Identification of a selective small molecule inhibitor of breast cancer stem cells.

PubMed

Germain, Andrew R; Carmody, Leigh C; Morgan, Barbara; Fernandez, Cristina; Forbeck, Erin; Lewis, Timothy A; Nag, Partha P; Ting, Amal; VerPlank, Lynn; Feng, Yuxiong; Perez, Jose R; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S; Gupta, Piyush B; Schreiber, Stuart L; Munoz, Benito

2012-05-15

A high-throughput screen (HTS) with the National Institute of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP). Copyright © 2012 Elsevier Ltd. All rights reserved.

Group selection on population size affects life-history patterns in the entomopathogenic nematode Steinernema carpocapsae.

PubMed

Bashey, Farrah; Lively, Curtis M

2009-05-01

Selection is recognized to operate on multiple levels. In disease organisms, selection among hosts is thought to provide an important counterbalance to selection for faster growth within hosts. We performed three experiments, each selecting for a divergence in group size in the entomopathogenic nematode, Steinernema carpocapsae. These nematodes infect and kill insect larvae, reproduce inside the host carcass, and emerge as infective juveniles. We imposed selection on group size by selecting among hosts for either high or low numbers of emerging nematodes. Our goal was to determine whether this trait could respond to selection at the group level, and if so, to examine what other traits would evolve as correlated responses. One of the three experiments showed a significant response to group selection. In that experiment, the high-selected treatment consistently produced more emerging nematodes per host than the low-selected treatment. In addition, nematodes were larger and they emerged later from hosts in the low-selected lines. Despite small effective population sizes, the effects of inbreeding were small in this experiment. Thus, selection among hosts can be effective, leading to both a direct evolutionary response at the population level, as well as to correlated responses in populational and individual traits.

Selective photocatalytic transformations on microporous titanosilicate ETS-10 driven by size and polarity of molecules.

PubMed

Shiraishi, Yasuhiro; Tsukamoto, Daijiro; Hirai, Takayuki

2008-11-04

Photocatalytic activity of microporous titanosilicate ETS-10 has been studied in water. The photoactivated ETS-10 shows catalytic activity driven by size and polarity of substrates. ETS-10 efficiently catalyzes a conversion of substrates with a size larger than the pore diameter of ETS-10. In contrast, the reactivity of small substrates depends strongly on substrate polarity; less polar substrates show higher reactivity on ETS-10. Electron spin resonance analysis reveals that large substrates or less polar substrates scarcely diffuse inside the highly polarized micropores of ETS-10 and, hence, react efficiently with hydroxyl radicals (*OH) formed on titanol (Ti-OH) groups exposed on the external surface of ETS-10. In contrast, small polar substrates diffuse easily inside the micropores of ETS-10 and scarcely react with *OH, resulting in low reactivity. The photocatalytic activity of ETS-10 is successfully applicable to selective transformations of large reactants or less polar reactants to small polar products, enabling highly selective dehalogenation and hydroxylation of aromatics.

Lessons in Success: A Multi-Campus Study of Factors Influencing Academic Accomplishment among High-Achieving African American Students at Private Liberal Arts Colleges

ERIC Educational Resources Information Center

Johnson, Ryan A.

2013-01-01

The purpose of this study was to explore the academic experiences of highly successful African-American male graduates of small, private liberal arts colleges using a qualitative approach. Fourteen highly successful alumni from selective, private colleges were purposefully selected for the study, including seven African-American males and seven…

Selective Chemical Labeling of Proteins with Small Fluorescent Molecules Based on Metal-Chelation Methodology

PubMed Central

Soh, Nobuaki

2008-01-01

Site-specific chemical labeling utilizing small fluorescent molecules is a powerful and attractive technique for in vivo and in vitro analysis of cellular proteins, which can circumvent some problems in genetic encoding labeling by large fluorescent proteins. In particular, affinity labeling based on metal-chelation, advantageous due to the high selectivity/simplicity and the small tag-size, is promising, as well as enzymatic covalent labeling, thereby a variety of novel methods have been studied in recent years. This review describes the advances in chemical labeling of proteins, especially highlighting the metal-chelation methodology. PMID:27879749

A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells

PubMed Central

2012-01-01

The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 μM), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33. PMID:23256033

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

Stachel, Shawn J.; Sanders, John M.; Henze, Darrell A.

We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions. This endeavor resulted in the identification of several small molecule pan-Trk inhibitor series that exhibit high selectivity for TrkA/B/C versus a diverse panel of kinases. We have also demonstratedmore » efficacy in both inflammatory and neuropathic pain models upon oral dosing. Herein we describe the identification process, hit-to-lead progression, and binding profiles of these selective pan-Trk kinase inhibitors.« less

Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.

PubMed

Germain, Andrew R; Carmody, Leigh C; Nag, Partha P; Morgan, Barbara; Verplank, Lynn; Fernandez, Cristina; Donckele, Etienne; Feng, Yuxiong; Perez, Jose R; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S; Gupta, Piyush B; Schreiber, Stuart L; Munoz, Benito

2013-03-15

A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations. Copyright © 2013. Published by Elsevier Ltd.

Logistic regression trees for initial selection of interesting loci in case-control studies

PubMed Central

Nickolov, Radoslav Z; Milanov, Valentin B

2007-01-01

Modern genetic epidemiology faces the challenge of dealing with hundreds of thousands of genetic markers. The selection of a small initial subset of interesting markers for further investigation can greatly facilitate genetic studies. In this contribution we suggest the use of a logistic regression tree algorithm known as logistic tree with unbiased selection. Using the simulated data provided for Genetic Analysis Workshop 15, we show how this algorithm, with incorporation of multifactor dimensionality reduction method, can reduce an initial large pool of markers to a small set that includes the interesting markers with high probability. PMID:18466557

DEVELOPING THE OCCUPATIONAL BUSINESS EDUCATION PROGRAM IN THE SMALL HIGH SCHOOL. BUSINESS EDUCATION CURRICULUM DEVELOPMENT SERIES.

ERIC Educational Resources Information Center

AIKIN, BRENTON R.

SOME OF THE PROBLEMS INVOLVED IN BUSINESS EDUCATION IN THE SMALL SCHOOL WITH AN ENROLLMENT OF 350 OR LESS, ARE EXPLORED. SUGGESTIONS ARE BASED ON OBSERVATIONS OF PRACTICES IN SELECTED SMALL SCHOOLS, AN EXAMINATION OF THE LITERATURE IN THE FIELD, AND CONFERENCES WITH SCHOOL ADMINISTRATORS, TEACHERS, AND BUSINESSMEN. GUIDELINES FOR DEVELOPING…

Genome-wide association and prediction of grain and semolina quality traits in durum wheat breeding populations

USDA-ARS?s Scientific Manuscript database

Grain yield and semolina quality traits are essential selection criteria in durum wheat breeding. However, high cost of phenotypic screening limited the selection only on small number of lines and at later generations. This leads to relatively low selection efficiency due to the advancement of undes...

An enhancement of binary particle swarm optimization for gene selection in classifying cancer classes

PubMed Central

2013-01-01

Background Gene expression data could likely be a momentous help in the progress of proficient cancer diagnoses and classification platforms. Lately, many researchers analyze gene expression data using diverse computational intelligence methods, for selecting a small subset of informative genes from the data for cancer classification. Many computational methods face difficulties in selecting small subsets due to the small number of samples compared to the huge number of genes (high-dimension), irrelevant genes, and noisy genes. Methods We propose an enhanced binary particle swarm optimization to perform the selection of small subsets of informative genes which is significant for cancer classification. Particle speed, rule, and modified sigmoid function are introduced in this proposed method to increase the probability of the bits in a particle’s position to be zero. The method was empirically applied to a suite of ten well-known benchmark gene expression data sets. Results The performance of the proposed method proved to be superior to other previous related works, including the conventional version of binary particle swarm optimization (BPSO) in terms of classification accuracy and the number of selected genes. The proposed method also requires lower computational time compared to BPSO. PMID:23617960

The physical environment mediates male harm and its effect on selection in females.

PubMed

Yun, Li; Chen, Patrick J; Singh, Amardeep; Agrawal, Aneil F; Rundle, Howard D

2017-07-12

Recent experiments indicate that male preferential harassment of high-quality females reduces the variance in female fitness, thereby weakening natural selection through females and hampering adaptation and purging. We propose that this phenomenon, which results from a combination of male choice and male-induced harm, should be mediated by the physical environment in which intersexual interactions occur. Using Drosophila melanogaster , we examined intersexual interactions in small and simple (standard fly vials) versus slightly more realistic (small cages with spatial structure) environments. We show that in these more realistic environments, sexual interactions are less frequent, are no longer biased towards high-quality females, and that overall male harm is reduced. Next, we examine the selective advantage of high- over low-quality females while manipulating the opportunity for male choice. Male choice weakens the viability advantage of high-quality females in the simple environment, consistent with previous work, but strengthens selection on females in the more realistic environment. Laboratory studies in simple environments have strongly shaped our understanding of sexual conflict but may provide biased insight. Our results suggest that the physical environment plays a key role in the evolutionary consequences of sexual interactions and ultimately the alignment of natural and sexual selection. © 2017 The Author(s).

Social causes of correlational selection and the resolution of a heritable throat color polymorphism in a lizard.

PubMed

Sinervo, B; Bleay, C; Adamopoulou, C

2001-10-01

When selection acts on social or behavioral traits, the fitness of an individual depends on the phenotypes of its competitors. Here, we describe methods and statistical inference for measuring natural selection in small social groups. We measured selection on throat color alleles that arises from microgeographic variation in allele frequency at natal sites of side-blotched lizards (Uta stansburiana). Previous game-theoretic analysis indicates that two color morphs of female side-blotched lizards are engaged in an offspring quantity-quality game that promotes a density- and frequency-dependent cycle. Orange-throated females are r-strategists. They lay large clutches of small progeny, which have poor survival at high density, but good survival at low density. In contrast, yellow-throated females are K-strategists. They lay small clutches of large progeny, which have good survival at high density. We tested three predictions of the female game: (1) orange progeny should have a fitness advantage at low density; (2) correlational selection acts to couple color alleles and progeny size; and (3) this correlational selection arises from frequency-dependent selection in which large hatchling size confers an advantage, but only when yellow alleles are rare. We also confirmed the heritability of color, and therefore its genetic basis, by producing progeny from controlled matings. A parsimonious cause of the high heritability is that three alleles (o, b, y) segregate as one genetic factor. We review the physiology of color formation to explain the possible genetic architecture of the throat color trait. Heritability of color was nearly additive in our breeding study, allowing us to compute a genotypic value for each individual and thus predict the frequency of progeny alleles released on 116 plots. Rather than study the fitness of individual progeny, we studied how the fitness of their color alleles varied with allele frequency on plots. We confirmed prediction 1: When orange alleles are present in female progeny, they have higher fitness at low density when compared to other alleles. Even though the difference in egg size of the female morphs was small (0.02 g), it led to knife-edged survival effects for their progeny depending on local social context. Selection on hatchling survival was not only dependent on color alleles, but on a fitness interaction between color alleles and hatchling size, which confirmed prediction 2. Sire effects, which are not confounded by maternal phenotype, allowed us to resolve the frequency dependence of correlational selection on egg size and color alleles and thereby confirmed prediction 3. Selection favored large size when yellow sire alleles were rare, but small size when they were common. Correlational selection promotes the formation of a self-reinforcing genetic correlation between the morphs and life-history variation, which causes selection in the next density and frequency cycle to be exacerbated. We discuss general conditions for the evolution of self-reinforcing genetic correlations that arise from social selection associated with frequency-dependent sexual and natural selection.

Energetics, scaling and sexual size dimorphism of spiders.

PubMed

Grossi, B; Canals, M

2015-03-01

The extreme sexual size dimorphism in spiders has motivated studies for many years. In many species the male can be very small relative to the female. There are several hypotheses trying to explain this fact, most of them emphasizing the role of energy in determining spider size. The aim of this paper is to review the role of energy in sexual size dimorphism of spiders, even for those spiders that do not necessarily live in high foliage, using physical and allometric principles. Here we propose that the cost of transport or equivalently energy expenditure and the speed are traits under selection pressure in male spiders, favoring those of smaller size to reduce travel costs. The morphology of the spiders responds to these selective forces depending upon the lifestyle of the spiders. Climbing and bridging spiders must overcome the force of gravity. If bridging allows faster dispersal, small males would have a selective advantage by enjoying more mating opportunities. In wandering spiders with low population density and as a consequence few male-male interactions, high speed and low energy expenditure or cost of transport should be favored by natural selection. Pendulum mechanics show the advantages of long legs in spiders and their relationship with high speed, even in climbing and bridging spiders. Thus small size, compensated by long legs should be the expected morphology for a fast and mobile male spider.

Challenges and opportunities in genetic improvement of local livestock breeds

PubMed Central

Biscarini, Filippo; Nicolazzi, Ezequiel L.; Stella, Alessandra; Boettcher, Paul J.; Gandini, Gustavo

2015-01-01

Sufficient genetic variation in livestock populations is necessary both for adaptation to future changes in climate and consumer demand, and for continual genetic improvement of economically important traits. Unfortunately, the current trend is for reduced genetic variation, both within and across breeds. The latter occurs primarily through the loss of small, local breeds. Inferior production is a key driver for loss of small breeds, as they are replaced by high-output international transboundary breeds. Selection to improve productivity of small local breeds is therefore critical for their long term survival. The objective of this paper is to review the technology options available for the genetic improvement of small local breeds and discuss their feasibility. Most technologies have been developed for the high-input breeds and consequently are more favorably applied in that context. Nevertheless, their application in local breeds is not precluded and can yield significant benefits, especially when multiple technologies are applied in close collaboration with farmers and breeders. Breeding strategies that require cooperation and centralized decision-making, such as optimal contribution selection, may in fact be more easily implemented in small breeds. PMID:25763010

Band selective small flip angle COSY: a simple experiment for the analyses of 1H NMR spectra of small chiral molecules.

PubMed

Prabhu, Uday Ramesh; Suryaprakash, N

2008-12-01

The NMR spectroscopic discrimination of enantiomers in the chiral liquid crystalline solvent is more often carried out using (2)H detection in its natural abundance. The employment of (1)H detection for such a purpose is severely hampered due to significant loss of resolution in addition to indistinguishable overlap of the spectra from the two enantiomers. This study demonstrates that the band selected small flip angle homonuclear correlation experiment is a simple and robust technique that provides unambiguous discrimination, very high spectral resolution, reduced multiplicity of transitions, relative signs of the couplings and enormous saving of instrument time.

Generality of the Matching Law as a Descriptor of Shot Selection in Basketball

ERIC Educational Resources Information Center

Alferink, Larry A.; Critchfield, Thomas S.; Hitt, Jennifer L.; Higgins, William J.

2009-01-01

Based on a small sample of highly successful teams, past studies suggested that shot selection (two- vs. three-point field goals) in basketball corresponds to predictions of the generalized matching law. We examined the generality of this finding by evaluating shot selection of college (Study 1) and professional (Study 3) players. The matching law…

A Triazole-Containing Metal-Organic Framework as a Highly Effective and Substrate Size-Dependent Catalyst for CO2 Conversion.

PubMed

Li, Pei-Zhou; Wang, Xiao-Jun; Liu, Jia; Lim, Jie Sheng; Zou, Ruqiang; Zhao, Yanli

2016-02-24

A highly porous metal-organic framework (MOF) incorporating both exposed metal sites and nitrogen-rich triazole groups was successfully constructed via solvothermal assembly of a clicked octcarboxylate ligand and Cu(II) ions, which presents a high affinity toward CO2 molecules clearly verified by gas adsorption and Raman spectral detection. The constructed MOF featuring CO2-adsorbing property and exposed Lewis-acid metal sites could serve as an excellent catalyst for CO2-based chemical fixation. Catalytic activity of the MOF was confirmed by remarkably high efficiency on CO2 cycloaddition with small epoxides. When extending the substrates to larger ones, its activity showed a sharp decrease. These observations reveal that MOF-catalyzed CO2 cycloaddition of small substrates was carried out within the framework, while large ones cannot easily enter into the porous framework for catalytic reactions. Thus, the synthesized MOF exhibits high catalytic selectivity to different substrates on account of the confinement of the pore diameter. The high efficiency and size-dependent selectivity toward small epoxides on catalytic CO2 cycloaddition make this MOF a promising heterogeneous catalyst for carbon fixation.

Evidence for r- and K-selection in a wild bird population: a reciprocal link between ecology and evolution.

PubMed

Sæther, Bernt-Erik; Visser, Marcel E; Grøtan, Vidar; Engen, Steinar

2016-04-27

Understanding the variation in selection pressure on key life-history traits is crucial in our rapidly changing world. Density is rarely considered as a selective agent. To study its importance, we partition phenotypic selection in fluctuating environments into components representing the population growth rate at low densities and the strength of density dependence, using a new stochastic modelling framework. We analysed the number of eggs laid per season in a small song-bird, the great tit, and found balancing selection favouring large clutch sizes at small population densities and smaller clutches in years with large populations. A significant interaction between clutch size and population size in the regression for the Malthusian fitness reveals that those females producing large clutch sizes at small population sizes also are those that show the strongest reduction in fitness when population size is increased. This provides empirical support for ongoing r- and K-selection in this population, favouring phenotypes with large growth rates r at small population sizes and phenotypes with high competitive skills when populations are close to the carrying capacity K This selection causes long-term fluctuations around a stable mean clutch size caused by variation in population size, implying that r- and K-selection is an important mechanism influencing phenotypic evolution in fluctuating environments. This provides a general link between ecological dynamics and evolutionary processes, operating through a joint influence of density dependence and environmental stochasticity on fluctuations in population size. © 2016 The Author(s).

Development of Single-Stranded DNA Aptamers for Specific Bisphenol A Detection

PubMed Central

Jo, Minjoung; Ahn, Ji-Young; Lee, Joohyung; Lee, Seram; Hong, Sun Woo; Yoo, Jae-Wook; Kang, Jeehye; Dua, Pooja

2011-01-01

The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 1015 random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4′-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol–gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules. PMID:21413891

Challenges and Perspectives on the Development of Small-Molecule EGFR Inhibitors against T790M-Mediated Resistance in Non-Small-Cell Lung Cancer.

PubMed

Song, Zhendong; Ge, Yang; Wang, Changyuan; Huang, Shanshan; Shu, Xiaohong; Liu, Kexin; Zhou, Youwen; Ma, Xiaodong

2016-07-28

Because of the development of drug-resistance mutations, particularly the "gatekeeper" threonine(790)-to-methionine(790) (T790M) mutation in the ATP-binding pocket of the epidermal growth factor receptor (EGFR), the current generation of EGFR tyrosine kinase inhibitors lost their clinical efficacy. Recently, a large number of small-molecule inhibitors with striking inhibitory potency against EGFR mutants with the T790M change have been identified. In particular, the inhibitors rociletinib and osimertinib, which can selectively target both sensitizing mutations and the T790M resistance while sparing the wild-type (WT) form of the receptor, have been designated as breakthrough therapies in the treatment of mutant non-small-cell lung cancer (NSCLC) by the U.S. FDA in 2014. We hope that this review on the small-molecule EGFR T790M inhibitors, along with their discovery strategies, will assist in the design of future T790M-containing EGFR inhibitors with high levels of selectivity over WT EGFR, broad kinase selectivity, and desirable physicochemical properties.

Wavelength band selection method for multispectral target detection.

PubMed

Karlholm, Jörgen; Renhorn, Ingmar

2002-11-10

A framework is proposed for the selection of wavelength bands for multispectral sensors by use of hyperspectral reference data. Using the results from the detection theory we derive a cost function that is minimized by a set of spectral bands optimal in terms of detection performance for discrimination between a class of small rare targets and clutter with known spectral distribution. The method may be used, e.g., in the design of multispectral infrared search and track and electro-optical missile warning sensors, where a low false-alarm rate and a high-detection probability for detection of small targets against a clutter background are of critical importance, but the required high frame rate prevents the use of hyperspectral sensors.

High brilliance negative ion and neutral beam source

DOEpatents

Compton, Robert N.

1991-01-01

A high brilliance mass selected (Z-selected) negative ion and neutral beam source having good energy resolution. The source is based upon laser resonance ionization of atoms or molecules in a small gaseous medium followed by charge exchange through an alkali oven. The source is capable of producing microampere beams of an extremely wide variety of negative ions, and milliampere beams when operated in the pulsed mode.

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor.

PubMed

Seifertová, Marta; Čechová, Eliška; Llansola, Marta; Felipo, Vicente; Vykoukalová, Martina; Kočan, Anton

2017-10-01

We developed a simple analytical method for the simultaneous determination of representatives of various groups of neurotoxic insecticides (carbaryl, chlorpyrifos, cypermethrin, and α-endosulfan and β-endosulfan and their metabolite endosulfan sulfate) in limited amounts of animal tissues containing different amounts of lipids. Selected tissues (rodent fat, liver, and brain) were extracted in a special in-house-designed mini-extractor constructed on the basis of the Soxhlet and Twisselmann extractors. A dried tissue sample placed in a small cartridge was extracted, while the nascent extract was simultaneously filtered through a layer of sodium sulfate. The extraction was followed by combined clean-up, including gel permeation chromatography (in case of high lipid content), ultrasonication, and solid-phase extraction chromatography using C 18 on silica and aluminum oxide. Gas chromatography coupled with high-resolution mass spectrometry was used for analyte separation, detection, and quantification. Average recoveries for individual insecticides ranged from 82 to 111%. Expanded measurement uncertainties were generally lower than 35%. The developed method was successfully applied to rat tissue samples obtained from an animal model dealing with insecticide exposure during brain development. This method may also be applied to the analytical treatment of small amounts of various types of animal and human tissue samples. A significant advantage achieved using this method is high sample throughput due to the simultaneous treatment of many samples. Graphical abstract Optimized workflow for the determination of selected insecticides in small amounts of animal tissue including newly developed mini-extractor.

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors

PubMed Central

2014-01-01

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure. PMID:25589934

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.

PubMed

Halland, Nis; Schmidt, Friedemann; Weiss, Tilo; Saas, Joachim; Li, Ziyu; Czech, Jörg; Dreyer, Matthias; Hofmeister, Armin; Mertsch, Katharina; Dietz, Uwe; Strübing, Carsten; Nazare, Marc

2015-01-08

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure.

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique[S

PubMed Central

Yamaguchi, Satoshi; Zhang, Bo; Tomonaga, Takeshi; Seino, Utako; Kanagawa, Akiko; Segawa, Masaru; Nagasaka, Hironori; Suzuki, Akira; Miida, Takashi; Yamada, Sohsuke; Sasaguri, Yasuyuki; Doi, Takefumi; Saku, Keijiro; Okazaki, Mitsuyo; Tochino, Yoshihiro; Hirano, Ken-ichi

2014-01-01

The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been difficult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible filtration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors. PMID:24569139

Improved Sparse Multi-Class SVM and Its Application for Gene Selection in Cancer Classification

PubMed Central

Huang, Lingkang; Zhang, Hao Helen; Zeng, Zhao-Bang; Bushel, Pierre R.

2013-01-01

Background Microarray techniques provide promising tools for cancer diagnosis using gene expression profiles. However, molecular diagnosis based on high-throughput platforms presents great challenges due to the overwhelming number of variables versus the small sample size and the complex nature of multi-type tumors. Support vector machines (SVMs) have shown superior performance in cancer classification due to their ability to handle high dimensional low sample size data. The multi-class SVM algorithm of Crammer and Singer provides a natural framework for multi-class learning. Despite its effective performance, the procedure utilizes all variables without selection. In this paper, we propose to improve the procedure by imposing shrinkage penalties in learning to enforce solution sparsity. Results The original multi-class SVM of Crammer and Singer is effective for multi-class classification but does not conduct variable selection. We improved the method by introducing soft-thresholding type penalties to incorporate variable selection into multi-class classification for high dimensional data. The new methods were applied to simulated data and two cancer gene expression data sets. The results demonstrate that the new methods can select a small number of genes for building accurate multi-class classification rules. Furthermore, the important genes selected by the methods overlap significantly, suggesting general agreement among different variable selection schemes. Conclusions High accuracy and sparsity make the new methods attractive for cancer diagnostics with gene expression data and defining targets of therapeutic intervention. Availability: The source MATLAB code are available from http://math.arizona.edu/~hzhang/software.html. PMID:23966761

Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data.

PubMed

Wang, Shuaiqun; Aorigele; Kong, Wei; Zeng, Weiming; Hong, Xiaomin

2016-01-01

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes.

Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data

PubMed Central

Aorigele; Zeng, Weiming; Hong, Xiaomin

2016-01-01

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes. PMID:27579323

Elucidating the mechanism of protein water channels by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Grubmuller, Helmut

2004-03-01

Aquaporins are highly selective water channels. Molecular dynamics simulations of multiple water permeation events correctly predict the measured rate and explain at the atomic level why these membrane channels are so efficient, while blocking other small molecules, ions, and even protons. High efficiency is achieved through a carefully tailored balance of hydrogen bonds that the protein substitutes for the bulk interactions; selectivity is achieved mainly by electrostatic barriers.

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

ClinicalTrials.gov

2018-05-15

Cervical Cancer; Microsatellite Instability (MSI)-High Endometrial Cancer; Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Esophageal Cancer; Hepatocellular Carcinoma; Melanoma (Uveal Melanoma Excluded); Merkel Cell Carcinoma; Mesothelioma; MSI-high Colorectal Cancer; Non-small Cell Lung Cancer (NSCLC); Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Small Cell Lung Cancer (SCLC); Renal Cell Carcinoma (RCC); Triple-negative Breast Cancer; Urothelial Carcinoma; Diffuse Large B-cell Lymphoma

Proceedings of the Annual Symposium on Frequency Control (44th) Held in Baltimore, Maryland on 23-25 May 1990

DTIC Science & Technology

1990-01-01

Miniature Crystal Oscillator Second, manufacturability improvements in order to (TMXO), is a very small, very low power , high stability, reduce...gives no velocity selection or dispersion power changes of only 1 dB. results in a very broad velocity spread in the atomic beam and a comparatively high ...vacuum envelope. The to servo such things as microwave power and C-field, which imaging nature of this system provides high selectivity have always been

Covering All the Bases: A Model Hazardous Waste Program for Small Universities.

ERIC Educational Resources Information Center

MacPherson, Robert A.

1991-01-01

The Colorado School of Mines' experience illustrates that with good planning and enough money, a small university can provide a high level of waste management service, complying with government regulations. Considerations in developing the plan include a segregation scheme for incompatible materials, vehicle selection, and costs of ongoing…

UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries

USDA-ARS?s Scientific Manuscript database

Generation of natural product libraries containing column fractions, each with only a few small molecules, by a high throughput, automated fractionation system has made it possible to implement an improved dereplication strategy for selection and prioritization of hits in a natural product discovery...

High-speed data word monitor

NASA Technical Reports Server (NTRS)

Wirth, M. N.

1975-01-01

Small, portable, self-contained device provides high-speed display of bit pattern or any selected portion of transmission, can suppress filler patterns so that display is not updated, and can freeze display so that specific event may be observed in detail.

Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small Animals at 3T and 7T, Respectively

PubMed Central

Ribot, Emeline J.; Wecker, Didier; Trotier, Aurélien J.; Dallaudière, Benjamin; Lefrançois, William; Thiaudière, Eric; Franconi, Jean-Michel; Miraux, Sylvain

2015-01-01

Introduction The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field. Methods In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7T and 3T, respectively to perform whole-body and musculoskeletal imaging. “Sum-Of-Square” reconstruction was performed and combined or not with parallel imaging. Results The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body small animal 3D imaging was performed at 7T and enabled visualization of small structures within adipose tissue like lymph nodes. In parallel, this method allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3T. The combination with parallel imaging allowed the acquisition of knee images with ~500μm resolution images in less than 2min. In addition, ankles, full head coverage and legs of volunteers were imaged, demonstrating the possible application of the method also for large FOV. Conclusion In conclusion, this robust method can be applied in small animals and humans at high magnetic fields. The high SNR and tissue contrast obtained in short acquisition times allows to prescribe bSSFP sequence for several preclinical and clinical applications. PMID:26426849

Optimizing the selection of small-town wastewater treatment processes

NASA Astrophysics Data System (ADS)

Huang, Jianping; Zhang, Siqi

2018-04-01

Municipal wastewater treatment is energy-intensive. This high energy consumption causes high sewage treatment plant operating costs and increases the energy burden. To mitigate the adverse impacts of China’s development, sewage treatment plants should adopt effective energy-saving technologies. Artificial fortified natural water treatment and use of activated sludge and biofilm are all suitable technologies for small-town sewage treatment. This study features an analysis of the characteristics of small and medium-sized township sewage, an overview of current technologies, and a discussion of recent progress in sewage treatment. Based on this, an analysis of existing problems in municipal wastewater treatment is presented, and countermeasures to improve sewage treatment in small and medium-sized towns are proposed.

Landscape management of fire and grazing regimes alters the fine-scale habitat utilisation by feral cats.

PubMed

McGregor, Hugh W; Legge, Sarah; Jones, Menna E; Johnson, Christopher N

2014-01-01

Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores.

Landscape Management of Fire and Grazing Regimes Alters the Fine-Scale Habitat Utilisation by Feral Cats

PubMed Central

McGregor, Hugh W.; Legge, Sarah; Jones, Menna E.; Johnson, Christopher N.

2014-01-01

Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores. PMID:25329902

An anti-PDGFRβ aptamer for selective delivery of small therapeutic peptide to cardiac cells.

PubMed

Romanelli, Alessandra; Affinito, Alessandra; Avitabile, Concetta; Catuogno, Silvia; Ceriotti, Paola; Iaboni, Margherita; Modica, Jessica; Condorelli, Geroloma; Catalucci, Daniele

2018-01-01

Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4.T aptamer to MP, a small mimetic peptide that via targeting of the Cavβ2 subunit of the L-type calcium channel (LTCC) can recover myocardial function in pathological heart conditions associated with defective LTCC function. The conjugation reaction was performed by click chemistry in the presence of N,N,N',N',N"-pentamethyldiethylenetriamine as a Cu (I) stabilizing agent in a DMSO-free aqueous buffer. When administered to cardiac cells, the Gint4.T-MP aptamer-peptide chimera was successfully internalized in cells, allowing the functional targeting of MP to LTCC. This approach represents the first example of the use of an internalizing aptamer for selective delivery of a small therapeutic peptide to cardiac cells.

Computational Design of Ligand Binding Proteins with High Affinity and Selectivity

PubMed Central

Dou, Jiayi; Doyle, Lindsey; Nelson, Jorgen W.; Schena, Alberto; Jankowski, Wojciech; Kalodimos, Charalampos G.; Johnsson, Kai; Stoddard, Barry L.; Baker, David

2014-01-01

The ability to design proteins with high affinity and selectivity for any given small molecule would have numerous applications in biosensing, diagnostics, and therapeutics, and is a rigorous test of our understanding of the physiochemical principles that govern molecular recognition phenomena. Attempts to design ligand binding proteins have met with little success, however, and the computational design of precise molecular recognition between proteins and small molecules remains an “unsolved problem”1. We describe a general method for the computational design of small molecule binding sites with pre-organized hydrogen bonding and hydrophobic interfaces and high overall shape complementary to the ligand, and use it to design protein binding sites for the steroid digoxigenin (DIG). Of 17 designs that were experimentally characterized, two bind DIG; the highest affinity design has the lowest predicted interaction energy and the most pre-organized binding site in the set. A comprehensive binding-fitness landscape of this design generated by library selection and deep sequencing was used to guide optimization of binding affinity to a picomolar level, and two X-ray co-crystal structures of optimized complexes show atomic level agreement with the design models. The designed binder has a high selectivity for DIG over the related steroids digitoxigenin, progesterone, and β-estradiol, which can be reprogrammed through the designed hydrogen-bonding interactions. Taken together, the binding fitness landscape, co-crystal structures, and thermodynamic binding parameters illustrate how increases in binding affinity can result from distal sequence changes that limit the protein ensemble to conformers making the most energetically favorable interactions with the ligand. The computational design method presented here should enable the development of a new generation of biosensors, therapeutics, and diagnostics. PMID:24005320

Weak Lensing by Large-Scale Structure: A Dark Matter Halo Approach.

