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

PubMed Central

2012-01-01

Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

Calocybe cyanea : a rare and beautiful agaric is discovered in Puerto Rico

Treesearch

Timothy J. Baroni; Nick W. Legon; Rytas Vilgalys; D. Jean. Lodge

1999-01-01

A rare find of Calocybe cyanea from Puerto Rico is described and illustrated. A discussion of all species of Calocybe found in the Caribbean is provided. Since nearly one-half of the described species of Calocybe can be found in the Neotropics (nine out of the 20 or so known taxa), a key to the species of Calocybe which are found in the Neotropics is included.

"Creating a Comic Strip Is Very Creative and Thanks to It We Learn and Remember"--Student Perceptions of a Biology Challenge in a Gamified Extracurricular CLIL Project

ERIC Educational Resources Information Center

Pitura, Joanna; Chmielarz, Dagmara

2017-01-01

Upper-secondary school students must prepare for adult life, which--among others--entails acquiring relevant skills and discovering their own potential. Efforts at European and national levels have been made to ensure that students gain the competences, the so-called key competences, which facilitate functioning in the modern world. However, in…

Liberia’s Post-War Recovery: Key Issues and Developments

DTIC Science & Technology

2007-08-30

Firestone rights to large plantation areas for the cultivation of rubber.56 The contract was amended, in part, because Firestone contended that it was...is reportedly under negotiation.66 According to Global Witness, a non-governmental organization critic of the original Mittal contract, improvements in...often far from their point of origin . In January 2006, however, the firm Diamond Fields International (DFI) Ltd. announced that it had discovered

Integrated omics for the identification of key functionalities in biological wastewater treatment microbial communities.

PubMed

Narayanasamy, Shaman; Muller, Emilie E L; Sheik, Abdul R; Wilmes, Paul

2015-05-01

Biological wastewater treatment plants harbour diverse and complex microbial communities which prominently serve as models for microbial ecology and mixed culture biotechnological processes. Integrated omic analyses (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum towards providing enhanced understanding of community structure, function and dynamics in situ as well as offering the potential to discover novel biological functionalities within the framework of Eco-Systems Biology. The integration of information from genome to metabolome allows the establishment of associations between genetic potential and final phenotype, a feature not realizable by only considering single 'omes'. Therefore, in our opinion, integrated omics will become the future standard for large-scale characterization of microbial consortia including those underpinning biological wastewater treatment processes. Systematically obtained time and space-resolved omic datasets will allow deconvolution of structure-function relationships by identifying key members and functions. Such knowledge will form the foundation for discovering novel genes on a much larger scale compared with previous efforts. In general, these insights will allow us to optimize microbial biotechnological processes either through better control of mixed culture processes or by use of more efficient enzymes in bioengineering applications. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Expression profiling reveals Spot 42 small RNA as a key regulator in the central metabolism of Aliivibrio salmonicida

PubMed Central

2012-01-01

Background Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42. Results We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ≥ 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose. Conclusions We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin. PMID:22272603

Origins of Inner Solar Systems

NASA Astrophysics Data System (ADS)

Dawson, Rebekah Ilene

2017-06-01

Over the past couple decades, thousands of extra-solar planetshave been discovered orbiting other stars. The exoplanets discovered to date exhibit a wide variety of orbital and compositional properties; most are dramatically different from the planets in our own Solar System. Our classical theories for the origins of planetary systems were crafted to account for the Solar System and fail to account for the diversity of planets now known. We are working to establish a new blueprint for the origin of planetary systems and identify the key parameters of planet formation and evolution that establish the distribution of planetary properties observed today. The new blueprint must account for the properties of planets in inner solar systems, regions of planetary systems closer to their star than Earth’s separation from the Sun and home to most exoplanets detected to data. I present work combining simulations and theory with data analysis and statistics of observed planets to test theories of the origins of inner solars, including hot Jupiters, warm Jupiters, and tightly-packed systems of super-Earths. Ultimately a comprehensive blueprint for planetary systems will allow us to better situate discovered planets in the context of their system’s formation and evolution, important factors in whether the planets may harbor life.

MicroRNA-dependent regulation of metamorphosis and identification of microRNAs in the red flour beetle, Tribolium castaneum.

PubMed

Wu, Wei; Xiong, Wenfeng; Li, Chengjun; Zhai, Mengfan; Li, Yao; Ma, Fei; Li, Bin

2017-10-01

To date, although some microRNAs (miRNAs) have been discovered in the holometabolism insect Tribolium castaneum, large numbers of miRNAs still require investigation. Knocking down Dicer-1 (Dcr-1) and Argonaute-1 (Ago-1) in late larvae impaired miRNA synthesis, affected the juvenile hormone pathway by up-regulating Methoprene-tolerant (Met) and Krüppel-homolog1 (Kr-h1) transcript levels, and resulted in a series of defects in T. castaneum development and metamorphosis. Thus, high-throughput Illumina/Solexa sequencing was performed with a mixed sample of eight key developmental stages of T. castaneum. In total, 1154 unique miRNAs were discovered containing 274 conserved miRNAs belong to 68 miRNA families, 108 known candidate miRNAs and 772 novel miRNAs. Genome locus analysis showed that miRNA clusters are more abundant in T. castaneum than other species. The results indicated that RNAi of Dcr-1 and Ago-1 in T. castaneum resulted in miRNA-induced metamorphosis defects. Furthermore, large numbers of novel miRNAs were discovered in T. castaneum and localized to T. castaneum genome loci. Copyright © 2017 Elsevier Inc. All rights reserved.

An application of data mining in district heating substations for improving energy performance

NASA Astrophysics Data System (ADS)

Xue, Puning; Zhou, Zhigang; Chen, Xin; Liu, Jing

2017-11-01

Automatic meter reading system is capable of collecting and storing a huge number of district heating (DH) data. However, the data obtained are rarely fully utilized. Data mining is a promising technology to discover potential interesting knowledge from vast data. This paper applies data mining methods to analyse the massive data for improving energy performance of DH substation. The technical approach contains three steps: data selection, cluster analysis and association rule mining (ARM). Two-heating-season data of a substation are used for case study. Cluster analysis identifies six distinct heating patterns based on the primary heat of the substation. ARM reveals that secondary pressure difference and secondary flow rate have a strong correlation. Using the discovered rules, a fault occurring in remote flow meter installed at secondary network is detected accurately. The application demonstrates that data mining techniques can effectively extrapolate potential useful knowledge to better understand substation operation strategies and improve substation energy performance.

Rhodium dihydride (RhH2) with high volumetric hydrogen density

PubMed Central

Li, Bing; Ding, Yang; Kim, Duck Young; Ahuja, Rajeev; Zou, Guangtian; Mao, Ho-Kwang

2011-01-01

Materials with very high hydrogen density have attracted considerable interest due to a range of motivations, including the search for chemically precompressed metallic hydrogen and hydrogen storage applications. Using high-pressure synchrotron X-ray diffraction technique and theoretical calculations, we have discovered a new rhodium dihydride (RhH2) with high volumetric hydrogen density (163.7 g/L). Compressing rhodium in fluid hydrogen at ambient temperature, the fcc rhodium metal absorbs hydrogen and expands unit-cell volume by two discrete steps to form NaCl-typed fcc rhodium monohydride at 4 GPa and fluorite-typed fcc RhH2 at 8 GPa. RhH2 is the first dihydride discovered in the platinum group metals under high pressure. Our low-temperature experiments show that RhH2 is recoverable after releasing pressure cryogenically to 1 bar and is capable of retaining hydrogen up to 150 K for minutes and 77 K for an indefinite length of time. PMID:22039219

Systematic Serendipity: A Method to Discover the Anomalous

NASA Astrophysics Data System (ADS)

Giles, Daniel; Walkowicz, Lucianne

2018-01-01

One of the challenges in the era of big data astronomical surveys is identifying anomalous data, data that exhibits as-of-yet unobserved behavior. These data may result from systematic errors, extreme (or rare) forms of known phenomena, or, most interestingly, truly novel phenomena that has historically required a trained eye and often fortuitous circumstance to identify. We describe a method that uses machine clustering techniques to discover anomalous data in Kepler lightcurves, as a step towards systematizing the detection of novel phenomena in the era of LSST. As a proof of concept, we apply our anomaly detection method to Kepler data including Boyajian's Star (KIC 8462852). We examine quarters 4, 8, 11, and 16 of the Kepler data which contain Boyajian’s Star acting normally (quarters 4 and 11) and anomalously (quarters 8 and 16). We demonstrate that our method is capable of identifying Boyajian’s Star’s anomalous behavior in quarters of interest, and we further identify other anomalous light curves that exhibit a range of interesting variability.

Melatonin: a universal time messenger.

PubMed

Erren, Thomas C; Reiter, Russel J

2015-01-01

Temporal organization plays a key role in humans, and presumably all species on Earth. A core building block of the chronobiological architecture is the master clock, located in the suprachi asmatic nuclei [SCN], which organizes "when" things happen in sub-cellular biochemistry, cells, organs and organisms, including humans. Conceptually, time messenging should follow a 5 step-cascade. While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is central time information transmitted througout the body?" awaits elucidation. Step 1: Light provides information on environmental (external) time; Step 2: Ocular interfaces between light and biological (internal) time are intrinsically photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the retinohypothalamic tract external time information reaches the light-dependent master clock in the brain, viz the SCN; Step 4: The SCN translate environmental time information into biological time and distribute this information to numerous brain structures via a melanopsin-based network. Step 5: Melatonin, we propose, transmits, or is a messenger of, internal time information to all parts of the body to allow temporal organization which is orchestrated by the SCN. Key reasons why we expect melatonin to have such role include: First, melatonin, as the chemical expression of darkness, is centrally involved in time- and timing-related processes such as encoding clock and calendar information in the brain; Second, melatonin travels throughout the body without limits and is thus a ubiquitous molecule. The chemial conservation of melatonin in all tested species could make this molecule a candidate for a universal time messenger, possibly constituting a legacy of an all-embracing evolutionary history.

Differential Effects of Monovalent Cations and Anions on Key Nanoparticle Attributes

EPA Science Inventory

Understanding the key particle attributes such as particle size, size distribution and surface charge of both the nano- and micron-sized particles is the first step in drug formulation as such attributes are known to directly influence several characteristics of drugs including d...

Making Sense of Turmoil: How Women Reconcile Their Emotional Response to Discovery of a Potential Breast Cancer Symptom.

PubMed

O'Mahony, Máirín; Hegarty, Josephine; Rooney, Vivien M

2017-11-07

Breast cancer continues to be a major public health problem for women. Early detection and treatment are key to improved outcomes. Whereas most women seek help promptly, some postpone seeking help for self-discovered breast symptoms. Investigation of women's help-seeking behavior and the associated influencing factors on self-discovery of a breast symptom were sought. The aim of this article is to report the qualitative data from women who had self-discovered a breast symptom. Women (n = 167) with a self-discovered breast symptom (who were part of a large quantitative correlational study) commented in an open-ended question on their overall experience. Comments were analyzed using Discourse Analysis. Four linked discourses were identified: (1) "being and remaining normal," (2) "emotion," (3) "becoming and being abnormal," and (4) "rationality." A sidelined discourse of emotion is drawn on to defer taking action based on rational knowledge. The tension between discourses "emotion" and "rationality" further informs our understanding of women's help-seeking behavior following self-discovered symptoms. Findings provide a deeper understanding of the emotional aspects of women's experience around symptom discovery. Findings will be of benefit to all healthcare professionals involved in assessment and screening of breast changes suggestive of breast cancer. They provide a novel insight into the meaning of breast cancer, its diagnosis and treatment, and how this impacts women's emotions as they await consultation in a breast clinic.

Easier detection of invertebrate "identification-key characters" with light of different wavelengths

PubMed Central

2011-01-01

The marine α-taxonomist often encounters two problems. Firstly, the "environmental dirt" that is frequently present on the specimens and secondly the difficulty in distinguishing key-features due to the uniform colours which fixed animals often adopt. Here we show that illuminating animals with deep-blue or ultraviolet light instead of the normal white-light abrogates both difficulties; dirt disappears and important details become clearly visible. This light regime has also two other advantages. It allows easy detection of very small, normally invisible, animals (0.1 μm range). And as these light wavelengths can induce fluorescence, new identification markers may be discovered by this approach. PMID:22040277

Identification and detoxification of glycolaldehyde, an unattended bioethanol fermentation inhibitor.

PubMed

Jayakody, Lahiru N; Ferdouse, Jannatul; Hayashi, Nobuyuki; Kitagaki, Hiroshi

2017-03-01

Although there have been approximately 60 chemical compounds identified as potent fermentation inhibitors in lignocellulose hydrolysate, our research group recently discovered glycolaldehyde as a key fermentation inhibitor during second generation biofuel production. Accordingly, we have developed a yeast S. cerevisiae strain exhibiting tolerance to glycolaldehyde. During this glycolaldehyde study, we established novel approaches for rational engineering of inhibitor-tolerant S. cerevisiae strains, including engineering redox cofactors and engineering the SUMOylation pathway. These new technical dimensions provide a novel platform for engineering S. cerevisiae strains to overcome one of the key barriers for industrialization of lignocellulosic ethanol production. As such, this review discusses novel biochemical insight of glycolaldehyde in the context of the biofuel industry.