PubMed

Cooray; Hu; Miralda-Escudé

2000-05-20

Weak gravitational lensing observations probe the spectrum and evolution of density fluctuations and the cosmological parameters that govern them, but they are currently limited to small fields and subject to selection biases. We show how the expected signal from large-scale structure arises from the contributions from and correlations between individual halos. We determine the convergence power spectrum as a function of the maximum halo mass and so provide the means to interpret results from surveys that lack high-mass halos either through selection criteria or small fields. Since shot noise from rare massive halos is mainly responsible for the sample variance below 10&arcmin;, our method should aid our ability to extract cosmological information from small fields.

r- and K-selection in fluctuating populations is determined by the evolutionary trade-off between two fitness measures: Growth rate and lifetime reproductive success.

PubMed

Engen, Steinar; Saether, Bernt-Erik

2017-01-01

In a stable environment, evolution maximizes growth rates in populations that are not density regulated and the carrying capacity in the case of density regulation. In a fluctuating environment, evolution maximizes a function of growth rate, carrying capacity and environmental variance, tending to r-selection and K-selection under large and small environmental noise, respectively. Here we analyze a model in which birth and death rates depend on density through the same function but with independent strength of density dependence. As a special case, both functions may be linear, corresponding to logistic dynamics. It is shown that evolution maximizes a function of the deterministic growth rate r 0 and the lifetime reproductive success (LRS) R 0 , both defined at small densities, as well as the environmental variance. Under large noise this function is dominated by r 0 and average lifetimes are small, whereas R 0 dominates and lifetimes are larger under small noise. Thus, K-selection is closely linked to selection for large R 0 so that evolution tends to maximize LRS in a stable environment. Consequently, different quantities (r 0 and R 0 ) tend to be maximized at low and high densities, respectively, favoring density-dependent changes in the optimal life history. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Accuracy of estimation of genomic breeding values in pigs using low-density genotypes and imputation.

PubMed

Badke, Yvonne M; Bates, Ronald O; Ernst, Catherine W; Fix, Justin; Steibel, Juan P

2014-04-16

Genomic selection has the potential to increase genetic progress. Genotype imputation of high-density single-nucleotide polymorphism (SNP) genotypes can improve the cost efficiency of genomic breeding value (GEBV) prediction for pig breeding. Consequently, the objectives of this work were to: (1) estimate accuracy of genomic evaluation and GEBV for three traits in a Yorkshire population and (2) quantify the loss of accuracy of genomic evaluation and GEBV when genotypes were imputed under two scenarios: a high-cost, high-accuracy scenario in which only selection candidates were imputed from a low-density platform and a low-cost, low-accuracy scenario in which all animals were imputed using a small reference panel of haplotypes. Phenotypes and genotypes obtained with the PorcineSNP60 BeadChip were available for 983 Yorkshire boars. Genotypes of selection candidates were masked and imputed using tagSNP in the GeneSeek Genomic Profiler (10K). Imputation was performed with BEAGLE using 128 or 1800 haplotypes as reference panels. GEBV were obtained through an animal-centric ridge regression model using de-regressed breeding values as response variables. Accuracy of genomic evaluation was estimated as the correlation between estimated breeding values and GEBV in a 10-fold cross validation design. Accuracy of genomic evaluation using observed genotypes was high for all traits (0.65-0.68). Using genotypes imputed from a large reference panel (accuracy: R(2) = 0.95) for genomic evaluation did not significantly decrease accuracy, whereas a scenario with genotypes imputed from a small reference panel (R(2) = 0.88) did show a significant decrease in accuracy. Genomic evaluation based on imputed genotypes in selection candidates can be implemented at a fraction of the cost of a genomic evaluation using observed genotypes and still yield virtually the same accuracy. On the other side, using a very small reference panel of haplotypes to impute training animals and candidates for selection results in lower accuracy of genomic evaluation.

Simulation Models of the Effects of Race- and Socioeconomic-Based Affirmative Action Policies on Elite College Enrollment Patterns

ERIC Educational Resources Information Center

Reardon, Sean; Baker, Rachel; Kasman, Matt; Townsend, Joe; Klasik, Daniel

2014-01-01

The creation of racially diverse colleges at all levels of selectivity has proven to be no small task, even with the legal use of race-conscious affirmative action. As evidenced in the postsecondary destinations of the high school class of 2004, very selective schools (those with Barron's Selectivity rankings of 1, 2 or 3) have many more White,…

Evolution of high-level resistance during low-level antibiotic exposure.

PubMed

Wistrand-Yuen, Erik; Knopp, Michael; Hjort, Karin; Koskiniemi, Sanna; Berg, Otto G; Andersson, Dan I

2018-04-23

It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are found, whereas at sub-MIC selection resistance is generated by several small-effect resistance mutations that combined confer high-level resistance via three different mechanisms: (i) alteration of the ribosomal RNA target (gidB mutations), (ii) reduction in aminoglycoside uptake (cyoB, nuoG, and trkH mutations), and (iii) induction of the aminoglycoside-modifying enzyme AadA (znuA mutations). These results demonstrate how the strength of the selective pressure influences evolutionary trajectories and that even weak selective pressures can cause evolution of high-level resistance.

Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease

PubMed Central

Zheng, Wei; Padia, Janak; Urban, Daniel J.; Jadhav, Ajit; Goker-Alpan, Ozlem; Simeonov, Anton; Goldin, Ehud; Auld, Douglas; LaMarca, Mary E.; Inglese, James; Austin, Christopher P.; Sidransky, Ellen

2007-01-01

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene. Missense mutations result in reduced enzyme activity that may be due to misfolding, raising the possibility of small-molecule chaperone correction of the defect. Screening large compound libraries by quantitative high-throughput screening (qHTS) provides comprehensive information on the potency, efficacy, and structure–activity relationships (SAR) of active compounds directly from the primary screen, facilitating identification of leads for medicinal chemistry optimization. We used qHTS to rapidly identify three structural series of potent, selective, nonsugar glucocerebrosidase inhibitors. The three structural classes had excellent potencies and efficacies and, importantly, high selectivity against closely related hydrolases. Preliminary SAR data were used to select compounds with high activity in both enzyme and cell-based assays. Compounds from two of these structural series increased N370S mutant glucocerebrosidase activity by 40–90% in patient cell lines and enhanced lysosomal colocalization, indicating chaperone activity. These small molecules have potential as leads for chaperone therapy for Gaucher disease, and this paradigm promises to accelerate the development of leads for other rare genetic disorders. PMID:17670938

Small Body Size at Birth and Behavioural Symptoms of ADHD in Children Aged Five to Six Years

ERIC Educational Resources Information Center

Lahti, J.; Raikkonen, K.; Kajantie, E.; Heinonen, K.; Pesonen, A.-K.; Jarvenpaa, A.-L.; Strandberg, T.

2006-01-01

Background: Behavioural disorders with a neurodevelopmental background, such as attention deficit hyperactivity disorder (ADHD), have been associated with a non-optimal foetal environment, reflected in small body size at birth. However, the evidence stems from highly selected groups with birth outcomes biased towards the extreme low end of the…

Parent oriented teacher selection causes language diversity.

PubMed

Cimentepe, Ibrahim; Bingol, Haluk O

2017-09-21

An evolutionary model for emergence of diversity in language is developed. We investigated the effects of two real life observations, namely, people prefer people that they communicate with well, and people interact with people that are physically close to each other. Clearly these groups are relatively small compared to the entire population. We restrict selection of the teachers from such small groups, called imitation sets, around parents. Then the child learns language from a teacher selected within the imitation set of her parent. As a result, there are subcommunities with their own languages developed. Within subcommunity comprehension is found to be high. The number of languages is related to the relative size of imitation set by a power law. Copyright © 2017 Elsevier Ltd. All rights reserved.

Echolocation by the harbour porpoise: life in coastal waters.

PubMed

Miller, Lee A; Wahlberg, Magnus

2013-01-01

The harbor porpoise is one of the smallest and most widely spread of all toothed whales. They are found abundantly in coastal waters all around the northern hemisphere. They are among the 11 species known to use high frequency sonar of relative narrow bandwidth. Their narrow biosonar beam helps isolate echoes from prey among those from unwanted items and noise. Obtaining echoes from small objects like net mesh, net floats, and small prey is facilitated by the very high peak frequency around 130 kHz with a wavelength of about 12 mm. We argue that such echolocation signals and narrow band auditory filters give the harbor porpoise a selective advantage in a coastal environment. Predation by killer whales and a minimum noise region in the ocean around 130 kHz may have provided selection pressures for using narrow bandwidth high frequency biosonar signals.

Echolocation by the harbour porpoise: life in coastal waters

PubMed Central

Miller, Lee A.; Wahlberg, Magnus

2013-01-01

The harbor porpoise is one of the smallest and most widely spread of all toothed whales. They are found abundantly in coastal waters all around the northern hemisphere. They are among the 11 species known to use high frequency sonar of relative narrow bandwidth. Their narrow biosonar beam helps isolate echoes from prey among those from unwanted items and noise. Obtaining echoes from small objects like net mesh, net floats, and small prey is facilitated by the very high peak frequency around 130 kHz with a wavelength of about 12 mm. We argue that such echolocation signals and narrow band auditory filters give the harbor porpoise a selective advantage in a coastal environment. Predation by killer whales and a minimum noise region in the ocean around 130 kHz may have provided selection pressures for using narrow bandwidth high frequency biosonar signals. PMID:23596420

EDITORIAL: Selected papers from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009) Selected papers from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009)

NASA Astrophysics Data System (ADS)

Ghodssi, Reza; Livermore, Carol; Arnold, David

2010-10-01

This special section of the Journal of Micromechanics and Microengineering presents papers selected from the 9th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2009), which was held in Washington DC, USA from 1-4 December 2009. Since it was first held in Sendai, Japan in 2000, the PowerMEMS workshop has focused on small-scale systems that process, convert, or generate macroscopically significant amounts of power, typically with high power density or high energy density. In the workshop's early years, much of the research presented was on small-scale fueled systems, such as micro heat engines and micro fuel cells. The past nine years have seen a dramatic expansion in the range of technologies that are brought to bear on the challenge of high-power, small-scale systems, as well as an increase in the applications for such technologies. At this year's workshop, 158 contributed papers were presented, along with invited and plenary presentations. The papers focused on applications from micro heat engines and fuel cells, to energy harvesting and its enabling electronics, to thermal management and propulsion. Also presented were the technologies that enable these applications, such as the structuring of microscale, nanoscale and biological systems for power applications, as well as combustion and catalysis at small scales. This special section includes a selection of 12 expanded papers representing energy harvesting, chemical and fueled systems, and elastic energy storage at small scales. We would like to express our appreciation to the members of the International Steering Committee, the Technical Program Committee, the Local Organizing Committee, and to the workshop's financial supporters. We are grateful to the referees for their contributions to the review process. Finally, we would like to thank Dr Ian Forbes, the editorial staff of the Journal of Micromechanics and Microengineering, and the staff of IOP Publishing for making this special section possible.

Application of advanced technologies to small, short-haul transport aircraft

NASA Technical Reports Server (NTRS)

Coussens, T. G.; Tullis, R. H.

1980-01-01

The performance and economic benefits available by incorporation of advanced technologies into the small, short haul air transport were assessed. Low cost structure and advanced composite material, advanced turboprop engines and new propellers, advanced high lift systems and active controls; and alternate aircraft configurations with aft mounted engines were investigated. Improvements in fuel consumed and aircraft economics (acquisition cost and direct operating cost) are available by incorporating selected advanced technologies into the small, short haul aircraft.

Interdependent effects of male and female body size plasticity on mating behaviour of predatory mites.

PubMed

Walzer, Andreas; Schausberger, Peter

2015-02-01

The adaptive canalization hypothesis predicts that traits with low phenotypic plasticity are more fitness relevant, because they have been canalized via strong past selection, than traits with high phenotypic plasticity. Based on differing male body size plasticities of the predatory mites Phytoseiulus persimilis (low plasticity) and Neoseiulus californicus (high plasticity), we accordingly hypothesized that small male body size entails higher costs in female choice and male-male competition in P. persimilis than N. californicus . Males of both species are highly polygynous but females differ in the level of polyandry (low level in P. persimilis ; medium level in N. californicus ). We videotaped the mating interactions in triplets of either P. persimilis or N. californicus , consisting of a virgin female (small or standard-sized) and a small and a standard-sized male. Mating by both small and standard-sized P. persimilis females was biased towards standard-sized males, resulting from the interplay between female preference for standard-sized males and the inferiority of small males in male-male competition. In contrast, mating by N. californicus females was equally balanced between small and standard-sized males. Small N. californicus males were more aggressive ('Napoleon complex') in male-male competition, reducing the likelihood of encounter between the standard-sized male and the female, and thus counterbalancing female preference for standard-sized males. Our results support the hypothesis that male body size is more important to fitness in the low-level polyandrous P. persimilis than in the medium-level polyandrous N. californicus and provide a key example of the implications of sexually selected body size plasticity on mating behaviour.

Interdependent effects of male and female body size plasticity on mating behaviour of predatory mites

PubMed Central

Walzer, Andreas; Schausberger, Peter

2015-01-01

The adaptive canalization hypothesis predicts that traits with low phenotypic plasticity are more fitness relevant, because they have been canalized via strong past selection, than traits with high phenotypic plasticity. Based on differing male body size plasticities of the predatory mites Phytoseiulus persimilis (low plasticity) and Neoseiulus californicus (high plasticity), we accordingly hypothesized that small male body size entails higher costs in female choice and male–male competition in P. persimilis than N. californicus. Males of both species are highly polygynous but females differ in the level of polyandry (low level in P. persimilis; medium level in N. californicus). We videotaped the mating interactions in triplets of either P. persimilis or N. californicus, consisting of a virgin female (small or standard-sized) and a small and a standard-sized male. Mating by both small and standard-sized P. persimilis females was biased towards standard-sized males, resulting from the interplay between female preference for standard-sized males and the inferiority of small males in male–male competition. In contrast, mating by N. californicus females was equally balanced between small and standard-sized males. Small N. californicus males were more aggressive (‘Napoleon complex’) in male–male competition, reducing the likelihood of encounter between the standard-sized male and the female, and thus counterbalancing female preference for standard-sized males. Our results support the hypothesis that male body size is more important to fitness in the low-level polyandrous P. persimilis than in the medium-level polyandrous N. californicus and provide a key example of the implications of sexually selected body size plasticity on mating behaviour. PMID:25673881

High mobility high efficiency organic films based on pure organic materials

DOEpatents

Salzman, Rhonda F [Ann Arbor, MI; Forrest, Stephen R [Ann Arbor, MI

2009-01-27

A method of purifying small molecule organic material, performed as a series of operations beginning with a first sample of the organic small molecule material. The first step is to purify the organic small molecule material by thermal gradient sublimation. The second step is to test the purity of at least one sample from the purified organic small molecule material by spectroscopy. The third step is to repeat the first through third steps on the purified small molecule material if the spectroscopic testing reveals any peaks exceeding a threshold percentage of a magnitude of a characteristic peak of a target organic small molecule. The steps are performed at least twice. The threshold percentage is at most 10%. Preferably the threshold percentage is 5% and more preferably 2%. The threshold percentage may be selected based on the spectra of past samples that achieved target performance characteristics in finished devices.

High resolution electron microscopy of a small crack at the superficial layer of enamel.

PubMed

Hayashi, Y

1994-12-01

A small enamel crack was investigated using a high resolution electron microscope. The inside of the crack was filled with aggregates of irregularly oriented plate-like crystals. Amorphous mineral deposits were observed among these aggregates at a low magnification. Selected area electron diffractions indicated that the plate-like crystals consisted of hydroxyapatite (OH-AP), and that the amorphous mineral deposits were a mixture of OH-AP and whitlockite. These findings indicate that this crack may have been formed by occlusal and/or masticatory stress, and that a natural occlusion might occur through mineral deposition at the small crack such as in this case.

High School Gay Youth: Invisible Diversity.

ERIC Educational Resources Information Center

Reed, Donald B.

The high school experiences of gay young men, the management of these experiences, and the relationships of these experiences and their management with organizational and personal factors provide the focus of this study of a small, carefully selected sample of gay young men who attended public high schools in the state of Washington. An…

Capture-SELEX: Selection of DNA Aptamers for Aminoglycoside Antibiotics

PubMed Central

2012-01-01

Small organic molecules are challenging targets for an aptamer selection using the SELEX technology (SELEX—Systematic Evolution of Ligans by EXponential enrichment). Often they are not suitable for immobilization on solid surfaces, which is a common procedure in known aptamer selection methods. The Capture-SELEX procedure allows the selection of DNA aptamers for solute targets. A special SELEX library was constructed with the aim to immobilize this library on magnetic beads or other surfaces. For this purpose a docking sequence was incorporated into the random region of the library enabling hybridization to a complementary oligo fixed on magnetic beads. Oligonucleotides of the library which exhibit high affinity to the target and a secondary structure fitting to the target are released from the beads for binding to the target during the aptamer selection process. The oligonucleotides of these binding complexes were amplified, purified, and immobilized via the docking sequence to the magnetic beads as the starting point of the following selection round. Based on this Capture-SELEX procedure, the successful DNA aptamer selection for the aminoglycoside antibiotic kanamycin A as a small molecule target is described. PMID:23326761

Do Small Schools Improve Performance in Large, Urban Districts? Causal Evidence from New York City. Working Paper #01-12

ERIC Educational Resources Information Center

Schwartz, Amy Ellen; Stiefel, Leanna; Wiswall, Matthew

2012-01-01

We evaluate the effectiveness of small high school reform in the country's largest school district, New York City. Using a rich administrative dataset for multiple cohorts of students and distance between student residence and school to instrument for endogenous school selection, we find substantial heterogeneity in school effects: newly created…

Academic Staff Retention in Private Higher Education Institute--Case Study of Private Colleges in Kuala Lumpur

ERIC Educational Resources Information Center

Manogharan, Melissa Wane; Thivaharan, Thinagaran; Rahman, Radziah Abd

2018-01-01

This case study attempts to identify the reasons for high turnover of academic staff in private higher institutions especially in small colleges. Three small colleges that shared almost the same type of background were being selected to participate in this study. The academic coordinator from these three institutions was interviewed. This case…

The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy.

PubMed

Favoni, Valentina; Liguori, Rocco; Incensi, Alex; Fileccia, Enrico; Donadio, Vincenzo

2018-05-15

Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Insect Detection of Small Targets Moving in Visual Clutter

PubMed Central

Barnett, Paul D; O'Carroll, David C

2006-01-01

Detection of targets that move within visual clutter is a common task for animals searching for prey or conspecifics, a task made even more difficult when a moving pursuer needs to analyze targets against the motion of background texture (clutter). Despite the limited optical acuity of the compound eye of insects, this challenging task seems to have been solved by their tiny visual system. Here we describe neurons found in the male hoverfly,Eristalis tenax, that respond selectively to small moving targets. Although many of these target neurons are inhibited by the motion of a background pattern, others respond to target motion within the receptive field under a surprisingly large range of background motion stimuli. Some neurons respond whether or not there is a speed differential between target and background. Analysis of responses to very small targets (smaller than the size of the visual field of single photoreceptors) or those targets with reduced contrast shows that these neurons have extraordinarily high contrast sensitivity. Our data suggest that rejection of background motion may result from extreme selectivity for small targets contrasting against local patches of the background, combined with this high sensitivity, such that background patterns rarely contain features that satisfactorily drive the neuron. PMID:16448249

BMC Ecology image competition 2014: the winning images

PubMed Central

2014-01-01

BMC Ecology showcases the winning entries from its second Ecology Image Competition. More than 300 individual images were submitted from an international array of research scientists, depicting life on every continent on earth. The journal’s Editorial Board and guest judge Caspar Henderson outline why their winning selections demonstrated high levels of technical skill and aesthetic sense in depicting the science of ecology, and we also highlight a small selection of highly commended images that we simply couldn’t let you miss out on. PMID:25178017

BMC Ecology image competition 2014: the winning images.

PubMed

Harold, Simon; Henderson, Caspar; Baguette, Michel; Bonsall, Michael B; Hughes, David; Settele, Josef

2014-08-29

BMC Ecology showcases the winning entries from its second Ecology Image Competition. More than 300 individual images were submitted from an international array of research scientists, depicting life on every continent on earth. The journal's Editorial Board and guest judge Caspar Henderson outline why their winning selections demonstrated high levels of technical skill and aesthetic sense in depicting the science of ecology, and we also highlight a small selection of highly commended images that we simply couldn't let you miss out on.

Balancing selection and genetic drift at major histocompatibility complex class II genes in isolated populations of golden snub-nosed monkey (Rhinopithecus roxellana)

PubMed Central

2012-01-01

Background Small, isolated populations often experience loss of genetic variation due to random genetic drift. Unlike neutral or nearly neutral markers (such as mitochondrial genes or microsatellites), major histocompatibility complex (MHC) genes in these populations may retain high levels of polymorphism due to balancing selection. The relative roles of balancing selection and genetic drift in either small isolated or bottlenecked populations remain controversial. In this study, we examined the mechanisms maintaining polymorphisms of MHC genes in small isolated populations of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) by comparing genetic variation found in MHC and microsatellite loci. There are few studies of this kind conducted on highly endangered primate species. Results Two MHC genes were sequenced and sixteen microsatellite loci were genotyped from samples representing three isolated populations. We isolated nine DQA1 alleles and sixteen DQB1 alleles and validated expression of the alleles. Lowest genetic variation for both MHC and microsatellites was found in the Shennongjia (SNJ) population. Historical balancing selection was revealed at both the DQA1 and DQB1 loci, as revealed by excess non-synonymous substitutions at antigen binding sites (ABS) and maximum-likelihood-based random-site models. Patterns of microsatellite variation revealed population structure. FST outlier analysis showed that population differentiation at the two MHC loci was similar to the microsatellite loci. Conclusions MHC genes and microsatellite loci showed the same allelic richness pattern with the lowest genetic variation occurring in SNJ, suggesting that genetic drift played a prominent role in these isolated populations. As MHC genes are subject to selective pressures, the maintenance of genetic variation is of particular interest in small, long-isolated populations. The results of this study may contribute to captive breeding and translocation programs for endangered species. PMID:23083308

Selective etching of TiN over TaN and vice versa in chlorine-containing plasmas

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

Shin, Hyungjoo; Zhu Weiye; Liu Lei

2013-05-15

Selectivity of etching between physical vapor-deposited TiN and TaN was studied in chlorine-containing plasmas, under isotropic etching conditions. Etching rates for blanket films were measured in-situ using optical emission of the N{sub 2} (C{sup 3}{Pi}{sub u}{yields}B{sup 3}{Pi}{sub g}) bandhead at 337 nm to determine the etching time, and transmission electron microscopy to determine the starting film thickness. The etching selectivity in Cl{sub 2}/He or HCl/He plasmas was poor (<2:1). There was a window of very high selectivity of etching TiN over TaN by adding small amounts (<1%) of O{sub 2} in the Cl{sub 2}/He plasma. Reverse selectivity (10:1 of TaNmore » etching over TiN) was observed when adding small amounts of O{sub 2} to the HCl/He plasma. Results are explained on the basis of the volatility of plausible reaction products.« less

From a Helix to a Small Cycle: Metadynamics-Inspired αvβ6 Integrin Selective Ligands.

PubMed

Di Leva, Francesco Saverio; Tomassi, Stefano; Di Maro, Salvatore; Reichart, Florian; Notni, Johannes; Dangi, Abha; Marelli, Udaya Kiran; Brancaccio, Diego; Merlino, Francesco; Wester, Hans-Jürgen; Novellino, Ettore; Kessler, Horst; Marinelli, Luciana

2018-04-16

The RGD-recognizing αvβ6 integrin has only recently emerged as a major target for cancer diagnosis and therapy. Thus, the development of selective, low-molecular-weight ligands of this receptor is still in great demand. Here, a metadynamics-driven design strategy allowed us to successfully convert a helical nonapeptide into a cyclic pentapeptide (6) showing remarkable potency and αvβ6 specificity. NMR and docking studies elucidated the reasons for the high affinity and selectivity of this compound, setting the ground for the rational design of new αvβ6-specific small peptides or even peptidomimetics. In vivo PET imaging studies demonstrated the potential use of 6 for medical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isolation and Characterization of a microRNA-size Secretable Small RNA in Streptococcus sanguinis.

PubMed

Choi, Ji-Woong; Kwon, Tae-Yub; Hong, Su-Hyung; Lee, Heon-Jin

2018-06-01

MicroRNAs in eukaryotic cells are thought to control highly complex signal transduction and other biological processes by regulating coding transcripts, accounting for their important role in cellular events in eukaryotes. Recently, a novel class of bacterial RNAs similar in size [18-22 nucleotides (nt)] to microRNAs has been reported. Herein, we describe microRNAs, small RNAs from the oral pathogen Streptococcus sanguinis. The bacteria are normally present in the oral cavities and cause endocarditis by contaminating bloodstreams. Small RNAs were analyzed by deep sequencing. Selected highly expressed small RNAs were further validated by real-time polymerase chain reaction and northern blot analyses. We found that skim milk supplement changed the expression of small RNAs S.S-1964 in tandem with the nearby SSA_0513 gene involved in vitamin B 12 conversion. We furthermore observed small RNAs secreted via bacterial membrane vesicles. Although their precise function remains unclear, secretable small RNAs may represent an entirely new area of study in bacterial genetics.

Is First-Order Vector Autoregressive Model Optimal for fMRI Data?

PubMed

Ting, Chee-Ming; Seghouane, Abd-Krim; Khalid, Muhammad Usman; Salleh, Sh-Hussain

2015-09-01

We consider the problem of selecting the optimal orders of vector autoregressive (VAR) models for fMRI data. Many previous studies used model order of one and ignored that it may vary considerably across data sets depending on different data dimensions, subjects, tasks, and experimental designs. In addition, the classical information criteria (IC) used (e.g., the Akaike IC (AIC)) are biased and inappropriate for the high-dimensional fMRI data typically with a small sample size. We examine the mixed results on the optimal VAR orders for fMRI, especially the validity of the order-one hypothesis, by a comprehensive evaluation using different model selection criteria over three typical data types--a resting state, an event-related design, and a block design data set--with varying time series dimensions obtained from distinct functional brain networks. We use a more balanced criterion, Kullback's IC (KIC) based on Kullback's symmetric divergence combining two directed divergences. We also consider the bias-corrected versions (AICc and KICc) to improve VAR model selection in small samples. Simulation results show better small-sample selection performance of the proposed criteria over the classical ones. Both bias-corrected ICs provide more accurate and consistent model order choices than their biased counterparts, which suffer from overfitting, with KICc performing the best. Results on real data show that orders greater than one were selected by all criteria across all data sets for the small to moderate dimensions, particularly from small, specific networks such as the resting-state default mode network and the task-related motor networks, whereas low orders close to one but not necessarily one were chosen for the large dimensions of full-brain networks.

Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.

PubMed

Velagapudi, Sai Pradeep; Disney, Matthew D

2013-10-15

RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3×3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure-activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif-aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Defining RNA motif–aminoglycoside interactions via two-dimensional combinatorial screening and structure–activity relationships through sequencing

PubMed Central

Velagapudi, Sai Pradeep; Disney, Matthew D.

2013-01-01

RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3 × 3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure–activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif–aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. PMID:23719281

Selected-zone dark-field electron microscopy.

NASA Technical Reports Server (NTRS)

Heinemann, K.; Poppa, H.

1972-01-01

Description of a new method which makes it possible to reduce drastically the resolution-limiting influence of chromatic aberration, and thus to obtain high-quality images, by selecting the image-forming electrons that have passed through a small annular zone of an objective lens. In addition, the manufacture of special objective-lens aperture diaphragms that are needed for this method is also described.

Teaching World Literature at the High School Level.

ERIC Educational Resources Information Center

Piechowski, Marjorie

Selections from world literature can increase high school students' interest in reading, their familiarity with age-old literary themes, their understanding of literary genres, their awareness of varying cultures, and their skill in analyzing and writing about literature. A world literature course with those aims introduced in a small Wisconsin…

Paternal kin recognition in the high frequency / ultrasonic range in a solitary foraging mammal

PubMed Central

2012-01-01

Background Kin selection is a driving force in the evolution of mammalian social complexity. Recognition of paternal kin using vocalizations occurs in taxa with cohesive, complex social groups. This is the first investigation of paternal kin recognition via vocalizations in a small-brained, solitary foraging mammal, the grey mouse lemur (Microcebus murinus), a frequent model for ancestral primates. We analyzed the high frequency/ultrasonic male advertisement (courtship) call and alarm call. Results Multi-parametric analyses of the calls’ acoustic parameters and discriminant function analyses showed that advertisement calls, but not alarm calls, contain patrilineal signatures. Playback experiments controlling for familiarity showed that females paid more attention to advertisement calls from unrelated males than from their fathers. Reactions to alarm calls from unrelated males and fathers did not differ. Conclusions 1) Findings provide the first evidence of paternal kin recognition via vocalizations in a small-brained, solitarily foraging mammal. 2) High predation, small body size, and dispersed social systems may select for acoustic paternal kin recognition in the high frequency/ultrasonic ranges, thus limiting risks of inbreeding and eavesdropping by predators or conspecific competitors. 3) Paternal kin recognition via vocalizations in mammals is not dependent upon a large brain and high social complexity, but may already have been an integral part of the dispersed social networks from which more complex, kin-based sociality emerged. PMID:23198727

Selective removal of natural caries lesions from dentin and tooth occlusal surfaces using a diode-pumped Er:YAG laser

NASA Astrophysics Data System (ADS)

Jew, Jamison; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

2017-02-01

Selective removal of caries lesions with high precision is best accomplished using lasers operating at high pulse repetition rates utilizing small spot sizes. Conventional flash-lamp pumped Er:YAG lasers are poorly suited for this purpose, but new diode-pumped solid-state (DPSS) Er:YAG lasers have become available operating at high pulse repetition rates. Microradiography was used to determine the mineral content of the demineralized dentin of 200-μm thick sections with natural caries lesions prior to laser ablation. The purpose of this study was to explore the use of a DPSS Er:YAG laser for the selective removal of demineralized dentin and natural occlusal lesions on extracted teeth.

Identification of Conflicting Selective Effects on Highly Expressed Genes

PubMed Central

Higgs, Paul G.; Hao, Weilong; Golding, G. Brian

2007-01-01

Many different selective effects on DNA and proteins influence the frequency of codons and amino acids in coding sequences. Selection is often stronger on highly expressed genes. Hence, by comparing high- and low-expression genes it is possible to distinguish the factors that are selected by evolution. It has been proposed that highly expressed genes should (i) preferentially use codons matching abundant tRNAs (translational efficiency), (ii) preferentially use amino acids with low cost of synthesis, (iii) be under stronger selection to maintain the required amino acid content, and (iv) be selected for translational robustness. These effects act simultaneously and can be contradictory. We develop a model that combines these factors, and use Akaike’s Information Criterion for model selection. We consider pairs of paralogues that arose by whole-genome duplication in Saccharmyces cerevisiae. A codon-based model is used that includes asymmetric effects due to selection on highly expressed genes. The largest effect is translational efficiency, which is found to strongly influence synonymous, but not non-synonymous rates. Minimization of the cost of amino acid synthesis is implicated. However, when a more general measure of selection for amino acid usage is used, the cost minimization effect becomes redundant. Small effects that we attribute to selection for translational robustness can be identified as an improvement in the model fit on top of the effects of translational efficiency and amino acid usage. PMID:19430600

Design studies of large aperture, high-resolution Earth science microwave radiometers compatible with small launch vehicles

NASA Technical Reports Server (NTRS)

Schroeder, Lyle C.; Bailey, M. C.; Harrington, Richard F.; Kendall, Bruce M.; Campbell, Thomas G.

1994-01-01

High-spatial-resolution microwave radiometer sensing from space with reasonable swath widths and revisit times favors large aperture systems. However, with traditional precision antenna design, the size and weight requirements for such systems are in conflict with the need to emphasize small launch vehicles. This paper describes tradeoffs between the science requirements, basic operational parameters, and expected sensor performance for selected satellite radiometer concepts utilizing novel lightweight compactly packaged real apertures. Antenna, feed, and radiometer subsystem design and calibration are presented. Preliminary results show that novel lightweight real aperture coupled with state-of-the-art radiometer designs are compatible with small launch systems, and hold promise for high-resolution earth science measurements of sea ice, precipitation, soil moisture, sea surface temperature, and ocean wind speeds.

Powerful Voter Selection for Making Multistep Delegate Ballot Fair

NASA Astrophysics Data System (ADS)

Yamakawa, Hiroshi

For decision by majority, each voter often exercises his right by delegating to trustable other voters. Multi-step delegates rule allows indirect delegating through more than one voter, and this helps each voter finding his delegate voters. In this paper, we propose powerful voter selection method depending on the multi-step delegate rule. This method sequentially selects voters who is most delegated indirectly. Multi-agent simulation demonstrate that we can achieve highly fair poll results from small number of vote by using proposed method. Here, fairness is prediction accuracy to sum of all voters preferences for choices. In simulation, each voter selects choices arranged on one dimensional preference axis for voting. Acquaintance relationships among voters were generated as a random network, and each voter delegates some of his acquaintances who has similar preferences. We obtained simulation results from various acquaintance networks, and then averaged these results. Firstly, if each voter has enough acquaintances in average, proposed method can help predicting sum of all voters' preferences of choices from small number of vote. Secondly, if the number of each voter's acquaintances increases corresponding to an increase in the number of voters, prediction accuracy (fairness) from small number of vote can be kept in appropriate level.

Relationship between Small Animal Intern Rank and Performance at a University Teaching Hospital.

PubMed

Hofmeister, Erik H; Saba, Corey; Kent, Marc; Creevy, Kate E

2015-01-01

The purpose of this study was to determine if there is a relationship between selection committee rankings of internship applicants and the performance of small animal interns. The hypothesis was that there would be a relationship between selection committee rank order and intern performance; the more highly an application was ranked, the better the intern's performance scores would be. In 2007, the Department of Small Animal Medicine and Surgery instituted a standardized approach to its intern selection process both to streamline the process and to track its effectiveness. At the end of intern years 2010-2014, every faculty member in the department was provided an intern assessment form for that year's class. There was no relationship between an individual intern's final rank by the selection committee and his/her performance either as a percentile score or a Likert-type score (p=.25, R2=0.04; p=0.31, R2=0.03, respectively). Likewise, when interns were divided into the top and bottom quartile based on their final rank by the selection committee, there was no relationship between their rank and their performance as a percentile score (median rank 15 vs. 20; p=.14) or Likert-type score (median rank 14 vs. 19; p=.27). Institutions that use a similar intern selection method may need to reconsider the time and effort being expended for an outcome that does not predict performance. Alternatively, specific criteria more predictive of performance outcomes should be identified and employed in the internship selection process.

A Small Particle Solar Receiver for High Temperature Brayton Power Cycles

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

Miller, Fletcher John

The objective of this project is to design, construct, and test at the Sandia NSTTF a revolutionary high temperature air-cooled solar receiver in the multi-MW range that can be used to drive a gas turbine, to generate low-cost electricity at $.06/kWh when considered as part of an optimized CSP combined cycle system. The receiver being developed in this research uses a dilute suspension of selectively absorbing carbon nano-particles to absorb highly concentrated solar flux. The concept of a volumetric, selective, and continually replenishable absorber is unique in the solar field.

Novel inhibitors of IMPDH: a highly potent and selective quinolone-based series.

PubMed

Watterson, Scott H; Carlsen, Marianne; Dhar, T G Murali; Shen, Zhongqi; Pitts, William J; Guo, Junqing; Gu, Henry H; Norris, Derek; Chorba, John; Chen, Ping; Cheney, Daniel; Witmer, Mark; Fleener, Catherine A; Rouleau, Katherine; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

2003-02-10

A series of novel quinolone-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are described.

Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization.

PubMed

Quéméner, Agnès; Maillasson, Mike; Arzel, Laurence; Sicard, Benoit; Vomiandry, Romy; Mortier, Erwan; Dubreuil, Didier; Jacques, Yannick; Lebreton, Jacques; Mathé-Allainmat, Monique

2017-07-27

Interleukin (IL)-15 is a pleiotropic cytokine, which is structurally close to IL-2 and shares with it the IL-2 β and γ receptor (R) subunits. By promoting the activation and proliferation of NK, NK-T, and CD8+ T cells, IL-15 plays important roles in innate and adaptative immunity. Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseases has led to the development of various antagonistic approaches targeting IL-15. This study is an original approach aimed at discovering small-molecule inhibitors impeding IL-15/IL-15R interaction. A pharmacophore and docking-based virtual screening of compound libraries led to the selection of 240 high-scoring compounds, 36 of which were found to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rβ chain or the proliferation of IL-15-dependent cells or both. One of them was selected as a hit and optimized by a structure-activity relationship approach, leading to the first small-molecule IL-15 inhibitor with sub-micromolar activity.

Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

PubMed

Neelakantan, Harshini; Vance, Virginia; Wetzel, Michael D; Wang, Hua-Yu Leo; McHardy, Stanton F; Finnerty, Celeste C; Hommel, Jonathan D; Watowich, Stanley J

2018-01-01

There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors. Membrane permeability of NNMT inhibitors was characterized using parallel artificial membrane permeability and Caco-2 cell assays. Selectivity was tested against structurally-related methyltransferases and nicotinamide adenine dinucleotide (NAD + ) salvage pathway enzymes. Effects of NNMT inhibitors on lipogenesis and intracellular levels of metabolites, including NNMT reaction product 1-methylnicotianamide (1-MNA) were evaluated in cultured adipocytes. Effects of a potent NNMT inhibitor on obesity measures and plasma lipid were assessed in diet-induced obese mice fed a high-fat diet. Methylquinolinium scaffolds with primary amine substitutions displayed high permeability from passive and active transport across membranes. Importantly, methylquinolinium analogues displayed high selectivity, not inhibiting related SAM-dependent methyltransferases or enzymes in the NAD + salvage pathway. NNMT inhibitors reduced intracellular 1-MNA, increased intracellular NAD + and S-(5'-adenosyl)-l-methionine (SAM), and suppressed lipogenesis in adipocytes. Treatment of diet-induced obese mice systemically with a potent NNMT inhibitor significantly reduced body weight and white adipose mass, decreased adipocyte size, and lowered plasma total cholesterol levels. Notably, administration of NNMT inhibitors did not impact total food intake nor produce any observable adverse effects. These results support development of small molecule NNMT inhibitors as therapeutics to reverse diet-induced obesity and validate NNMT as a viable target to treat obesity and related metabolic conditions. Increased flux of key cellular energy regulators, including NAD + and SAM, may potentially define the therapeutic mechanism-of-action of NNMT inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications

PubMed Central

Ruscito, Annamaria; DeRosa, Maria C.

2016-01-01

Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then used in various applications. These applications range from therapeutic uses to biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is needed for the protection and wellbeing of humans and animals. However, the small molecular weights of these targets, including the drastic size difference between the target and the oligonucleotides, make it challenging to select, characterize, and apply aptamers for their detection. Thus, recent (since 2012) notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed. PMID:27242994

Plant community development after 28 years in small group-selection openings

Treesearch

Philip M. McDonald; Phillip E. Reynolds

1999-01-01

Thirty openings, 9, 18, and 27 meters in diameter, were created by group-selection harvest on a high quality site in northern California in 1963. In 1991, or 28 years after site preparation, the plant community in the openings had stabilized at 55 species. A major shift was from annuals to perennials. New seedlings of ponderosa and sugar pine were able to become...

Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent

NASA Astrophysics Data System (ADS)

Wadzinski, Tyler J.; Steinauer, Angela; Hie, Liana; Pelletier, Guillaume; Schepartz, Alanna; Miller, Scott J.

2018-06-01

Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH)2, proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.

Selectivity by Small-Molecule Inhibitors of Protein Interactions Can Be Driven by Protein Surface Fluctuations

PubMed Central

Johnson, David K.; Karanicolas, John

2015-01-01

Small-molecules that inhibit interactions between specific pairs of proteins have long represented a promising avenue for therapeutic intervention in a variety of settings. Structural studies have shown that in many cases, the inhibitor-bound protein adopts a conformation that is distinct from its unbound and its protein-bound conformations. This plasticity of the protein surface presents a major challenge in predicting which members of a protein family will be inhibited by a given ligand. Here, we use biased simulations of Bcl-2-family proteins to generate ensembles of low-energy conformations that contain surface pockets suitable for small molecule binding. We find that the resulting conformational ensembles include surface pockets that mimic those observed in inhibitor-bound crystal structures. Next, we find that the ensembles generated using different members of this protein family are overlapping but distinct, and that the activity of a given compound against a particular family member (ligand selectivity) can be predicted from whether the corresponding ensemble samples a complementary surface pocket. Finally, we find that each ensemble includes certain surface pockets that are not shared by any other family member: while no inhibitors have yet been identified to take advantage of these pockets, we expect that chemical scaffolds complementing these “distinct” pockets will prove highly selective for their targets. The opportunity to achieve target selectivity within a protein family by exploiting differences in surface fluctuations represents a new paradigm that may facilitate design of family-selective small-molecule inhibitors of protein-protein interactions. PMID:25706586

The selective conservative management of small traumatic pneumothoraces following stab injuries is safe: experience from a high-volume trauma service in South Africa.

PubMed

Kong, V Y; Oosthuizen, G V; Clarke, D L

2015-02-01

The selective conservative management of small pneumothoraces (PTXs) following stab injuries is controversial. We reviewed a cohort of patients managed conservatively in a high volume trauma service in South Africa. A retrospective review over a 2-year period identified 125 asymptomatic patients with small PTXs measuring <2 cm on chest radiograph who were managed conservatively. Of the 125 patients included in the study, 92% were male (115/125), and the median age for all patients was 21 years (19-24). Ninety-seven per cent (121/125) of the weapons involved were knives, and 3% (4/125) were screwdrivers. Sixty-one per cent of all injuries were on the left side. Eighty-two per cent (102/125) sustained a single stab, and 18% (23/125) had multiple stabs. Thirty-nine per cent (49/125) had a PTX <0.5 cm (Group A), 26% (32/125) were ≥ 0.5 to <1 cm (Group B), 19% (24/125) were ≥ 1 to <1.5 cm (Group C) and 15% (20/125) were ≥ 1.5 to <2 cm (Group D). Three per cent of all patients (4/125) eventually required ICDs (one in Group C, three in Group D). All four patients had ICDs in situ for 24 h. The remaining 97% (121/125) were all managed successfully by active clinical observation alone. There were no subsequent readmissions, morbidity or mortality as a direct result of our conservative approach. The selective conservative management of asymptomatic small PTXs from stab injuries is safe if undertaken in the appropriate setting.

Effects of Small Patch Cutting on Sugar Maple Regeneration in New Hampshire Northern Hardwoods

Treesearch

William B. Leak; William B. Leak

2005-01-01

In many northern hardwood stands in New Hampshire and New England, partial cutting or single-tree selection result,s in understories with a high proportion of beech and other species with low timber values. Patch cutting, using small openings of about 1/4-ac in size or larger coupled with sufficient logging disturbance, has proved to be an effective way to replace...

Comparative analysis of spectral unmixing and neural networks for estimating small diameter tree above-ground biomass in the State of Mississippi

Treesearch

Moham P. Tiruveedhula; Joseph Fan; Ravi R. Sadasivuni; Surya S. Durbha; David L. Evans

2010-01-01

The accumulation of small diameter trees (SDTs) is becoming a nationwide concern. Forest management practices such as fire suppression and selective cutting of high grade timber have contributed to an overabundance of SDTs in many areas. Alternative value-added utilization of SDTs (for composite wood products and biofuels) has prompted the need to estimate their...

Differences and changes in the physical characteristics of professional and amateur rugby union players.

PubMed

Smart, Daniel J; Hopkins, Will G; Gill, Nicholas D

2013-11-01

Numerous studies have highlighted differences between playing levels and positions in rugby union; however, few studies have investigated longitudinal progressions of body composition and physical performance. Between-player differences and within-player changes in body composition, strength, power, speed, and repeated sprint ability, from 1,161 New Zealand rugby union players from 2004 to 2007, were estimated using a mixed modeling procedure. Props had the highest mass, percent body fat, strength, and slowest speed times compared with the other positions, whereas outside backs had the fastest speed time and lowest percent body fat. For most measures, there were small-to-moderate differences (range, 1.1-14%) between players selected and not selected for provincial teams and small-to-large differences (range, 1.8-15%) between provincial and Super Rugby (professional) players. The faster 20-m sprint times in international compared with Super Rugby players was small in magnitude for both the forwards (1.9%) and backs (2.2%). The average annual improvements were small to moderate for strength (range, 2.1-15%) and small for repeated sprint ability within the lower playing levels (~1.5%). Small increases occurred in lower body strength (~7.0%) as players moved from Super Rugby to provincial competition. Small decreases in sprint time (~1.6%) and small increases in strength (~6.3%) occurred as players moved from Super Rugby to midyear international competition. The differences between levels in performance provide level-specific characteristics from Super Rugby and below, but international players may be selected because of greater skill and experience. Changes in physical performance between competitions may be a result of reduced training loads because of regular high-intensity matches and greater travel involved in the Super Rugby competition.

Breeding bird responses to three silvicultural treatments in the Oregon Coast Range

USGS Publications Warehouse

Chambers, C.L.; McComb, W.C.; Tappeiner, J. C.

1999-01-01

Silvicultural alternatives to clear-cutting have been suggested to promote development, retention, or creation of late-successional features such as large trees, multilayered canopies, snags, and logs. We assessed bird response to three silvicultural alternatives to clear-cutting that retained structural features found in old Douglas-fir (Pseudotsuga menziesii) forests and that imitated natural disturbance regimes more closely than did traditional clear-cutting: (1) small-patch group selection treatment representing a low-intensity disturbance; (2) two-story treatment, representing a moderate to high-intensity disturbance; and (3) modified clear-cut treatment, representing a high-intensity disturbance. We counted diurnal breeding birds 1 yr prior to and 2 yr after harvest to estimate effects of the silvicultural treatments on bird communities compared with uncut controls. The small-patch group selection treatment was most similar in species composition to control stands. The two-story treatment was more similar to the modified clear-cut treatment. Ten bird species remained abundant following the small-patch group selection treatment. They declined in abundance in modified clearcuts and two-story stands. These species included four neotropical migratory species and five species with restricted geographic ranges and habitat associations. Nine species increased in response to moderate and/or high-intensity disturbances. This group included a larger proportion of species that were habitat generalists. Silvicultural treatments imitating low-intensity disturbances were most effective in retaining bird communities associated with mature forest; high-intensity disturbances such as the two-story and modified clear-cut treatments greatly altered bird community composition. Bird responses to the silvicultural treatments that we studied indicate that a variety of stand types is needed to meet needs of all species.

An RNA motif that binds ATP

NASA Technical Reports Server (NTRS)

Sassanfar, M.; Szostak, J. W.

1993-01-01

RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

Wavelet Packet Feature Assessment for High-Density Myoelectric Pattern Recognition and Channel Selection toward Stroke Rehabilitation.

PubMed

Wang, Dongqing; Zhang, Xu; Gao, Xiaoping; Chen, Xiang; Zhou, Ping

2016-01-01

This study presents wavelet packet feature assessment of neural control information in paretic upper limb muscles of stroke survivors for myoelectric pattern recognition, taking advantage of high-resolution time-frequency representations of surface electromyogram (EMG) signals. On this basis, a novel channel selection method was developed by combining the Fisher's class separability index and the sequential feedforward selection analyses, in order to determine a small number of appropriate EMG channels from original high-density EMG electrode array. The advantages of the wavelet packet features and the channel selection analyses were further illustrated by comparing with previous conventional approaches, in terms of classification performance when identifying 20 functional arm/hand movements implemented by 12 stroke survivors. This study offers a practical approach including paretic EMG feature extraction and channel selection that enables active myoelectric control of multiple degrees of freedom with paretic muscles. All these efforts will facilitate upper limb dexterity restoration and improved stroke rehabilitation.

Selective and cell-active inhibitors of the USP1/UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells

PubMed Central

Chen, Junjun; Dexheimer, Thomas S.; Ai, Yongxing; Liang, Qin; Villamil, Mark A.; Inglese, James; Maloney, David J; Jadhav, Ajit; Simeonov, Anton; Zhuang, Zhihao

2012-01-01

Ubiquitin-specific proteases (USPs) have in recent years emerged as a promising therapeutic target class. We identified selective small-molecule inhibitors against a deubiquitinase complex, the human USP1/UAF1, through quantitative high throughput screening (qHTS) of a collection of bioactive molecules. The top inhibitors, pimozide and GW7647, inhibited USP1/UAF1 noncompetitively with a Ki of 0.5 and 0.7 μM respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase and cysteine proteases. The USP1/UAF1 inhibitors act synergistically with cisplatin in inhibiting cisplatin-resistant non-small cell lung cancer (NSCLC) cell proliferation. USP1/UAF1 represents a promising target for drug intervention because of its involvement in translesion synthesis and Fanconi anemia pathway important for normal DNA damage response. Our results support USP1/UAF1 as a potential therapeutic target and provide the first example of targeting the USP/WD40 repeat protein complex for inhibitor discovery. PMID:22118673

Multi-class computational evolution: development, benchmark evaluation and application to RNA-Seq biomarker discovery.

PubMed

Crabtree, Nathaniel M; Moore, Jason H; Bowyer, John F; George, Nysia I

2017-01-01

A computational evolution system (CES) is a knowledge discovery engine that can identify subtle, synergistic relationships in large datasets. Pareto optimization allows CESs to balance accuracy with model complexity when evolving classifiers. Using Pareto optimization, a CES is able to identify a very small number of features while maintaining high classification accuracy. A CES can be designed for various types of data, and the user can exploit expert knowledge about the classification problem in order to improve discrimination between classes. These characteristics give CES an advantage over other classification and feature selection algorithms, particularly when the goal is to identify a small number of highly relevant, non-redundant biomarkers. Previously, CESs have been developed only for binary class datasets. In this study, we developed a multi-class CES. The multi-class CES was compared to three common feature selection and classification algorithms: support vector machine (SVM), random k-nearest neighbor (RKNN), and random forest (RF). The algorithms were evaluated on three distinct multi-class RNA sequencing datasets. The comparison criteria were run-time, classification accuracy, number of selected features, and stability of selected feature set (as measured by the Tanimoto distance). The performance of each algorithm was data-dependent. CES performed best on the dataset with the smallest sample size, indicating that CES has a unique advantage since the accuracy of most classification methods suffer when sample size is small. The multi-class extension of CES increases the appeal of its application to complex, multi-class datasets in order to identify important biomarkers and features.

Novel selection methods for DNA-encoded chemical libraries

PubMed Central

Chan, Alix I.; McGregor, Lynn M.; Liu, David R.

2015-01-01

Driven by the need for new compounds to serve as biological probes and leads for therapeutic development and the growing accessibility of DNA technologies including high-throughput sequencing, many academic and industrial groups have begun to use DNA-encoded chemical libraries as a source of bioactive small molecules. In this review, we describe the technologies that have enabled the selection of compounds with desired activities from these libraries. These methods exploit the sensitivity of in vitro selection coupled with DNA amplification to overcome some of the limitations and costs associated with conventional screening methods. In addition, we highlight newer techniques with the potential to be applied to the high-throughput evaluation of DNA-encoded chemical libraries. PMID:25723146

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

Selecting the most appropriate time points to profile in high-throughput studies

PubMed Central

Kleyman, Michael; Sefer, Emre; Nicola, Teodora; Espinoza, Celia; Chhabra, Divya; Hagood, James S; Kaminski, Naftali; Ambalavanan, Namasivayam; Bar-Joseph, Ziv

2017-01-01

Biological systems are increasingly being studied by high throughput profiling of molecular data over time. Determining the set of time points to sample in studies that profile several different types of molecular data is still challenging. Here we present the Time Point Selection (TPS) method that solves this combinatorial problem in a principled and practical way. TPS utilizes expression data from a small set of genes sampled at a high rate. As we show by applying TPS to study mouse lung development, the points selected by TPS can be used to reconstruct an accurate representation for the expression values of the non selected points. Further, even though the selection is only based on gene expression, these points are also appropriate for representing a much larger set of protein, miRNA and DNA methylation changes over time. TPS can thus serve as a key design strategy for high throughput time series experiments. Supporting Website: www.sb.cs.cmu.edu/TPS DOI: http://dx.doi.org/10.7554/eLife.18541.001 PMID:28124972

Subnanometer and nanometer catalysts, method for preparing size-selected catalysts

DOEpatents

Vajda, Stefan , Pellin, Michael J.; Elam, Jeffrey W [Elmhurst, IL; Marshall, Christopher L [Naperville, IL; Winans, Randall A [Downers Grove, IL; Meiwes-Broer, Karl-Heinz [Roggentin, GR

2012-04-03

Highly uniform cluster based nanocatalysts supported on technologically relevant supports were synthesized for reactions of top industrial relevance. The Pt-cluster based catalysts outperformed the very best reported ODHP catalyst in both activity (by up to two orders of magnitude higher turn-over frequencies) and in selectivity. The results clearly demonstrate that highly dispersed ultra-small Pt clusters precisely localized on high-surface area supports can lead to affordable new catalysts for highly efficient and economic propene production, including considerably simplified separation of the final product. The combined GISAXS-mass spectrometry provides an excellent tool to monitor the evolution of size and shape of nanocatalyst at action under realistic conditions. Also provided are sub-nanometer gold and sub-nanometer to few nm size-selected silver catalysts which possess size dependent tunable catalytic properties in the epoxidation of alkenes. Invented size-selected cluster deposition provides a unique tool to tune material properties by atom-by-atom fashion, which can be stabilized by protective overcoats.

Subnanometer and nanometer catalysts, method for preparing size-selected catalysts

DOEpatents

Vajda, Stefan [Lisle, IL; Pellin, Michael J [Naperville, IL; Elam, Jeffrey W [Elmhurst, IL; Marshall, Christopher L [Naperville, IL; Winans, Randall A [Downers Grove, IL; Meiwes-Broer, Karl-Heinz [Roggentin, GR

2012-03-27

Highly uniform cluster based nanocatalysts supported on technologically relevant supports were synthesized for reactions of top industrial relevance. The Pt-cluster based catalysts outperformed the very best reported ODHP catalyst in both activity (by up to two orders of magnitude higher turn-over frequencies) and in selectivity. The results clearly demonstrate that highly dispersed ultra-small Pt clusters precisely localized on high-surface area supports can lead to affordable new catalysts for highly efficient and economic propene production, including considerably simplified separation of the final product. The combined GISAXS-mass spectrometry provides an excellent tool to monitor the evolution of size and shape of nanocatalyst at action under realistic conditions. Also provided are sub-nanometer gold and sub-nanometer to few nm size-selected silver catalysts which possess size dependent tunable catalytic properties in the epoxidation of alkenes. Invented size-selected cluster deposition provides a unique tool to tune material properties by atom-by-atom fashion, which can be stabilized by protective overcoats.

Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards

PubMed Central

Artacho, Paulina; Saravia, Julia; Ferrandière, Beatriz Decencière; Perret, Samuel; Le Galliard, Jean-François

2015-01-01

Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior. PMID:26380689

Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards.

PubMed

Artacho, Paulina; Saravia, Julia; Ferrandière, Beatriz Decencière; Perret, Samuel; Le Galliard, Jean-François

2015-09-01

Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior.

Small baseline subsets approach of DInSAR for investigating land surface deformation along the high-speed railway

NASA Astrophysics Data System (ADS)

Rao, Xiong; Tang, Yunwei

2014-11-01

Land surface deformation evidently exists in a newly-built high-speed railway in the southeast of China. In this study, we utilize the Small BAseline Subsets (SBAS)-Differential Synthetic Aperture Radar Interferometry (DInSAR) technique to detect land surface deformation along the railway. In this work, 40 Cosmo-SkyMed satellite images were selected to analyze the spatial distribution and velocity of the deformation in study area. 88 pairs of image with high coherence were firstly chosen with an appropriate threshold. These images were used to deduce the deformation velocity map and the variation in time series. This result can provide information for orbit correctness and ground control point (GCP) selection in the following steps. Then, more pairs of image were selected to tighten the constraint in time dimension, and to improve the final result by decreasing the phase unwrapping error. 171 combinations of SAR pairs were ultimately selected. Reliable GCPs were re-selected according to the previously derived deformation velocity map. Orbital residuals error was rectified using these GCPs, and nonlinear deformation components were estimated. Therefore, a more accurate surface deformation velocity map was produced. Precise geodetic leveling work was implemented in the meantime. We compared the leveling result with the geocoding SBAS product using the nearest neighbour method. The mean error and standard deviation of the error were respectively 0.82 mm and 4.17 mm. This result demonstrates the effectiveness of DInSAR technique for monitoring land surface deformation, which can serve as a reliable decision for supporting highspeed railway project design, construction, operation and maintenance.

Selected list of books and journals for the small medical library.

PubMed Central

Brandon, A N; Hill, D R

1987-01-01

The impact that the hospital librarian's use of management techniques and comprehension of the highly competitive health care environment can have on collection development and resulting information services in his or her library is reviewed in the introduction to this revised list of 600 books and 139 journals. The list is intended as a selection guide for the small or medium-size library in a hospital or comparable medical facility, or a core collection for a consortium of small hospital libraries. Books and journals are categorized by subject; the book list is followed by an author/editor index and the subject list of journals by an alphabetical title listing. Items suggested for initial purchase by smaller libraries are indicated by asterisks. To purchase the entire collection of books and to pay for 1987 subscriptions to all journals would require about $52,600. The cost of only the asterisked items totals approximately $21,000. PMID:3594025

Investigation of selected imagery from SKYLAB/EREP S190 system for medium and small scale mapping

NASA Technical Reports Server (NTRS)

Stewart, R. A.

1975-01-01

Satellite photography provided by the Skylab mission was investigated as a tool in planimetric mapping at medium and small scales over land surface in Canada. The main interest involved the potential usage of Skylab imagery for new and revision line mapping, photomapping possibilities, and the application of this photography as control for conventional high altitude aerial surveys. The results of six independent investigations clearly indicate that certain selected sets of this photography are adequate for planimetric mapping purposes at scales of 1:250,000 and smaller. In limited cases, the NATO planimetric accuracy requirements for Class B 1:50,000 scale mapping were also achieved. Of the S190A photography system, the camera containing the Pan X Aerial Black and White film offers the greatest potential to mapping at small scales. However, the S190B system continually proved to offer more versatility throughout the entire investigation.

High Spatial Resolution Europa Coverage by the Galileo Near Infrared Mapping Spectrometer NIMS

NASA Image and Video Library

1998-03-26

NASA Galileo spacecraft, which was used to map the mineral and ice properties over the surfaces of the Jovian moons, producing global spectral images for small selected regions on the satellites in 1996-97.

Selection on male size, leg length and condition during mate search in a sexually highly dimorphic orb-weaving spider.

PubMed

Foellmer, Matthias W; Fairbairn, Daphne J

2005-02-01

Mate search plays a central role in hypotheses for the adaptive significance of extreme female-biased sexual size dimorphism (SSD) in animals. Spiders (Araneae) are the only free-living terrestrial taxon where extreme SSD is common. The "gravity hypothesis" states that small body size in males is favoured during mate search in species where males have to climb to reach females, because body length is inversely proportional to achievable speed on vertical structures. However, locomotive performance of males may also depend on relative leg length. Here we examine selection on male body size and leg length during mate search in the highly dimorphic orb-weaving spider Argiope aurantia, using a multivariate approach to distinguish selection targeted at different components of size. Further, we investigate the scaling relationships between male size and energy reserves, and the differential loss of reserves. Adult males do not feed while roving, and a size-dependent differential energy storage capacity may thus affect male performance during mate search. Contrary to predictions, large body size was favoured in one of two populations, and this was due to selection for longer legs. Male size was not under selection in the second population, but we detected direct selection for longer third legs. Males lost energy reserves during mate search, but this was independent of male size and storage capacity scaled isometrically with size. Thus, mate search is unlikely to lead to selection for small male size, but the hypothesis that relatively longer legs in male spiders reflect a search-adapted morphology is supported.

Creation of a small high-throughput screening facility.

PubMed

Flak, Tod

2009-01-01

The creation of a high-throughput screening facility within an organization is a difficult task, requiring a substantial investment of time, money, and organizational effort. Major issues to consider include the selection of equipment, the establishment of data analysis methodologies, and the formation of a group having the necessary competencies. If done properly, it is possible to build a screening system in incremental steps, adding new pieces of equipment and data analysis modules as the need grows. Based upon our experience with the creation of a small screening service, we present some guidelines to consider in planning a screening facility.

A "Do It Yourself Kit" for Implementing a High School Peer Counseling Program in Three Easy Steps!

ERIC Educational Resources Information Center

Marsico, John; Nelson, Judith

Selected high school sophomores and juniors at Pomona Senior High School in Arvada, Colorado, are trained in counseling and group communication skills in order to be able to facilitate small peer groups in elective classes. The purpose is to help students find personal meaning in their lives and be more successful in school. An attempt is made to…

Selective isolation of hydrophobin SC3 by solid-phase extraction with polytetrafluoroethylene microparticles and subsequent mass spectrometric analysis.

PubMed

Kupčík, Rudolf; Zelená, Miroslava; Řehulka, Pavel; Bílková, Zuzana; Česlová, Lenka

2016-02-01

Hydrophobins are small proteins that play a role in a number of processes during the filamentous fungi growth and development. These proteins are characterized by the self-assembly of their molecules into an amphipathic membrane at hydrophilic-hydrophobic interfaces. Isolation and purification of hydrophobins generally present a challenge in their analysis. Hydrophobin SC3 from Schizophyllum commune was selected as a representative of class I hydrophobins in this work. A novel procedure for selective and effective isolation of hydrophobin SC3 based on solid-phase extraction with polytetrafluoroethylene microparticles loaded in a small self-made microcolumn is reported. The tailored binding of hydrophobins to polytetrafluoroethylene followed by harsh elution conditions resulted in a highly specific isolation of hydrophobin SC3 from the model mixture of ten proteins. The presented isolation protocol can have a positive impact on the analysis and utilization of these proteins including all class I hydrophobins. Hydrophobin SC3 was further subjected to reduction of its highly stable disulfide bonds and to chymotryptic digestion followed by mass spectrometric analysis. The isolation and digestion protocols presented in this work make the analysis of these highly hydrophobic and compact proteins possible. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High throughput selection of novel plant growth regulators: Assessing the translatability of small bioactive molecules from Arabidopsis to crops.

PubMed

Rodriguez-Furlán, Cecilia; Miranda, Giovanna; Reggiardo, Martín; Hicks, Glenn R; Norambuena, Lorena

2016-04-01

Plant growth regulators (PGRs) have become an integral part of agricultural and horticultural practices. Accordingly, there is an increased demand for new and cost-effective products. Nevertheless, the market is limited by insufficient innovation. In this context chemical genomics has gained increasing attention as a powerful approach addressing specific traits. Here is described the successful implementation of a highly specific, sensitive and efficient high throughput screening approach using Arabidopsis as a model. Using a combination of techniques, 10,000 diverse compounds were screened and evaluated for several important plant growth traits including root and leaf growth. The phenotype-based selection allowed the compilation of a collection of putative Arabidopsis growth regulators with a broad range of activities and specificities. A subset was selected for evaluating their bioactivity in agronomically valuable plants. Their validation as growth regulators in commercial species such as tomato, lettuce, carrot, maize and turfgrasses reinforced the success of the screening in Arabidopsis and indicated that small molecules activity can be efficiently translated to commercial species. Therefore, the chemical genomics approach in Arabidopsis is a promising field that can be incorporated in PGR discovery programs and has a great potential to develop new products that can be efficiently used in crops. Copyright © 2016. Published by Elsevier Ireland Ltd.

Small molecule inhibitors of mesotrypsin from a structure-based docking screen

DOE PAGES

Kayode, Olumide; Huang, Zunnan; Soares, Alexei S.; ...