A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta.

PubMed

Wei, Zhi-Liang; Kozikowski, Alan P

2003-11-14

The most potent and selective peroxisome proliferator-activated receptor delta (PPARdelta) agonist GW501516 (1) was synthesized in 4 steps and 78% overall yield starting from o-cresol by using a one-pot regiocontrolled dialkylation of mercaptophenol 5 as the key step.

A Miniature Wastewater Cleaning Plant to Demonstrate Primary Treatment in the Classroom

ERIC Educational Resources Information Center

Ne´el, Bastien; Cardoso, Catia; Perret, Didier; Bakker, Eric

2015-01-01

A small-scale wastewater cleaning plant is described that includes the key physical pretreatment steps followed by the chemical treatment of mud by flocculation. Water, clay particles, and riverside deposits mimicked odorless wastewater. After a demonstration of the optimization step, the flocculation process was carried out with iron(III)…

Strengthening the revenue cycle: a 4-step method for optimizing payment.

PubMed

Clark, Jonathan J

2008-10-01

Four steps for enhancing the revenue cycle to ensure optimal payment are: *Establish key performance indicator dashboards in each department that compare current with targeted performance; *Create proper organizational structures for each department; *Ensure that high-performing leaders are hired in all management and supervisory positions; *Implement efficient processes in underperforming operations.

First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

ERIC Educational Resources Information Center

Buford, Rhonda; Stegelin, Dolores A.

2003-01-01

Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

Physicochemical characterization of mozzarella cheese wheys and stretchwaters in comparison with several other sweet wheys.

PubMed

Gernigon, G; Piot, M; Beaucher, E; Jeantet, R; Schuck, P

2009-11-01

To better understand the origins of the problems occurring during mozzarella cheese whey concentration, lactose crystallization, and spray-drying steps, a physicochemical characterization was achieved. For this purpose, mozzarella cheese wheys were sampled and their content in different compounds such as total nitrogen, noncasein nitrogen, nonprotein nitrogen, lactate, citrate, chloride, sulfate, phosphate anions, calcium, magnesium, potassium, sodium cations, and the sugars glucose and galactose were measured. In a second step, the results were compared with the corresponding content in cheddar cheese wheys, raclette cheese wheys, soft cheese wheys, and Swiss-type cheese wheys. At the end of this survey, it was shown that mozzarella cheese wheys were more concentrated in lactate and in minerals--especially phosphate, calcium, and magnesium--than the other cheese wheys and that they contained galactose. These constituents are known to be hygroscopic. Complementary surveys are now necessary to compare the hygroscopicity of galactose and lactate and discover whether the amounts of these compounds found in mozzarella cheese wheys are a factor in the problems encountered during the concentration, lactose crystallization, and spray-drying steps.

Subsurface oxide plays a critical role in CO 2 activation by Cu(111) surfaces to form chemisorbed CO 2, the first step in reduction of CO 2

DOE PAGES

Favaro, Marco; Xiao, Hai; Cheng, Tao; ...

2017-06-12

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide ismore » essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.« less

Electrification in winter storms and the analysis of thunderstorm overflight data

NASA Technical Reports Server (NTRS)

Brook, Marx

1993-01-01

We have been focusing our study of electrification in winter storms on the lightning initiation process, making inferences about the magnitude of the electric fields from the initial pulses associated with breakdown, i.e., with the formation of the initial streamers. The essence of the most significant finding is as follows: (1) initial breakdown radiation pulses from stepped leaders prior to the first return stroke are very large, reaching values of 20-30 Volts/meter, comparable to return stroke radiation; and (2) the duration of the stepped leader, from the initial detectable radiation pulse to the return stroke onset, is very-short-ranging from a minimum 1.5 ms to a maximum of 4.5 ms. This past summer (June-August of 1991) we participated in the CAPE program at the Kennedy Space Center in order to acquire data on stepped leaders in summer storms with the same equipment used to get the winter storm data. We discovered that the vigorous leaders seen in winter so frequently were present in summer storms, although not as large in amplitude and certainly not as frequent.

Asthma management simulation for children: translating theory, methods, and strategies to effect behavior change.

PubMed

Shegog, Ross; Bartholomew, L Kay; Gold, Robert S; Pierrel, Elaine; Parcel, Guy S; Sockrider, Marianna M; Czyzewski, Danita I; Fernandez, Maria E; Berlin, Nina J; Abramson, Stuart

2006-01-01

Translating behavioral theories, models, and strategies to guide the development and structure of computer-based health applications is well recognized, although a continued challenge for program developers. A stepped approach to translate behavioral theory in the design of simulations to teach chronic disease management to children is described. This includes the translation steps to: 1) define target behaviors and their determinants, 2) identify theoretical methods to optimize behavioral change, and 3) choose educational strategies to effectively apply these methods and combine these into a cohesive computer-based simulation for health education. Asthma is used to exemplify a chronic health management problem and a computer-based asthma management simulation (Watch, Discover, Think and Act) that has been evaluated and shown to effect asthma self-management in children is used to exemplify the application of theory to practice. Impact and outcome evaluation studies have indicated the effectiveness of these steps in providing increased rigor and accountability, suggesting their utility for educators and developers seeking to apply simulations to enhance self-management behaviors in patients.

A Neural Dynamic Model Generates Descriptions of Object-Oriented Actions.

PubMed

Richter, Mathis; Lins, Jonas; Schöner, Gregor

2017-01-01

Describing actions entails that relations between objects are discovered. A pervasively neural account of this process requires that fundamental problems are solved: the neural pointer problem, the binding problem, and the problem of generating discrete processing steps from time-continuous neural processes. We present a prototypical solution to these problems in a neural dynamic model that comprises dynamic neural fields holding representations close to sensorimotor surfaces as well as dynamic neural nodes holding discrete, language-like representations. Making the connection between these two types of representations enables the model to describe actions as well as to perceptually ground movement phrases-all based on real visual input. We demonstrate how the dynamic neural processes autonomously generate the processing steps required to describe or ground object-oriented actions. By solving the fundamental problems of neural pointing, binding, and emergent discrete processing, the model may be a first but critical step toward a systematic neural processing account of higher cognition. Copyright © 2017 The Authors. Topics in Cognitive Science published by Wiley Periodicals, Inc. on behalf of Cognitive Science Society.

Development of a static bioactive stent prototype and dynamic aneurysm-on-a-chip(TM) model for the treatment of aneurysms

NASA Astrophysics Data System (ADS)

Reece, Lisa M.

Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. While these procedures can be effective, it would be advantageous to design a biologically active stent, modified with magnetic stent coatings, allowing cells to be manipulated to heal the arterial lining. Further, velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, but the shear force mechanisms effecting wound closure is elusive. Due to these factors, there is a definite need to cultivate a new stent device that will aid in healing an aneurysm in situ. To this end, a static bioactive stent device was synthesized. Additionally, to study aneurysm pathogenesis, a lab-on-a-chip device (a dynamic stent device) is the key to discovering the underlying mechanisms of these lesions. A first step to the reality of a true bioactive stent involves the study of cells that can be tested against the biomaterials that constitute the stent itself. The second step is to test particles/cells in a microfluidic environment. Therefore, biocompatability data was collected against PDMS, bacterial nanocellulose (BNC), and magnetic bacterial nanocellulose (MBNC). Preliminary static bioactive stents were synthesized whereby BNC was grown to cover standard nitinol stents. In an offshoot of the original research, a two-dimensional microfluidic model, the Aneurysm-on-a-ChipTM (AOC), was the logical answer to study particle flow within an aneurysm "sac" - this was the dynamic bioactive stent device. The AOC apparatus can track particles/cells when it is coupled to a particle image velocimetry software (PIV) package. The AOC fluid flow was visualized using standard microscopy techniques with commercial microparticles/cells. Movies were taken during fluid flow experiments and PIV was utilized to monitor.

Abasy Atlas: a comprehensive inventory of systems, global network properties and systems-level elements across bacteria

PubMed Central

Ibarra-Arellano, Miguel A.; Campos-González, Adrián I.; Treviño-Quintanilla, Luis G.; Tauch, Andreas; Freyre-González, Julio A.

2016-01-01

The availability of databases electronically encoding curated regulatory networks and of high-throughput technologies and methods to discover regulatory interactions provides an invaluable source of data to understand the principles underpinning the organization and evolution of these networks responsible for cellular regulation. Nevertheless, data on these sources never goes beyond the regulon level despite the fact that regulatory networks are complex hierarchical-modular structures still challenging our understanding. This brings the necessity for an inventory of systems across a large range of organisms, a key step to rendering feasible comparative systems biology approaches. In this work, we take the first step towards a global understanding of the regulatory networks organization by making a cartography of the functional architectures of diverse bacteria. Abasy (Across-bacteria systems) Atlas provides a comprehensive inventory of annotated functional systems, global network properties and systems-level elements (global regulators, modular genes shaping functional systems, basal machinery genes and intermodular genes) predicted by the natural decomposition approach for reconstructed and meta-curated regulatory networks across a large range of bacteria, including pathogenically and biotechnologically relevant organisms. The meta-curation of regulatory datasets provides the most complete and reliable set of regulatory interactions currently available, which can even be projected into subsets by considering the force or weight of evidence supporting them or the systems that they belong to. Besides, Abasy Atlas provides data enabling large-scale comparative systems biology studies aimed at understanding the common principles and particular lifestyle adaptions of systems across bacteria. Abasy Atlas contains systems and system-level elements for 50 regulatory networks comprising 78 649 regulatory interactions covering 42 bacteria in nine taxa, containing 3708 regulons and 1776 systems. All this brings together a large corpus of data that will surely inspire studies to generate hypothesis regarding the principles governing the evolution and organization of systems and the functional architectures controlling them. Database URL: http://abasy.ccg.unam.mx PMID:27242034

Using Key Performance Indicators to Drive Strategic Decision Making.

ERIC Educational Resources Information Center

Dolence, Michael G.; Norris, Donald M.

1994-01-01

A nine-step method for defining and pursuing key performance indicators (KPIs), derived from a strategic planning process, is outlined, and its applications at the University of Northern Colorado and Illinois Benedictine College are described and tabulated. A chart summarizes current and projected KPIs for Illinois Benedictine College for each…

Twenty-six key research questions in urban stream ecology: an assessment of the state of the science

EPA Science Inventory

Although urban streams have been the focus of much research activity in recent years, there remain many unanswered questions about the mechanisms driving the “urban stream syndrome.” Identification of these key research questions is an important step toward effective, efficient ...

Prior knowledge driven Granger causality analysis on gene regulatory network discovery

DOE PAGES

Yao, Shun; Yoo, Shinjae; Yu, Dantong

2015-08-28

Our study focuses on discovering gene regulatory networks from time series gene expression data using the Granger causality (GC) model. However, the number of available time points (T) usually is much smaller than the number of target genes (n) in biological datasets. The widely applied pairwise GC model (PGC) and other regularization strategies can lead to a significant number of false identifications when n>>T. In this study, we proposed a new method, viz., CGC-2SPR (CGC using two-step prior Ridge regularization) to resolve the problem by incorporating prior biological knowledge about a target gene data set. In our simulation experiments, themore » propose new methodology CGC-2SPR showed significant performance improvement in terms of accuracy over other widely used GC modeling (PGC, Ridge and Lasso) and MI-based (MRNET and ARACNE) methods. In addition, we applied CGC-2SPR to a real biological dataset, i.e., the yeast metabolic cycle, and discovered more true positive edges with CGC-2SPR than with the other existing methods. In our research, we noticed a “ 1+1>2” effect when we combined prior knowledge and gene expression data to discover regulatory networks. Based on causality networks, we made a functional prediction that the Abm1 gene (its functions previously were unknown) might be related to the yeast’s responses to different levels of glucose. In conclusion, our research improves causality modeling by combining heterogeneous knowledge, which is well aligned with the future direction in system biology. Furthermore, we proposed a method of Monte Carlo significance estimation (MCSE) to calculate the edge significances which provide statistical meanings to the discovered causality networks. All of our data and source codes will be available under the link https://bitbucket.org/dtyu/granger-causality/wiki/Home.« less

The space program's impact on society

NASA Astrophysics Data System (ADS)

Toffler, Alvin

In terms of human evolution, when viewed from 500 or 1000 years from now, today's primitive, still faltering steps beyond the Earth will be recognized as the most important human project of our era, matched only by what is going on in computers and biology. In this paper the social effects of space activity are addressed at three different levels: key social institutions, key social groups, and key social processes.