2017-05-02

PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. To date there are no mesotrypsin-selective pharmacological inhibitors which could serve as tools for deciphering the pathological role of this enzyme, and could potentially form the basis for novel therapeutic strategies targeting mesotrypsin. A virtual screen of the Natural Product Database (NPD) and Food and Drug Administration (FDA) approved Drug Database was conducted by high-throughput molecular docking utilizing crystal structures of mesotrypsin. Twelve high-scoring compounds were selected for testing based on lowest free energy docking scores, interaction with key mesotrypsin active sitemore » residues, and commercial availability. Diminazene (C1D22956468), along with two similar compounds presenting the bis-benzamidine substructure, was validated as a competitive inhibitor of mesotrypsin and other human trypsin isoforms. Diminazene is the most potent small molecule inhibitor of mesotrypsin reported to date with an inhibitory constant (K i) of 3.6±0.3 pM. Diminazene was subsequently co-crystalized with mesotrypsin and the crystal structure was solved and refined to 1.25 Å resolution. This high resolution crystal structure can now offer a foundation for structure-guided efforts to develop novel and potentially more selective mesotrypsin inhibitors based on similar molecular substructures.« less

Small molecule inhibitors of mesotrypsin from a structure-based docking screen

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

Kayode, Olumide; Huang, Zunnan; Soares, Alexei S.

PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. To date there are no mesotrypsin-selective pharmacological inhibitors which could serve as tools for deciphering the pathological role of this enzyme, and could potentially form the basis for novel therapeutic strategies targeting mesotrypsin. A virtual screen of the Natural Product Database (NPD) and Food and Drug Administration (FDA) approved Drug Database was conducted by high-throughput molecular docking utilizing crystal structures of mesotrypsin. Twelve high-scoring compounds were selected for testing based on lowest free energy docking scores, interaction with key mesotrypsin active sitemore » residues, and commercial availability. Diminazene (C1D22956468), along with two similar compounds presenting the bis-benzamidine substructure, was validated as a competitive inhibitor of mesotrypsin and other human trypsin isoforms. Diminazene is the most potent small molecule inhibitor of mesotrypsin reported to date with an inhibitory constant (K i) of 3.6±0.3 pM. Diminazene was subsequently co-crystalized with mesotrypsin and the crystal structure was solved and refined to 1.25 Å resolution. This high resolution crystal structure can now offer a foundation for structure-guided efforts to develop novel and potentially more selective mesotrypsin inhibitors based on similar molecular substructures.« less

Self Organizing Map-Based Classification of Cathepsin k and S Inhibitors with Different Selectivity Profiles Using Different Structural Molecular Fingerprints: Design and Application for Discovery of Novel Hits.

PubMed

Ihmaid, Saleh K; Ahmed, Hany E A; Zayed, Mohamed F; Abadleh, Mohammed M

2016-01-30

The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to study and hence predict compound selectivity properties. In this work, we propose an affordable machine learning method to perform compound selectivity classification and prediction. For this purpose, we have collected compounds with reported activity and built a selectivity database formed of 153 cathepsin K and S inhibitors that are considered of medicinal interest. This database has three compound sets, two K/S and S/K selective ones and one non-selective KS one. We have subjected this database to the selectivity classification tool 'Emergent Self-Organizing Maps' for exploring its capability to differentiate selective cathepsin inhibitors for one target over the other. The method exhibited good clustering performance for selective ligands with high accuracy (up to 100 %). Among the possibilites, BAPs and MACCS molecular structural fingerprints were used for such a classification. The results exhibited the ability of the method for structure-selectivity relationship interpretation and selectivity markers were identified for the design of further novel inhibitors with high activity and target selectivity.

Terrestrial habitat selection and strong density-dependent mortality in recently metamorphosed amphibians.

PubMed

Patrick, David A; Harper, Elizabeth B; Hunter, Malcolm L; Calhoun, Aram J K

2008-09-01

To predict the effects of terrestrial habitat change on amphibian populations, we need to know how amphibians respond to habitat heterogeneity, and whether habitat choice remains consistent throughout the life-history cycle. We conducted four experiments to evaluate how the spatial distribution of juvenile wood frogs, Rana sylvatica (including both overall abundance and localized density), was influenced by habitat choice and habitat structure, and how this relationship changed with spatial scale and behavioral phase. The four experiments included (1) habitat manipulation on replicated 10-ha landscapes surrounding breeding pools; (2) short-term experiments with individual frogs emigrating through a manipulated landscape of 1 m wide hexagonal patches; and habitat manipulations in (3) small (4-m2); and (4) large (100-m2) enclosures with multiple individuals to compare behavior both during and following emigration. The spatial distribution of juvenile wood frogs following emigration resulted from differences in the scale at which juvenile amphibians responded to habitat heterogeneity during active vs. settled behavioral phases. During emigration, juvenile wood frogs responded to coarse-scale variation in habitat (selection between 2.2-ha forest treatments) but not to fine-scale variation. After settling, however, animals showed habitat selection at much smaller scales (2-4 m2). This resulted in high densities of animals in small patches of suitable habitat where they experienced rapid mortality. No evidence of density-dependent habitat selection was seen, with juveniles typically choosing to remain at extremely high densities in high-quality habitat, rather than occupying low-quality habitat. These experiments demonstrate how prediction of the terrestrial distribution of juvenile amphibians requires understanding of the complex behavioral responses to habitat heterogeneity. Understanding these patterns is important, given that human alterations to amphibian habitats may generate extremely high densities of animals, resulting in high density-dependent mortality.

A miniaturized assay for measuring small molecule phosphorylation in the presence of complex matrices.

PubMed

Spry, Christina; Saliba, Kevin J; Strauss, Erick

2014-04-15

We describe here a simple, miniaturized radiation-based phosphorylation assay that can be used to monitor phosphorylation of a diverse range of small molecule substrates in the presence of purified and crude enzyme preparations. Ba(OH)2 and ZnSO4 are used to terminate phosphoryl transfer and to precipitate selectively the phosphorylated reaction product in a single step; non-phosphorylated substrate is removed by filtration prior to quantification. The key advantages over alternative radiation-based assays are that: (i) high-energy/short-lived radioactive emitters are not required; (ii) high-quality data can be obtained without the need for high radioactivity concentrations; and (iii) the assay is compatible with high-throughput applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Determination of atmospheric moisture structure and infrared cooling rates from high resolution MAMS radiance data

NASA Technical Reports Server (NTRS)

Menzel, W. Paul; Moeller, Christopher C.; Smith, William L.

1991-01-01

This program has applied Multispectral Atmospheric Mapping Sensor (MAMS) high resolution data to the problem of monitoring atmospheric quantities of moisture and radiative flux at small spatial scales. MAMS, with 100-m horizontal resolution in its four infrared channels, was developed to study small scale atmospheric moisture and surface thermal variability, especially as related to the development of clouds, precipitation, and severe storms. High-resolution Interferometer Sounder (HIS) data has been used to develop a high spectral resolution retrieval algorithm for producing vertical profiles of atmospheric temperature and moisture. The results of this program are summarized and a list of publications resulting from this contract is presented. Selected publications are attached as an appendix.

50 CFR 86.60 - What are the criteria used to select projects for grants?

Code of Federal Regulations, 2014 CFR

2014-10-01

... features add a high value compared with the funds from the proposal, for example, where you construct a small feature such as a transient mooring dock within an existing harbor that adds high value and... above features would add less value for the cost 0-10 points. (6) Provide a significant link to...

50 CFR 86.60 - What are the criteria used to select projects for grants?

Code of Federal Regulations, 2013 CFR

2013-10-01

... features add a high value compared with the funds from the proposal, for example, where you construct a small feature such as a transient mooring dock within an existing harbor that adds high value and... above features would add less value for the cost 0-10 points. (6) Provide a significant link to...

50 CFR 86.60 - What are the criteria used to select projects for grants?

Code of Federal Regulations, 2012 CFR

2012-10-01

... features add a high value compared with the funds from the proposal, for example, where you construct a small feature such as a transient mooring dock within an existing harbor that adds high value and... above features would add less value for the cost 0-10 points. (6) Provide a significant link to...

50 CFR 86.60 - What are the criteria used to select projects for grants?

Code of Federal Regulations, 2011 CFR

2011-10-01

... features add a high value compared with the funds from the proposal, for example, where you construct a small feature such as a transient mooring dock within an existing harbor that adds high value and... above features would add less value for the cost 0-10 points. (6) Provide a significant link to...

509-45-1: A C. annuum Pepper germplasm containing high concentrations of capsinoids

USDA-ARS?s Scientific Manuscript database

This publication reports the public release of pepper (Capsicum annuum) germplasm ‘509-45-1’. Pepper germplasm 509-45-1 is a small-fruited, non-pungent single plant selection from PI 645509. Fruit of ‘509-45-1’ contain high concentrations of capsinoids [capsiate ((4-hydroxy-3-methoxybenzyl (E)-8...

[Small renal mass].

PubMed

Prokofiev, D; Kreutzer, N; Kress, A; Wissing, F; Pfeifer, H; Stolzenburg, J-U; Dietel, A; Schwalenberg, T; Do, M; Truß, M C

2012-10-01

The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

DMH1, a Highly Selective Small Molecule BMP Inhibitor Promotes Neurogenesis of hiPSCs: Comparison of PAX6 and SOX1 Expression during Neural Induction

PubMed Central

2012-01-01

Recent successes in deriving human-induced pluripotent stem cells (hiPSCs) allow for the possibility of studying human neurons derived from patients with neurological diseases. Concomitant inhibition of the BMP and TGF-β1 branches of the TGF-β signaling pathways by the endogenous antagonist, Noggin, and the small molecule SB431542, respectively, induces efficient neuralization of hiPSCs, a method known as dual-SMAD inhibition. The use of small molecule inhibitors instead of their endogenous counterparts has several advantages including lower cost, consistent activity, and the maintenance of xeno-free culture conditions. We tested the efficacy of DMH1, a highly selective small molecule BMP-inhibitor for its potential to replace Noggin in the neuralization of hiPSCs. We compare Noggin and DMH1-induced neuralization of hiPSCs by measuring protein and mRNA levels of pluripotency and neural precursor markers over a period of seven days. The regulation of five of the six markers assessed was indistinguishable in the presence of concentrations of Noggin or DMH1 that have been shown to effectively inhibit BMP signaling in other systems. We observed that by varying the DMH1 or Noggin concentration, we could selectively modulate the number of SOX1 expressing cells, whereas PAX6, another neural precursor marker, remained the same. The level and timing of SOX1 expression have been shown to affect neural induction as well as neural lineage. Our observations, therefore, suggest that BMP-inhibitor concentrations need to be carefully monitored to ensure appropriate expression levels of all transcription factors necessary for the induction of a particular neuronal lineage. We further demonstrate that DMH1-induced neural progenitors can be differentiated into β3-tubulin expressing neurons, a subset of which also express tyrosine hydroxylase. Thus, the combined use of DMH1, a highly specific BMP-pathway inhibitor, and SB431542, a TGF-β1-pathway specific inhibitor, provides us with the tools to independently regulate these two pathways through the exclusive use of small molecule inhibitors. PMID:22860217

A new approach for selection of Oenococcus oeni strains in order to produce malolactic starters.

PubMed

Coucheney, Françoise; Desroche, Nicolas; Bou, Magali; Tourdot-Maréchal, Raphaëlle; Dulau, Laurent; Guzzo, Jean

2005-12-15

The lactic acid bacterium Oenococcus oeni, mainly responsible for malolactic fermentation (MLF), is used in new winery process as starter culture for direct inoculation. The difficulty to master MLF according to the wine led us to search a new approach to select effective O. oeni strains. Biochemical and molecular tests were performed in order to characterize three strains of O. oeni selected for malolactic starter elaboration. Malolactic and ATPase activities that appeared as a great interest in MLF were measured and the expression of a small heat shock protein Lo18 was evaluated by immunoblotting and real-time PCR. These results were correlated with the performances of strains in two red wines. Physiological and molecular characteristics of the three strains showed significant differences for the global malolactic activity on intact cell at pH 3.0 and at the level of induction of the small heat shock protein Lo18. These two parameters appeared of interest to evaluate in the ability of O. oeni strains to survive into wine after direct inoculation and to perform MLF. Indeed, a tested strain that presented the highest malolactic activity on intact cells at pH 3.0 and a high level of Lo18 induction showed a high growth rate and a high specific kinetic of malate consumption. The techniques used in this work carry out more quickly and more reliable than usual for the selection of effective strains intended for direct inoculation in wines.

Terminator oligo blocking efficiently eliminates rRNA from Drosophila small RNA sequencing libraries.

PubMed

Wickersheim, Michelle L; Blumenstiel, Justin P

2013-11-01

A large number of methods are available to deplete ribosomal RNA reads from high-throughput RNA sequencing experiments. Such methods are critical for sequencing Drosophila small RNAs between 20 and 30 nucleotides because size selection is not typically sufficient to exclude the highly abundant class of 30 nucleotide 2S rRNA. Here we demonstrate that pre-annealing terminator oligos complimentary to Drosophila 2S rRNA prior to 5' adapter ligation and reverse transcription efficiently depletes 2S rRNA sequences from the sequencing reaction in a simple and inexpensive way. This depletion is highly specific and is achieved with minimal perturbation of miRNA and piRNA profiles.

Remote sensing and GIS analyses for emergency manouvering and forced landing areas definition as a support for general aviation flights

NASA Astrophysics Data System (ADS)

Skocki, Krzysztof

2016-08-01

This paper summarizes the preliminary analyses of using existing remote sensing data, medium and high-resolution satellite and airborne data to define safe emergency landing and maneuvering areas to be used by small aircrafts operating from small airports and airfields in Poland. The pilots need to know such places in the interest of safe flight operations. In common practice, flying instructors typically show the student pilot fields around the airfield supposed to be suitable for emergency or precautionary landing (or ditching) in the initial phase of the training. Although it looks to cover the most basic needs, the problem still exists in relation to guest pilots. To fill this gap, the unified safety map document covering the safe emergency areas around the airfields is proposed in this research. Use of satellite high resolution data, as well as aerial photos, infrastructure information, with use of GIS tools (like buffer zones, distance, equal-time circles or position lines) enable to check the terrain around selected airfields and define possible areas suitable for emergency operations. In the second phase of work, selected areas will be described in terms of easy navigation, possible infrastructure around them, rescue possibilities, radio signal coverage, and others. The selected areas should be also checked for typical cover and surface hardness and stability (eg. with use of moisture estimation on the base of middle-resolution satellite data). Its planned to prepare one combined and separate sheets of the final map for various aircraft characteristics (`classes' of small Cessna-related, big Cessna-related, fast low-wing Diamond-like, two-engine Piper-like). The presented concept should highly increase the safety operations for small aviation in secondary airports and airfields, where the information available is limited. There is also a possibility to make a similar maps for `cruise', which means the areas with dense traffic between the airports/airfields.

Comparative mapping of quantitative trait loci for Fusarium head blight resistance and anther retention in the winter wheat population Capo × Arina.

PubMed

Buerstmayr, Maria; Buerstmayr, Hermann

2015-08-01

Fusarium resistance in Arina is highly quantitative and governed by multiple small effect QTL. Anther retention has a high correlation with FHB susceptibility and appears a practicable indirect selection target for enhancing FHB resistance. The Swiss winter wheat cultivar Arina possesses a high resistance level constituted by a number of small to medium effect QTL reported from three independent mapping populations. Yet these overlap only for one resistance QTL on the long arm of chromosome 1B. The present study characterized Fusarium head blight (FHB) resistance in a population of 171 recombinant inbred lines from a cross between Arina (resistant) and Capo (moderately resistant). The population was evaluated for FHB resistance under field conditions for 3 years. Additionally, we phenotyped anther retention, plant height and flowering date to analyze their association with resistance. Lines with a low proportion of retained anthers after flowering and tall plants were significantly less diseased, while flowering date had no association with FHB severity. QTL analysis identified eight small to medium effect QTL for FHB severity, of which QTL on 1BS, 3B, 4AL and 6BL likely correspond to resistance alleles already detected in previously studied Arina populations. QTL for anther retention mapped to 4AL, 6BL and 5AS. Notably, QTL on 4AL and 6BL overlapped with QTL for FHB severity. A single small effect QTL for plant height was detected on 5AS and no QTL was identified for flowering date. Genotypes having three or four resistance alleles in combination showed a good resistance level, indicating pyramiding resistance QTL as a powerful approach for breeding resistant cultivars. Selection for rapid and complete anther extrusion appears promising as an indirect selection criterion for enhancing FHB resistance.

America COMPETES Act: Programs, Funding, and Selected Issues

DTIC Science & Technology

2009-04-17

exhibited by the balance of trade in high -technology products, was declining as the U.S. share of world exports on research and development (R&D...fund high - risk research and development at small and medium-sized businesses. With respect to labor, the act takes actions that are intended to make...to fund high -risk, high -reward basic research projects. The act also expresses the sense of the Congress that appropriately funding NASA at the

Small molecules as therapy for uveitis: a selected perspective of new and developing agents.

PubMed

Pleyer, Uwe; Algharably, Engi Abdel-Hady; Feist, Eugen; Kreutz, Reinhold

2017-09-01

Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made. Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

Gold nanoparticle-sensitized quartz crystal microbalance sensor for rapid and highly selective determination of Cu(II) ions.

PubMed

Jin, Yulong; Huang, Yanyan; Liu, Guoquan; Zhao, Rui

2013-09-21

A novel quartz crystal microbalance (QCM) sensor for rapid, highly selective and sensitive detection of copper ions was developed. As a signal amplifier, gold nanoparticles (Au NPs) were self-assembled onto the surface of the sensor. A simple dip-and-dry method enabled the whole detection procedure to be accomplished within 20 min. High selectivity of the sensor towards copper ions is demonstrated by both individual and coexisting assays with interference ions. This gold nanoparticle mediated amplification allowed a detection limit down to 3.1 μM. Together with good repeatability and regeneration, the QCM sensor was also applied to the analysis of copper contamination in drinking water. This work provides a flexible method for fabricating QCM sensors for the analysis of important small molecules in environmental and biological samples.

Engineering of Bispecific Affinity Proteins with High Affinity for ERBB2 and Adaptable Binding to Albumin

PubMed Central

Nilvebrant, Johan; Åstrand, Mikael; Georgieva-Kotseva, Maria; Björnmalm, Mattias; Löfblom, John; Hober, Sophia

2014-01-01

The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein. PMID:25089830

The Genetic Architecture of Response to Long-Term Artificial Selection for Oil Concentration in the Maize Kernel

PubMed Central

Laurie, Cathy C.; Chasalow, Scott D.; LeDeaux, John R.; McCarroll, Robert; Bush, David; Hauge, Brian; Lai, Chaoqiang; Clark, Darryl; Rocheford, Torbert R.; Dudley, John W.

2004-01-01

In one of the longest-running experiments in biology, researchers at the University of Illinois have selected for altered composition of the maize kernel since 1896. Here we use an association study to infer the genetic basis of dramatic changes that occurred in response to selection for changes in oil concentration. The study population was produced by a cross between the high- and low-selection lines at generation 70, followed by 10 generations of random mating and the derivation of 500 lines by selfing. These lines were genotyped for 488 genetic markers and the oil concentration was evaluated in replicated field trials. Three methods of analysis were tested in simulations for ability to detect quantitative trait loci (QTL). The most effective method was model selection in multiple regression. This method detected ∼50 QTL accounting for ∼50% of the genetic variance, suggesting that >50 QTL are involved. The QTL effect estimates are small and largely additive. About 20% of the QTL have negative effects (i.e., not predicted by the parental difference), which is consistent with hitchhiking and small population size during selection. The large number of QTL detected accounts for the smooth and sustained response to selection throughout the twentieth century. PMID:15611182

An efficient employer strategy for dealing with adverse selection in multiple-plan offerings: an MSA example.

PubMed

Pauly, M V; Herring, B J

2000-07-01

This paper outlines a feasible employee premium contribution policy, which would reduce the inefficiency associated with adverse selection when a limited coverage insurance policy is offered alongside a more generous policy. The "efficient premium contribution" is defined and is shown to lead to an efficient allocation across plans of persons who differ by risk, but it may also redistribute against higher risks. A simulation of the additional option of a catastrophic health plan (CHP) accompanied by a medical savings account (MSA) is presented. The efficiency gains from adding the MSA/catastrophic health insurance plan (CHP) option are positive but small, and the adverse consequences for high risks under an efficient employee premium are also small.

Otoacoustic Estimates of Cochlear Tuning: Testing Predictions in Macaque

NASA Astrophysics Data System (ADS)

Shera, Christopher A.; Bergevin, Christopher; Kalluri, Radha; Mc Laughlin, Myles; Michelet, Pascal; van der Heijden, Marcel; Joris, Philip X.

2011-11-01

Otoacoustic estimates of cochlear frequency selectivity suggest substantially sharper tuning in humans. However, the logic and methodology underlying these estimates remain untested by direct measurements in primates. We report measurements of frequency tuning in macaque monkeys, Old-World primates phylogenetically closer to humans than the small laboratory animals often taken as models of human hearing (e.g., cats, guinea pigs, and chinchillas). We find that measurements of tuning obtained directly from individual nerve fibers and indirectly using otoacoustic emissions both indicate that peripheral frequency selectivity in macaques is significantly sharper than in small laboratory animals, matching that inferred for humans at high frequencies. Our results validate the use of otoacoustic emissions for noninvasive measurement of cochlear tuning and corroborate the finding of sharper tuning in humans.

Novel selection methods for DNA-encoded chemical libraries.

PubMed

Chan, Alix I; McGregor, Lynn M; Liu, David R

2015-06-01

Driven by the need for new compounds to serve as biological probes and leads for therapeutic development and the growing accessibility of DNA technologies including high-throughput sequencing, many academic and industrial groups have begun to use DNA-encoded chemical libraries as a source of bioactive small molecules. In this review, we describe the technologies that have enabled the selection of compounds with desired activities from these libraries. These methods exploit the sensitivity of in vitro selection coupled with DNA amplification to overcome some of the limitations and costs associated with conventional screening methods. In addition, we highlight newer techniques with the potential to be applied to the high-throughput evaluation of DNA-encoded chemical libraries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid response of brain metastases to alectinib in a patient with non-small-cell lung cancer resistant to crizotinib.

PubMed

Ajimizu, Hitomi; Kim, Young Hak; Mishima, Michiaki

2015-02-01

Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor. Alectinib is a highly selective, next-generation ALK inhibitor, and both preclinical and clinical studies have indicated that alectinib is also effective in crizotinib-resistant tumors. A recent in vitro study demonstrated significant antitumor activity of alectinib for brain metastases using mouse models of ALK-positive non-small-cell lung cancer. In this paper, we report a first case alectinib was highly effective against brain metastases refractory to crizotinib. Further investigation of alectinib in this setting would be particularly valuable.

Small business innovation research program solicitation: Closing date July 16, 1990

NASA Technical Reports Server (NTRS)

1990-01-01

This is the eighth annual solicitation by NASA addressed to small business firms, inviting them to submit proposals for research, or research and development, activities in some of the science and engineering areas of interest to NASA. The solicitation describes the Small Business Innovative Research (SBIR) program, identifies eligibility requirements, outlines the required proposal format and content, states proposal preparation and submission requirements, describes the proposal evaluation and award selection process, and provides other information to assist those interested in participating in NASA's SBIR program. It also identifies the technical topics and subtopics for which SBIR proposals are solicited. These cover a broad range of current NASA interests, but do not necessarily include all areas in which NASA plans or currently conducts research. High-risk high pay-off innovations are desired.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

PubMed

Wang, Yong; Wu, Qiao-Feng; Chen, Chen; Wu, Ling-Yun; Yan, Xian-Zhong; Yu, Shu-Guang; Zhang, Xiang-Sun; Liang, Fan-Rong

2012-01-01

Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Our result demonstrates that metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture. Comparing with other existing methods, LPFS shows better performance to select a small set of key molecules. In addition, LPFS is a general methodology and can be applied to other high-dimensional data analysis, for example cancer genomics.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection

PubMed Central

2012-01-01

Background Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use. Results In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment. Specifically, we generate and investigate the high-throughput metabolic profiles of acupuncture treatment at several acupoints in human. To select the subsets of metabolites that best characterize the acupuncture effect for each meridian point, an optimization model is proposed to identify biomarkers from high-dimensional metabolic data from case and control samples. Importantly, we use nearest centroid as the prototype to simultaneously minimize the number of selected features and the leave-one-out cross validation error of classifier. We compared the performance of LPFS to several state-of-the-art methods, such as SVM recursive feature elimination (SVM-RFE) and sparse multinomial logistic regression approach (SMLR). We find that our LPFS method tends to reveal a small set of metabolites with small standard deviation and large shifts, which exactly serves our requirement for good biomarker. Biologically, several metabolite biomarkers for acupuncture treatment are revealed and serve as the candidates for further mechanism investigation. Also biomakers derived from five meridian points, Zusanli (ST36), Liangmen (ST21), Juliao (ST3), Yanglingquan (GB34), and Weizhong (BL40), are compared for their similarity and difference, which provide evidence for the specificity of acupoints. Conclusions Our result demonstrates that metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture. Comparing with other existing methods, LPFS shows better performance to select a small set of key molecules. In addition, LPFS is a general methodology and can be applied to other high-dimensional data analysis, for example cancer genomics. PMID:23046877

The Broad Institute: Screening for Dependencies in Cancer Cell Lines Using Small Molecules | Office of Cancer Genomics

Cancer.gov

Using cancer cell-line profiling, we established an ongoing resource to identify, as comprehensively as possible, the drug-targetable dependencies that specific genomic alterations impart on human cancers. We measured the sensitivity of hundreds of genetically characterized cancer cell lines to hundreds of small-molecule probes and drugs that have highly selective interactions with their targets, and that collectively modulate many distinct nodes in cancer cell circuitry.

Movement is the glue connecting home ranges and habitat selection.

PubMed

Van Moorter, Bram; Rolandsen, Christer M; Basille, Mathieu; Gaillard, Jean-Michel

2016-01-01

Animal space use has been studied by focusing either on geographic (e.g. home ranges, species' distribution) or on environmental (e.g. habitat use and selection) space. However, all patterns of space use emerge from individual movements, which are the primary means by which animals change their environment. Individuals increase their use of a given area by adjusting two key movement components: the duration of their visit and/or the frequency of revisits. Thus, in spatially heterogeneous environments, animals exploit known, high-quality resource areas by increasing their residence time (RT) in and/or decreasing their time to return (TtoR) to these areas. We expected that spatial variation in these two movement properties should lead to observed patterns of space use in both geographic and environmental spaces. We derived a set of nine predictions linking spatial distribution of movement properties to emerging space-use patterns. We predicted that, at a given scale, high variation in RT and TtoR among habitats leads to strong habitat selection and that long RT and short TtoR result in a small home range size. We tested these predictions using moose (Alces alces) GPS tracking data. We first modelled the relationship between landscape characteristics and movement properties. Then, we investigated how the spatial distribution of predicted movement properties (i.e. spatial autocorrelation, mean, and variance of RT and TtoR) influences home range size and hierarchical habitat selection. In landscapes with high spatial autocorrelation of RT and TtoR, a high variation in both RT and TtoR occurred in home ranges. As expected, home range location was highly selective in such landscapes (i.e. second-order habitat selection); RT was higher and TtoR lower within the selected home range than outside, and moose home ranges were small. Within home ranges, a higher variation in both RT and TtoR was associated with higher selectivity among habitat types (i.e. third-order habitat selection). Our findings show how patterns of geographic and environmental space use correspond to the two sides of a coin, linked by movement responses of individuals to environmental heterogeneity. By demonstrating the potential to assess the consequences of altering RT or TtoR (e.g. through human disturbance or climatic changes) on home range size and habitat selection, our work sets the basis for new theoretical and methodological advances in movement ecology. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Evolution of High Mobility Group Nucleosome-Binding Proteins and Its Implications for Vertebrate Chromatin Specialization

PubMed Central

González-Romero, Rodrigo; Eirín-López, José M.; Ausió, Juan

2015-01-01

High mobility group (HMG)-N proteins are a family of small nonhistone proteins that bind to nucleosomes (N). Despite the amount of information available on their structure and function, there is an almost complete lack of information on the molecular evolutionary mechanisms leading to their exclusive differentiation. In the present work, we provide evidence suggesting that HMGN lineages constitute independent monophyletic groups derived from a common ancestor prior to the diversification of vertebrates. Based on observations of the functional diversification across vertebrate HMGN proteins and on the extensive silent nucleotide divergence, our results suggest that the long-term evolution of HMGNs occurs under strong purifying selection, resulting from the lineage-specific functional constraints of their different protein domains. Selection analyses on independent lineages suggest that their functional specialization was mediated by bursts of adaptive selection at specific evolutionary times, in a small subset of codons with functional relevance—most notably in HMGN1, and in the rapidly evolving HMGN5. This work provides useful information to our understanding of the specialization imparted on chromatin metabolism by HMGNs, especially on the evolutionary mechanisms underlying their functional differentiation in vertebrates. PMID:25281808

Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

PubMed

Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

2008-03-01

Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

Preparation and composition of superconducting copper oxides based on Ga-O layers

DOEpatents

Dabrowski, Bogdan; Vaughey, J. T.; Poeppelmeier, Kenneth R.

1994-01-01

A high temperature superconducting material with the general formula GaSr.sub.2 Ln.sub.1-x MxCu.sub.2 O.sub.7.+-.w wherein Ln is selected from the group consisting of La, Ce, Pt, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Y and M is selected from the group consisting of Ca and Sr, 0.2.ltoreq.x.ltoreq.0.4 and w is a small fraction of one. A method of preparing this high temperature superconducting material is provided which includes heating and cooling a mixture to produce a crystalline material which is subsequently fired, ground and annealed at high pressure and temperature in oxygen to establish superconductivity.

Comenius Project: Are e-Learning Collaborations of High School Students across Europe in Maths Possible?

ERIC Educational Resources Information Center

Simonovits, Reinhard; McElroy, Jim; O'Loughlin, James; Townsend, Colin

2013-01-01

The overall aim of the project is to allow for the collaboration of high school students of different European countries on small, selected maths topics. This involves the use of technology, student mobility and English language competency. Benefits are also expected to accrue to teachers of mathematics by providing the opportunity to work with…

The Effects of Computer Animated Dissection versus Preserved Animal Dissection on the Student Achievement in a High School Biology Class.

ERIC Educational Resources Information Center

Kariuki, Patrick; Paulson, Ronda

The purpose of this study was to examine the effectiveness of computer-animated dissection techniques versus the effectiveness of traditional dissection techniques as related to student achievement. The sample used was 104 general biology students from a small, rural high school in Northeast Tennessee. Random selection was used to separate the…

A machine learning heuristic to identify biologically relevant and minimal biomarker panels from omics data

PubMed Central

2015-01-01

Background Investigations into novel biomarkers using omics techniques generate large amounts of data. Due to their size and numbers of attributes, these data are suitable for analysis with machine learning methods. A key component of typical machine learning pipelines for omics data is feature selection, which is used to reduce the raw high-dimensional data into a tractable number of features. Feature selection needs to balance the objective of using as few features as possible, while maintaining high predictive power. This balance is crucial when the goal of data analysis is the identification of highly accurate but small panels of biomarkers with potential clinical utility. In this paper we propose a heuristic for the selection of very small feature subsets, via an iterative feature elimination process that is guided by rule-based machine learning, called RGIFE (Rule-guided Iterative Feature Elimination). We use this heuristic to identify putative biomarkers of osteoarthritis (OA), articular cartilage degradation and synovial inflammation, using both proteomic and transcriptomic datasets. Results and discussion Our RGIFE heuristic increased the classification accuracies achieved for all datasets when no feature selection is used, and performed well in a comparison with other feature selection methods. Using this method the datasets were reduced to a smaller number of genes or proteins, including those known to be relevant to OA, cartilage degradation and joint inflammation. The results have shown the RGIFE feature reduction method to be suitable for analysing both proteomic and transcriptomics data. Methods that generate large ‘omics’ datasets are increasingly being used in the area of rheumatology. Conclusions Feature reduction methods are advantageous for the analysis of omics data in the field of rheumatology, as the applications of such techniques are likely to result in improvements in diagnosis, treatment and drug discovery. PMID:25923811

High Selection Pressure Promotes Increase in Cumulative Adaptive Culture

PubMed Central

Vegvari, Carolin; Foley, Robert A.

2014-01-01

The evolution of cumulative adaptive culture has received widespread interest in recent years, especially the factors promoting its occurrence. Current evolutionary models suggest that an increase in population size may lead to an increase in cultural complexity via a higher rate of cultural transmission and innovation. However, relatively little attention has been paid to the role of natural selection in the evolution of cultural complexity. Here we use an agent-based simulation model to demonstrate that high selection pressure in the form of resource pressure promotes the accumulation of adaptive culture in spite of small population sizes and high innovation costs. We argue that the interaction of demography and selection is important, and that neither can be considered in isolation. We predict that an increase in cultural complexity is most likely to occur under conditions of population pressure relative to resource availability. Our model may help to explain why culture change can occur without major environmental change. We suggest that understanding the interaction between shifting selective pressures and demography is essential for explaining the evolution of cultural complexity. PMID:24489724

Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Zhang, Yucheng; Oikonomou, Anastasia; Wong, Alexander; Haider, Masoom A.; Khalvati, Farzad

2017-04-01

Radiomics characterizes tumor phenotypes by extracting large numbers of quantitative features from radiological images. Radiomic features have been shown to provide prognostic value in predicting clinical outcomes in several studies. However, several challenges including feature redundancy, unbalanced data, and small sample sizes have led to relatively low predictive accuracy. In this study, we explore different strategies for overcoming these challenges and improving predictive performance of radiomics-based prognosis for non-small cell lung cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who underwent stereotactic body radiotherapy were used to predict recurrence, death, and recurrence-free survival using a comprehensive radiomics analysis. Different feature selection and predictive modeling techniques were used to determine the optimal configuration of prognosis analysis. To address feature redundancy, comprehensive analysis indicated that Random Forest models and Principal Component Analysis were optimum predictive modeling and feature selection methods, respectively, for achieving high prognosis performance. To address unbalanced data, Synthetic Minority Over-sampling technique was found to significantly increase predictive accuracy. A full analysis of variance showed that data endpoints, feature selection techniques, and classifiers were significant factors in affecting predictive accuracy, suggesting that these factors must be investigated when building radiomics-based predictive models for cancer prognosis.

The allele-frequency spectrum in a decoupled Moran model with mutation, drift, and directional selection, assuming small mutation rates.

PubMed

Vogl, Claus; Clemente, Florian

2012-05-01

We analyze a decoupled Moran model with haploid population size N, a biallelic locus under mutation and drift with scaled forward and backward mutation rates θ(1)=μ(1)N and θ(0)=μ(0)N, and directional selection with scaled strength γ=sN. With small scaled mutation rates θ(0) and θ(1), which is appropriate for single nucleotide polymorphism data in highly recombining regions, we derive a simple approximate equilibrium distribution for polymorphic alleles with a constant of proportionality. We also put forth an even simpler model, where all mutations originate from monomorphic states. Using this model we derive the sojourn times, conditional on the ancestral and fixed allele, and under equilibrium the distributions of fixed and polymorphic alleles and fixation rates. Furthermore, we also derive the distribution of small samples in the diffusion limit and provide convenient recurrence relations for calculating this distribution. This enables us to give formulas analogous to the Ewens-Watterson estimator of θ for biased mutation rates and selection. We apply this theory to a polymorphism dataset of fourfold degenerate sites in Drosophila melanogaster. Copyright © 2012 Elsevier Inc. All rights reserved.

The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

PubMed

Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

2013-12-01

3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

DNA-encoded libraries - an efficient small molecule discovery technology for the biomedical sciences.

PubMed

Kunig, Verena; Potowski, Marco; Gohla, Anne; Brunschweiger, Andreas

2018-06-27

DNA-encoded compound libraries are a highly attractive technology for the discovery of small molecule protein ligands. These compound collections consist of small molecules covalently connected to individual DNA sequences carrying readable information about the compound structure. DNA-tagging allows for efficient synthesis, handling and interrogation of vast numbers of chemically synthesized, drug-like compounds. They are screened on proteins by an efficient, generic assay based on Darwinian principles of selection. To date, selection of DNA-encoded libraries allowed for the identification of numerous bioactive compounds. Some of these compounds uncovered hitherto unknown allosteric binding sites on target proteins; several compounds proved their value as chemical biology probes unraveling complex biology; and the first examples of clinical candidates that trace their ancestry to a DNA-encoded library were reported. Thus, DNA-encoded libraries proved their value for the biomedical sciences as a generic technology for the identification of bioactive drug-like molecules numerous times. However, large scale experiments showed that even the selection of billions of compounds failed to deliver bioactive compounds for the majority of proteins in an unbiased panel of target proteins. This raises the question of compound library design.

Molecular self-assembly for biological investigations and nanoscale lithography

NASA Astrophysics Data System (ADS)

Cheunkar, Sarawut

Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly selective biorecognition. By carefully tuning the polar surface energy of polymeric stamps, problems associated with patterning hydrophilic tether molecules inserted into hydrophilic preformed SAMs are surmounted. The patterned substrates presenting neurotransmitter precursors selectively capture membrane-associated receptors. These advances provide new avenues for fabricating small-molecule arrays. Furthermore, a novel strategy based on a conventional microcontact printing, called chemical lift-off lithography, was invented to overcome the micrometer-scale resolution limits of molecular ink diffusion in soft lithography. Self-assembled monolayers of hydroxyl-terminated alkanethiols, preformed on gold substrates, were selectively removed by oxygen-plasma-treated polymeric stamps in a subtractive stamping process with high pattern fidelity. The covalent interactions formed at the stamp-substrate interface are believed to be responsible for removing not only alkanethiol molecules but also a monolayer of gold atoms from the substrates. A variety of high-resolution patterned features were fabricated, and stamps were cleaned and reused many times without feature deterioration. The remaining SAMs acted as resists for etching exposed gold features. Monolayer backfilling into lifted-off areas enabled patterned protein capture, and 40-nanometer chemical patterns were achieved.

Small, high pressure ratio compressor: Aerodynamic and mechanical design

NASA Technical Reports Server (NTRS)

Bryce, C. A.; Erwin, J. R.; Perrone, G. L.; Nelson, E. L.; Tu, R. K.; Bosco, A.

1973-01-01

The Small, High-Pressure-Ratio Compressor Program was directed toward the analysis, design, and fabrication of a centrifugal compressor providing a 6:1 pressure ratio and an airflow rate of 2.0 pounds per second. The program consists of preliminary design, detailed areodynamic design, mechanical design, and mechanical acceptance tests. The preliminary design evaluate radial- and backward-curved blades, tandem bladed impellers, impeller-and diffuser-passage boundary-layer control, and vane, pipe, and multiple-stage diffusers. Based on this evaluation, a configuration was selected for detailed aerodynamic and mechanical design. Mechanical acceptance test was performed to demonstrate that mechanical design objectives of the research package were met.

Techniques for predicting high-risk drivers for alcohol countermeasures. Volume 2, User manual

DOT National Transportation Integrated Search

1978-06-01

This user manual, a companion to the Volume I Technical Report by the same name, is designed to aid the alcohol program administrator in his decisions concerning implementation of countermeasures to selected individuals or small groups of drivers. Vo...

Accelerating rejection-based simulation of biochemical reactions with bounded acceptance probability

NASA Astrophysics Data System (ADS)

Thanh, Vo Hong; Priami, Corrado; Zunino, Roberto

2016-06-01

Stochastic simulation of large biochemical reaction networks is often computationally expensive due to the disparate reaction rates and high variability of population of chemical species. An approach to accelerate the simulation is to allow multiple reaction firings before performing update by assuming that reaction propensities are changing of a negligible amount during a time interval. Species with small population in the firings of fast reactions significantly affect both performance and accuracy of this simulation approach. It is even worse when these small population species are involved in a large number of reactions. We present in this paper a new approximate algorithm to cope with this problem. It is based on bounding the acceptance probability of a reaction selected by the exact rejection-based simulation algorithm, which employs propensity bounds of reactions and the rejection-based mechanism to select next reaction firings. The reaction is ensured to be selected to fire with an acceptance rate greater than a predefined probability in which the selection becomes exact if the probability is set to one. Our new algorithm improves the computational cost for selecting the next reaction firing and reduces the updating the propensities of reactions.

Accelerating rejection-based simulation of biochemical reactions with bounded acceptance probability

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

Thanh, Vo Hong, E-mail: vo@cosbi.eu; Priami, Corrado, E-mail: priami@cosbi.eu; Department of Mathematics, University of Trento, Trento

Stochastic simulation of large biochemical reaction networks is often computationally expensive due to the disparate reaction rates and high variability of population of chemical species. An approach to accelerate the simulation is to allow multiple reaction firings before performing update by assuming that reaction propensities are changing of a negligible amount during a time interval. Species with small population in the firings of fast reactions significantly affect both performance and accuracy of this simulation approach. It is even worse when these small population species are involved in a large number of reactions. We present in this paper a new approximatemore » algorithm to cope with this problem. It is based on bounding the acceptance probability of a reaction selected by the exact rejection-based simulation algorithm, which employs propensity bounds of reactions and the rejection-based mechanism to select next reaction firings. The reaction is ensured to be selected to fire with an acceptance rate greater than a predefined probability in which the selection becomes exact if the probability is set to one. Our new algorithm improves the computational cost for selecting the next reaction firing and reduces the updating the propensities of reactions.« less

Alectinib: a selective, next-generation ALK inhibitor for treatment of ALK-rearranged non-small-cell lung cancer.

PubMed

Santarpia, Mariacarmela; Altavilla, Giuseppe; Rosell, Rafael

2015-06-01

Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC). Despite initial responses, acquired resistance to crizotinib inevitably develops, with the brain being a common site of relapse. Alectinib is a highly selective, next-generation ALK inhibitor with potent inhibitory activity also against ALK mutations conferring resistance to crizotinib, including the gatekeeper L1196M substitution. In a Phase I/II study from Japan, alectinib was found to be highly active and safe in crizotinib-naïve, ALK-rearranged NSCLC patients. Alectinib also demonstrated promising antitumor activity in crizotinib-resistant patients, including those with CNS metastases. Based on these data, the drug received Breakthrough Therapy Designation by the US FDA and has been recently approved in Japan for the treatment of ALK-positive, advanced NSCLC patients. However, patients may eventually develop resistance to alectinib, highlighting the need for novel therapeutic strategies to further improve the management of ALK-rearranged NSCLC.

Photoactivable antibody binding protein: site-selective and covalent coupling of antibody.

PubMed

Jung, Yongwon; Lee, Jeong Min; Kim, Jung-won; Yoon, Jeongwon; Cho, Hyunmin; Chung, Bong Hyun

2009-02-01

Here we report new photoactivable antibody binding proteins, which site-selectively capture antibodies and form covalent conjugates with captured antibodies upon irradiation. The proteins allow the site-selective tagging and/or immobilization of antibodies with a highly preferred orientation and omit the need for prior antibody modifications. The minimal Fc-binding domain of protein G, a widely used antibody binding protein, was genetically and chemically engineered to contain a site-specific photo cross-linker, benzophenone. In addition, the domain was further mutated to have an enhanced Fc-targeting ability. This small engineered protein was successfully cross-linked only to the Fc region of the antibody without any nonspecific reactivity. SPR analysis indicated that antibodies can be site-selectively biotinylated through the present photoactivable protein. Furthermore, the system enabled light-induced covalent immobilization of antibodies directly on various solid surfaces, such as those of glass slides, gold chips, and small particles. Antibody coupling via photoactivable antibody binding proteins overcomes several limitations of conventional approaches, such as random chemical reactions or reversible protein binding, and offers a versatile tool for the field of immunosensors.

Selection methods for resistance to and tolerance of helminths in livestock

PubMed Central

McManus, Concepta; Paim, Tiago do Prado; de Melo, Cristiano Barros; Brasil, Bruno S. A. F.; Paiva, Samuel R.

2014-01-01

Helminthiases are among the most important livestock diseases worldwide, in particular for small ruminants, which are the focus of this review. Resource Allocation Theory implies that high-productivity farm animals proportionate insufficient resources for adequate coping with stressful conditions. Significant differences between breeds and within breeds are seen, as well as genotype vs. environment interactions. With improvement of genetic host resistance to infection, transmission of infection will be impacted. On the other hand, genetic improvement of resilience can lead to a reduction in clinical signs of disease, but not necessarily reduce transmission of infection to other animals. Faecal egg count (FEC) is the main measurement used to evaluate helminthiasis load, despite the fact that the protocols and analytical methods can affect the results, and the FEC data frequently shows aggregative, negative skewed distribution, and a high coefficient of variation. Mass selection where heritability is generally medium to low generally produces slow results and low economic returns. Many studies have been published linking resistance to nematodes in livestock to Quantitative Trait Loci and most studies have concentrated on chromosomes where the major histocompatibility complex region is located. Nevertheless, these complex traits have been seen to be affected by thousands of variants that each has a small effect. More recent studies have shown that genome-wide selection strategies can be useful in selecting animals for improved production and resistance traits in this case. PMID:25350972

SamSelect: a sample sequence selection algorithm for quorum planted motif search on large DNA datasets.

PubMed

Yu, Qiang; Wei, Dingbang; Huo, Hongwei

2018-06-18

Given a set of t n-length DNA sequences, q satisfying 0 < q ≤ 1, and l and d satisfying 0 ≤ d < l < n, the quorum planted motif search (qPMS) finds l-length strings that occur in at least qt input sequences with up to d mismatches and is mainly used to locate transcription factor binding sites in DNA sequences. Existing qPMS algorithms have been able to efficiently process small standard datasets (e.g., t = 20 and n = 600), but they are too time consuming to process large DNA datasets, such as ChIP-seq datasets that contain thousands of sequences or more. We analyze the effects of t and q on the time performance of qPMS algorithms and find that a large t or a small q causes a longer computation time. Based on this information, we improve the time performance of existing qPMS algorithms by selecting a sample sequence set D' with a small t and a large q from the large input dataset D and then executing qPMS algorithms on D'. A sample sequence selection algorithm named SamSelect is proposed. The experimental results on both simulated and real data show (1) that SamSelect can select D' efficiently and (2) that the qPMS algorithms executed on D' can find implanted or real motifs in a significantly shorter time than when executed on D. We improve the ability of existing qPMS algorithms to process large DNA datasets from the perspective of selecting high-quality sample sequence sets so that the qPMS algorithms can find motifs in a short time in the selected sample sequence set D', rather than take an unfeasibly long time to search the original sequence set D. Our motif discovery method is an approximate algorithm.

Effects of medical school selection on student motivation: a PhD thesis report.

PubMed

Wouters, Anouk

2018-02-01

High stakes are involved in student selection, for both medical schools and applicants. This thesis investigated the effects of selection on the medical student population and applicant pool in the Dutch setting. This thesis consists of six papers: two quantitative studies, one qualitative study, two mixed methods studies and one perspective paper based on a review of the literature. (1) Compared with a lottery, selection does not result in a student population with better motivation, engagement and performance, both in the clinical and pre-clinical phases of the study. (2) Selection seems to have a temporary stimulating effect on student motivation through enhancing perceived autonomy, competence and relatedness. (3) Applicants adopt a strategic approach, based on the selection procedure, in their choice of medical school. (4) The description of an applicant's motivation is not a reliable and valid tool to assess motivation during selection. (5) Gaining healthcare experience is crucial for applicants' motivation, but inequalities in access to such experiences can demotivate certain student groups from applying to medical school. (6) The gains yielded from selection compared with a lottery seem to be small. Unintentionally induced self-selection among certain groups of students and biased selection procedures may compromise student diversity. The added value of selection procedures compared with a weighted lottery for admitting students to medical school is questionable. Students are generally motivated and perform well, irrespective of how they enrolled in medical school. Selection yields only small gains, while student diversity may be hampered.

Regioselective alkane hydroxylation with a mutant CYP153A6 enzyme

DOEpatents

Koch, Daniel J.; Arnold, Frances H.

2013-01-29

Cytochrome P450 CYP153A6 from Myobacterium sp. strain HXN1500 was engineered using in-vivo directed evolution to hydroxylate small-chain alkanes regioselectively. Mutant CYP153A6-BMO1 selectively hydroxylates butane and pentane at the terminal carbon to form 1-butanol and 1-pentanol, respectively, at rates greater than wild-type CYP153A6 enzymes. This biocatalyst is highly active for small-chain alkane substrates and the regioselectivity is retained in whole-cell biotransformations.

Neonatal size and infant mortality at high altitude in the western Himalaya.

PubMed

Wiley, A S

1994-07-01

A prospective study was undertaken in Ladakh, India, a high-altitude region of the Himalaya, to investigate the effects of small average birth size on neonatal mortality. While such studies exist from high-altitude regions of the New World and shed light on the adaptive status of high-altitude-dwelling populations there, this is the first to examine this relationship in the Himalaya. In a sample of 168 newborns, birthweight and other anthropometric measurements were reduced relative to Andean and Tibetan newborns. Logistic regression and hazard analysis showed that neonatal biological characteristics such as weight, fatness, and circumferences were important predictors of survival probabilities of infants, especially in the neonatal period. Low Rohrer's Ponderal Index (PI) was particularly strongly related to poor survival outcome. Males and females showed no significant differences in mortality risk. Data derived from reproductive histories revealed that neonatal mortality accounted for 70-80% of total infant mortality in Ladakh. Compared to other high-altitude studies, small newborn size in Ladakh was associated with much higher mortality risks; mortality risk rose dramatically with birthweights below the mean (2,764 grams), which characterized 50% of all newborns. It is argued that newborns in Ladakh are subject to strong directional selective forces that favor higher birthweights that incur lower risks of neonatal mortality, while Andean infants are subject to relatively mild selection pressure at both ends of the birthweight distribution. Given the overall small size at birth of Ladakhi newborns and the poor survival outcomes of newborns below the mean, it is suggested that this population is less well adapted in a biological sense to the stresses inherent in this high-altitude environment than are Andean populations, perhaps due to the relatively recent colonization of the area and the substantial genetic admixture that has occurred in the past.

The Development of a Small High Speed Steam Microturbine Generator System

NASA Astrophysics Data System (ADS)

Alford, Adrian; Nichol, Philip; Frisby, Ben

2015-08-01

The efficient use of energy is paramount in every kind of business today. Steam is a widely used energy source. In many situations steam is generated at high pressures and then reduced in pressure through control valves before reaching point of use. An opportunity was identified to convert some of the energy at the point of pressure reduction into electricity. This can be accomplished using steam turbines driving alternators on large scale systems. To take advantage of a market identified for small scale systems, a microturbine generator was designed based on a small high speed turbo machine. This gave rise to a number of challenges which are described with the solutions adopted. The challenges included aerodynamic design of high efficiency impellers, sealing of a high speed shaft, thrust control and material selection to avoid steam erosion. The machine was packaged with a sophisticated control system to allow connection to the electricity grid. Some of the challenges in packaging the machine are also described. The Spirax Sarco TurboPower has now concluded performance and initial endurance tests which are described with a summary of the results.

A comparison of working in small-scale and large-scale nursing homes: A systematic review of quantitative and qualitative evidence.

PubMed

Vermeerbergen, Lander; Van Hootegem, Geert; Benders, Jos

2017-02-01

Ongoing shortages of care workers, together with an ageing population, make it of utmost importance to increase the quality of working life in nursing homes. Since the 1970s, normalised and small-scale nursing homes have been increasingly introduced to provide care in a family and homelike environment, potentially providing a richer work life for care workers as well as improved living conditions for residents. 'Normalised' refers to the opportunities given to residents to live in a manner as close as possible to the everyday life of persons not needing care. The study purpose is to provide a synthesis and overview of empirical research comparing the quality of working life - together with related work and health outcomes - of professional care workers in normalised small-scale nursing homes as compared to conventional large-scale ones. A systematic review of qualitative and quantitative studies. A systematic literature search (April 2015) was performed using the electronic databases Pubmed, Embase, PsycInfo, CINAHL and Web of Science. References and citations were tracked to identify additional, relevant studies. We identified 825 studies in the selected databases. After checking the inclusion and exclusion criteria, nine studies were selected for review. Two additional studies were selected after reference and citation tracking. Three studies were excluded after requesting more information on the research setting. The findings from the individual studies suggest that levels of job control and job demands (all but "time pressure") are higher in normalised small-scale homes than in conventional large-scale nursing homes. Additionally, some studies suggested that social support and work motivation are higher, while risks of burnout and mental strain are lower, in normalised small-scale nursing homes. Other studies found no differences or even opposing findings. The studies reviewed showed that these inconclusive findings can be attributed to care workers in some normalised small-scale homes experiencing isolation and too high job demands in their work roles. This systematic review suggests that normalised small-scale homes are a good starting point for creating a higher quality of working life in the nursing home sector. Higher job control enables care workers to manage higher job demands in normalised small-scale homes. However, some jobs would benefit from interventions to address care workers' perceptions of too low social support and of too high job demands. More research is needed to examine strategies to enhance these working life issues in normalised small-scale settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theoretical studies on FGFR isoform selectivity of FGFR1/FGFR4 inhibitors by molecular dynamics simulations and free energy calculations.

PubMed

Fu, Weitao; Chen, Lingfeng; Wang, Zhe; Kang, Yanting; Wu, Chao; Xia, Qinqin; Liu, Zhiguo; Zhou, Jianmin; Liang, Guang; Cai, Yuepiao

2017-02-01

The activation and overexpression of fibroblast growth factor receptors (FGFRs) are highly correlated with a variety of cancers. Most small molecule inhibitors of FGFRs selectively target FGFR1-3, but not FGFR4. Hence, designing highly selective inhibitors towards FGFR4 remains a great challenge because FGFR4 and FGFR1 have a high sequence identity. Recently, two small molecule inhibitors of FGFRs, ponatinib and AZD4547, have attracted huge attention. Ponatinib, a type II inhibitor, has high affinity towards FGFR1/4 isoforms, but AZD4547, a type I inhibitor of FGFR1, displays much reduced inhibition toward FGFR4. In this study, conventional molecular dynamics (MD) simulations, molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculations and umbrella sampling (US) simulations were carried out to reveal the principle of the binding preference of ponatinib and AZD4547 towards FGFR4/FGFR1. The results provided by MM/GBSA illustrate that ponatinib has similar binding affinities to FGFR4 and FGFR1, while AZD4547 has much stronger binding affinity to FGFR1 than to FGFR4. A comparison of the individual energy terms suggests that the selectivity of AZD4547 towards FGFR1 versus FGFR4 is primarily controlled by the variation of the van der Waals interactions. The US simulations reveal that the PMF profile of FGFR1/AZD4547 has more peaks and valleys compared with that of FGFR4/AZD4547, suggesting that the dissociation process of AZD4547 from FGFR1 are easily trapped into local minima. Moreover, it is observed that FGFR1/AZD4547 has much higher PMF depth than FGFR4/AZD4547, implying that it is more difficult for AZD4547 to escape from FGFR1 than from FGFR4. The physical principles provided by this study extend our understanding of the binding mechanisms and provide valuable guidance for the rational design of FGFR isoform selective inhibitors.

Analysis of Gas Membrane Ultra-High Purification of Small Quantities of Mono-Isotopic Silane

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

de Almeida, Valmor F.; Hart, Kevin J.

A small quantity of high-value, crude, mono-isotopic silane is a prospective gas for a small-scale, high-recovery, ultra-high membrane purification process. This is an unusual application of gas membrane separation for which we provide a comprehensive analysis of a simple purification model. The goal is to develop direct analytic expressions for estimating the feasibility and efficiency of the method, and guide process design; this is only possible for binary mixtures of silane in the dilute limit which is a somewhat realistic case. Among the common impurities in crude silane, methane poses a special membrane separation challenge since it is chemically similarmore » to silane. Other potential problematic surprises are: ethylene, diborane and ethane (in this order). Nevertheless, we demonstrate, theoretically, that a carefully designed membrane system may be able to purify mono-isotopic, crude silane to electronics-grade level in a reasonable amount of time and expenses. We advocate a combination of membrane materials that preferentially reject heavy impurities based on mobility selectivity, and light impurities based on solubility selectivity. We provide estimates for the purification of significant contaminants of interest. To improve the separation selectivity, it is advantageous to use a permeate chamber under vacuum, however this also requires greater control of in-leakage of impurities in the system. In this study, we suggest cellulose acetate and polydimethylsiloxane as examples of membrane materials on the basis of limited permeability data found in the open literature. We provide estimates on the membrane area needed and priming volume of the cell enclosure for fabrication purposes when using the suggested membrane materials. These estimates are largely theoretical in view of the absence of reliable experimental data for the permeability of silane. Last but not least, future extension of this work to the non-dilute limit may apply to the recovery of silane from rejected streams of natural silicon semi-conductor processes.« less

Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin with Current Modulation

PubMed Central

Hagen, Joshua A.; Kim, Sang N.; Bayraktaroglu, Burhan; Leedy, Kevin; Chávez, Jorge L.; Kelley-Loughnane, Nancy; Naik, Rajesh R.; Stone, Morley O.

2011-01-01

Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3′ terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels. PMID:22163977

Ligand-regulated peptide aptamers.

PubMed

Miller, Russell A

2009-01-01

The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain

PubMed Central

Lintner, Nathanael G.; McClure, Kim F.; Petersen, Donna; Londregan, Allyn T.; Piotrowski, David W.; Wei, Liuqing; Xiao, Jun; Bolt, Michael; Loria, Paula M.; Maguire, Bruce; Geoghegan, Kieran F.; Huang, Austin; Rolph, Tim; Liras, Spiros; Doudna, Jennifer A.; Dullea, Robert G.

2017-01-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts. PMID:28323820

Evaluating Gaze-Based Interface Tools to Facilitate Point-and-Select Tasks with Small Targets

ERIC Educational Resources Information Center

Skovsgaard, Henrik; Mateo, Julio C.; Hansen, John Paulin

2011-01-01

Gaze interaction affords hands-free control of computers. Pointing to and selecting small targets using gaze alone is difficult because of the limited accuracy of gaze pointing. This is the first experimental comparison of gaze-based interface tools for small-target (e.g. less than 12 x 12 pixels) point-and-select tasks. We conducted two…

40 CFR Appendix A to Subpart F of... - Sampling Plans for Selective Enforcement Auditing of Small Nonroad Engines

Code of Federal Regulations, 2010 CFR

2010-07-01

... Enforcement Auditing of Small Nonroad Engines A Appendix A to Subpart F of Part 90 Protection of Environment...-IGNITION ENGINES AT OR BELOW 19 KILOWATTS Selective Enforcement Auditing Pt. 90, Subpt. F, App. A Appendix A to Subpart F of Part 90—Sampling Plans for Selective Enforcement Auditing of Small Nonroad Engines...

High Impact Practices: Student Engagement and Retention

ERIC Educational Resources Information Center

Bonet, Giselle; Walters, Barbara R.

2016-01-01

Community college students face special challenges that can impede their academic progress, resulting in lower grades and persistence than students in selective four-year colleges. Kingsborough Community College in Brooklyn, New York, successfully addresses these challenges with learning communities: small cohorts of students in a blocked program…

Leadership Preparation in an Education Doctorate Program

ERIC Educational Resources Information Center

Ryerson, Dean

2011-01-01

This was a study of an education doctorate program at a small, private college. It examined the following nine components: theory of leadership for school improvement; candidate recruitment and selection based on leadership; coherent curriculum; use of active learning strategies; knowledgeable faculty; high quality internships; social and…

Sediment source detection by stable isotope analysis, carbon and nitrogen content and CSSI in a small river of the Swiss Plateau

NASA Astrophysics Data System (ADS)

SchindlerWildhaber, Yael; Alewell, Christine; Birkholz, Axel

2014-05-01

Suspended sediment (SS) and organic matter in rivers can harm the fauna by affecting health and fitness of free swimming fish and by causing siltation of the riverbed. The temporal and spatial dynamics of sediment, carbon (C) and nitrogen (N) during the brown trout spawning season in a small river of the Swiss Plateau were assessed and C isotopes as well as the C/N atomic ratio were used to distinguish autochthonous and allochthonous sources of organic matter in SS loads. The visual basic program IsoSource with 13Ctot and 15N as input isotopes was used to quantify the temporal and spatial sources of SS. We determined compound specific stable carbon isotopes (CSSI) in fatty acids of possible sediment source areas to the stream in addition and compared them to SS from selected high flow and low flow events. Organic matter concentrations in the infiltrated and suspended sediment were highest during low flow periods with small sediment loads and lowest during high flow periods with high sediment loads. Peak values in nitrate and dissolved organic C were measured during high flow and high rainfall, probably due to leaching from pasture and arable land. The organic matter was of allochthonous sources as indicated by the C/N atomic ratio and δ13Corg. Organic matter in SS increased from up- to downstream due to an increase in sediment delivery from pasture and arable land downstream of the river. While the major sources of SS are pasture and arable land during base flow conditions, SS from forest soils increased during heavy rain events and warmer winter periods most likely due to snow melt which triggered erosion. Preliminary results of CSSI analysis of sediment source areas and comparison to SS of selected events indicate that differences in d13C values of individual fatty acids are too small to differentiate unambiguously between sediment sources.

On the Use of Spreadsheet Algebra Programs in the Professional Development of Teachers from Selected Township High Schools

ERIC Educational Resources Information Center

Gierdien, M. Faaiz

2014-01-01

This paper reports on the initial stages of a small-scale project involving the use of "spreadsheet algebra programs" in the professional development of eight teachers from three township high schools. In terms of the education context, the paper draws on social practice theory. It then details what is meant by spreadsheet algebra. An…

Selection for low or high primary dormancy in Lolium rigidum Gaud seeds results in constitutive differences in stress protein expression and peroxidase activity

PubMed Central

Goggin, Danica E.; Powles, Stephen B.; Steadman, Kathryn J.

2011-01-01

Seed dormancy in wild Lolium rigidum Gaud (annual ryegrass) populations is highly variable and not well characterized at the biochemical level. To identify some of the determinants of dormancy level in these seeds, the proteomes of subpopulations selected for low and high levels of primary dormancy were compared by two-dimensional polyacrylamide gel electrophoresis of extracts from mature, dry seeds. High-dormancy seeds showed higher expression of small heat shock proteins, enolase, and glyoxalase I than the low-dormancy seeds. The functional relevance of these differences in protein expression was confirmed by the fact that high-dormancy seeds were more tolerant to high temperatures imposed at imbibition and had consistently higher glyoxalase I activity over 0–42 d dark stratification. Higher expression of a putative glutathione peroxidase in low-dormancy seeds was not accompanied by higher activity, but these seeds had a slightly more oxidized glutathione pool and higher total peroxidase activity. Overall, these biochemical and physiological differences suggest that L. rigidum seeds selected for low dormancy are more prepared for rapid germination via peroxidase-mediated cell wall weakening, whilst seeds selected for high dormancy are constitutively prepared to survive environmental stresses, even in the absence of stress during seed development. PMID:20974739

Iterative Refinement of a Binding Pocket Model: Active Computational Steering of Lead Optimization

PubMed Central

2012-01-01

Computational approaches for binding affinity prediction are most frequently demonstrated through cross-validation within a series of molecules or through performance shown on a blinded test set. Here, we show how such a system performs in an iterative, temporal lead optimization exercise. A series of gyrase inhibitors with known synthetic order formed the set of molecules that could be selected for “synthesis.” Beginning with a small number of molecules, based only on structures and activities, a model was constructed. Compound selection was done computationally, each time making five selections based on confident predictions of high activity and five selections based on a quantitative measure of three-dimensional structural novelty. Compound selection was followed by model refinement using the new data. Iterative computational candidate selection produced rapid improvements in selected compound activity, and incorporation of explicitly novel compounds uncovered much more diverse active inhibitors than strategies lacking active novelty selection. PMID:23046104

Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox Biology Applications.

PubMed

Jiang, Xiqian; Wang, Lingfei; Carroll, Shaina L; Chen, Jianwei; Wang, Meng C; Wang, Jin

2018-02-16

The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small-molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development, allowing more selective and quantitative detection of ROS/RNS, especially in live cells. Improvements have been made in sensing reactions, fluorophores, and bioavailability of probe molecules. In this review, we will not only summarize redox-related small-molecule fluorescent probes but also lay out the challenges of designing probes to help redox biologists independently evaluate the quality of reported small-molecule fluorescent probes, especially in the chemistry literature. We specifically highlight the advantages of reversibility in sensing reactions and its applications in ratiometric probe design for quantitative measurements in living cells. In addition, we compare the advantages and disadvantages of small-molecule probes and protein-based probes. The low physiological relevant concentrations of most ROS/RNS call for new sensing reactions with better selectivity, kinetics, and reversibility; fluorophores with high quantum yield, wide wavelength coverage, and Stokes shifts; and structural design with good aqueous solubility, membrane permeability, low protein interference, and organelle specificity. Antioxid. Redox Signal. 00, 000-000.