An Updated Review of Tyrosinase Inhibitors

PubMed Central

Chang, Te-Sheng

2009-01-01

Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed. PMID:19582213

Unusual case of left atrial myxoma with gastroesophageal junction adenocarcinoma.

PubMed

Singh, Narinder Pal; Nagpal, Swapan Deep Singh; Goel, Arun Kumar; Dhingra, Bhupendra Kr

2018-02-01

Cardiac myxomas are rare tumors. Esophageal adenocarcinomas are common tumors of the gastrointestinal tract. Simultaneous occurrence of these tumors has not been reported. A 52-year-old gentleman presented to our hospital with dysphagia and was diagnosed with esophageal adenocarcinoma. Routine echocardiography discovered a cardiac tumor in the left atrium. The cardiac tumor was surgically removed and biopsy confirmed a myxoma. We removed the cardiac tumor as the first step and then initiated neoadjuvant chemotherapy. It is ideal to constitute a multidisciplinary team to decide on the course of treatment in such cases.

Identification of miRNAs and Their Targets in the Liverwort Marchantia polymorpha by Integrating RNA-Seq and Degradome Analyses

PubMed Central

Lin, Pin-Chun; Lu, Chia-Wei; Shen, Bing-Nan; Lee, Guan-Zong; Bowman, John L.; Arteaga-Vazquez, Mario A.; Liu, Li-Yu Daisy; Hong, Syuan-Fei; Lo, Chu-Fang; Su, Gong-Min; Kohchi, Takayuki; Ishizaki, Kimitsune; Zachgo, Sabine; Althoff, Felix; Takenaka, Mizuki; Yamato, Katsuyuki T.; Lin, Shih-Shun

2016-01-01

Bryophytes (liverworts, hornworts and mosses) comprise the three earliest diverging lineages of land plants (embryophytes). Marchantia polymorpha, a complex thalloid Marchantiopsida liverwort that has been developed into a model genetic system, occupies a key phylogenetic position. Therefore, M. polymorpha is useful in studies aiming to elucidate the evolution of gene regulation mechanisms in plants. In this study, we used computational, transcriptomic, small RNA and degradome analyses to characterize microRNA (miRNA)-mediated pathways of gene regulation in M. polymorpha. The data have been integrated into the open access ContigViews-miRNA platform for further reference. In addition to core components of the miRNA pathway, 129 unique miRNA sequences, 11 of which could be classified into seven miRNA families that are conserved in embryophytes (miR166a, miR390, miR529c, miR171-3p, miR408a, miR160 and miR319a), were identified. A combination of computational and degradome analyses allowed us to identify and experimentally validate 249 targets. In some cases, the target genes are orthologous to those of other embryophytes, but in other cases, the conserved miRNAs target either paralogs or members of different gene families. In addition, the newly discovered Mpo-miR11707.1 and Mpo-miR11707.2 are generated from a common precursor and target MpARGONAUTE1 (LW1759). Two other newly discovered miRNAs, Mpo-miR11687.1 and Mpo-miR11681.1, target the MADS-box transcription factors MpMADS1 and MpMADS2, respectively. Interestingly, one of the pentatricopeptide repeat (PPR) gene family members, MpPPR_66 (LW9825), the protein products of which are generally involved in various steps of RNA metabolism, has a long stem–loop transcript that can generate Mpo-miR11692.1 to autoregulate MpPPR_66 (LW9825) mRNA. This study provides a foundation for further investigations of the RNA-mediated silencing mechanism in M. polymorpha as well as of the evolution of this gene silencing pathway in embryophytes. PMID:26861787

Rational assignment of key motifs for function guides in silico enzyme identification.

PubMed

Höhne, Matthias; Schätzle, Sebastian; Jochens, Helge; Robins, Karen; Bornscheuer, Uwe T

2010-11-01

Biocatalysis has emerged as a powerful alternative to traditional chemistry, especially for asymmetric synthesis. One key requirement during process development is the discovery of a biocatalyst with an appropriate enantiopreference and enantioselectivity, which can be achieved, for instance, by protein engineering or screening of metagenome libraries. We have developed an in silico strategy for a sequence-based prediction of substrate specificity and enantiopreference. First, we used rational protein design to predict key amino acid substitutions that indicate the desired activity. Then, we searched protein databases for proteins already carrying these mutations instead of constructing the corresponding mutants in the laboratory. This methodology exploits the fact that naturally evolved proteins have undergone selection over millions of years, which has resulted in highly optimized catalysts. Using this in silico approach, we have discovered 17 (R)-selective amine transaminases, which catalyzed the synthesis of several (R)-amines with excellent optical purity up to >99% enantiomeric excess.

Smoking, social class, and gender: what can public health learn from the tobacco industry about disparities in smoking?

PubMed Central

Barbeau, E; Leavy-Sperounis, A; Balbach, E

2004-01-01

Objective: To discover how the tobacco industry considers social class and gender in its efforts to market cigarettes in the USA, particularly to socially disadvantaged young women. Methods: A systematic on-line search of tobacco industry documents using selected keywords was conducted, and epidemiological data on smoking rates reviewed. Results: The two largest cigarette manufacturers in the USA consider "working class" young adults to be a critical market segment to promote growth of key brands. Through their own market research, these companies discovered that socially disadvantaged young women do not necessarily desire a "feminine" cigarette brand. Conclusions: Considering the tobacco industry's efforts, alongside the persistent and growing disparities in cigarette smoking by social class, and the narrowing of differences in smoking by gender, it is concluded that additional tobacco control resources ought to be directed toward working class women. PMID:15175523

Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

PubMed Central

Muñoz-Soriano, Verónica; Paricio, Nuria

2011-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. PMID:21512585

Rotating Radio Transients and Their Place Among Pulsars

NASA Technical Reports Server (NTRS)

Burke-Spolaor, S.

2012-01-01

Six years ago, the discovery of Rotating Radio Transients (RRATs) marked what appeared to be a new type of sparsely-emitting pulsar. Since 2006, more than 70 of these objects have been discovered in single-pulse searches of archival and new surveys. With a continual inflow of new information about the RRAT population in the form of new discoveries, multi-frequency follow ups, coherent timing solutions, and pulse rate statistics, a view is beginning to form of the place in the pulsar population RRATs hold. Here we review the properties of neutron stars discovered through single pulse searches. We first seek to clarify the definition of the term RRAT, emphasising that "the RRAT population" encompasses several phenomenologies. A large subset of RRATs appears to represent the tail of an extended distribution of pulsar nulling fractions and activity cycles; these objects present several key open questions remaining in this field.

Big Biomedical data as the key resource for discovery science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toga, Arthur W.; Foster, Ian; Kesselman, Carl

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage,more » aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s.« less

Big biomedical data as the key resource for discovery science

PubMed Central

Toga, Arthur W; Foster, Ian; Kesselman, Carl; Madduri, Ravi; Chard, Kyle; Deutsch, Eric W; Price, Nathan D; Glusman, Gustavo; Heavner, Benjamin D; Dinov, Ivo D; Ames, Joseph; Van Horn, John; Kramer, Roger; Hood, Leroy

2015-01-01

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s. PMID:26198305

Constellation Pharmacology: A new paradigm for drug discovery

PubMed Central

Schmidt, Eric W.; Olivera, Baldomero M.

2015-01-01

Constellation Pharmacology is a cell-based high-content phenotypic-screening platform that utilizes subtype-selective pharmacological agents to elucidate the cell-specific combinations (“constellations”) of key signaling proteins that define specific cell types. Heterogeneous populations of native cells, in which the different individual cell types have been identified and characterized, are the foundation for this screening platform. Constellation Pharmacology is useful for screening small molecules or for deconvoluting complex mixtures of biologically-active natural products. This platform has been used to purify natural products and discover their molecular mechanisms. In the on-going development of Constellation Pharmacology, there is a positive-feedback loop between the pharmacological characterization of cell types and screening for new drug candidates. As Constellation Pharmacology is used to discover compounds with novel targeting-selectivity profiles, those new compounds then further help to elucidate the constellations of specific cell types, thereby increasing the content of this high-content platform. PMID:25562646

Decoding sORF translation - from small proteins to gene regulation.

PubMed

Cabrera-Quio, Luis Enrique; Herberg, Sarah; Pauli, Andrea

2016-11-01

Translation is best known as the fundamental mechanism by which the ribosome converts a sequence of nucleotides into a string of amino acids. Extensive research over many years has elucidated the key principles of translation, and the majority of translated regions were thought to be known. The recent discovery of wide-spread translation outside of annotated protein-coding open reading frames (ORFs) came therefore as a surprise, raising the intriguing possibility that these newly discovered translated regions might have unrecognized protein-coding or gene-regulatory functions. Here, we highlight recent findings that provide evidence that some of these newly discovered translated short ORFs (sORFs) encode functional, previously missed small proteins, while others have regulatory roles. Based on known examples we will also speculate about putative additional roles and the potentially much wider impact that these translated regions might have on cellular homeostasis and gene regulation.

The Stenus cirrus group (Coleoptera, Staphylinidae) in Fujian, East China.

PubMed

Liu, Sheng-Nan; Tang, Liang; Luo, Yong-Ting

2018-01-23

Species of the Stenus cirrus group in Fujian Province, East China, are reviewed and two new species are described: S. mangdangshanus sp. n. and S. fujianensis sp. n. The females of S. cooterianus Puthz, 2003 and S. wuyiensis Puthz, 2003 are discovered and illustrated for the first time. The diagnostic characters of the new species are illustrated, and a key to species of the Stenus cirrus group of Fujian Province is provided.

Kids Just Wanna Have Fun: The Best Way to Encourage Early Literacy Is Also the Most Amusing

ERIC Educational Resources Information Center

Arnold, Renea; Colburn, Nell

2004-01-01

The authors think fun is a key word when it comes to early literacy. Learning to read is hard work for most children--and kids, like adults, enjoy things that bring them pleasure. So as professionals who work with young children, their job is to make sure that kids discover the joy of books. And one of the best ways to do that is by providing…

Evaluation of the Navys Sea/Shore Flow Policy

DTIC Science & Technology

2016-06-01

CNA developed an independent Discrete -Event Simulation model to evaluate and assess the effect of alternative sea/shore flow policies. In this study...remains, even if the system is optimized. In building a Discrete -Event Simulation model, we discovered key factors that should be included in the... Discrete -Event Simulation model to evaluate the impact of sea/shore flow policy (the DES-SSF model) and compared the results with the SSFM for one

Competition for Shared Resources in the Cellular Chassis: Impact on Synthetic Circuits

DTIC Science & Technology

2013-11-01

glyceraldehyde dehydrogenase from E. coli and it is very abundant in the bacterial cytoplasm. The control MBP-dRFP does not display an effect on GFP ...discover how key parameters control the extent of coupling we constructed an analytical model that predicts how the concentration of one protein ( GFP ...SECURITY CLASSIFICATION OF: Protein overexpression leads to growth inhibition and decreased expression of native proteins. This effect is mostly due

KOJAK: Scalable Semantic Link Discovery Via Integrated Knowledge-Based and Statistical Reasoning

DTIC Science & Technology

2006-11-01

program can find interesting connections in a network without having to learn the patterns of interestingness beforehand. The key advantage of our...Interesting Instances in Semantic Graphs Below we describe how the UNICORN framework can discover interesting instances in a multi-relational dataset...We can now describe how UNICORN solves the first problem of finding the top interesting nodes in a semantic net by ranking them according to

Correlation between Gas Bubble Formation and Hydrogen Evolution Reaction Kinetics at Nanoelectrodes.

PubMed

Chen, Qianjin; Luo, Long

2018-04-17

We report the correlation between H 2 gas bubble formation potential and hydrogen evolution reaction (HER) activity for Au and Pt nanodisk electrodes (NEs). Microkinetic models were formulated to obtain the HER kinetic information for individual Au and Pt NEs. We found that the rate-determining steps for the HER at Au and Pt NEs were the Volmer step and the Heyrovsky step, respectively. More interestingly, the standard rate constant ( k 0 ) of the rate-determining step was found to vary over 2 orders of magnitude for the same type of NEs. The observed variations indicate the HER activity heterogeneity at the nanoscale. Furthermore, we discovered a linear relationship between bubble formation potential ( E bubble ) and log( k 0 ) with a slope of 125 mV/decade for both Au and Pt NEs. As log ( k 0 ) increases, E bubble shifts linearly to more positive potentials, meaning NEs with higher HER activities form H 2 bubbles at less negative potentials. Our theoretical model suggests that such linear relationship is caused by the similar critical bubble formation condition for Au and Pt NEs with varied sizes. Our results have potential implications for using gas bubble formation to evaluate the HER activity distribution of nanoparticles in an ensemble.