Preparation and composition of superconducting copper oxides based on Ga-O layers

DOEpatents

Dabrowski, B.; Vaughey, J.T.; Poeppelmeier, K.R.

1994-12-20

A high temperature superconducting material with the general formula GaSr[sub 2]Ln[sub 1[minus]x]M[sub x]Cu[sub 2]O[sub 7[+-]w] wherein Ln is selected from the group consisting of La, Ce, Pt, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Y and M is selected from the group consisting of C and Sr, 0.2[<=]x[<=]0.4 and w is a small fraction of one. A method of preparing this high temperature superconducting material is provided which includes heating and cooling a mixture to produce a crystalline material which is subsequently fired, ground and annealed at high pressure and temperature in oxygen to establish superconductivity. 14 figures.

An investigation and analysis of safety issues in Polish small construction plants.

PubMed

Dąbrowski, Andrzej

2015-01-01

The construction industry is a booming sector of the Polish economy; however, it is stigmatised by a lower classification due to high occupational risks and an unsatisfactory state of occupational safety. Safety on construction sites is compromised by small construction firms which dominate the market and have high accident rates. This article presents the results of studies (using a checklist) conducted in small Polish construction companies in terms of selected aspects of safety, such as co-operation with the general contractor, occupational health and safety documents, occupational risk assessment, organization of work, protective gear and general work equipment. The mentioned studies and analyses provided the grounds to establish the main directions of preventive measures decreasing occupational risk in small construction companies, e.g., an increase in engagement of investors and general contractors, improvement of occupational health and safety (OSH) documents, an increase in efficiency of construction site managers, better stability of employment and removal of opposing objectives between economic strategy and work safety.

An investigation and analysis of safety issues in Polish small construction plants

PubMed Central

Dąbrowski, Andrzej

2015-01-01

The construction industry is a booming sector of the Polish economy; however, it is stigmatised by a lower classification due to high occupational risks and an unsatisfactory state of occupational safety. Safety on construction sites is compromised by small construction firms which dominate the market and have high accident rates. This article presents the results of studies (using a checklist) conducted in small Polish construction companies in terms of selected aspects of safety, such as co-operation with the general contractor, occupational health and safety documents, occupational risk assessment, organization of work, protective gear and general work equipment. The mentioned studies and analyses provided the grounds to establish the main directions of preventive measures decreasing occupational risk in small construction companies, e.g., an increase in engagement of investors and general contractors, improvement of occupational health and safety (OSH) documents, an increase in efficiency of construction site managers, better stability of employment and removal of opposing objectives between economic strategy and work safety. PMID:26694002

Differentiation of flea communities infesting small mammals across selected habitats of the Baltic coast, central lowlands, and southern mountains of Poland.

PubMed

Kowalski, Krzysztof; Eichert, Urszula; Bogdziewicz, Michał; Rychlik, Leszek

2014-05-01

Only a few studies comparing flea composition on the coast and in the mountains have been conducted. We investigated differences in flea communities infesting small mammals in selected habitats in northern, central, and southern Poland. We predicted (1) a greater number of flea species in the southeastern Poland and a lower number in the north, (2) a greater number of flea species in fertile and wet habitats than in poor and arid habitats, and (3) a low similarity of flea species between flea communities in western and eastern Poland. We found a negative effect of increasing latitude on flea species richness. We suppose that the mountains providing a variety of environments and the limits of the geographic ranges of several flea subspecies in southeastern Poland result in a higher number of flea species. There was a positive effect of increasing wetness of habitat on flea species richness. We found a high diversity in flea species composition between western and eastern Poland (beta diversity = 11) and between central and eastern Poland (beta diversity = 12). Re-colonization of Poland by small mammals and their ectoparasites from different (western and eastern) refugees can affect on this high diversity of flea species.

Binary and ternary gas mixtures for use in glow discharge closing switches

DOEpatents

Hunter, Scott R.; Christophorou, Loucas G.

1990-01-01

Highly efficient binary and ternary gas mixtures for use in diffuse glow discharge closing switches are disclosed. The binary mixtures are combinations of helium or neon and selected perfluorides. The ternary mixtures are combinations of helium, neon, or argon, a selected perfluoride, and a small amount of gas that exhibits enhanced ionization characteristics. These mixtures are shown to be the optimum choices for use in diffuse glow discharge closing switches by virtue of the combined physio-electric properties of the mixture components.

Sexual selection is influenced by both developmental and adult environments.

PubMed

Gillespie, Stephanie R; Scarlett Tudor, M; Moore, Allen J; Miller, Christine W

2014-12-01

Sexual selection is often assumed to be strong and consistent, yet increasing research shows it can fluctuate over space and time. Few experimental studies have examined changes in sexual selection in response to natural environmental variation. Here, we use a difference in resource quality to test for the influence of past environmental conditions and current environmental conditions on male and female mate choice and resulting selection gradients for leaf-footed cactus bugs, Narnia femorata. We raised juveniles on natural high- and low-quality diets, cactus pads with and without ripe cactus fruits. New adults were again assigned a cactus pad with or without fruit, paired with a potential mate, and observed for mating behaviors. We found developmental and adult encounter environments affected mating decisions and the resulting patterns of sexual selection for both males and females. Males were not choosy in the low-quality encounter environment, cactus without fruit, but they avoided mating with small females in the high-quality encounter environment. Females were choosy in both encounter environments, avoiding mating with small males. However, they were the choosiest when they were in the low-quality encounter environment. Female mate choice was also context dependent by male developmental environment. Females were more likely to mate with males that had developed on cactus with fruit when they were currently in the cactus with fruit environment. This pattern disappeared when females were in the cactus without fruit environment. Altogether, these results experimentally demonstrate context-dependent mate choice by both males and females. Furthermore, we demonstrate that simple, seasonal changes in resources can lead to fluctuations in sexual selection. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Achieving Success in Small Business: A Self-Instruction Program for Small Business Owner-Managers. Improving Employee Selection, Training and Supervision.

ERIC Educational Resources Information Center

Virginia Polytechnic Inst. and State Univ., Blacksburg. Div. of Vocational-Technical Education.

This self-instructional module on improving employee selection, training, and supervision is the tenth in a set of twelve modules designed for small business owner-managers. Competencies for this module are (1) describe the three-step approach to selecting effective employees and (2) describe two of the most important characteristics possessed by…

Hyperspectral small animal fluorescence imaging: spectral selection imaging

NASA Astrophysics Data System (ADS)

Leavesley, Silas; Jiang, Yanan; Patsekin, Valery; Hall, Heidi; Vizard, Douglas; Robinson, J. Paul

2008-02-01

Molecular imaging is a rapidly growing area of research, fueled by needs in pharmaceutical drug-development for methods for high-throughput screening, pre-clinical and clinical screening for visualizing tumor growth and drug targeting, and a growing number of applications in the molecular biology fields. Small animal fluorescence imaging employs fluorescent probes to target molecular events in vivo, with a large number of molecular targeting probes readily available. The ease at which new targeting compounds can be developed, the short acquisition times, and the low cost (compared to microCT, MRI, or PET) makes fluorescence imaging attractive. However, small animal fluorescence imaging suffers from high optical scattering, absorption, and autofluorescence. Much of these problems can be overcome through multispectral imaging techniques, which collect images at different fluorescence emission wavelengths, followed by analysis, classification, and spectral deconvolution methods to isolate signals from fluorescence emission. We present an alternative to the current method, using hyperspectral excitation scanning (spectral selection imaging), a technique that allows excitation at any wavelength in the visible and near-infrared wavelength range. In many cases, excitation imaging may be more effective at identifying specific fluorescence signals because of the higher complexity of the fluorophore excitation spectrum. Because the excitation is filtered and not the emission, the resolution limit and image shift imposed by acousto-optic tunable filters have no effect on imager performance. We will discuss design of the imager, optimizing the imager for use in small animal fluorescence imaging, and application of spectral analysis and classification methods for identifying specific fluorescence signals.

A Highly Diastereoselective Oxidant Contributes to Ligninolysis by the White Rot Basidiomycete Ceriporiopsis subvermispora

Treesearch

Daniel J. Yelle; Alexander N. Kapich; Carl J. Houtman; Fachuang Lu; Vitaliy I. Timokhin; Raymond C. Fort Jr.; John Ralph; Kenneth E. Hammel

2014-01-01

The white rot basidiomycete Ceriporiopsis subvermispora delignifies wood selectively and has potential biotechnological applications. Its ability to remove lignin before the substrate porosity has increased enough to admit enzymes suggests that small diffusible oxidants contribute to delignification. A key question is whether these unidentified...

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

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

Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.

The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4,more » bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.« less

Vulnerability of age-0 pallid sturgeon Scaphirhynchus albus to predation; effects of predator type, turbidity, body size, and prey density

USGS Publications Warehouse

French, William E.; Graeb, Brian D. S.; Chipps, Steven R.; Klumb, Robert A.

2014-01-01

Predation can play an important role in the recruitment dynamics of fishes with intensity regulated by behavioral (i.e., prey selectivity) and/or environmental conditions that may be especially important for rare or endangered fishes. We conducted laboratory experiments to quantify prey selection and capture efficiency by three predators employing distinct foraging strategies: pelagic piscivore (walleye Sander vitreus); benthic piscivore (flathead catfish Pylodictis olivaris) and generalist predator (smallmouth bass Micropterus dolomieu) foraging on two size classes of age-0 pallid sturgeon: large (75–100 mm fork length [FL]) and small (40–50 mm FL). Experiments at high (> 70 nephalometric turbidity units [NTU]) and low (< 5 NTU) turbidity for each predator were conducted with high and low densities of pallid sturgeon and contrasting densities of an alternative prey, fathead minnow Pimephales promelas. Predator behaviors (strikes, captures, and consumed prey) were also quantified for each prey type. Walleye and smallmouth bass negatively selected pallid sturgeon (Chesson’s α = 0.04–0.1) across all treatments, indicating low relative vulnerability to predation. Relative vulnerability to predation by flathead catfish was moderate for small pallid sturgeon (α = 0.44, neutral selection), but low for large pallid sturgeon (α = 0.11, negative selection). Turbidity (up to 100 NTU) did not affect pallid sturgeon vulnerability, even at low density of alternative prey. Age-0 pallid sturgeon were easily captured by all predators, but were rarely consumed, suggesting mechanisms other than predator capture efficiency govern sturgeon predation vulnerability.

Ultrasmall visible-to-near-infrared emitting silver-sulfide quantum dots for cancer detection and imaging

NASA Astrophysics Data System (ADS)

Tang, Rui; Xu, Baogang; Shen, Duanwen; Sudlow, Gail; Achilefu, Samuel

2018-02-01

The large size of many near infrared (NIR) fluorescent nanoparticles prevents rapid extravasation from blood vessels and subsequent diffusion to tumors. This confines in vivo uptake to the peritumoral space and results in high liver retention. We developed a viscosity modulated approach to synthesize ultrasmall silver sulfide quantum dots (QDs) with distinct tunable light emission from visible to near-infrared in spectrum and a QD core diameter between less than 5 nm. Further functionalization of these Ag2S QDs with different type of molecules such as targeting peptides, retains monodisperse, relatively small water soluble QDs without loss of the functionality of the peptide's high binding affinity to cancerous tumor. Fluorescence and electron microscopy showed that selective integrin-mediated internalization was observed only in cancer cells treated with the peptide-labeled QDs, demonstrating that the unlabeled hydrophilic nanoparticles exhibit characteristics of negatively charged fluorescent dye molecules, which typically do not internalize in cells. The biodistribution profiles of intravenously administered QDs in different mouse models of cancer reveal an exceptionally high tumor-to-liver uptake ratio, suggesting that the small sized QDs evaded conventional opsonization and subsequent high uptake in the liver and spleen. The seamless tunability of the QDs over a wide spectral range with only a small increase in size, as well as the ease of labeling the bright and non-cytotoxic QDs with biomolecules, provides a platform for multiplexing information, tracking the trafficking of single molecules in cells, and selectively targeting disease biomarkers in living organisms without premature QD opsonization in circulating blood.

Spatial variation in selection on corolla shape in a generalist plant is promoted by the preference patterns of its local pollinators.

PubMed

Gómez, José M; Bosch, Jordi; Perfectti, Francisco; Fernández, J D; Abdelaziz, Mohamed; Camacho, J P M

2008-10-07

An adaptive role of corolla shape has been often asserted without an empirical demonstration of how natural selection acts on this trait. In generalist plants, in which flowers are visited by diverse pollinator fauna that commonly vary spatially, detecting pollinator-mediated selection on corolla shape is even more difficult. In this study, we explore the mechanisms promoting selection on corolla shape in the generalist crucifer Erysimum mediohispanicum Polatschek (Brassicaceae). We found that the main pollinators of E. mediohispanicum (large bees, small bees and bee flies) discriminate between different corolla shapes when offered artificial flowers without reward. Importantly, different pollinators prefer different shapes: bees prefer flowers with narrow petals, whereas bee flies prefer flowers with rounded overlapping petals. We also found that flowers with narrow petals (those preferred by bees) produce both more pollen and nectar than those with rounded petals. Finally, different plant populations were visited by different faunas. As a result, we found spatial variation in the selection acting on corolla shape. Selection favoured flowers with narrow petals in the populations where large or small bees are the most abundant pollinator groups. Our study suggests that pollinators, by preferring flowers with high reward, exert strong selection on the E. mediohispanicum corolla shape. The geographical variation in the pollinator-mediated selection on E. mediohispanicum corolla shape suggests that phenotypic evolution and diversification can occur in this complex floral trait even without specialization.

MAGNETIC METHOD FOR PRODUCING HIGH VELOCITY SHOCK WAVES IN GASES

DOEpatents

Josephson, V.

1960-01-26

A device is described for producing high-energy plasmas comprising a tapered shock tube of dielectric material and having a closed small end, an exceedingly low-inductance coll supported about and axially aligned with the small end of the tapered tube. an elongated multiturn coil supported upon the remninder of the exterior wall of the shock tube. a potential source and switch connected in series with the low-inductance coil, a potential source and switch connected in series with the elongated coil, means for hermetically sealing the large end of the tube, means for purging the tube of gases, and means for admitting a selected gas into the shock tube.

Habitat Selection Response of Small Pelagic Fish in Different Environments. Two Examples from the Oligotrophic Mediterranean Sea

PubMed Central

Bonanno, Angelo; Giannoulaki, Marianna; Barra, Marco; Basilone, Gualtiero; Machias, Athanassios; Genovese, Simona; Goncharov, Sergey; Popov, Sergey; Rumolo, Paola; Di Bitetto, Massimiliano; Aronica, Salvatore; Patti, Bernardo; Fontana, Ignazio; Giacalone, Giovanni; Ferreri, Rosalia; Buscaino, Giuseppa; Somarakis, Stylianos; Pyrounaki, Maria-Myrto; Tsoukali, Stavroula; Mazzola, Salvatore

2014-01-01

A number of scientific papers in the last few years singled out the influence of environmental conditions on the spatial distribution of fish species, highlighting the need for the fisheries scientific community to investigate, besides biomass estimates, also the habitat selection of commercially important fish species. The Mediterranean Sea, although generally oligotrophic, is characterized by high habitat variability and represents an ideal study area to investigate the adaptive behavior of small pelagics under different environmental conditions. In this study the habitat selection of European anchovy Engraulis encrasicolus and European sardine Sardina pilchardus is analyzed in two areas of the Mediterranean Sea that largely differentiate in terms of environmental regimes: the Strait of Sicily and the North Aegean Sea. A number of environmental parameters were used to investigate factors influencing anchovy and sardine habitat selection. Acoustic surveys data, collected during the summer period 2002–2010, were used for this purpose. The quotient analysis was used to identify the association between high density values and environmental variables; it was applied to the entire dataset in each area in order to identify similarities or differences in the “mean” spatial behavioral pattern for each species. Principal component analysis was applied to selected environmental variables in order to identify those environmental regimes which drive each of the two ecosystems. The analysis revealed the effect of food availability along with bottom depth selection on the spatial distribution of both species. Furthermore PCA results highlighted that observed selectivity for shallower waters is mainly associated to specific environmental processes that locally increase productivity. The common trends in habitat selection of the two species, as observed in the two regions although they present marked differences in hydrodynamics, seem to be driven by the oligotrophic character of the study areas, highlighting the role of areas where the local environmental regimes meet ‘the ocean triad hypothesis’. PMID:24992576

76 FR 16703 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... or cooperative research and development set aside for small business concerns shall be deemed an... SMALL BUSINESS ADMINISTRATION 13 CFR Parts 121, 124, 125, 126, and 127 [Docket No. SBA-2011-0006] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S...

76 FR 26948 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

...] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S... series of public meetings on the implementation of provisions of the Small Business Jobs Act of 2010... INFORMATION CONTACT: Richard L. Miller, Small Business Job's Act Tour-Office of Government Contracting and...

Small-mammal responses to pine regeneration treatments in the Ouachita Mountains of Arkansas and Oklahoma, USA

Treesearch

Roger W. Perry; Ronald E. Thill

2005-01-01

We compared the initial effects of four forest regeneration treatments (single-tree selection, group selection, shelterwood, and clearcut), and unharvested controls (mature, second-growth forest) on relative abundance of small mammals and small-mammal habitat throughout the Ouachita Mountains of western Arkansas and eastern Oklahoma. We compared small-mammal capture...

Supporting observation campaigns with high resolution modeling

NASA Astrophysics Data System (ADS)

Klocke, Daniel; Brueck, Matthias; Voigt, Aiko

2017-04-01

High resolution simulation in support of measurement campaigns offers a promising and emerging way to create large-scale context for small-scale observations of clouds and precipitation processes. As these simulation include the coupling of measured small-scale processes with the circulation, they also help to integrate the research communities from modeling and observations and allow for detailed model evaluations against dedicated observations. In connection with the measurement campaign NARVAL (August 2016 and December 2013) simulations with a grid-spacing of 2.5 km for the tropical Atlantic region (9000x3300 km), with local refinement to 1.2 km for the western part of the domain, were performed using the icosahedral non-hydrostatic (ICON) general circulation model. These simulations are again used to drive large eddy resolving simulations with the same model for selected days in the high definition clouds and precipitation for advancing climate prediction (HD(CP)2) project. The simulations are presented with the focus on selected results showing the benefit for the scientific communities doing atmospheric measurements and numerical modeling of climate and weather. Additionally, an outlook will be given on how similar simulations will support the NAWDEX measurement campaign in the North Atlantic and AC3 measurement campaign in the Arctic.

Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans

NASA Astrophysics Data System (ADS)

Zong, Yunbing; Yao, Shengkun; Crawford, Gary W.; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

2017-02-01

When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P.

Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans

PubMed Central

Zong, Yunbing; Yao, Shengkun; Crawford, Gary W.; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

2017-01-01

When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P. PMID:28240321

Selection for Oil Content During Soybean Domestication Revealed by X-Ray Tomography of Ancient Beans.

PubMed

Zong, Yunbing; Yao, Shengkun; Crawford, Gary W; Fang, Hui; Lang, Jianfeng; Fan, Jiadong; Sun, Zhibin; Liu, Yang; Zhang, Jianhua; Duan, Xiulan; Zhou, Guangzhao; Xiao, Tiqiao; Luan, Fengshi; Wang, Qing; Chen, Xuexiang; Jiang, Huaidong

2017-02-27

When and under what circumstances domestication related traits evolved in soybean (Glycine max) is not well understood. Seed size has been a focus of archaeological attention because increased soybean seed weight/size is a trait that distinguishes most modern soybeans from their ancestors; however, archaeological seed size analysis has had limited success. Modern domesticated soybean has a significantly higher oil content than its wild counterpart so oil content is potentially a source of new insight into soybean domestication. We investigated soybean oil content using X-ray computed tomography (CT; specifically, synchrotron radiation X-ray CT or SRX-CT) of charred, archaeological soybean seeds. CT identified holes in the specimens that are associated with oil content. A high oil content facilitates the development of small holes, whereas a high protein content results in larger holes. The volume of small holes increased slowly from 7,500 to 4,000 cal B.P. We infer that human selection for higher oil content began as early as 7,500 cal B.P. and that high oil content cultivars were well established by 4,000 cal B.P.

Aeromagnetic Expression of Buried Basaltic Volcanoes Near Yucca Mountain, Nevada

USGS Publications Warehouse

O'Leary, Dennis W.; Mankinen, E.A.; Blakely, R.J.; Langenheim, V.E.; Ponce, D.A.

2002-01-01

A high-resolution aeromagnetic survey has defined a number of small dipolar anomalies indicating the presence of magnetic bodies buried beneath the surface of Crater Flat and the Amargosa Desert. Results of potential-field modeling indicate that isolated, small-volume, highly magnetic bodies embedded within the alluvial deposits of both areas produce the anomalies. Their physical characteristics and the fact that they tend to be aligned along major structural trends provide strong support for the hypothesis that the anomalies reflect buried basaltic volcanic centers. Other, similar anomalies are identified as possible targets for further investigation. High-resolution gravity and ground-magnetic surveys, perhaps along with drilling sources of selected anomalies and radiometric age determinations, can provide valuable constraints in estimating potential volcanic hazard to the potential nuclear waste repository at Yucca Mountain.

GENERALITY OF THE MATCHING LAW AS A DESCRIPTOR OF SHOT SELECTION IN BASKETBALL

PubMed Central

Alferink, Larry A; Critchfield, Thomas S; Hitt, Jennifer L; Higgins, William J

2009-01-01

Based on a small sample of highly successful teams, past studies suggested that shot selection (two- vs. three-point field goals) in basketball corresponds to predictions of the generalized matching law. We examined the generality of this finding by evaluating shot selection of college (Study 1) and professional (Study 3) players. The matching law accounted for the majority of variance in shot selection, with undermatching and a bias for taking three-point shots. Shot-selection matching varied systematically for players who (a) were members of successful versus unsuccessful teams, (b) competed at different levels of collegiate play, and (c) served as regulars versus substitutes (Study 2). These findings suggest that the matching law is a robust descriptor of basketball shot selection, although the mechanism that produces matching is unknown. PMID:20190921

Kin groups and trait groups: population structure and epidemic disease selection.

PubMed

Fix, A G

1984-10-01

A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of extinction, individual selection, and migration and a population structure realistic in its general form, has implications for specific human polymorphisms such as hemoglobin variants and for the more general problem of the tempo of evolution as well.

Weak orientation and direction selectivity in lateral geniculate nucleus representing central vision in the gray squirrel Sciurus carolinensis

PubMed Central

Zaltsman, Julia B.; Heimel, J. Alexander

2015-01-01

Classic studies of lateral geniculate nucleus (LGN) and visual cortex (V1) in carnivores and primates have found that a majority of neurons in LGN exhibit a center-surround organization, while V1 neurons exhibit strong orientation selectivity and, in many species, direction selectivity. Recent work in the mouse and the monkey has discovered previously unknown classes of orientation- and direction-selective neurons in LGN. Furthermore, some recent studies in the mouse report that many LGN cells exhibit pronounced orientation biases that are of comparable strength to the subthreshold inputs to V1 neurons. These results raise the possibility that, in rodents, orientation biases of individual LGN cells make a substantial contribution to cortical orientation selectivity. Alternatively, the size and contribution of orientation- or direction-selective channels from LGN to V1 may vary across mammals. To address this question, we examined orientation and direction selectivity in LGN and V1 neurons of a highly visual diurnal rodent: the gray squirrel. In the representation of central vision, only a few LGN neurons exhibited strong orientation or direction selectivity. Across the population, LGN neurons showed weak orientation biases and were much less selective for orientation compared with V1 neurons. Although direction selectivity was weak overall, LGN layers 3abc, which contain neurons that express calbindin, exhibited elevated direction selectivity index values compared with LGN layers 1 and 2. These results suggest that, for central visual fields, the contribution of orientation- and direction-selective channels from the LGN to V1 is small in the squirrel. As in other mammals, this small contribution is elevated in the calbindin-positive layers of the LGN PMID:25717157

Advances in metaheuristics for gene selection and classification of microarray data.

PubMed

Duval, Béatrice; Hao, Jin-Kao

2010-01-01

Gene selection aims at identifying a (small) subset of informative genes from the initial data in order to obtain high predictive accuracy for classification. Gene selection can be considered as a combinatorial search problem and thus be conveniently handled with optimization methods. In this article, we summarize some recent developments of using metaheuristic-based methods within an embedded approach for gene selection. In particular, we put forward the importance and usefulness of integrating problem-specific knowledge into the search operators of such a method. To illustrate the point, we explain how ranking coefficients of a linear classifier such as support vector machine (SVM) can be profitably used to reinforce the search efficiency of Local Search and Evolutionary Search metaheuristic algorithms for gene selection and classification.

Conjugates of classical DNA/RNA binder with nucleobase: chemical, biochemical and biomedical applications.

PubMed

Saftic, Dijana; Ban, Zeljka; Matic, Josipa; Tumir, Lidija-Marija; Piantanida, Ivo

2018-05-07

Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class are nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder - nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of a small molecule as an initiator for interchain staudinger reaction: A new ATP sensing platform using product fluorescence.

PubMed

Yu, Huan; Zheng, Jing; Yang, Sheng; Asiri, Abdullah M; Alamry, Khalid A; Sun, Mingtai; Zhang, Kui; Wang, Suhua; Yang, Ronghua

2018-02-01

We demonstrated that a small molecule induced interchain Staudinger reaction can be employed for highly selective detection of adenosine triphosphate (ATP), an important energy-storage biomolecule. A designed ATP split aptamer (A1) was first functionalized with a weakly fluorescent coumarin derivative due to an azide group (azido-coumarin). The second DNA strand (A2) was covalently linked with triphenylphosphine, which could selectively and efficiently reduce azido to amino group through the Staudinger reaction. The A2 was then hybridized with a half of another designed longer DNA strand (T1). The second half of T1 was a split aptamer and selectively recognized ATP with A1 to form a sandwich structure. The specific interaction between ATP and the aptamers drew the two functionalized DNA strands (A1 and A2) together to initiate the interchain Staudinger reduction at fmol-nmol concentration level, hence produced fluorescent 7-aminocoumarin which could be used as an indicator for the presence of trace ATP. The reaction process had a concentration dependent manner with ATP in a large concentration range. Such a strategy of interchain Staudinger reaction can be extended to construct biosensors for other small functional molecules on the basis of judiciously designed aptamers. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2

NASA Astrophysics Data System (ADS)

Kalinić, Marko; Zloh, Mire; Erić, Slavica

2014-11-01

Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein-ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2.

Model selection bias and Freedman's paradox

USGS Publications Warehouse

Lukacs, P.M.; Burnham, K.P.; Anderson, D.R.

2010-01-01

In situations where limited knowledge of a system exists and the ratio of data points to variables is small, variable selection methods can often be misleading. Freedman (Am Stat 37:152-155, 1983) demonstrated how common it is to select completely unrelated variables as highly "significant" when the number of data points is similar in magnitude to the number of variables. A new type of model averaging estimator based on model selection with Akaike's AIC is used with linear regression to investigate the problems of likely inclusion of spurious effects and model selection bias, the bias introduced while using the data to select a single seemingly "best" model from a (often large) set of models employing many predictor variables. The new model averaging estimator helps reduce these problems and provides confidence interval coverage at the nominal level while traditional stepwise selection has poor inferential properties. ?? The Institute of Statistical Mathematics, Tokyo 2009.

Investigation of NO(x) Removal from Small Engine Exhaust

NASA Technical Reports Server (NTRS)

Akyurtlu, Ates; Akyurtlu, Jale F.

1999-01-01

Contribution of emissions from small engines to the air pollution is significant. Due to differences in operating conditions and economics, the pollution control systems designed for automobiles will be neither suitable nor economically feasible for use on small engines. The objective of this project was to find a catalyst for the removal of NOx from the exhaust of small engines which use a rich air to fuel ratio. The desired catalyst should be inexpensive so that the cost of the pollution control unit will be only a small fraction of the total equipment cost. The high cost of noble metals makes them too expensive for use as NOx catalyst for small engines. Catalytic reduction of NO can also be accomplished by base-metal oxide catalysts. The main disadvantage of base-metal catalysts is their deactivation by poisons and high temperatures. Requirements for the length of the life of the small engine exhaust catalysts are much less than those for automobile exhaust catalysts. Since there is no oxygen in the exhaust gases, reduction selectivity is not a problem. Also, the reducing exhaust gases might help prevent the harmful interactions of the catalyst with the support. For these reasons only the supported metal oxide catalysts were investigated in this project.

Investigation of NOx Removal from Small Engine Exhaust

NASA Technical Reports Server (NTRS)

Akyurtlu, Ates; Akyurtlu, Jale F.

1999-01-01

Contribution of emissions from small engines to the air pollution is significant. Due to differences in operating conditions and economics, the pollution control systems designed for automobiles will be neither suitable nor economically feasible for use on small engines. The objective of this project was to find a catalyst for the removal of NOx from the exhaust of small engines which use a rich air to fuel ratio. The desired catalyst should be inexpensive so that the cost of the pollution control unit will be only a small fraction of the total equipment cost. The high cost of noble metals makes them too expensive for use as NOx catalyst for small engines. Catalytic reduction of Nitrogen Oxide (NO) can also be accomplished by base-metal oxide catalysts. The main disadvantage of base-metal catalysts is their deactivation by poisons and high temperatures. Requirements for the length of the life of the small engine exhaust catalysts are much less than those for automobile exhaust catalysts. Since there is no oxygen in the exhaust gases, reduction selectivity is not a problem. Also, the reducing exhaust gases might help prevent the harmful interactions of the catalyst with the support. For these reasons only the supported metal oxide catalysts were investigated in this project.

Competitive Selection from Single Domain Antibody Libraries Allows Isolation of High-Affinity Antihapten Antibodies That Are Not Favored in the llama Immune Response

PubMed Central

Rosa, Sofia Tabares-da; Rossotti, Martin; Carleiza, Carmen; Carrión, Federico; Pritsch, Otto; Ahn, Ki Chang; Last, Jerold A.; Hammock, Bruce D; González-Sapienza, Gualberto

2011-01-01

Single-domain antibodies (sdAbs) found in camelids, lack a light chain and their antigen-binding site sits completely in the heavy-chain variable domain (VHH). Their simplicity, thermostability, and ease in expression have made VHHs highly attractive. While this has been successfully exploited for macromolecular antigens, their application to the detection of small molecules is still limited to a very few reports, mostly describing low affinity VHHs. Using triclocarban (TCC) as a model hapten, we found that conventional antibodies, IgG1 fraction, reacted with free TCC with a higher relative affinity (IC50 51.0 ng/mL) than did the sdAbs (IgG2 and IgG3, 497 and 370 ng/mL, respectively). A VHH library was prepared, and by elution of phage with limiting concentrations of TCC and competitive selection of binders, we were able to isolate high-affinity clones, KD 0.98–1.37 nM (SPR) which allowed development of a competitive assay for TCC with an IC50 = 3.5 ng/mL (11 nM). This represents a 100-fold improvement with regard to the performance of the sdAb serum fraction, and it is 100-fold better than the IC50 attained with other anti-hapten VHHs reported thus far. Despite the modest overall anti-hapten sdAbs response in llamas, a small subpopulation of high affinity VHHs are generated that can be isolated by carefully design of the selection process. PMID:21827167

Comm for Small Sats: The Lunar Atmosphere and Dust Environment Explorer (LADEE) Communications Subsystem

NASA Technical Reports Server (NTRS)

Kuroda, Vanessa M.; Allard, Mark R.; Lewis, Brian; Lindsay, Michael

2014-01-01

September 6, 2013 through April 21, 2014 marked the mission lifecycle of the highly successful LADEE (Lunar Atmosphere and Dust Environment Explorer) mission that orbited the moon to gather detailed information about the thin lunar atmosphere. This paper will address the development, risks, and lessons learned regarding the specification, selection, and deployment of LADEE's unique Radio Frequency based communications subsystem and supporting tools. This includes the Electronic Ground Support Equipment (EGSE), test regimes, and RF dynamic link analysis environment developed to meet mission requirements for small, flexible, low cost, high performance, fast turnaround, and reusable spacecraft communication capabilities with easy and reliable application to future similar low cost small satellite missions over widely varying needs for communications and communications system complexity. LADEE communication subsystem key components, architecture, and mission performance will be reviewed toward applicability for future mission planning, design, and utilization.