Ultra low signals in ballistic electron emission microscopy

NASA Astrophysics Data System (ADS)

Heller, Eric

The extension of Scanning Tunneling Microscopy known as Ballistic Electron Emission Microscopy (BEEM) was expanded to allow useful data collection at lower signal levels than previously possible, and a critical BEEM shortcoming was discovered and quantified. As a separate effort, a new method for measuring SB-type step energies on Si(001) SA-type steps that under some circumstances is more accurate than previous methods was used and will be presented. Finally, extensive modifications to a Scanning Tunneling Microscope used for most of this research will be presented. First, it will be shown theoretically and experimentally that by amplifying the hot BEEM electrons that make up the useful BEEM signal before they are thermalized, internal gain can be applied specifically to these electrons without amplifying standard BEEM noise sources. It will be shown that BEEM with single hot electron sensitivity (approximately a factor of 1000 improvement in the minimum detectable BEEM signal) is attainable with modified commercially existing avalanche photodiodes. With this new low-signal capability, it was obvious that a new BEEM-like signal was being detected. We have discovered that photons generated by STM tunneling will create a false signal in most BEEM samples. Furthermore, we have characterized this effect which we call "STM-PC" and it will be demonstrated with Pd/SiO2/Si and Au/SiO2/Si samples that this false signal closely mimics BEEM and is easily confused for BEEM. We will discuss ways to separate real BEEM from this new effect. Separately, thermally generated kinks on A-type steps on the Si(001) surface were counted and analyzed to find the SB-type step energy. Previous work by others was extended by counting a new type of feature, the "switch" kink, to allow a more accurate determination of the energy of SB-steps in the presence of defects that can bow steps and cause non-thermal kinks. Considerable data collection along with this new extension allowed a more accurate determination of the SB-type kink energy than before and the first experimental evidence that it increases with tensile strain on the Si(001) surface. Modifications to an Omicron Variable Temperature Scanning Tunneling Microscope (VT-STM) will be presented. The VT-STM will be moved to the Electrical Engineering Department cleanroom of The Ohio State University and will allow in-situ studies of Molecular Beam Epitaxy (MBE) grown samples. Modifications, repairs, and operating procedures will be discussed for the VT-STM and supporting hardware. Last, work on Low Temperature Grown Gallium Arsenide (LTG-GaAs) will be presented. The ultimate goal of detecting mm-scale arsenic precipitates that form with annealing using BEEM was not successful. Precipitates were imaged with atomic force microscopy, but these same precipitates are not seen with BEEM under some conditions.

Preprocessing and Analysis of LC-MS-Based Proteomic Data

PubMed Central

Tsai, Tsung-Heng; Wang, Minkun; Ressom, Habtom W.

2016-01-01

Liquid chromatography coupled with mass spectrometry (LC-MS) has been widely used for profiling protein expression levels. This chapter is focused on LC-MS data preprocessing, which is a crucial step in the analysis of LC-MS based proteomics. We provide a high-level overview, highlight associated challenges, and present a step-by-step example for analysis of data from LC-MS based untargeted proteomic study. Furthermore, key procedures and relevant issues with the subsequent analysis by multiple reaction monitoring (MRM) are discussed. PMID:26519169

Hospital cost accounting: implementing the system successfully.

PubMed

Burik, D; Duvall, T J

1985-05-01

To successfully implement a cost accounting system, certain key steps should be undertaken. These steps include developing and installing software; developing cost center budgets and inter-cost center allocations; developing service item standard costs; generating cost center level and patient level standard cost reports and reconciling these costs to actual costs; generating product line profitability reports and reconciling these reports to the financial statements; and providing ad hoc reporting capabilities. By following these steps, potential problems in the implementation process can be anticipated and avoided.

Discovery of novel drugs for promising targets.

PubMed

Martell, Robert E; Brooks, David G; Wang, Yan; Wilcoxen, Keith

2013-09-01

Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging. The goal of this study was to provide a road map to navigate drug discovery. Review general steps for drug discovery and provide illustrating references. A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed. Drug discovery is a complex process that has significantly evolved in recent years. © 2013 Elsevier HS Journals, Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Favaro, Marco; Xiao, Hai; Cheng, Tao

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide ismore » essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.« less

Project visual analysis for the Allegheny National Forest

Treesearch

Gary W. Kell

1979-01-01

The Project Visual Analysis is a landscape assessment procedure involving forest vegetative manipulation. A logical step by step analysis leads the user to a specific set of landscape management guidelines to be used as an aid in designing a project or in evaluating whether the proposed project impacts will meet visual objectives. Key elements within the procedure are...

Synthesis of fisetin and 2',4',6'-trihydroxydihyrochalcone 4'-O-β-neohesperidoside based on site-selective deacetylation and deoxygenation.

PubMed

Tsunekawa, Ryuji; Hanaya, Kengo; Higashibayashi, Shuhei; Sugai, Takeshi

2018-04-26

Fisetin and 2',4',6'-trihydroxydihyrochalcone 4'-O-β-neohesperidoside were synthesized from commercially available quercetin and naringin in five steps. The key steps are site-selective deacetylation and subsequent deoxygenation. The target molecules were obtained in 37% and 23% yields from the starting materials, respectively.

How to Develop Children as Researchers: A Step-by-Step Guide to Teaching the Research Process

ERIC Educational Resources Information Center

Kellett, Mary

2005-01-01

The importance of research in professional and personal development is increasingly being acknowledged. So why should children not benefit in a similar way? Traditionally, children have been excluded from this learning process because research methodology is considered too difficult for them. Principal obstacles focus around three key barriers:…

Reinventing Your Board: A Step-by-Step Guide to Implementing Policy Governance. The Jossey-Bass Nonprofit and Public Management Series.

ERIC Educational Resources Information Center

Carver, John; Carver, Miriam Mayhew

This guide provides practical advice regarding implementation of the Policy Governance model for school boards. Chapter 1, "Setting the Stage," explores questions commonly raised by boards prior to implementation of the Policy Governance model. Chapter 2, "The Theoretical Foundation," reviews the key theoretical principles of…

Healthy Connections. A Training Program for Volunteers Working with At-Risk Pregnant Women. Leader's Manual.

ERIC Educational Resources Information Center

Harris, Carolyn DeMeyer; McKinney, David D., Ed.

This leader's manual, keyed to an accompanying videotape, contains step-by-step instructions for conducting a training session for volunteers who are preparing to work with young unmarried pregnant women. The manual, which includes transparency masters of handouts, is laid out with the outside column of each page containing instructions to the…

Linking Costs and Postsecondary Degrees: Key Issues for Policymakers. Working Paper 2011-03

ERIC Educational Resources Information Center

Johnson, Nate

2011-01-01

In this paper the author offers practical advice for decision-makers who are struggling to rein in college costs while improving productivity. He provides a step-by-step guide to different approaches for calculating costs, highlights the tremendous variability in cost across programs within institutions, and documents some of the "hidden costs" of…

Taking a Step Back: Learning without the Facilitator on Solo Activities

ERIC Educational Resources Information Center

Williams, Andy

2012-01-01

The purpose of this study is to report on the nature of student learning resulting from an open facilitation approach to solo activities. Three key moments of facilitator intervention were identified at which the facilitator was encouraged to take a step back from directing the experience. They are the pre-activity brief, the mid-activity visit…

Positioning the Learning Asset Portfolio as a Key Component in an Organization's Enterprise Risk Management Strategy

ERIC Educational Resources Information Center

McAliney, Peter J.

2009-01-01

This article presents a process for valuing a portfolio of learning assets used by line executives across industries to value traditional business assets. Embedded within the context of enterprise risk management, this strategic asset allocation process is presented step by step, providing readers the operational considerations to implement this…

IMAT graphics manual

NASA Technical Reports Server (NTRS)

Stockwell, Alan E.; Cooper, Paul A.

1991-01-01

The Integrated Multidisciplinary Analysis Tool (IMAT) consists of a menu driven executive system coupled with a relational database which links commercial structures, structural dynamics and control codes. The IMAT graphics system, a key element of the software, provides a common interface for storing, retrieving, and displaying graphical information. The IMAT Graphics Manual shows users of commercial analysis codes (MATRIXx, MSC/NASTRAN and I-DEAS) how to use the IMAT graphics system to obtain high quality graphical output using familiar plotting procedures. The manual explains the key features of the IMAT graphics system, illustrates their use with simple step-by-step examples, and provides a reference for users who wish to take advantage of the flexibility of the software to customize their own applications.

Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grambow, Colin A.; Jamal, Adeel; Li, Yi -Pei

Ketohydroperoxides are important in liquid-phase autoxidation and in gas-phase partial oxidation and pre-ignition chemistry, but because of their low concentration, instability, and various analytical chemistry limitations, it has been challenging to experimentally determine their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimolecular reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of density functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The presentmore » joint approach significantly outperforms previous manual and automated transition-state searches – 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chemical reactions involve promising new chemistry that may be relevant in atmospheric and combustion systems. Our study highlights the complexity of chemical space exploration and the advantage of combined application of several approaches. Altogether, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).« less

Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods

DOE PAGES

Grambow, Colin A.; Jamal, Adeel; Li, Yi -Pei; ...

2017-12-22

Ketohydroperoxides are important in liquid-phase autoxidation and in gas-phase partial oxidation and pre-ignition chemistry, but because of their low concentration, instability, and various analytical chemistry limitations, it has been challenging to experimentally determine their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimolecular reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of density functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The presentmore » joint approach significantly outperforms previous manual and automated transition-state searches – 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chemical reactions involve promising new chemistry that may be relevant in atmospheric and combustion systems. Our study highlights the complexity of chemical space exploration and the advantage of combined application of several approaches. Altogether, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).« less

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds, with Systematic Review for Peak Oxygen Consumption, Ejection Fraction and BNP

PubMed Central

Leong, Tora; Rehman, Michaela B.; Pastormerlo, Luigi Emilio; Harrell, Frank E.; Coats, Andrew J. S.; Francis, Darrel P.

2014-01-01

Background Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies. Objectives We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO2), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF). Data Sources and Eligibility Criteria Studies testing pVO2, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed. Methods First, we examined studies testing pVO2, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk. Results 33 studies (8946 patients) tested a pVO2 threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population's mean pVO2 (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001). Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001). Limitations This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds. Key Findings First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies' average pVO2, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis. Conclusions Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist. PMID:24475020

Methodology for the development of a Canadian national EMS research agenda

PubMed Central

2011-01-01

Background Many health care disciplines use evidence-based decision making to improve patient care and system performance. While the amount and quality of emergency medical services (EMS) research in Canada has increased over the past two decades, there has not been a unified national plan to enable research, ensure efficient use of research resources, guide funding decisions and build capacity in EMS research. Other countries have used research agendas to identify barriers and opportunities in EMS research and define national research priorities. The objective of this project is to develop a national EMS research agenda for Canada that will: 1) explore what barriers to EMS research currently exist, 2) identify current strengths and opportunities that may be of benefit to advancing EMS research, 3) make recommendations to overcome barriers and capitalize on opportunities, and 4) identify national EMS research priorities. Methods/Design Paramedics, educators, EMS managers, medical directors, researchers and other key stakeholders from across Canada will be purposefully recruited to participate in this mixed methods study, which consists of three phases: 1) qualitative interviews with a selection of the study participants, who will be asked about their experience and opinions about the four study objectives, 2) a facilitated roundtable discussion, in which all participants will explore and discuss the study objectives, and 3) an online Delphi consensus survey, in which all participants will be asked to score the importance of each topic discovered during the interviews and roundtable as they relate to the study objectives. Results will be analyzed to determine the level of consensus achieved for each topic. Discussion A mixed methods approach will be used to address the four study objectives. We anticipate that the keys to success will be: 1) ensuring a representative sample of EMS stakeholders, 2) fostering an open and collaborative roundtable discussion, and 3) adhering to a predefined approach to measure consensus on each topic. Steps have been taken in the methodology to address each of these a priori concerns. PMID:21961624

Morphological Study on Porous Silicon Carbide Membrane Fabricated by Double-Step Electrochemical Etching

NASA Astrophysics Data System (ADS)

Omiya, Takuma; Tanaka, Akira; Shimomura, Masaru

2012-07-01

The structure of porous silicon carbide membranes that peeled off spontaneously during electrochemical etching was studied. They were fabricated from n-type 6H SiC(0001) wafers by a double-step electrochemical etching process in a hydrofluoric electrolyte. Nanoporous membranes were obtained after double-step etching with current densities of 10-20 and 60-100 mA/cm2 in the first and second steps, respectively. Microporous membranes were also fabricated after double-step etching with current densities of 100 and 200 mA/cm2. It was found that the pore diameter is influenced by the etching current in step 1, and that a higher current is required in step 2 when the current in step 1 is increased. During the etching processes in steps 1 and 2, vertical nanopore and lateral crack formations proceed, respectively. The influx pathway of hydrofluoric solution, expansion of generated gases, and transfer limitation of positive holes to the pore surface are the key factors in the peeling-off mechanism of the membrane.

The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

PubMed

Steiner, Ulrike; Kucht, Sabine Hellwig neé; Ahimsa-Müller, Mahalia A; Grundmann, Nicola; Li, Shu-Ming; Drewke, Christel; Leistner, Eckhard

2015-04-16

Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant.