Laser-induced fluorescence spectroscopy in tissue local necrosis detection

NASA Astrophysics Data System (ADS)

Cip, Ondrej; Buchta, Zdenek; Lesundak, Adam; Randula, Antonin; Mikel, Bretislav; Lazar, Josef; Veverkova, Lenka

2014-03-01

The recent effort leads to reliable imaging techniques which can help to a surgeon during operations. The fluorescence spectroscopy was selected as very useful online in vivo imaging method to organics and biological materials analysis. The presented work scopes to a laser induced fluorescence spectroscopy technique to detect tissue local necrosis in small intestine surgery. In first experiments, we tested tissue auto-fluorescence technique but a signal-to-noise ratio didn't express significant results. Then we applied a contrast dye - IndoCyanine Green (ICG) which absorbs and emits wavelengths in the near IR. We arranged the pilot experimental setup based on highly coherent extended cavity diode laser (ECDL) used for stimulating of some critical areas of the small intestine tissue with injected ICG dye. We demonstrated the distribution of the ICG exciter with the first file of shots of small intestine tissue of a rabbit that was captured by high sensitivity fluorescent cam.

Sirenum Fossae Trough

NASA Technical Reports Server (NTRS)

2000-01-01

[figure removed for brevity, see original site]

The Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) orbits the red planet twelve times each day. The number of pictures that MOC can take varies from orbit to orbit, depending upon whether the data are being stored in MGS's onboard tape recorder for playback at a later time, or whether the data are being sent directly back to Earth via a real-time radio link. More data can be acquired during orbits with real-time downlink.

During real-time orbits, the MOC team often will take a few random or semi-random pictures in between the carefully-selected, hand-targeted images. On rare occasions, one of these random pictures will surprise the MOC team. The picture shown here is an excellent example, because the high resolution view (top) is centered so nicely on a trough and an adjacent, shallow crater that it is as if someone very carefully selected the target for MOC. The high-resolution view covers an area only 1.1 km (0.7 mi) wide by 2.3 km (1.4 mi) long. Hitting a target such as this with such a small image is very difficult to do, on purpose, because there are small uncertainties in the predicted orbit, the maps used to select targets, and the minor adjustments of spacecraft pointing at any given moment. Nevertheless, a very impressive image was received.

The high resolution view crosses one of the troughs of the Sirenum Fossae near 31.2oS, 152.3oW. The context image (above) was acquired at the same time as the high resolution view on July 23, 2000. The small white box shows the location of the high resolution picture. The lines running diagonally across the context image from upper right toward lower left are the Sirenum Fossae troughs, formed by faults that are radial to the volcanic region of Tharsis. Both pictures are illuminated from the upper left. The scene shows part of the martian southern hemisphere nearly autumn.

Risk selection and risk adjustment: improving insurance in the individual and small group markets.

PubMed

Baicker, Katherine; Dow, William H

2009-01-01

Insurance market reforms face the key challenge of addressing the threat that risk selection poses to the availability, of stable, high-value insurance policies that provide long-term risk protection. Many of the strategies in use today fail to address this breakdown in risk pooling, and some even exacerbate it. Flexible risk adjustment schemes are a promising avenue for promoting market stability and limiting insurer cream-skimming, potentially providing greater benefits at lower cost. Reforms intended to increase insurance coverage and the value of care delivered will be much more effective if implemented in conjunction with policies that address these fundamental selection issues.

The LILIA experiment: Energy selection and post-acceleration of laser generated protons

NASA Astrophysics Data System (ADS)

Turchetti, Giorgio; Sinigardi, Stefano; Londrillo, Pasquale; Rossi, Francesco; Sumini, Marco; Giove, Dario; De Martinis, Carlo

2012-12-01

The LILIA experiment is planned at the SPARCLAB facility of the Frascati INFN laboratories. We have simulated the laser acceleration of protons, the transport and energy selection with collimators and a pulsed solenoid and the post-acceleration with a compact high field linac. For the highest achievable intensity corresponding to a = 30 over 108 protons at 30 MeV with a 3% spread are selected, and at least107 protons are post-accelerated up to 60 MeV. If a 10 Hz repetition rated can be achieved the delivered dose would be suitable for the treatment of small superficial tumors.

Qualitative medical sociology: what are its crowning achievements?

PubMed Central

Chard, J A; Lilford, R J; Court, B V

1997-01-01

Doctors and epidemiologists seldom read or cite qualitative medical sociology; it is little published in medical journals. A large number of articles bewail this lack and provide arguments explaining and justifying the subject. Any examples used in such articles are selected ad hoc. We made a systematic search for the literature and used citation analysis to select the world's top 100 articles. We analysed this trawl and provide resumés of a selection from the 'classics'. Mental health and the organization of medicine are the themes within medical sociology with highest impact. Much highly cited work consists of historical and theoretical analysis done 'at the desk' rather than observation or interview 'in the field'. Citation rates, even for the most famous works in medical sociology, are a small fraction of those for high impact biomedical research. PMID:9496271

Prediction-Oriented Marker Selection (PROMISE): With Application to High-Dimensional Regression.

PubMed

Kim, Soyeon; Baladandayuthapani, Veerabhadran; Lee, J Jack

2017-06-01

In personalized medicine, biomarkers are used to select therapies with the highest likelihood of success based on an individual patient's biomarker/genomic profile. Two goals are to choose important biomarkers that accurately predict treatment outcomes and to cull unimportant biomarkers to reduce the cost of biological and clinical verifications. These goals are challenging due to the high dimensionality of genomic data. Variable selection methods based on penalized regression (e.g., the lasso and elastic net) have yielded promising results. However, selecting the right amount of penalization is critical to simultaneously achieving these two goals. Standard approaches based on cross-validation (CV) typically provide high prediction accuracy with high true positive rates but at the cost of too many false positives. Alternatively, stability selection (SS) controls the number of false positives, but at the cost of yielding too few true positives. To circumvent these issues, we propose prediction-oriented marker selection (PROMISE), which combines SS with CV to conflate the advantages of both methods. Our application of PROMISE with the lasso and elastic net in data analysis shows that, compared to CV, PROMISE produces sparse solutions, few false positives, and small type I + type II error, and maintains good prediction accuracy, with a marginal decrease in the true positive rates. Compared to SS, PROMISE offers better prediction accuracy and true positive rates. In summary, PROMISE can be applied in many fields to select regularization parameters when the goals are to minimize false positives and maximize prediction accuracy.

Method for carbon dioxide sequestration

DOEpatents

Wang, Yifeng; Bryan, Charles R.; Dewers, Thomas; Heath, Jason E.

2015-09-22

A method for geo-sequestration of a carbon dioxide includes selection of a target water-laden geological formation with low-permeability interbeds, providing an injection well into the formation and injecting supercritical carbon dioxide (SC--CO.sub.2) into the injection well under conditions of temperature, pressure and density selected to cause the fluid to enter the formation and splinter and/or form immobilized ganglia within the formation. This process allows for the immobilization of the injected SC--CO.sub.2 for very long times. The dispersal of scCO2 into small ganglia is accomplished by alternating injection of SC--CO.sub.2 and water. The injection rate is required to be high enough to ensure the SC--CO.sub.2 at the advancing front to be broken into pieces and small enough for immobilization through viscous instability.

Discovery and Validation of a Series of Aryl Sulfonamides as Selective Inhibitors of Tissue-Nonspecific Alkaline Phosphatase (TNAP)

PubMed Central

Dahl, Russell; Sergienko, Eduard A.; Mostofi, Yalda S.; Yang, Li; Su, Ying; Simao, Ana Maria; Narisawa, Sonoko; Brown, Brock; Mangravita-Novo, Arianna; Vicchiarelli, Michael; Smith, Layton H.; O’Neill, W. Charles; Millán, José Luis; Cosford, Nicholas D. P.

2009-01-01

We report the characterization and optimization of drug-like small molecule inhibitors of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme critical for the regulation of extracellular matrix calcification during bone formation and growth. High-throughput screening (HTS) of a small molecule library led to the identification of arylsulfonamides as potent and selective inhibitors of TNAP. Critical structural requirements for activity were determined, and the compounds were subsequently profiled for in vitro activity and bioavailability parameters including metabolic stability and permeability. The plasma levels following subcutaneous administration of a member of the lead series in rat was determined, demonstrating the potential of these TNAP inhibitors as systemically active therapeutic agents to target various diseases involving soft tissue calcification. A representative member of the series was also characterized in mechanistic and kinetic studies. PMID:19821572

Selection methods for resistance to and tolerance of helminths in livestock.

PubMed

McManus, Concepta; do Prado Paim, Tiago; de Melo, Cristiano Barros; Brasil, Bruno S A F; Paiva, Samuel R

2014-01-01

Helminthiases are among the most important livestock diseases worldwide, in particular for small ruminants, which are the focus of this review. Resource Allocation Theory implies that high-productivity farm animals proportionate insufficient resources for adequate coping with stressful conditions. Significant differences between breeds and within breeds are seen, as well as genotype vs. environment interactions. With improvement of genetic host resistance to infection, transmission of infection will be impacted. On the other hand, genetic improvement of resilience can lead to a reduction in clinical signs of disease, but not necessarily reduce transmission of infection to other animals. Faecal egg count (FEC) is the main measurement used to evaluate helminthiasis load, despite the fact that the protocols and analytical methods can affect the results, and the FEC data frequently shows aggregative, negative skewed distribution, and a high coefficient of variation. Mass selection where heritability is generally medium to low generally produces slow results and low economic returns. Many studies have been published linking resistance to nematodes in livestock to Quantitative Trait Loci and most studies have concentrated on chromosomes where the major histocompatibility complex region is located. Nevertheless, these complex traits have been seen to be affected by thousands of variants that each has a small effect. More recent studies have shown that genome-wide selection strategies can be useful in selecting animals for improved production and resistance traits in this case. © C. McManus et al., published by EDP Sciences, 2014.

High-throughput screening identifies Ceefourin 1 and Ceefourin 2 as highly selective inhibitors of multidrug resistance protein 4 (MRP4).

PubMed

Cheung, Leanna; Flemming, Claudia L; Watt, Fujiko; Masada, Nanako; Yu, Denise M T; Huynh, Tony; Conseil, Gwenaëlle; Tivnan, Amanda; Polinsky, Alexander; Gudkov, Andrei V; Munoz, Marcia A; Vishvanath, Anasuya; Cooper, Dermot M F; Henderson, Michelle J; Cole, Susan P C; Fletcher, Jamie I; Haber, Michelle; Norris, Murray D

2014-09-01

Multidrug resistance protein 4 (MRP4/ABCC4), a member of the ATP-binding cassette (ABC) transporter superfamily, is an organic anion transporter capable of effluxing a wide range of physiologically important signalling molecules and drugs. MRP4 has been proposed to contribute to numerous functions in both health and disease; however, in most cases these links remain to be unequivocally established. A major limitation to understanding the physiological and pharmacological roles of MRP4 has been the absence of specific small molecule inhibitors, with the majority of established inhibitors also targeting other ABC transporter family members, or inhibiting the production, function or degradation of important MRP4 substrates. We therefore set out to identify more selective and well tolerated inhibitors of MRP4 that might be used to study the many proposed functions of this transporter. Using high-throughput screening, we identified two chemically distinct small molecules, Ceefourin 1 and Ceefourin 2, that inhibit transport of a broad range of MRP4 substrates, yet are highly selective for MRP4 over other ABC transporters, including P-glycoprotein (P-gp), ABCG2 (Breast Cancer Resistance Protein; BCRP) and MRP1 (multidrug resistance protein 1; ABCC1). Both compounds are more potent MRP4 inhibitors in cellular assays than the most widely used inhibitor, MK-571, requiring lower concentrations to effect a comparable level of inhibition. Furthermore, Ceefourin 1 and Ceefourin 2 have low cellular toxicity, and high microsomal and acid stability. These newly identified inhibitors should be of great value for efforts to better understand the biological roles of MRP4, and may represent classes of compounds with therapeutic application. Copyright © 2014 Elsevier Inc. All rights reserved.

Population differentiation in Pacific salmon: local adaptation, genetic drift, or the environment?

USGS Publications Warehouse

Adkison, Milo D.

1995-01-01

Morphological, behavioral, and life-history differences between Pacific salmon (Oncorhynchus spp.) populations are commonly thought to reflect local adaptation, and it is likewise common to assume that salmon populations separated by small distances are locally adapted. Two alternatives to local adaptation exist: random genetic differentiation owing to genetic drift and founder events, and genetic homogeneity among populations, in which differences reflect differential trait expression in differing environments. Population genetics theory and simulations suggest that both alternatives are possible. With selectively neutral alleles, genetic drift can result in random differentiation despite many strays per generation. Even weak selection can prevent genetic drift in stable populations; however, founder effects can result in random differentiation despite selective pressures. Overlapping generations reduce the potential for random differentiation. Genetic homogeneity can occur despite differences in selective regimes when straying rates are high. In sum, localized differences in selection should not always result in local adaptation. Local adaptation is favored when population sizes are large and stable, selection is consistent over large areas, selective diffeentials are large, and straying rates are neither too high nor too low. Consideration of alternatives to local adaptation would improve both biological research and salmon conservation efforts.

Short human occupations in the Middle Palaeolithic level i of the Abric Romani rock-shelter (Capellades, Barcelona, Spain)

USGS Publications Warehouse

Vallerdu, J.; Allue, E.; Bischoff, J.L.; Caceres, I.; Carbonell, E.; Cebria, A.; Garcia-Anton, D.; Huguet, R.; Ibanez, N.; Martinez, K.; Pasto, I.; Rosell, J.; Saladie, P.; Vaquero, Manola

2005-01-01

The small occupation surfaces and restricted provisioning strategies suggest short settlements in the Abric Romani. This shorter occupation model complements the longer diversified provisioning strategy recorded in both small and medium-sized occupied surfaces. The selection of precise elements for transport and the possible deferred consumption in the diversified provision strategy suggest an individual supply. In this respect, Neanderthal occupations in the Romani rock-shelter show a direct relation to: 1) hunting strategic resources; 2) high, linear mobility.

Evaluation of two main RNA-seq approaches for gene quantification in clinical RNA sequencing: polyA+ selection versus rRNA depletion.

PubMed

Zhao, Shanrong; Zhang, Ying; Gamini, Ramya; Zhang, Baohong; von Schack, David

2018-03-19

To allow efficient transcript/gene detection, highly abundant ribosomal RNAs (rRNA) are generally removed from total RNA either by positive polyA+ selection or by rRNA depletion (negative selection) before sequencing. Comparisons between the two methods have been carried out by various groups, but the assessments have relied largely on non-clinical samples. In this study, we evaluated these two RNA sequencing approaches using human blood and colon tissue samples. Our analyses showed that rRNA depletion captured more unique transcriptome features, whereas polyA+ selection outperformed rRNA depletion with higher exonic coverage and better accuracy of gene quantification. For blood- and colon-derived RNAs, we found that 220% and 50% more reads, respectively, would have to be sequenced to achieve the same level of exonic coverage in the rRNA depletion method compared with the polyA+ selection method. Therefore, in most cases we strongly recommend polyA+ selection over rRNA depletion for gene quantification in clinical RNA sequencing. Our evaluation revealed that a small number of lncRNAs and small RNAs made up a large fraction of the reads in the rRNA depletion RNA sequencing data. Thus, we recommend that these RNAs are specifically depleted to improve the sequencing depth of the remaining RNAs.

Successes of Small Business Innovation Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Kim, Walter S.; Bitler, Dean W.; Prok, George M.; Metzger, Marie E.; Dreibelbis, Cindy L.; Ganss, Meghan

2002-01-01

This booklet of success stories highlights the NASA Glenn Research Center's accomplishments and successes by the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs. These success stories are the results of selecting projects that support NASA missions and also have high commercialization potential. Each success story describes the innovation accomplished, commercialization of the technology, and further applications and usages. This booklet emphasizes the integration and incorporation of technologies into NASA missions and other government projects. The company name and the NASA contact person are identified to encourage further usage and application of the SBIR developed technologies and also to promote further commercialization of these products.

Life-history strategies associated with local population variability confer regional stability.

PubMed

Pribil, Stanislav; Houlahan, Jeff E

2003-07-07

A widely held ecological tenet is that, at the local scale, populations of K-selected species (i.e. low fecundity, long lifespan and large body size) will be less variable than populations of r-selected species (i.e. high fecundity, short lifespan and small body size). We examined the relationship between long-term population trends and life-history attributes for 185 bird species in the Czech Republic and found that, at regional spatial scales and over moderate temporal scales (100-120 years), K-selected bird species were more likely to show both large increases and decreases in population size than r-selected species. We conclude that life-history attributes commonly associated with variable populations at the local scale, confer stability at the regional scale.

Risk for highly pathogenic avian influenza H5N1 virus infection in chickens in small-scale commercial farms, in a high-risk area, Bangladesh, 2008.

PubMed

Biswas, P K; Rahman, M H; Das, A; Ahmed, S S U; Giasuddin, M; Christensen, J P

2011-12-01

Small-scale commercial chicken farms (FAO-defined system 3) with poor biosecurity predominate in developing countries including Bangladesh. By enroling fifteen highly pathogenic avian influenza (HPAI) cases occurring in such farms - (February - April 2008) and 45 control farms (March-May 2008) with similar set up, we conducted a case-control study to evaluate the risk factors associated with HPAI H5N1 virus infections in chickens reared in small-scale commercial farms in a spatially high-risk area in Bangladesh. Data collected by a questionnaire from the selected farms were analysed by univariable analysis and multivariable conditional logistic regression. The risk factors independently associated were 'dead crow seen at or near farm' [odds ratio (OR) 47.4, 95% confidence interval (CI) 4.7-480.3, P = 0.001], 'exchanging eggtrays with market vendors' (OR 20.4, 95% CI 1.9-225.5, P = 0.014) and 'mortality seen in backyard chicken reared nearby' (OR 19.4, 95% CI 2.8-131.9, P = 0.002). These observations suggest that improved biosecurity might reduce the occurrence of HPAI outbreaks in small-scale commercial farms in Bangladesh. © 2011 Blackwell Verlag GmbH.

Public reporting and market area exit decisions by home health agencies.

PubMed

Jung, Kyoungrae; Feldman, Roger

2012-01-01

To examine whether home health agencies selectively discontinue services to areas with socio-economically disadvantaged people after the introduction of Home Health Compare (HHC), a public reporting program initiated by Medicare in 2003. We focused on agencies' initial responses to HHC and examined selective market-area exits by agencies between 2002 and 2004. We measured HHC effects by the percentage of quality indicators reported in public HHC data in 2003. Socio-economic status was measured by per capita income and percent college-educated at the market-area level. 2002 and 2004 Outcome and Assessment Information Set (OASIS); 2000 US Census file; 2004 Area Resource File; and 2002 Provider of Service File. WE FOUND A SMALL AND WEAK EFFECT OF PUBLIC REPORTING ON SELECTIVE EXITS: a 10-percent increase in reporting (reporting one more indicator) increased the probability of leaving an area with less-educated people by 0.3 percentage points, compared with leaving an area with high education. The small level of market-area exits under public reporting is unlikely to be practically meaningful, suggesting that HHC did not lead to a disruption in access to home health care through selective exits during the initial year of the program.

Design and performance investigation of a highly accurate apodized fiber Bragg grating-based strain sensor in single and quasi-distributed systems.

PubMed

Ali, Taha A; Shehata, Mohamed I; Mohamed, Nazmi A

2015-06-01

In this work, fiber Bragg grating (FBG) strain sensors in single and quasi-distributed systems are investigated, seeking high-accuracy measurement. Since FBG-based strain sensors of small lengths are preferred in medical applications, and that causes the full width at half-maximum (FWHM) to be larger, a new apodization profile is introduced for the first time, to the best of our knowledge, with a remarkable FWHM at small sensor lengths compared to the Gaussian and Nuttall profiles, in addition to a higher mainlobe slope at these lengths. A careful selection of apodization profiles with detailed investigation is performed-using sidelobe analysis and the FWHM, which are primary judgment factors especially in a quasi-distributed configuration. A comparison between the elite selection of apodization profiles (extracted from related literature) and the proposed new profile is carried out covering the reflectivity peak, FWHM, and sidelobe analysis. The optimization process concludes that the proposed new profile with a chosen small length (L) of 10 mm and Δn_ac of 1.4×10^-4 is the optimum choice for single stage and quasi-distributed strain-sensor networks, even better than the Gaussian profile at small sensor lengths. The proposed profile achieves the smallest FWHM of 15 GHz (suitable for UDWDM), and the highest mainlobe slope of 130 dB/nm. For the quasi-distributed scenario, a noteworthy high isolation of 6.953 dB is achieved while applying a high strain value of 1500 μstrain (με) for a five-stage strain-sensing network. Further investigation was undertaken, proving that consistency in choosing the apodization profile in the quasi-distributed network is mandatory. A test was made of the inclusion of a uniform apodized sensor among other apodized sensors with the proposed profile in an FBG strain-sensor network.

Microwave absorption in powders of small conducting particles for heating applications.

PubMed

Porch, Adrian; Slocombe, Daniel; Edwards, Peter P

2013-02-28

In microwave chemistry there is a common misconception that small, highly conducting particles heat profusely when placed in a large microwave electric field. However, this is not the case; with the simple physical explanation that the electric field (which drives the heating) within a highly conducting particle is highly screened. Instead, it is the magnetic absorption associated with induction that accounts for the large experimental heating rates observed for small metal particles. We present simple principles for the effective heating of particles in microwave fields from calculations of electric and magnetic dipole absorptions for a range of practical values of particle size and conductivity. For highly conducting particles, magnetic absorption dominates electric absorption over a wide range of particle radii, with an optimum absorption set by the ratio of mean particle radius a to the skin depth δ (specifically, by the condition a = 2.41δ). This means that for particles of any conductivity, optimized magnetic absorption (and hence microwave heating by magnetic induction) can be achieved by simple selection of the mean particle size. For weakly conducting samples, electric dipole absorption dominates, and is maximized when the conductivity is approximately σ ≈ 3ωε(0) ≈ 0.4 S m(-1), independent of particle radius. Therefore, although electric dipole heating can be as effective as magnetic dipole heating for a powder sample of the same volume, it is harder to obtain optimized conditions at a fixed frequency of microwave field. The absorption of sub-micron particles is ineffective in both magnetic and electric fields. However, if the particles are magnetic, with a lossy part to their complex permeability, then magnetic dipole losses are dramatically enhanced compared to their values for non-magnetic particles. An interesting application of this is the use of very small magnetic particles for the selective microwave heating of biological samples.

Canalization of body size matters for lifetime reproductive success of male predatory mites (Acari: Phytoseiidae).

PubMed

Walzer, Andreas; Schausberger, Peter

2014-04-01

The adaptive canalization hypothesis predicts that highly fitness-relevant traits are canalized via past selection, resulting in low phenotypic plasticity and high robustness to environmental stress. Accordingly, we hypothesized that the level of phenotypic plasticity of male body size of the predatory mites Phytoseiulus persimilis (low plasticity) and Neoseiulus californicus (high plasticity) reflects the effects of body size variation on fitness, especially male lifetime reproductive success (LRS). We first generated small and standard-sized males of P. persimilis and N. californicus by rearing them to adulthood under limited and ample prey supply, respectively. Then, adult small and standard-sized males were provided with surplus virgin females throughout life to assess their mating and reproductive traits. Small male body size did not affect male longevity or the number of fertilized females but reduced male LRS of P. persimilis but not N. californicus . Proximately, the lower LRS of small than standard-sized P. persimilis males correlated with shorter mating durations, probably decreasing the amount of transferred sperm. Ultimately, we suggest that male body size is more strongly canalized in P. persimilis than N. californicus because deviation from standard body size has larger detrimental fitness effects in P. persimilis than N. californicus .

Prevailing practices in the use of antibiotics by dairy farmers in Eastern Haryana region of India

PubMed Central

Kumar, Vikash; Gupta, Jancy

2018-01-01

Aim: The aim of the study was to assess the antibiotic use in dairy animals and to trace its usage pattern among the small, medium, and large dairy farmers in Eastern Haryana region of India. Materials and Methods: Karnal and Kurukshetra districts from Eastern region of Haryana state were purposively selected, and four villages from each district were selected randomly. From each village, 21 farmers were selected using stratified random sampling by categorizing into small, medium, and large farmers constituting a total of 168 farmers as respondents. An antibiotic usage index (AUI) was developed to assess usage of antibiotics by dairy farmers. Results: Frequency of veterinary consultancy was high among large dairy farmers, and they mostly preferred veterinarians over para-veterinarians for treatment of dairy animals. Small farmers demanded low-cost antibiotics from veterinarians whereas large farmers rarely went for it. Antibiotics were used maximum for therapeutic purposes by all categories of farmers. Completion of treatment schedules and follow-up were strictly practiced by the majority of large farmers. AUI revealed that large farmers were more consistent on decision-making about prudent use of antibiotics. Routine use of antibiotics after parturition to prevent disease and sale of milk without adhering to withdrawal period was responsible for aggravating the antibiotic resistance. The extent of antibiotic use by small farmers depended on the severity of disease. The large farmers opted for the prophylactic use of antibiotics at the herd level. Conclusion: Antibiotic usage practices were judicious among large dairy farmers, moderately prudent by medium dairy farmers and faulty by small farmers. The frequency of veterinary consultancy promoted better veterinary-client relationship among large farmers. PMID:29657416

Comparative Study of SVM Methods Combined with Voxel Selection for Object Category Classification on fMRI Data

PubMed Central

Song, Sutao; Zhan, Zhichao; Long, Zhiying; Zhang, Jiacai; Yao, Li

2011-01-01

Background Support vector machine (SVM) has been widely used as accurate and reliable method to decipher brain patterns from functional MRI (fMRI) data. Previous studies have not found a clear benefit for non-linear (polynomial kernel) SVM versus linear one. Here, a more effective non-linear SVM using radial basis function (RBF) kernel is compared with linear SVM. Different from traditional studies which focused either merely on the evaluation of different types of SVM or the voxel selection methods, we aimed to investigate the overall performance of linear and RBF SVM for fMRI classification together with voxel selection schemes on classification accuracy and time-consuming. Methodology/Principal Findings Six different voxel selection methods were employed to decide which voxels of fMRI data would be included in SVM classifiers with linear and RBF kernels in classifying 4-category objects. Then the overall performances of voxel selection and classification methods were compared. Results showed that: (1) Voxel selection had an important impact on the classification accuracy of the classifiers: in a relative low dimensional feature space, RBF SVM outperformed linear SVM significantly; in a relative high dimensional space, linear SVM performed better than its counterpart; (2) Considering the classification accuracy and time-consuming holistically, linear SVM with relative more voxels as features and RBF SVM with small set of voxels (after PCA) could achieve the better accuracy and cost shorter time. Conclusions/Significance The present work provides the first empirical result of linear and RBF SVM in classification of fMRI data, combined with voxel selection methods. Based on the findings, if only classification accuracy was concerned, RBF SVM with appropriate small voxels and linear SVM with relative more voxels were two suggested solutions; if users concerned more about the computational time, RBF SVM with relative small set of voxels when part of the principal components were kept as features was a better choice. PMID:21359184

Comparative study of SVM methods combined with voxel selection for object category classification on fMRI data.

PubMed

Song, Sutao; Zhan, Zhichao; Long, Zhiying; Zhang, Jiacai; Yao, Li

2011-02-16

Support vector machine (SVM) has been widely used as accurate and reliable method to decipher brain patterns from functional MRI (fMRI) data. Previous studies have not found a clear benefit for non-linear (polynomial kernel) SVM versus linear one. Here, a more effective non-linear SVM using radial basis function (RBF) kernel is compared with linear SVM. Different from traditional studies which focused either merely on the evaluation of different types of SVM or the voxel selection methods, we aimed to investigate the overall performance of linear and RBF SVM for fMRI classification together with voxel selection schemes on classification accuracy and time-consuming. Six different voxel selection methods were employed to decide which voxels of fMRI data would be included in SVM classifiers with linear and RBF kernels in classifying 4-category objects. Then the overall performances of voxel selection and classification methods were compared. Results showed that: (1) Voxel selection had an important impact on the classification accuracy of the classifiers: in a relative low dimensional feature space, RBF SVM outperformed linear SVM significantly; in a relative high dimensional space, linear SVM performed better than its counterpart; (2) Considering the classification accuracy and time-consuming holistically, linear SVM with relative more voxels as features and RBF SVM with small set of voxels (after PCA) could achieve the better accuracy and cost shorter time. The present work provides the first empirical result of linear and RBF SVM in classification of fMRI data, combined with voxel selection methods. Based on the findings, if only classification accuracy was concerned, RBF SVM with appropriate small voxels and linear SVM with relative more voxels were two suggested solutions; if users concerned more about the computational time, RBF SVM with relative small set of voxels when part of the principal components were kept as features was a better choice.

Rural and Small School Principal Candidates: Perspectives of Hiring Superintendents

ERIC Educational Resources Information Center

Cruzeiro, Patricia A.; Boone, Mike

2009-01-01

This article reports the results of an inquiry into the dynamics of principal selection in rural school districts in two mid-American states with high numbers of rural schools. The study focuses on two questions: (1) are rural school districts experiencing a shortage of qualified applicants for vacant principal's positions; and (2) what…

Site-Species Relationships for Southern Hardwoods

Treesearch

B. G. Blackmon

1978-01-01

The high cost of land and forest management make selection of sites suitable for planting hardwoods particularly important. Hardwoods have exacting soil requirements, and productivity can change significantly with small changes in conditions. The purpose of this paper is to review some of the attempts to evaluate sites for southern hardwoods, with emphasis on an...

Returning the Human to the Humanities at All Levels.

ERIC Educational Resources Information Center

Quayhagen, Patricia A.

A high school English teacher in rural Louisiana installed a small "library" in her classroom in order to give students a love of literature and of reading. The library included a motley selection of paperbacks, many from local secondhand bookstores, ranging from children's books through the classics. As a spur to students' interest and…

Planning Guide for Career Academies

ERIC Educational Resources Information Center

Dayton, Charles

2010-01-01

A career academy is a small learning community within a high school, which selects a subset of students and teachers for a two-, three-, or four-year period. Students enter through a voluntary process; they must apply and be accepted, with parental knowledge and support. A career academy involves teachers from different subjects working together…

Internal Structure of 15 nm 3-Helix Micelle Revealed by Small-Angle Neutron Scattering and Coarse-Grained MD Simulation.

PubMed

Ang, JooChuan; Ma, Dan; Lund, Reidar; Keten, Sinan; Xu, Ting

2016-10-10

3-Helix micelles (3HM) formed by self-assembly of peptide-polymer conjugate amphiphiles have shown promise as a nanocarrier platform due to their long-circulation, deep tumor penetration, selective accumulation in tumor, and ability to cross the blood-brain barrier (BBB) for glioblastoma therapy. There is a need to understand the structural contribution to the high in vivo stability and performance of 3HM. Using selective deuteration, the contrast variation technique in small-angle neutron scattering, and coarse-grained molecular dynamics simulation, we determined the spatial distribution of each component within 3HM. Our results show a slightly deformed polyethylene glycol (PEG) conformation within the micelle that is radially offset from its conjugation site toward the exterior of the micelle and a highly solvated shell. Surprisingly, ∼85 v/v % of 3HM is water, unusually higher than any micellar nanocarrier based on our knowledge. The result will provide important structural insights for future studies to uncover the molecular origin of 3HM's in vivo performance, and development of the nanocarriers.

Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch

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

Howe, John A.; Xiao, Li; Fischmann, Thierry O.

2016-08-02

Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil ismore » structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.« less

Use of New and Minority-Owned Architectural and Engineering Firms by Selected Army and Navy Activities.