Discovering new variable stars at Key Stage 3

NASA Astrophysics Data System (ADS)

Chubb, Katy; Hood, Rosie; Wilson, Thomas; Holdship, Jonathan; Hutton, Sarah

2017-05-01

Details of the London pilot of the ‘Discovery Project’ are presented, where university-based astronomers were given the chance to pass on some real and applied knowledge of astronomy to a group of selected secondary school pupils. It was aimed at students in Key Stage 3 of their education, allowing them to be involved in real astronomical research at an early stage of their education, the chance to become the official discoverer of a new variable star, and to be listed in the International Variable Star Index database (The International Variable Star Index, Version 1.1, American Association of Variable Star Observers (AAVSO), 2016, http://aavso.org/vsx), all while learning and practising research-level skills. Future plans are discussed.

Discovering novel subsystems using comparative genomics

PubMed Central

Ferrer, Luciana; Shearer, Alexander G.; Karp, Peter D.

2011-01-01

Motivation: Key problems for computational genomics include discovering novel pathways in genome data, and discovering functional interaction partners for genes to define new members of partially elucidated pathways. Results: We propose a novel method for the discovery of subsystems from annotated genomes. For each gene pair, a score measuring the likelihood that the two genes belong to a same subsystem is computed using genome context methods. Genes are then grouped based on these scores, and the resulting groups are filtered to keep only high-confidence groups. Since the method is based on genome context analysis, it relies solely on structural annotation of the genomes. The method can be used to discover new pathways, find missing genes from a known pathway, find new protein complexes or other kinds of functional groups and assign function to genes. We tested the accuracy of our method in Escherichia coli K-12. In one configuration of the system, we find that 31.6% of the candidate groups generated by our method match a known pathway or protein complex closely, and that we rediscover 31.2% of all known pathways and protein complexes of at least 4 genes. We believe that a significant proportion of the candidates that do not match any known group in E.coli K-12 corresponds to novel subsystems that may represent promising leads for future laboratory research. We discuss in-depth examples of these findings. Availability: Predicted subsystems are available at http://brg.ai.sri.com/pwy-discovery/journal.html. Contact: lferrer@ai.sri.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21775308

A step-by-step methodology for enterprise interoperability projects

NASA Astrophysics Data System (ADS)

Chalmeta, Ricardo; Pazos, Verónica

2015-05-01

Enterprise interoperability is one of the key factors for enhancing enterprise competitiveness. Achieving enterprise interoperability is an extremely complex process which involves different technological, human and organisational elements. In this paper we present a framework to help enterprise interoperability. The framework has been developed taking into account the three domains of interoperability: Enterprise Modelling, Architecture and Platform and Ontologies. The main novelty of the framework in comparison to existing ones is that it includes a step-by-step methodology that explains how to carry out an enterprise interoperability project taking into account different interoperability views, like business, process, human resources, technology, knowledge and semantics.

Application of homomorphism to secure image sharing

NASA Astrophysics Data System (ADS)

Islam, Naveed; Puech, William; Hayat, Khizar; Brouzet, Robert

2011-09-01

In this paper, we present a new approach for sharing images between l players by exploiting the additive and multiplicative homomorphic properties of two well-known public key cryptosystems, i.e. RSA and Paillier. Contrary to the traditional schemes, the proposed approach employs secret sharing in a way that limits the influence of the dealer over the protocol and allows each player to participate with the help of his key-image. With the proposed approach, during the encryption step, each player encrypts his own key-image using the dealer's public key. The dealer encrypts the secret-to-be-shared image with the same public key and then, the l encrypted key-images plus the encrypted to-be shared image are multiplied homomorphically to get another encrypted image. After this step, the dealer can safely get a scrambled image which corresponds to the addition or multiplication of the l + 1 original images ( l key-images plus the secret image) because of the additive homomorphic property of the Paillier algorithm or multiplicative homomorphic property of the RSA algorithm. When the l players want to extract the secret image, they do not need to use keys and the dealer has no role. Indeed, with our approach, to extract the secret image, the l players need only to subtract their own key-image with no specific order from the scrambled image. Thus, the proposed approach provides an opportunity to use operators like multiplication on encrypted images for the development of a secure privacy preserving protocol in the image domain. We show that it is still possible to extract a visible version of the secret image with only l-1 key-images (when one key-image is missing) or when the l key-images used for the extraction are different from the l original key-images due to a lossy compression for example. Experimental results and security analysis verify and prove that the proposed approach is secure from cryptographic viewpoint.

Cultural diversity in heart failure management: findings from the DISCOVER study (Part 2).

PubMed

Davidson, Patricia M; Macdonald, Peter; Moser, Debra K; Ang, Esther; Paull, Glenn; Choucair, Sam; Daly, John; Gholizadeh, Leila; Dracup, Kathleen

2007-01-01

Self-management is a critical dimension in managing chronic conditions, particularly in heart failure (HF). Knowledge, attitudes and beliefs, relating to both illness and wellness, are strongly influenced by culture and ethnicity, impacting upon an individual's capacity to engage in self-care behaviours. Effective management of HF is largely dependent on facilitation of culturally informed, self-care behaviours to increase adherence to both pharmacological and non-pharmacological strategies. The Understanding the cultural experiences of individuals with chronic heart failure (CHF) in South East Health (DISCOVER) study is an exploratory, observational study investigating health patterns, information needs and the adjustment process for overseas-born people with HF living in Australia. An integrative literature review was augmented by qualitative data derived from key informant interviews, focus groups and individual interviews. A key finding of this study is that culture provides an important context to aid interpretations of attitudes, values, beliefs and behaviours, not only in illness but in health. While individual differences in attitudes and beliefs were observed among participants, common themes and issues were identified across cultural groups. Data from the DISCOVER study revealed the primacy of family and kinship ties. These relationships were important in making decisions about treatment choices and care plans. Participants also revealed the critical role of the 'family doctor' in assisting people and their families in brokering the health care system. In this study, heart disease was considered to be a significant condition but cancer was the condition that people both feared and dreaded the most, despite the high mortality rates of HF. This sample reported that religious and traditional beliefs became more important as people aged and considered their mortality. As HF is predominately a condition of ageing, the information derived from this study will assist clinicians to tailor health care service delivery for older people with HF, across multiple ethnic backgrounds.

Studies of Phlebotomine Sand Flies.

DTIC Science & Technology

1981-05-01

20, It different from Report) IS. SUPPLEMENTARY NOTES 9’. KEY WOFDS (Continue an teers*e aide it necessa y mid identify by block number) Lutzomyia ...illustrations and a description of a new species. Other new Lutzomyia sand flies were discovered in Mexico and Ecuador. A species group of Lutzomyia ...egg structure of some Lutzomyia D IN J OBSOLETE Continued-- / ’DD , j. 1473 EtnT oN OFNvS = LT Unclaggi;fi;R~d y - SECURITY CLASSIFICA rIOm OF THIS

Notes on the Stenus cirrus group of Zhejiang, East China, with descriptions of two new species (Coleoptera, Staphylinidae).

PubMed

Liu, Sheng-Nan; Tang, Liang; Luo, Rong-Ting

2017-01-01

Two new Stenus species of the cirrus group collected from Zhejiang Province, East China, are described, S. wuyanlingus Liu, Tang & Luo, sp. n. , S. yuyimingi Liu, Tang & Luo, sp. n. and a new distributional locality for S. ovalis Tang, Li & Zhao, 2005 was discovered. The diagnostic characters of the new species are illustrated, and a key to species of the group from Zhejiang Province is provided.

Prokaryotic Argonaute proteins: novel genome-editing tools?

PubMed

Hegge, Jorrit W; Swarts, Daan C; van der Oost, John

2018-01-01

Argonaute proteins constitute a highly diverse family of nucleic acid-guided proteins. They were first discovered in eukaryotes as key proteins in RNA interference systems, but homologous prokaryotic Argonaute proteins (pAgos) have also been found in archaea and bacteria. In this Progress article, we focus on long pAgo variants, a class of pAgos that are involved in nucleic acid-guided host defence against invading nucleic acids, and discuss the potential of pAgos in genome editing.

Notes on the Stenus cirrus group of Zhejiang, East China, with descriptions of two new species (Coleoptera, Staphylinidae)

PubMed Central

Liu, Sheng-Nan; Tang, Liang; Luo, Rong-Ting

2017-01-01

Abstract Two new Stenus species of the cirrus group collected from Zhejiang Province, East China, are described, S. wuyanlingus Liu, Tang & Luo, sp. n., S. yuyimingi Liu, Tang & Luo, sp. n. and a new distributional locality for S. ovalis Tang, Li & Zhao, 2005 was discovered. The diagnostic characters of the new species are illustrated, and a key to species of the group from Zhejiang Province is provided. PMID:28769734

Inner solar system material discovered in the Oort cloud

PubMed Central

Meech, Karen J.; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R.; Berdyugina, Svetlana; Keane, Jacqueline V.; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J.

2016-01-01

We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud. PMID:27386512

Inner solar system material discovered in the Oort cloud.

PubMed

Meech, Karen J; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R; Berdyugina, Svetlana; Keane, Jacqueline V; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J

2016-04-01

We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud.

Evaluation of Image Segmentation and Object Recognition Algorithms for Image Parsing

DTIC Science & Technology

2013-09-01

generation of the features from the key points. OpenCV uses Euclidean distance to match the key points and has the option to use Manhattan distance...feature vector includes polarity and intensity information. Final step is matching the key points. In OpenCV , Euclidean distance or Manhattan...the code below is one way and OpenCV offers the function radiusMatch (a pair must have a distance less than a given maximum distance). OpenCV’s

The total synthesis of calcium atorvastatin.

PubMed

Dias, Luiz C; Vieira, Adriano S; Barreiro, Eliezer J

2016-02-21

A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.

Monterrey, La Ciudad Dorada/Monterrey, The Golden City. Curriculum Projects. Fulbright-Hays Summer Seminars Abroad Program, 2002 (Mexico).

ERIC Educational Resources Information Center

Quintyne, Susan

This curriculum project is designed for high school classes in Spanish, social studies, or global studies. The project's lesson plan lists materials needed; poses seven key questions about Mexico and Monterrey; outlines background notes on Mexico; and provides a detailed, step-by-step procedure for classroom implementation during three days. Also…

Shifting the Curve: Fostering Academic Success in a Diverse Student Body

PubMed Central

Herbert-Carter, Janice; Smith, Marjorie; Klement, Brenda; Knight, Brandi Brandon; Anachebe, Ngozi F.

2018-01-01

Problem Diversity in the health care workforce is key to achieving health equity. Although U.S. medical schools have worked to increase the matriculation and academic success of underrepresented minority (URM) students (African Americans, Latinos, others), they have had only limited success. Lower standardized test scores, including on the Medical College Admission Test (MCAT), have been a barrier to matriculation for many URM applicants. Lower subsequent standardized exam scores, including on the United States Medical Licensing Exam Step 1, also have been an impediment to students’ progress, with mean scores for URM students lagging behind those for others. Approach Faculty at the Morehouse School of Medicine developed and implemented interventions to enhance the academic success of their URM students (about 75% are African American, and 5% are from other URM groups). To assess the outcomes of this work, the authors analyzed the MCAT scores and subsequent Step 1 scores of students in the graduating classes of 2009–2014. They also reviewed course evaluations, Graduation Questionnaires, and student and faculty interviews and focus groups. Outcomes Students’ Step 1 scores exceeded those expected based on their MCAT scores. This success was due to three key elements: (1) milieu and mentoring, (2) structure and content of the curriculum, and (3) monitoring. Next Steps A series of mixed-method studies are planned to better discern the core elements of faculty–student relationships that are key to students’ success. Lower test scores are not a fixed attribute; with the elements described, success is attainable for all students. PMID:28678099

Deliberation Makes a Difference: Preparation Strategies for TeamSTEPPS Implementation in Small and Rural Hospitals

PubMed Central

Zhu, Xi; Baloh, Jure; Ward, Marcia M.; Stewart, Greg L.

2016-01-01

Small and rural hospitals face special challenges to implement and sustain organization-wide quality improvement (QI) initiatives due to limited resources and infrastructures. We studied the implementation of TeamSTEPPS, a national QI initiative, in 14 critical access hospitals. Drawing on QI and organization development theories, we propose five strategic preparation steps for TeamSTEPPS: assess needs, reflect on the context, set goals, develop a shared understanding, and select change agents. We explore how hospitals’ practices correspond to suggested best practices by analyzing qualitative data collected through quarterly interviews with key informants. We find that the level of deliberation was a key factor that differentiated hospitals’ practices. Hospitals that were more deliberate in preparing for the five strategic steps were more likely to experience engagement, perceive efficacy, foresee and manage barriers, and achieve progress during implementation. We discuss potential steps that hospitals may take to better prepare for TeamSTEPPS implementation. PMID:26429835

Deciphering the function and regulation of SbCAD2: A key lignin gene to improve sorghum biomass degradability

USDA-ARS?s Scientific Manuscript database

Genetic modification of lignin biosynthesis in the cell wall of biofuel feedstocks is likely one of the most effective ways to improve the conversion efficiency of cellulosic biomass to biofuel for the bioenergy industry. As a key enzyme that catalyzes the last step of monolignol synthesis, cinnamy...

EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (Volume 1) (Interagency Science Discussion Draft)

EPA Science Inventory

EPA is releasing the draft report, EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (Volume 1), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the How Strategic Planning Keeps You Sane when Delivering Distance Programs

ERIC Educational Resources Information Center

MacNeil, Dixie; Luzius, Kim; Dunkin, Sonya

2010-01-01

This paper details the advantages of creating a strategic plan in the development and delivery of distance programs at the authors' own institution. The steps involved in the planning process and the three key elements of a successful strategic plan are addressed. The key elements include a program plan explaining the roles/responsibilities of…

Antitumor activity of a novel and orally available inhibitor of serine palmitoyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaguchi, Masahiro; Shibata, Sachio; Satomi, Yoshinori

Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin. In the presence of compound-2, exogenously added S1P partially compensated the intracellular sphingolipid levels through the salvage pathway bymore » partially rescuing compound-2-induced cytotoxicity. This suggested that the mechanism underlying the anti-proliferative effect of compound-2 involved the reduction of sphingolipid levels. Indeed, compound-2 promoted multinuclear formation with reduced endogenous sphingomyelin levels specifically in a compound-2-sensitive cell line, indicating that the effect was induced by sphingolipid reduction. Furthermore, compound-2 showed potent antitumor activity without causing significant body weight loss in the PL-21 acute myeloid leukemia mouse xenograft model. Therefore, SPT may be an attractive therapeutic anti-cancer drug target for which compound-2 may be a promising new drug. - Highlights: • We discovered compound-2, a novel and orally available SPT inhibitor. • Compound-2 was cytotoxic against PL-21 acute myeloid leukemia cells. • Compound-2 showed antitumor activity in the PL-21 mouse xenograft model.« less

Subcellular localisations of the CPTI collection of YFP-tagged proteins in Drosophila embryos

PubMed Central

Lye, Claire M.; Naylor, Huw W.; Sanson, Bénédicte

2014-01-01

A key challenge in the post-genomic area is to identify the function of the genes discovered, with many still uncharacterised in all metazoans. A first step is transcription pattern characterisation, for which we now have near whole-genome coverage in Drosophila. However, we have much more limited information about the expression and subcellular localisation of the corresponding proteins. The Cambridge Protein Trap Consortium generated, via piggyBac transposition, over 600 novel YFP-trap proteins tagging just under 400 Drosophila loci. Here, we characterise the subcellular localisations and expression patterns of these insertions, called the CPTI lines, in Drosophila embryos. We have systematically analysed subcellular localisations at cellularisation (stage 5) and recorded expression patterns at stage 5, at mid-embryogenesis (stage 11) and at late embryogenesis (stages 15-17). At stage 5, 31% of the nuclear lines (41) and 26% of the cytoplasmic lines (67) show discrete localisations that provide clues on the function of the protein and markers for organelles or regions, including nucleoli, the nuclear envelope, nuclear speckles, centrosomes, mitochondria, the endoplasmic reticulum, Golgi, lysosomes and peroxisomes. We characterised the membranous/cortical lines (102) throughout stage 5 to 10 during epithelial morphogenesis, documenting their apico-basal position and identifying those secreted in the extracellular space. We identified the tricellular vertices as a specialized membrane domain marked by the integral membrane protein Sidekick. Finally, we categorised the localisation of the membranous/cortical proteins during cytokinesis. PMID:25294944

Imaging Transcriptional Regulation of Eukaryotic mRNA Genes: Advances and Outlook.

PubMed

Yao, Jie

2017-01-06

Regulation of eukaryotic transcription in vivo occurs at distinct stages. Previous research has identified many active or repressive transcription factors (TFs) and core transcription components and studied their functions in vitro and in vivo. Nonetheless, how individual TFs act in concert to regulate mRNA gene expression in a single cell remains poorly understood. Direct observation of TF assembly and disassembly and various biochemical reactions during transcription of a single-copy gene in vivo is the ideal approach to study this problem. Research in this area requires developing novel techniques for single-cell transcription imaging and integrating imaging studies into understanding the molecular biology of transcription. In the past decade, advanced cell imaging has enabled unprecedented capabilities to visualize individual TF molecules, to track single transcription sites, and to detect individual mRNA in fixed and living cells. These studies have raised several novel insights on transcriptional regulation such as the "hit-and-run" model and transcription bursting that could not be obtained by in vitro biochemistry analysis. At this point, the key question is how to achieve deeper understandings or discover novel mechanisms of eukaryotic transcriptional regulation by imaging transcription in single cells. Meanwhile, further technical advancements are likely required for visualizing distinct kinetic steps of transcription on a single-copy gene in vivo. This review article summarizes recent progress in the field and describes the challenges and opportunities ahead. Copyright © 2016 Elsevier Ltd. All rights reserved.

MSU-Northern Bio-Energy Center of Excellence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kegel, Greg; Alcorn-Windy Boy, Jessica; Abedin, Md. Joynal

2014-09-30

MSU-Northern established the Bio-Energy Center (the Center) into a Regional Research Center of Excellence to address the obstacles concerning biofuels, feedstock, quality, conversion process, economic viability and public awareness. The Center built its laboratories and expertise in order to research and support product development and commercialization for the bio-energy industry in our region. The Center wanted to support the regional agricultural based economy by researching biofuels based on feedstock’s that can be grown in our region in an environmentally responsible manner. We were also interested in any technology that will improve the emissions and fuel economy performance of heavy dutymore » diesel engines. The Center had a three step approach to accomplish these goals: 1. Enhance the Center’s research and testing capabilities 2. Develop advanced biofuels from locally grown agricultural crops. 3. Educate and outreach for public understanding and acceptance of new technology. The Center was very successful in completing the tasks as outlined in the project plan. Key successes include discovering and patenting a new chemical conversion process for converting camelina oil to jet fuel, as well as promise in developing a heterogeneous Grubs catalyst to support the new chemical conversion process. The Center also successfully fragmented and deoxygenated naturally occurring lignin with a Ni-NHC catalyst, showing promise for further exploration of using lignin for fuels and fuel additives. This would create another value-added product for lignin that can be sourced from beetle kill trees or waste products from cellulose ethanol fuel facilities.« less

THE OPPORTUNISTIC PATHOGEN TOXOPLASMA GONDII DEPLOYS A DIVERSE LEGION OF INVASION AND SURVIVAL PROTEINS

PubMed Central

Zhou, Xing W.; Kafsack, Björn F. C.; Cole, Robert N.; Beckett, Phil; Shen, Rong F.; Carruthers, Vern B.

2006-01-01

Host cell invasion is an essential step during infection by Toxoplasma gondii, an intracellular protozoan that causes the severe opportunistic disease toxoplasmosis in humans. Recent evidence strongly suggests that proteins discharged from Toxoplasma apical secretory organelles (micronemes, dense granules, and rhoptries) play key roles in host cell invasion and survival during infection. However, to date, only a limited number of secretory proteins have been discovered and the full spectrum of effector molecules involved in parasite invasion and survival remains unknown. To address these issues, we analyzed a large cohort of freely released Toxoplasma secretory proteins using two complementary methodologies, 2-DE/MS and LC/ESI-MS-MS (MudPIT, shotgun proteomics). Visualization of Toxoplasma secretory products by 2-DE revealed ∼100 spots, most of which were successfully identified by protein microsequencing or MALDI-MS analysis. Many proteins were present in multiple species suggesting they are subjected to substantial posttranslational modification. Shotgun proteomic analysis of the secretory fraction revealed several additional products including novel putative adhesive proteins, proteases, and hypothetical secretory proteins similar to products expressed by other related parasites including Plasmodium, the etiologic agent of malaria. A subset of novel proteins were re-expressed as fusions to yellow fluorescent protein and this initial screen revealed shared and distinct localizations within secretory compartments of T. gondii tachyzoites. The findings provide a uniquely broad view of Toxoplasma secretory proteins that participate in parasite survival and pathogenesis during infection. PMID:16002397

My Green Car: The Adventure Begins (Ep. 1) – DOE Lab-Corps Video Series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saxena, Samveg; Shah, Nihar; Hansen, Dana

One key difference between a great technology that stays in the lab and one that reaches the marketplace is customer interest. In Episode 1, the Lab’s MyGreenCar team gets ready to step outside the lab and test their technology’s value to consumers in a scientific way. What makes a new technology compelling enough to transition out of the lab and become a consumer product? That’s the question Berkeley Lab researchers Samveg Saxena, Nihar Shah, and Dana Hansen plus industry mentor Russell Carrington set out to answer for MyGreenCar, an app providing personalized fuel economy or electric vehicle range estimates formore » consumers researching new cars. DOE’s Lab-Corps program offered the technology team some answers. The EERE-funded program, based on the National Science Foundation’s I-Corps™ model for entrepreneurial training, provides tools and training to move energy-related inventions to the marketplace. During Lab-Corp’s intensive six-week session, technology teams interview 100 customer and value chain members to discover which potential products based on their technologies will have significant market pull. A six video series follows the MyGreenCar team’s Lab-Corps experience, from pre-training preparation with the Lab’s Innovation and Partnerships Office through the ups and downs of the customer discovery process. Will the app make it to the marketplace? You’ll just have to watch.« less

Automated mapping of clinical terms into SNOMED-CT. An application to codify procedures in pathology.

PubMed

Allones, J L; Martinez, D; Taboada, M

2014-10-01

Clinical terminologies are considered a key technology for capturing clinical data in a precise and standardized manner, which is critical to accurately exchange information among different applications, medical records and decision support systems. An important step to promote the real use of clinical terminologies, such as SNOMED-CT, is to facilitate the process of finding mappings between local terms of medical records and concepts of terminologies. In this paper, we propose a mapping tool to discover text-to-concept mappings in SNOMED-CT. Name-based techniques were combined with a query expansion system to generate alternative search terms, and with a strategy to analyze and take advantage of the semantic relationships of the SNOMED-CT concepts. The developed tool was evaluated and compared to the search services provided by two SNOMED-CT browsers. Our tool automatically mapped clinical terms from a Spanish glossary of procedures in pathology with 88.0% precision and 51.4% recall, providing a substantial improvement of recall (28% and 60%) over other publicly accessible mapping services. The improvements reached by the mapping tool are encouraging. Our results demonstrate the feasibility of accurately mapping clinical glossaries to SNOMED-CT concepts, by means a combination of structural, query expansion and named-based techniques. We have shown that SNOMED-CT is a great source of knowledge to infer synonyms for the medical domain. Results show that an automated query expansion system overcomes the challenge of vocabulary mismatch partially.

Diverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection.

PubMed

Dorjsuren, Dorjbal; Kim, Daemyung; Vyjayanti, Vaddadi N; Maloney, David J; Jadhav, Ajit; Wilson, David M; Simeonov, Anton

2012-01-01

The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment.

A Common STEP in the Synaptic Pathology of Diverse Neuropsychiatric Disorders

PubMed Central

Johnson, Micah A.; Lombroso, Paul J.

2012-01-01

Synaptic function is critical for proper cognition, and synaptopathologies have been implicated in diverse neuropsychiatric disorders. STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-enriched tyrosine phosphatase that normally opposes synaptic strengthening by dephosphorylating key neuronal signaling molecules. STEP targets include N-methyl D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), as well as extracellular signal-regulated kinase (ERK) and the tyrosine kinase Fyn. STEP-mediated dephosphorylation promotes the internalization of NMDARs and AMPARs and the inactivation of ERK and Fyn. Regulation of STEP is complex, and recent work has implicated STEP dysregulation in the pathophysiology of several neuropsychiatric disorders. Both high levels and low levels of STEP are found in a diverse group of illnesses. This review focuses on the role of STEP in three disorders in which STEP levels are elevated: Alzheimer’s disease, fragile X syndrome, and schizophrenia. The presence of elevated STEP in all three of these disorders raises the intriguing possibility that cognitive deficits resulting from diverse etiologies may share a common molecular pathway. PMID:23239949

Cellular metabolic network analysis: discovering important reactions in Treponema pallidum.

PubMed

Chen, Xueying; Zhao, Min; Qu, Hong

2015-01-01

T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis.

Synthesis of tumor necrosis factor α for use as a mirror-image phage display target.

PubMed

Petersen, Mark E; Jacobsen, Michael T; Kay, Michael S

2016-06-21

Tumor Necrosis Factor alpha (TNFα) is an inflammatory cytokine that plays a central role in the pathogenesis of chronic inflammatory disease. Here we describe the chemical synthesis of l-TNFα along with the mirror-image d-protein for use as a phage display target. The synthetic strategy utilized native chemical ligation and desulfurization to unite three peptide segments, followed by oxidative folding to assemble the 52 kDa homotrimeric protein. This synthesis represents the foundational step for discovering an inhibitory d-peptide with the potential to improve current anti-TNFα therapeutic strategies.

Brief communication: ikaite (CaCO3*6H2O) discovered in Arctic sea ice

NASA Astrophysics Data System (ADS)

Dieckmann, G. S.; Nehrke, G.; Uhlig, C.; Göttlicher, J.; Gerland, S.; Granskog, M. A.; Thomas, D. N.

2010-02-01

We report for the first time on the discovery of calcium carbonate crystals as ikaite (CaCO3*6H2O) in sea ice from the Arctic (Kongsfjorden, Svalbard). This finding demonstrates that the precipitation of calcium carbonate during the freezing of sea ice is not restricted to the Antarctic, where it was observed for the first time in 2008. This finding is an important step in the quest to quantify its impact on the sea ice driven carbon cycle and should in the future enable improvement parametrization sea ice carbon models.

Segregated nodal domains of two-dimensional multispecies Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Chang, Shu-Ming; Lin, Chang-Shou; Lin, Tai-Chia; Lin, Wen-Wei

2004-09-01

In this paper, we study the distribution of m segregated nodal domains of the m-mixture of Bose-Einstein condensates under positive and large repulsive scattering lengths. It is shown that components of positive bound states may repel each other and form segregated nodal domains as the repulsive scattering lengths go to infinity. Efficient numerical schemes are created to confirm our theoretical results and discover a new phenomenon called verticillate multiplying, i.e., the generation of multiple verticillate structures. In addition, our proposed Gauss-Seidel-type iteration method is very effective in that it converges linearly in 10-20 steps.

Discover the missing links in the inventory knowledge chain--achieve 98% integrity in just 90 days? Yes you can!

PubMed

Ribar, T F

2000-05-01

You don't need any imagination to understand how to reconnect the Missing Links in the Knowledge Chain to improvement. The corrective action plan has been described clearly in eight easy steps that everyone can and should execute immediately to get their inventory integrity permanently up to 95 to 98% and keep it there. Nothing has been left to the imagination or to conjecture. This is the "how to" prescription to getting it done. It has worked effectively for others. It can work for you too.

Diversity of the human intestinal microbial flora.

PubMed

Eckburg, Paul B; Bik, Elisabeth M; Bernstein, Charles N; Purdom, Elizabeth; Dethlefsen, Les; Sargent, Michael; Gill, Steven R; Nelson, Karen E; Relman, David A

2005-06-10

The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

The Nine-Step Minnesota Grading System for Eyebank Eyes With Age Related Macular Degeneration: A Systematic Approach to Study Disease Stages.

PubMed

Olsen, Timothy W; Liao, Albert; Robinson, Hershonna S; Palejwala, Neal V; Sprehe, Nicholas

2017-10-01

To refine the Minnesota Grading System (MGS) using definitions from the Age-Related Eye Disease Studies (AREDS) into a nine-step grading scale (MGS-9). A nine-step grading scale descriptive analysis using three key phenotypic features (total drusen area, increased, and decreased pigmentation) of human eyebank eyes that were graded according to definitions from the AREDS criteria in order to harmonize studies of disease progression for research involving human tissue. From 2005 through February 2017, we have analyzed 1159 human eyes, procured from two eyebanks. Each macula was imaged using high-resolution, stereoscopic color fundus photography with both direct- and transillumination. Fundus images were digitally overlaid with a grading template and triangulated for foveal centration. We documented and stratified risk for each globe by applying the AREDS nine-step grading scale to the key clinical features from the MGS-9. We found a good distribution within the MGS categories (1-9) with few level eight globes. Eyes were processed within 12.1 ± 6.3, hours from the time of death through imaging, dissection, and freezing or fixation. Applying the MGS-9 to 331 pairs (662 eyes were simultaneously graded), 84% were within one-grading step and 93% within two steps of the fellow eye. We also document reticular pseudodrusen, basal laminar drusen, and pattern dystrophy. The MGS nine-step grading scale enables researchers using human tissue to refine the risk assessment of donor tissue. This analysis will harmonize results among researchers when grading human tissue using MGS criteria. Most importantly, the MGS-9 links directly to the known risk for progression from the AREDS.

Guiding gate-etch process development using 3D surface reaction modeling for 7nm and beyond

NASA Astrophysics Data System (ADS)

Dunn, Derren; Sporre, John R.; Deshpande, Vaibhav; Oulmane, Mohamed; Gull, Ronald; Ventzek, Peter; Ranjan, Alok

2017-03-01

Increasingly, advanced process nodes such as 7nm (N7) are fundamentally 3D and require stringent control of critical dimensions over high aspect ratio features. Process integration in these nodes requires a deep understanding of complex physical mechanisms to control critical dimensions from lithography through final etch. Polysilicon gate etch processes are critical steps in several device architectures for advanced nodes that rely on self-aligned patterning approaches to gate definition. These processes are required to meet several key metrics: (a) vertical etch profiles over high aspect ratios; (b) clean gate sidewalls free of etch process residue; (c) minimal erosion of liner oxide films protecting key architectural elements such as fins; and (e) residue free corners at gate interfaces with critical device elements. In this study, we explore how hybrid modeling approaches can be used to model a multi-step finFET polysilicon gate etch process. Initial parts of the patterning process through hardmask assembly are modeled using process emulation. Important aspects of gate definition are then modeled using a particle Monte Carlo (PMC) feature scale model that incorporates surface chemical reactions.1 When necessary, species and energy flux inputs to the PMC model are derived from simulations of the etch chamber. The modeled polysilicon gate etch process consists of several steps including a hard mask breakthrough step (BT), main feature etch steps (ME), and over-etch steps (OE) that control gate profiles at the gate fin interface. An additional constraint on this etch flow is that fin spacer oxides are left intact after final profile tuning steps. A natural optimization required from these processes is to maximize vertical gate profiles while minimizing erosion of fin spacer films.2

Feature Selection Using Information Gain for Improved Structural-Based Alert Correlation

PubMed Central

Siraj, Maheyzah Md; Zainal, Anazida; Elshoush, Huwaida Tagelsir; Elhaj, Fatin

2016-01-01

Grouping and clustering alerts for intrusion detection based on the similarity of features is referred to as structurally base alert correlation and can discover a list of attack steps. Previous researchers selected different features and data sources manually based on their knowledge and experience, which lead to the less accurate identification of attack steps and inconsistent performance of clustering accuracy. Furthermore, the existing alert correlation systems deal with a huge amount of data that contains null values, incomplete information, and irrelevant features causing the analysis of the alerts to be tedious, time-consuming and error-prone. Therefore, this paper focuses on selecting accurate and significant features of alerts that are appropriate to represent the attack steps, thus, enhancing the structural-based alert correlation model. A two-tier feature selection method is proposed to obtain the significant features. The first tier aims at ranking the subset of features based on high information gain entropy in decreasing order. The‏ second tier extends additional features with a better discriminative ability than the initially ranked features. Performance analysis results show the significance of the selected features in terms of the clustering accuracy using 2000 DARPA intrusion detection scenario-specific dataset. PMID:27893821

Modified Multi Prime RSA Cryptosystem

NASA Astrophysics Data System (ADS)

Ghazali Kamardan, M.; Aminudin, N.; Che-Him, Norziha; Sufahani, Suliadi; Khalid, Kamil; Roslan, Rozaini

2018-04-01

RSA [1] is one of the mostly used cryptosystem in securing data and information. Though, it has been recently discovered that RSA has some weaknesses and in advance technology, RSA is believed to be inefficient especially when it comes to decryption. Thus, a new algorithm called Multi prime RSA, an extended version of the standard RSA is studied. Then, a modification is made to the Multi prime RSA where another keys is shared secretly between the receiver and the sender to increase the securerity. As in RSA, the methodology used for modified Multi-prime RSA also consists of three phases; 1. Key Generation in which the secret and public keys are generated and published. In this phase, the secrecy is improved by adding more prime numbers and addition of secret keys. 2. Encryption of the message using the public and secret keys given. 3. Decryption of the secret message using the secret key generated. For the decryption phase, a method called Chinese Remainder Theorem is used which helps to fasten the computation. Since Multi prime RSA use more than two prime numbers, the algorithm is more efficient and secure when compared to the standard RSA. Furthermore, in modified Multi prime RSA another secret key is introduced to increase the obstacle to the attacker. Therefore, it is strongly believed that this new algorithm is better and can be an alternative to the RSA.

Easy access to a cyclic key intermediate for the synthesis of trisporic acids and related compounds.

PubMed

González-Delgado, José A; Escobar, Gustavo; Arteaga, Jesús F; Barrero, Alejandro F

2014-02-03

The synthesis of a cyclohexane skeleton possessing different oxygenated functional groups at C-3, C-8 and C-9, and a D1,6-double bond has been accomplished in 10 steps with an overall 17% yield. This compound is a key intermediate for access to a wide range of compounds of the bioactive trisporoid family. The synthetic sequence consists of the preparation of a properly functionalized epoxygeraniol derivative, and its subsequent stereoselective cyclization mediated by Ti(III). This last step implies a domino process that starts with a homolytic epoxide opening followed by a radical cyclization and regioselective elimination. This concerted process gives access to the cyclohexane moiety with stereochemical control of five of its six carbon atoms.

Machine Learning: A Crucial Tool for Sensor Design

PubMed Central

Zhao, Weixiang; Bhushan, Abhinav; Santamaria, Anthony D.; Simon, Melinda G.; Davis, Cristina E.

2009-01-01

Sensors have been widely used for disease diagnosis, environmental quality monitoring, food quality control, industrial process analysis and control, and other related fields. As a key tool for sensor data analysis, machine learning is becoming a core part of novel sensor design. Dividing a complete machine learning process into three steps: data pre-treatment, feature extraction and dimension reduction, and system modeling, this paper provides a review of the methods that are widely used for each step. For each method, the principles and the key issues that affect modeling results are discussed. After reviewing the potential problems in machine learning processes, this paper gives a summary of current algorithms in this field and provides some feasible directions for future studies. PMID:20191110

3D Scientific Visualization with Blender

NASA Astrophysics Data System (ADS)

Kent, Brian R.

2015-03-01

This is the first book written on using Blender for scientific visualization. It is a practical and interesting introduction to Blender for understanding key parts of 3D rendering and animation that pertain to the sciences via step-by-step guided tutorials. 3D Scientific Visualization with Blender takes you through an understanding of 3D graphics and modelling for different visualization scenarios in the physical sciences.

Initiation precursors and initiators in laser-induced copolymerization of styrene and maleic anhydride in acetone

NASA Technical Reports Server (NTRS)

Miner, Gilda A.; Meador, Willard E.; Chang, C. Ken

1990-01-01

The initiation step of photopolymerized styrene/maleic anhydride copolymer was investigated at 365 nm. UV absorption measurements provide decisive evidence that the styrene/maleic anhydride charge transfer complex is the sole absorbing species; however, key laser experiments suggest intermediate reactions lead to a monoradical initiating species. A mechanism for the photoinitiation step of the copolymer is proposed.

The Complexity Trap

DTIC Science & Technology

2012-01-01

proactively and effectively to today’s international environment, prioritization is the key first step —and precisely the opposite reaction to the complacency...formidable than just endless grains of sand.”32 This is not to deny the possibility of nonlinear phenomena, butterfly effects, self-organizing systems...The first step is replac- ing the current reactive worship of complexity with proactive prioritization. To escape the complexity trap, let us dare

10 Tips for Getting Grants to Keep Your Library Afloat

ERIC Educational Resources Information Center

McCune, Bonnie

2007-01-01

In this article, the author, taking the view of the foundation or the grant giver, shares the basic steps on how funders assess requests for grants. Each of these steps may be waived if a key member of the selection process, such as a board member, has a personal interest in the application. The following are 10 tips from the funders' point of…

The mechanism of oxidation in chromophore maturation of wild-type green fluorescent protein: a theoretical study.

PubMed

Ma, Yingying; Sun, Qiao; Smith, Sean C

2017-05-24

Oxidation is viewed as the second and rate-limiting step in the chromophore maturation process of the wild-type green fluorescent protein (GFP) under aerobic conditions. Molecular oxygen is the necessary oxidant for GFP chromophore biosynthesis. In this study, density functional theory (DFT) calculations were employed to study the mechanism of oxidation. Our results indicate that the deprotonation of the Tyr66 α-carbon is probably the rate-limiting step in the oxidation step. Electron transfer from the enolate form of the five-membered heterocycle (EFMH) to molecular oxygen, generating the triplet radical complex [EFMH˙O 2 - ˙] T , is an important step. This complex undergoes intersystem crossing to form an open-shell singlet diradical complex before it forms the closed-shell singlet hydroperoxy adduct. The formation of the hydroperoxy adduct is a proton-coupled electron transfer process. The energy barrier of H 2 O 2 elimination is 16.5 kcal mol -1 . The oxidation product IFMHH 2 O 2 that we discovered is a hydroxylated cyclic imine structure, which is consistent with the crystal structure trapped in the colorless Y66L variant. The relative energy of the oxidation product is -48.7 kcal mol -1 , which is in accordance with the experimental observation that the thermodynamically unfavourable cyclized product is trapped by oxidation. The results herein support the cyclization-oxidation-dehydration mechanism for the chromophore maturation of GFP.

Modification of the nuclear landscape in the inverse problem framework using the generalized Bethe-Weizsäcker mass formula

NASA Astrophysics Data System (ADS)

Mavrodiev, S. Cht.; Deliyergiyev, M. A.

We formalized the nuclear mass problem in the inverse problem framework. This approach allows us to infer the underlying model parameters from experimental observation, rather than to predict the observations from the model parameters. The inverse problem was formulated for the numerically generalized semi-empirical mass formula of Bethe and von Weizsäcker. It was solved in a step-by-step way based on the AME2012 nuclear database. The established parametrization describes the measured nuclear masses of 2564 isotopes with a maximum deviation less than 2.6MeV, starting from the number of protons and number of neutrons equal to 1. The explicit form of unknown functions in the generalized mass formula was discovered in a step-by-step way using the modified least χ2 procedure, that realized in the algorithms which were developed by Lubomir Aleksandrov to solve the nonlinear systems of equations via the Gauss-Newton method, lets us to choose the better one between two functions with same χ2. In the obtained generalized model, the corrections to the binding energy depend on nine proton (2, 8, 14, 20, 28, 50, 82, 108, 124) and ten neutron (2, 8, 14, 20, 28, 50, 82, 124, 152, 202) magic numbers as well on the asymptotic boundaries of their influence. The obtained results were compared with the predictions of other models.

Kinetic Landscape of a Peptide Bond-Forming Prolyl Oligopeptidase

PubMed Central

2017-01-01

Prolyl oligopeptidase B from Galerina marginata (GmPOPB) has recently been discovered as a peptidase capable of breaking and forming peptide bonds to yield a cyclic peptide. Despite the relevance of prolyl oligopeptidases in human biology and disease, a kinetic analysis pinpointing rate-limiting steps for a member of this enzyme family is not available. Macrocyclase enzymes are currently exploited to produce cyclic peptides with potential therapeutic applications. Cyclic peptides are promising druglike molecules because of their stability and conformational rigidity. Here we describe an in-depth kinetic characterization of a prolyl oligopeptidase acting as a macrocyclase enzyme. By combining steady-state and pre-steady-state kinetics, we propose a kinetic sequence in which a step after macrocyclization limits steady-state turnover. Additionally, product release is ordered, where the cyclic peptide departs first followed by the peptide tail. Dissociation of the peptide tail is slow and significantly contributes to the turnover rate. Furthermore, trapping of the enzyme by the peptide tail becomes significant beyond initial rate conditions. The presence of a burst of product formation and a large viscosity effect further support the rate-limiting nature of a physical step occurring after macrocyclization. This is the first detailed description of the kinetic sequence of a macrocyclase enzyme from this class. GmPOPB is among the fastest macrocyclases described to date, and this work is a necessary step toward designing broad-specificity efficient macrocyclases. PMID:28332820

Neonatal Atlas Construction Using Sparse Representation

PubMed Central

Shi, Feng; Wang, Li; Wu, Guorong; Li, Gang; Gilmore, John H.; Lin, Weili; Shen, Dinggang

2014-01-01

Atlas construction generally includes first an image registration step to normalize all images into a common space and then an atlas building step to fuse the information from all the aligned images. Although numerous atlas construction studies have been performed to improve the accuracy of the image registration step, unweighted or simply weighted average is often used in the atlas building step. In this article, we propose a novel patch-based sparse representation method for atlas construction after all images have been registered into the common space. By taking advantage of local sparse representation, more anatomical details can be recovered in the built atlas. To make the anatomical structures spatially smooth in the atlas, the anatomical feature constraints on group structure of representations and also the overlapping of neighboring patches are imposed to ensure the anatomical consistency between neighboring patches. The proposed method has been applied to 73 neonatal MR images with poor spatial resolution and low tissue contrast, for constructing a neonatal brain atlas with sharp anatomical details. Experimental results demonstrate that the proposed method can significantly enhance the quality of the constructed atlas by discovering more anatomical details especially in the highly convoluted cortical regions. The resulting atlas demonstrates superior performance of our atlas when applied to spatially normalizing three different neonatal datasets, compared with other start-of-the-art neonatal brain atlases. PMID:24638883

The Way We Walked with Immunology.

PubMed

Ishizaka, Kimishige

2018-04-26

It has been a little more than 50 years since we discovered IgE, a key molecule for the allergic response and a target for treating allergies and severe asthma. Here, I trace my career, from the kindling of my interest in immunochemistry to groundbreaking discoveries in the biology and chemistry of immunoglobulins. I describe my service to the broader community of immunologists and my role in shaping departments and research institutes. My course starts in Japan and includes Southern California, Baltimore, and Denver.

What do lollipops and influenza have in common?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekiert, Damian

2012-06-22

Human drug trials have begun to test a new way to treat influenza that has the potential to create a universal vaccine. The powerful x-ray beams from the Advanced Light Source at Argonne National Laboratory outside of Chicago enabled scientists to see the structure of the influenza virus clear enough to discover a key commonality among influenza strains. Scientist Damien Ekiert, who won a 2012 award for his work in this discovery, explains why drug manufacturers could capitalize on this.

The HST Key Project on the Extragalactic Distance Scale VI. The Cepheids in NGC925

NASA Technical Reports Server (NTRS)

Silbermann, N. A.; Harding, Paul; Madore, Barry F.; Kennicutt, Robert C., Jr.; Saha, Abhijit; Stetson, Peter; Freedman, Wendy L.; Mould, Jeremy R.; Graham, John A.; Hill, Robert J.;

Key and Essential Elements of a U.S. Government Interagency Plan

DTIC Science & Technology

2008-03-15

Jim Blackburn was assigned a member of USAID to his staff and was perplexed as to why the individual would be sent to his unit. Blackburn’s initial...thought was to find him a place for him to sit and not much else as Blackburn did not know what else to do with him. The situation continued like...that for several weeks. As the two dialogued, Blackburn discovered the USAID member could bring money from the Iraqi government for R/S projects. At

Gnostic cells in the 21st century.

PubMed

Quiroga, Rodrigo Quian

2013-01-01

In this short review, I revise the notion of gnostic cells posited by Konorski, together with similar arguments by James, Lettvin and Barlow--namely, the idea of pontifical, grandmother and cardinal cells, respectively. I then discuss whether the characteristics of the recently discovered concept cells, i.e. neurons in the human medial temporal lobe with a very high degree of specificity and invariance, fit the conjecture of gnostic or grandmother cells and then discuss the key role of concept cells in memory formation.

The Influenza Virus and the 2009 H1N1 Outbreak

DTIC Science & Technology

2016-04-08

Envelope L’ol • Sequencing Figure 1 Influenza Virus Anatomy -Neuramlnldase (Sialldase) ’ Hemagglutlnln 9 Key laboratory techniques...discover the 2009 H1 N1 influenza virus Phylogenetic Tree Out of the over 400 human H1 ’s USAFSAM sequenced this season no specimen has had less than a...surveillance/vaccine contents • Shot Versus Flu Mist • How does Tamiflu work • Sequencing HA - Culture, HAI, PCR, Serology ••• • t.tt

Two Birds With One Stone: Application of Fundamental Cognitive Theory of Visual Perception Supporting Fratricide Prevention and Sensor Modeling Experimentation

DTIC Science & Technology

2008-12-01

tools capable of reducing fratricide and collateral damage. The theory of recognition-by-components developed by Dr. Irving Biederman presented a...trainer. The key to thermal combat identification was discovered in an unusual place: chick sexing. Biederman and Shiffrar [11] conducted object...professional sexers was .82. Biederman and Shiffrar conclude that “…after instruction the performance of the naïve subjects more closely resemble that of the

Identifying Key Features of Student Performance in Educational Video Games and Simulations through Cluster Analysis

ERIC Educational Resources Information Center

Kerr, Deirdre; Chung, Gregory K. W. K.

2012-01-01

The assessment cycle of "evidence-centered design" (ECD) provides a framework for treating an educational video game or simulation as an assessment. One of the main steps in the assessment cycle of ECD is the identification of the key features of student performance. While this process is relatively simple for multiple choice tests, when…

Molecular underpinnings of neurodegenerative disorders: striatal-enriched protein tyrosine phosphatase signaling and synaptic plasticity

PubMed Central

Lombroso, Paul J.; Ogren, Marilee; Kurup, Pradeep; Nairn, Angus C.

2016-01-01

This commentary focuses on potential molecular mechanisms related to the dysfunctional synaptic plasticity that is associated with neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Specifically, we focus on the role of striatal-enriched protein tyrosine phosphatase (STEP) in modulating synaptic function in these illnesses. STEP affects neuronal communication by opposing synaptic strengthening and does so by dephosphorylating several key substrates known to control synaptic signaling and plasticity. STEP levels are elevated in brains from patients with Alzheimer’s and Parkinson’s disease. Studies in model systems have found that high levels of STEP result in internalization of glutamate receptors as well as inactivation of ERK1/2, Fyn, Pyk2, and other STEP substrates necessary for the development of synaptic strengthening. We discuss the search for inhibitors of STEP activity that may offer potential treatments for neurocognitive disorders that are characterized by increased STEP activity. Future studies are needed to examine the mechanisms of differential and region-specific changes in STEP expression pattern, as such knowledge could lead to targeted therapies for disorders involving disrupted STEP activity. PMID:29098072

Distinctions between fraud, bias, errors, misunderstanding, and incompetence.

PubMed

DeMets, D L

1997-12-01

Randomized clinical trials are challenging not only in their design and analysis, but in their conduct as well. Despite the best intentions and efforts, problems often arise in the conduct of trials, including errors, misunderstandings, and bias. In some instances, key players in a trial may discover that they are not able or competent to meet requirements of the study. In a few cases, fraudulent activity occurs. While none of these problems is desirable, randomized clinical trials are usually found sufficiently robust by many key individuals to produce valid results. Other problems are not tolerable. Confusion may arise among scientists, scientific and lay press, and the public about the distinctions between these areas and their implications. We shall try to define these problems and illustrate their impact through a series of examples.

Making sense of the sensory regulation of hunger neurons.

PubMed

Chen, Yiming; Knight, Zachary A

2016-04-01

AgRP and POMC neurons are two key cell types that regulate feeding in response to hormones and nutrients. Recently, it was discovered that these neurons are also rapidly modulated by the mere sight and smell of food. This rapid sensory regulation "resets" the activity of AgRP and POMC neurons before a single bite of food has been consumed. This surprising and counterintuitive discovery challenges longstanding assumptions about the function and regulation of these cells. Here we review these recent findings and discuss their implications for our understanding of feeding behavior. We propose several alternative hypotheses for how these new observations might be integrated into a revised model of the feeding circuit, and also highlight some of the key questions that remain to be answered. © 2016 WILEY Periodicals, Inc.

Making sense of the sensory regulation of hunger neurons

PubMed Central

Chen, Yiming; Knight, Zachary A.

2016-01-01

AgRP and POMC neurons are two key cell types that regulate feeding in response to hormones and nutrients. Recently, it was discovered that these neurons are also rapidly modulated by the mere sight and smell of food. This rapid sensory regulation “resets” the activity of AgRP and POMC neurons before a single bite of food has been consumed. This surprising and counterintuitive discovery challenges longstanding assumptions about the function and regulation of these cells. Here we review these recent findings and discuss their implications for our understanding of feeding behavior. We propose several alternative hypotheses for how these new observations might be integrated into a revised model of the feeding circuit, and also highlight some of the key questions that remain to be answered. PMID:26898524

RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants

PubMed Central

Cho, Seok Keun; Ryu, Moon Young; Kim, Jong Hum; Hong, Jeong Soo; Oh, Tae Rin; Kim, Woo Taek; Yang, Seong Wook

2017-01-01

Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants. PMID:28712388

Inhibitors of Protein Methyltransferases and Demethylases

PubMed Central

2017-01-01

Post-translational modifications of histones by protein methyltransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene expression and transcription and are implicated in cancer and many other diseases. Many of these enzymes also target various nonhistone proteins impacting numerous crucial biological pathways. Given their key biological functions and implications in human diseases, there has been a growing interest in assessing these enzymes as potential therapeutic targets. Consequently, discovering and developing inhibitors of these enzymes has become a very active and fast-growing research area over the past decade. In this review, we cover the discovery, characterization, and biological application of inhibitors of PMTs and KDMs with emphasis on key advancements in the field. We also discuss challenges, opportunities, and future directions in this emerging, exciting research field. PMID:28338320