DTIC Science & Technology

1981-10-30

we directed our review to the preselection and selection processes for direct A/E awards,.not awards made under the Small Business Administration’s 8...policy of the United States that small busi - ness concerns and small business concerns owned and controlled by socially and economically disadvantaged...contracts exceeding $10,000 must contain the above state- ment. The Small Business Administration has defined small business concerns for A/E services

Pure-phase selective excitation in fast-relaxing systems.

PubMed

Zangger, K; Oberer, M; Sterk, H

2001-09-01

Selective pulses have been used frequently for small molecules. However, their application to proteins and other macromolecules has been limited. The long duration of shaped-selective pulses and the short T(2) relaxation times in proteins often prohibited the use of highly selective pulses especially on larger biomolecules. A very selective excitation can be obtained within a short time by using the selective excitation sequence presented in this paper. Instead of using a shaped low-intensity radiofrequency pulse, a cluster of hard 90 degrees pulses, delays of free precession, and pulsed field gradients can be used to selectively excite a narrow chemical shift range within a relatively short time. Thereby, off-resonance magnetization, which is allowed to evolve freely during the free precession intervals, is destroyed by the gradient pulses. Off-resonance excitation artifacts can be removed by random variation of the interpulse delays. This leads to an excitation profile with selectivity as well as phase and relaxation behavior superior to that of commonly used shaped-selective pulses. Since the evolution of scalar coupling is inherently suppressed during the double-selective excitation of two different scalar-coupled nuclei, the presented pulse cluster is especially suited for simultaneous highly selective excitation of N-H and C-H fragments. Experimental examples are demonstrated on hen egg white lysozyme (14 kD) and the bacterial antidote ParD (19 kD). Copyright 2001 Academic Press.

Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010.

PubMed

Sun, Shaoyi; Cohen, Charles J; Dehnhardt, Christoph M

2014-09-01

There has been intense interest in developing inhibitors of the sodium channel Nav1.7 because genetic studies have established very strong validation for the efficacy to alleviate both inflammatory and neuropathic pain. This review summarizes patent applications targeting Nav1.7 since 2010 until May, 2014. We have classified the patents into three categories as follows: small molecules with well-defined molecular selectivity among sodium channel isoforms; biologicals with well-defined molecular selectivity; and, small molecules that inhibit Nav1.7 with unknown molecular selectivity. Most of the review is dedicated to small molecule selective compounds.

The NAICS Code Selection Process And Small Business Participation

DTIC Science & Technology

2016-03-01

specialist 15. NUMBER OF PAGES 59 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE...FPDS-NG) website and information gathered from interviews with small business specialists . The data include contract actions from 276 contracts with...used interviews to determine if small businesses are affected by inappropriate NAICS code selection. None of the six small business specialists we

Optimizing classification performance in an object-based very-high-resolution land use-land cover urban application

NASA Astrophysics Data System (ADS)

Georganos, Stefanos; Grippa, Tais; Vanhuysse, Sabine; Lennert, Moritz; Shimoni, Michal; Wolff, Eléonore

2017-10-01

This study evaluates the impact of three Feature Selection (FS) algorithms in an Object Based Image Analysis (OBIA) framework for Very-High-Resolution (VHR) Land Use-Land Cover (LULC) classification. The three selected FS algorithms, Correlation Based Selection (CFS), Mean Decrease in Accuracy (MDA) and Random Forest (RF) based Recursive Feature Elimination (RFE), were tested on Support Vector Machine (SVM), K-Nearest Neighbor, and Random Forest (RF) classifiers. The results demonstrate that the accuracy of SVM and KNN classifiers are the most sensitive to FS. The RF appeared to be more robust to high dimensionality, although a significant increase in accuracy was found by using the RFE method. In terms of classification accuracy, SVM performed the best using FS, followed by RF and KNN. Finally, only a small number of features is needed to achieve the highest performance using each classifier. This study emphasizes the benefits of rigorous FS for maximizing performance, as well as for minimizing model complexity and interpretation.

Rational Methods for the Selection of Diverse Screening Compounds

PubMed Central

Huggins, David J.; Venkitaraman, Ashok R.; Spring, David R.

2016-01-01

Traditionally a pursuit of large pharmaceutical companies, high-throughput screening assays are becoming increasingly common within academic and government laboratories. This shift has been instrumental in enabling projects that have not been commercially viable, such as chemical probe discovery and screening against high risk targets. Once an assay has been prepared and validated, it must be fed with screening compounds. Crafting a successful collection of small molecules for screening poses a significant challenge. An optimized collection will minimize false positives whilst maximizing hit rates of compounds that are amenable to lead generation and optimization. Without due consideration of the relevant protein targets and the downstream screening assays, compound filtering and selection can fail to explore the great extent of chemical diversity and eschew valuable novelty. Herein, we discuss the different factors to be considered and methods that may be employed when assembling a structurally diverse compound screening collection. Rational methods for selecting diverse chemical libraries are essential for their effective use in high-throughput screens. PMID:21261294

Factual knowledge about AIDS and dating practices among high school students from selected schools.

PubMed

Nyachuru-Sihlangu, R H; Ndlovu, J

1992-06-01

Following various educational strategies by governmental and non-governmental organisations to educate youths and school teachers about HIV infection and prevention, this KABP survey was one attempt to evaluate the results. The study sample of 478 high school students was drawn from four randomly selected schools in Mashonaland and Matabeleland including high and low density, government and mission co-educational schools. The sample was randomly selected and stratified to represent sex and grade level. The KABP self administered questionnaire was used. The paper analyses the relationship between the knowledge and dating patterns. Generally, respondents demonstrated a 50pc to 80pc accuracy of factual knowledge. Of the 66pc Forms I through IV pupils who dated, 30pc preferred only sexually involved relationships and a small number considered the possibility of HIV/AIDS infection. A theoretically based tripartite coalition involving the school, the family health care services for education, guidance and support to promote responsible behaviour throughout childhood was suggested.

Probabilistic Selection of High-redshift Quasars with Subaru/Hyper Suprime-Cam Survey

NASA Astrophysics Data System (ADS)

Onoue, Masafusa

High-redshift quasars are an important probe of the distant Universe. They enable observational studies of the early growth of supermassive blackholes, cosmic reionization, chemical enrichment of host galaxies, and so on. Through pioneering optical and near-infrared wide-area surveys such as the SDSS and the VIKING Survey, about one hundred quasars have been found at z > 6 (e.g., Fan et al. (2006b), Venemans et al. (2013)). However, its current small sample size and the fact that most of them are the most luminous (M 1450 <~ -24) population in this epoch prevents one from constraining statistics on high-redshift quasars, namely quasar luminosity function (QLF), and redshift evolution of IGM neutral fraction. Thus, discovery of large number of z > 6 quasars, especially low-luminous or z > 7 quasars, is highly desired for further understanding of the early universe. We are now starting a new ground-breaking survey of high-redshift (z > 6) quasars using the exquisite imaging data provided by the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP) Survey. Thanks to its extremely wide coverage and its high sensitivity thorough five optical bands (1,400 deg2 to the depth of r ~ 26 in HSC-Wide layer), it is one of the most powerful contemporary surveys that makes it possible for us to increase the number of z > 6 quasars by almost an order of magnitude, i.e., 300 at z ~ 6 and 50 at z ~ 7, based on the current estimate of the QLF at z > 6 by Willott et al. (2010b). One of the biggest challenges in z > 6 quasar candidate selection is contamination of Galactic brown dwarfs, which have the same point-like appearance as and similarly red colors to the quasars. To overcome this issue and maximize the selection efficiency, we apply a double-layered approach to the HSC survey products, namely combination of two probabilistic selections: SED-fitting and Bayesian selection. In particular, we have developed a template SED fitting method optimized to high-redshift quasars selection. Its application with 27 photometric bands to the COSMOS quasars at 3 < z < 5 have shown that almost all of the known quasars are correctly classified with small dispersion σ|Δz|/(1+z)=0.01 and as low as η=2.5% outlier rate. At present, the HSC survey have successfully covered ~100 deg2 of HSC-Wide area in full colors. From the first-year data products, we have already started z > 6 quasar selection, and it is expected that the first HSC quasar discovery will be in the near future.

A solar thermal electric power plant for small communities

NASA Technical Reports Server (NTRS)

Holl, R. J.

1979-01-01

A solar power plant has been designed with a rating of 1000-kW electric and a 0.4 annual capacity factor. It was configured as a prototype for plants in the 1000 to 10,000-kWe size range for application to small communities or industrial users either grid-connected or isolated from a utility grid. A small central receiver was selected for solar energy collection after being compared with alternative distributed collectors. Further trade studies resulted in the selection of Hitec (heat transfer salt composed of 53 percent KNO3, 40 percent NaNO2, 7 percent NaNO3) as both the receiver coolant and the sensible heat thermal stroage medium and the steam Rankine cycle for power conversion. The plant is configured with road-transportable units to accommodate remote sites and minimize site assembly requirements. Results of the analyses indicate that busbar energy costs are competitive with diesel-electric plants in certain situations, e.g., off-grid, remote regions with high insolation. Sensitivity of energy costs to plant power rating and system capacity factor are given.

Selected list of books and journals for the small medical library.

PubMed

Brandon, A N; Hill, D R

1995-04-01

The complementary informational access roles of the traditional hospital library book and journal collection and the high-tech Internet are viewed from a 1995 perspective. Predecessors of this list have been intended as selection guides for a small or medium-size library in a hospital or comparable medical facility. As the prices of books and journals continue on an upward spiral, the secondary purpose as a core collection for a consortium of small hospital libraries or a network sharing library resources is fast becoming its primary use. Books (610) and journals (141) are categorized by subject; the book list is followed by an author/editor index and the subject list of journals by an alphabetical title listing. Due to requests from librarians, a "minimal core" book collection consisting of 82 titles has been pulled out from the 200 asterisked initial-purchase books. To purchase the entire collection of books and to pay for 1995 subscriptions would require $93,300. The cost of only the asterisked items totals $39,000. The "minimal core" book collection costs $12,700.

Selected list of books and journals for the small medical library.

PubMed Central

Brandon, A N; Hill, D R

1995-01-01

The complementary informational access roles of the traditional hospital library book and journal collection and the high-tech Internet are viewed from a 1995 perspective. Predecessors of this list have been intended as selection guides for a small or medium-size library in a hospital or comparable medical facility. As the prices of books and journals continue on an upward spiral, the secondary purpose as a core collection for a consortium of small hospital libraries or a network sharing library resources is fast becoming its primary use. Books (610) and journals (141) are categorized by subject; the book list is followed by an author/editor index and the subject list of journals by an alphabetical title listing. Due to requests from librarians, a "minimal core" book collection consisting of 82 titles has been pulled out from the 200 asterisked initial-purchase books. To purchase the entire collection of books and to pay for 1995 subscriptions would require $93,300. The cost of only the asterisked items totals $39,000. The "minimal core" book collection costs $12,700. PMID:7599581

Biological effects of simple changes in functionality on rhodium metalloinsertors

PubMed Central

Weidmann, Alyson G.; Komor, Alexis C.; Barton, Jacqueline K.

2013-01-01

DNA mismatch repair (MMR) is crucial to ensuring the fidelity of the genome. The inability to correct single base mismatches leads to elevated mutation rates and carcinogenesis. Using metalloinsertors–bulky metal complexes that bind with high specificity to mismatched sites in the DNA duplex–our laboratory has adopted a new chemotherapeutic strategy through the selective targeting of MMR-deficient cells, that is, those that have a propensity for cancerous transformation. Rhodium metalloinsertors display inhibitory effects selectively in cells that are deficient in the MMR machinery, consistent with this strategy. However, a highly sensitive structure–function relationship is emerging with the development of new complexes that highlights the importance of subcellular localization. We have found that small structural modifications, for example a hydroxyl versus a methyl functional group, can yield profound differences in biological function. Despite similar binding affinities and selectivities for DNA mismatches, only one metalloinsertor shows selective inhibition of cellular proliferation in MMR-deficient versus -proficient cells. Studies of whole-cell, nuclear and mitochondrial uptake reveal that this selectivity depends upon targeting DNA mismatches in the cell nucleus. PMID:23776288

Resource selection and its implications for wide-ranging mammals of the brazilian cerrado.

PubMed

Vynne, Carly; Keim, Jonah L; Machado, Ricardo B; Marinho-Filho, Jader; Silveira, Leandro; Groom, Martha J; Wasser, Samuel K

2011-01-01

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing that a multi-faceted approach is required to protect these species.

Resource Selection and Its Implications for Wide-Ranging Mammals of the Brazilian Cerrado

PubMed Central

Vynne, Carly; Keim, Jonah L.; Machado, Ricardo B.; Marinho-Filho, Jader; Silveira, Leandro; Groom, Martha J.; Wasser, Samuel K.

2011-01-01

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing that a multi-faceted approach is required to protect these species. PMID:22205984

Binary and ternary gas mixtures for use in glow discharge closing switches

DOEpatents

Hunter, S.R.; Christophorou, L.G.

1988-04-27

Highly efficient binary and ternary gas mixtures for use in diffuse glow discharge closing switches are disclosed. The binary mixtures are combinations of helium or neon and selected perfluorides. The ternary mixtures are combinations of helium, neon, or argon, a selected perfluoride, and a small amount of gas that exhibits enhanced ionization characteristics. These mixtures are shown to be the optimum choices for use in diffuse glow discharge closing switches by virtue if the combines physio-electric properties of the mixture components. 9 figs.

Selective small-molecule inhibitors as chemical tools to define the roles of matrix metalloproteinases in disease.

PubMed

Meisel, Jayda E; Chang, Mayland

2017-11-01

The focus of this article is to highlight novel inhibitors and current examples where the use of selective small-molecule inhibitors has been critical in defining the roles of matrix metalloproteinases (MMPs) in disease. Selective small-molecule inhibitors are surgical chemical tools that can inhibit the targeted enzyme; they are the method of choice to ascertain the roles of MMPs and complement studies with knockout animals. This strategy can identify targets for therapeutic development as exemplified by the use of selective small-molecule MMP inhibitors in diabetic wound healing, spinal cord injury, stroke, traumatic brain injury, cancer metastasis, and viral infection. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

Phenology and Cover of Plant Growth Forms Predict Herbivore Habitat Selection in a High Latitude Ecosystem

PubMed Central

Fauchald, Per; Langeland, Knut; Ims, Rolf A.; Yoccoz, Nigel G.; Bråthen, Kari Anne

2014-01-01

The spatial and temporal distribution of forage quality is among the most central factors affecting herbivore habitat selection. Yet, for high latitude areas, forage quantity has been found to be more important than quality. Studies on large ungulate foraging patterns are faced with methodological challenges in both assessing animal movements at the scale of forage distribution, and in assessing forage quality with relevant metrics. Here we use first-passage time analyses to assess how reindeer movements relate to forage quality and quantity measured as the phenology and cover of growth forms along reindeer tracks. The study was conducted in a high latitude ecosystem dominated by low-palatable growth forms. We found that the scale of reindeer movement was season dependent, with more extensive area use as the summer season advanced. Small-scale movement in the early season was related to selection for younger stages of phenology and for higher abundances of generally phenologically advanced palatable growth forms (grasses and deciduous shrubs). Also there was a clear selection for later phenological stages of the most dominant, yet generally phenologically slow and low-palatable growth form (evergreen shrubs). As the summer season advanced only quantity was important, with selection for higher quantities of one palatable growth form and avoidance of a low palatable growth form. We conclude that both forage quality and quantity are significant predictors to habitat selection by a large herbivore at high latitude. The early season selectivity reflected that among dominating low palatability growth forms there were palatable phenological stages and palatable growth forms available, causing herbivores to be selective in their habitat use. The diminishing selectivity and the increasing scale of movement as the season developed suggest a response by reindeer to homogenized forage availability of low quality. PMID:24972188

Phenology and cover of plant growth forms predict herbivore habitat selection in a high latitude ecosystem.

PubMed

Iversen, Marianne; Fauchald, Per; Langeland, Knut; Ims, Rolf A; Yoccoz, Nigel G; Bråthen, Kari Anne

2014-01-01

The spatial and temporal distribution of forage quality is among the most central factors affecting herbivore habitat selection. Yet, for high latitude areas, forage quantity has been found to be more important than quality. Studies on large ungulate foraging patterns are faced with methodological challenges in both assessing animal movements at the scale of forage distribution, and in assessing forage quality with relevant metrics. Here we use first-passage time analyses to assess how reindeer movements relate to forage quality and quantity measured as the phenology and cover of growth forms along reindeer tracks. The study was conducted in a high latitude ecosystem dominated by low-palatable growth forms. We found that the scale of reindeer movement was season dependent, with more extensive area use as the summer season advanced. Small-scale movement in the early season was related to selection for younger stages of phenology and for higher abundances of generally phenologically advanced palatable growth forms (grasses and deciduous shrubs). Also there was a clear selection for later phenological stages of the most dominant, yet generally phenologically slow and low-palatable growth form (evergreen shrubs). As the summer season advanced only quantity was important, with selection for higher quantities of one palatable growth form and avoidance of a low palatable growth form. We conclude that both forage quality and quantity are significant predictors to habitat selection by a large herbivore at high latitude. The early season selectivity reflected that among dominating low palatability growth forms there were palatable phenological stages and palatable growth forms available, causing herbivores to be selective in their habitat use. The diminishing selectivity and the increasing scale of movement as the season developed suggest a response by reindeer to homogenized forage availability of low quality.

Long life reference electrode

DOEpatents

Yonco, R.M.; Nagy, Z.

1987-07-30

An external, reference electrode is provided for long term use with a high temperature, high pressure system. The electrode is arranged in a vertical, electrically insulative tube with an upper portion serving as an electrolyte reservoir and a lower portion in electrolytic communication with the system to be monitored. The lower end portion includes a flow restriction such as a porous plug to limit the electrolyte release into the system. A piston equalized to the system pressure is fitted into the upper portion of the tube to impart a small incremental pressure to the electrolyte. The piston is selected of suitable size and weight to cause only a slight flow of electrolyte through the porous plug into the high pressure system. This prevents contamination of the electrolyte but is of such small flow rate that operating intervals of a month or more can be achieved. 2 figs.

Long life reference electrode

DOEpatents

Yonco, R.M.; Nagy, Z.

1989-04-04

An external, reference electrode is provided for long term use with a high temperature, high pressure system. The electrode is arranged in a vertical, electrically insulative tube with an upper portion serving as an electrolyte reservoir and a lower portion in electrolytic communication with the system to be monitored. The lower end portion includes a flow restriction such as a porous plug to limit the electrolyte release into the system. A piston equalized to the system pressure is fitted into the upper portion of the tube to impart a small incremental pressure to the electrolyte. The piston is selected of suitable size and weight to cause only a slight flow of electrolyte through the porous plug into the high pressure system. This prevents contamination of the electrolyte but is of such small flow rate that operating intervals of a month or more can be achieved. 2 figs.

Long life reference electrode

DOEpatents

Yonco, Robert M.; Nagy, Zoltan

1989-01-01

An external, reference electrode is provided for long term use with a high temperature, high pressure system. The electrode is arranged in a vertical, electrically insulative tube with an upper portion serving as an electrolyte reservior and a lower portion in electrolytic communication with the system to be monitored. The lower end portion includes a flow restriction such as a porous plug to limit the electrolyte release into the system. A piston equalized to the system pressure is fitted into the upper portion of the tube to impart a small incremental pressure to the electrolyte. The piston is selected of suitable size and weight to cause only a slight flow of electrolyte through the porous plug into the high pressure system. This prevents contamination of the electrolyte but is of such small flow rate that operating intervals of a month or more can be achieved.

The contemporary role of ablative treatment approaches in the management of renal cell carcinoma (RCC): focus on radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), and cryoablation.

PubMed

Klatte, Tobias; Kroeger, Nils; Zimmermann, Uwe; Burchardt, Martin; Belldegrun, Arie S; Pantuck, Allan J

2014-06-01

Currently, most of renal tumors are small, low grade, with a slow growth rate, a low metastatic potential, and with up to 30 % of these tumors being benign on the final pathology. Moreover, they are often diagnosed in elderly patients with preexisting medical comorbidities in whom the underlying medical conditions may pose a greater risk of death than the small renal mass. Concerns regarding overdiagnosis and overtreatment of patients with indolent small renal tumors have led to an increasing interest in minimally invasive, ablative as an alternative to extirpative interventions for selected patients. To provide an overview about the state of the art in radiofrequency ablation (RFA), high-intensity focused ultrasound, and cryoablation in the clinical management of renal cell carcinoma. A PubMed wide the literature search of was conducted. International consensus panels recommend ablative techniques in patients who are unfit for surgery, who are not considered candidates for or elect against elective surveillance, and who have small renal masses. The most often used techniques are cryoablation and RFA. These ablative techniques offer potentially curative outcomes while conferring several advantages over extirpative surgery, including improved patient procedural tolerance, faster recovery, preservation of renal function, and reduction in the risk of intraoperative and postsurgical complications. While it is likely that outcomes associated with ablative modalities will improve with further advances in technology, their application will expand to more elective indications as longer-term efficacy data become available. Ablative techniques pose a valid treatment option in selected patients.

The contribution of attenuated selection in utero to small-for-gestational-age (SGA) among term African American male infants.

PubMed

Goodman, Julia M; Karasek, Deborah; Anderson, Elizabeth; Catalano, Ralph A

2013-07-01

Natural selection conserves mechanisms allowing women to spontaneously abort gestations least likely to yield fit offspring. Small gestational size has been proposed as an indicator of fitness observable by maternal biology. Previous research suggests that exposure to ambient stress in utero results in more "culling" of small fetuses and therefore lower rates of small-for-gestational-age (SGA). However, African American women persistently have higher rates of SGA than non-Hispanic white women, despite experiencing more ambient stress. This paper tests whether attenuation of the stress response among highly stressed African American women, as suggested by the weathering hypothesis, may help to explain this apparent inconsistency. We apply time-series modeling to over 2 million African American and non-Hispanic white male term births in California over the period of January 1989 through December 2010. We test for the parabolic (i.e., "U" shaped) relationship, implied by an attenuated stress response, between unusually strong labor market contraction and the rate of SGA among African American term male infants, and a linear relationship among non-Hispanic whites. We find the hypothesized parabolic relationship among term male African American infants. As expected, we find a linear relationship between unexpected layoffs and the rate of SGA among term male non-Hispanic whites. These results are robust to sensitivity analyses. These results may help to explain the high rates of SGA among term male African American infants, despite greater maternal exposure to ambient stress during pregnancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Au Nanocage Functionalized with Ultra-small Fe3O4 Nanoparticles for Targeting T1-T2Dual MRI and CT Imaging of Tumor

NASA Astrophysics Data System (ADS)

Wang, Guannan; Gao, Wei; Zhang, Xuanjun; Mei, Xifan

2016-06-01

Diagnostic approaches based on multimodal imaging of clinical noninvasive imaging (eg. MRI/CT scanner) are highly developed in recent years for accurate selection of the therapeutic regimens in critical diseases. Therefore, it is highly demanded in the development of appropriate all-in-one multimodal contrast agents (MCAs) for the MRI/CT multimodal imaging. Here a novel ideal MCAs (F-AuNC@Fe3O4) were engineered by assemble Au nanocages (Au NC) and ultra-small iron oxide nanoparticles (Fe3O4) for simultaneous T1-T2dual MRI and CT contrast imaging. In this system, the Au nanocages offer facile thiol modification and strong X-ray attenuation property for CT imaging. The ultra-small Fe3O4 nanoparticles, as excellent contrast agent, is able to provide great enhanced signal of T1- and T2-weighted MRI (r1 = 6.263 mM-1 s-1, r2 = 28.117 mM-1 s-1) due to their ultra-refined size. After functionalization, the present MCAs nanoparticles exhibited small average size, low aggregation and excellent biocompatible. In vitro and In vivo studies revealed that the MCAs show long-term circulation time, renal clearance properties and outstanding capability of selective accumulation in tumor tissues for simultaneous CT imaging and T1- and T2-weighted MRI. Taken together, these results show that as-prepared MCAs are excellent candidates as MRI/CT multimodal imaging contrast agents.

Evaluation of H.264 and H.265 full motion video encoding for small UAS platforms

NASA Astrophysics Data System (ADS)

McGuinness, Christopher D.; Walker, David; Taylor, Clark; Hill, Kerry; Hoffman, Marc

2016-05-01

Of all the steps in the image acquisition and formation pipeline, compression is the only process that degrades image quality. A selected compression algorithm succeeds or fails to provide sufficient quality at the requested compression rate depending on how well the algorithm is suited to the input data. Applying an algorithm designed for one type of data to a different type often results in poor compression performance. This is mostly the case when comparing the performance of H.264, designed for standard definition data, to HEVC (High Efficiency Video Coding), which the Joint Collaborative Team on Video Coding (JCT-VC) designed for high-definition data. This study focuses on evaluating how HEVC compares to H.264 when compressing data from small UAS platforms. To compare the standards directly, we assess two open-source traditional software solutions: x264 and x265. These software-only comparisons allow us to establish a baseline of how much improvement can generally be expected of HEVC over H.264. Then, specific solutions leveraging different types of hardware are selected to understand the limitations of commercial-off-the-shelf (COTS) options. Algorithmically, regardless of the implementation, HEVC is found to provide similar quality video as H.264 at 40% lower data rates for video resolutions greater than 1280x720, roughly 1 Megapixel (MPx). For resolutions less than 1MPx, H.264 is an adequate solution though a small (roughly 20%) compression boost is earned by employing HEVC. New low cost, size, weight, and power (CSWAP) HEVC implementations are being developed and will be ideal for small UAS systems.

DNA sequence variation of wild barley Hordeum spontaneum (L.) across environmental gradients in Israel

PubMed Central

Bedada, G; Westerbergh, A; Nevo, E; Korol, A; Schmid, K J

2014-01-01

Wild barley Hordeum spontaneum (L.) shows a wide geographic distribution and ecological diversity. A key question concerns the spatial scale at which genetic differentiation occurs and to what extent it is driven by natural selection. The Levant region exhibits a strong ecological gradient along the North–South axis, with numerous small canyons in an East–West direction and with small-scale environmental gradients on the opposing North- and South-facing slopes. We sequenced 34 short genomic regions in 54 accessions of wild barley collected throughout Israel and from the opposing slopes of two canyons. The nucleotide diversity of the total sample is 0.0042, which is about two-thirds of a sample from the whole species range (0.0060). Thirty accessions collected at ‘Evolution Canyon' (EC) at Nahal Oren, close to Haifa, have a nucleotide diversity of 0.0036, and therefore harbor a large proportion of the genetic diversity. There is a high level of genetic clustering throughout Israel and within EC, which roughly differentiates the slopes. Accessions from the hot and dry South-facing slope have significantly reduced genetic diversity and are genetically more distinct from accessions from the North-facing slope, which are more similar to accessions from other regions in Northern Israel. Statistical population models indicate that wild barley within the EC consist of three separate genetic clusters with substantial gene flow. The data indicate a high level of population structure at large and small geographic scales that shows isolation-by-distance, and is also consistent with ongoing natural selection contributing to genetic differentiation at a small geographic scale. PMID:24619177

A non-volatile flip-flop based on diode-selected PCM for ultra-low power systems

NASA Astrophysics Data System (ADS)

Ye, Yong; Du, Yuan; Gao, Dan; Kang, Yong; Song, Zhitang; Chen, Bomy

2016-10-01

As the process technology is continuously shrinking, low power consumption is a major issue in VLSI Systems-on-Chip (SoCs), especially for standby-power-critical applications. Recently, the emerging CMOS-compatible non-volatile memories (NVMs), such as Phase Change Memory (PCM), have been used as on-chip storage elements, which can obtain non-volatile processing, nearly-zero standby power and instant-on capability. PCM has been considered as the best candidate for the next generation of NVMs for its low cost, high density and high resistance transformation ratio. In this paper, for the first time, we present a diode-selected PCM based non-volatile flip-flop (NVFF) which is optimized for better power consumption and process variation tolerance. With dual trench isolation process, the diode-selected PCM realizes ultra small area, which is very suitable for multi-context configuration and large scale flip-flops matrix. Since the MOS-selected PCM is hard to shrink further due to large amount of PCM write current, the proposed NVFF achieves higher power efficiency without loss of current driving capability. Using the 40nm manufacturing process, the area of the cell (1D1R) is as small as 0.016 μm2. Simulation results show that the energy consumption during the recall operation is 62 fJ with 1.1 standard supply voltage, which is reduced by 54.9% compared to the previous 2T2R based NVFF. When the supply voltage reduces to 0.7 V, the recall energy is as low as 17 fJ. With the great advantages in cell size and energy, the proposed diode-selected NVFF is very applicable and cost-effective for ULP systems.

Small Business Participation in Air Force Procurement: Participation Trends and the Effect of Acquisition Reform Initiatives on Air Force Procurement via Selected Contract Types in Selected Product Categories

DTIC Science & Technology

2004-06-01

directed the SBA to provide several types of assistance to small businesses , including technical and management assistance, loans, and assistance in...Directed the SBA to provide small businesses with technical and management assistance - Authorized the SBA to enter into contracts with Federal...command and center directors of small business , small business specialists, data managers , and Air Force Institute of Technology student researchers

Non-invasive MRI detection of individual pellets in the human stomach.

PubMed

Knörgen, Manfred; Spielmann, Rolf Peter; Abdalla, Ahmed; Metz, Hendrik; Mäder, Karsten

2010-01-01

MRI is a powerful and non-invasive method to follow the fate of oral drug delivery systems in humans. Until now, most MRI studies focused on monolithic dosage forms (tablets and capsules). Small-sized multi-particulate drug delivery systems are very difficult to detect due to the poor differentiation between the delivery system and the food. A new approach was developed to overcome the described difficulties and permit the selective imaging of small multi-particulate dosage forms within the stomach. We took advantage of the different sensitivities to susceptibility artefacts of T(2)-weighted spin-echo sequences and T(2)-weighted gradient echo pulse sequences. Using a combination of both methods within a breath hold followed by a specific mathematical image analysis involving co-registration, motion correction, voxel-by-voxel comparison of the maps from different pulse sequences and graphic 2D-/3D-presentation, we were able to obtain pictures with a high sensitivity due to susceptibility effects caused by a 1% magnetite load. By means of the new imaging sequence, single pellets as small as 1mm can be detected with high selectivity within surrounding heterogeneous food in the human stomach. The developed method greatly expands the use of MRI to study the fate of oral multi-particulate drug delivery systems and their food dependency in men. Copyright 2009 Elsevier B.V. All rights reserved.

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

Zhang, W.; Chang, Q.G.; Liu, W.D.

A series of follow-up investigations were performed to produce data for improving the four-indicator carbon selection method that we developed to identify high-potential activated carbons effective for removing specific organic water pollutants. The carbon's pore structure and surface chemistry are dependent on the raw material and the activation process. Coconut carbons have relatively more small pores than large pores; coal and apricot nutshell/walnut shell fruit carbons have the desirable pore structures for removing adsorbates of all sizes. Chemical activation, excessive activation, and/or thermal reactivation enlarge small pores, resulting in reduced phenol number and higher tannic acid number. Activated carbon's phenol,more » iodine, methylene blue, and tannic acid numbers are convenient indicators of its surface area and pore volume of pore diameters < 10, 10-15, 15-28, and > 28 angstrom, respectively. The phenol number of a carbon is also a good indicator of its surface acidity of oxygen-containing organic functional groups that affect the adsorptive capacity for aromatic and other small polar organics. The tannic acid number is an indicator of carbon's capacity for large, high-molecular-weight natural organic precursors of disinfection by-products in water treatment. The experimental results for removing nitrobenzene, methyl-tert-butyl ether, 4,4-bisphenol, humic acid, and the organic constituents of a biologically treated coking-plant effluent have demonstrated the effectiveness of this capacity-indicator-based method of carbon selection.« less

Highly selective hydrogenation of furfural to furfuryl alcohol over Pt nanoparticles supported on g-C3N4 nanosheets catalysts in water.

PubMed

Chen, Xiufang; Zhang, Ligang; Zhang, Bo; Guo, Xingcui; Mu, Xindong

2016-06-22

Graphitic carbon nitride nanosheets were investigated for developing effective Pt catalyst supports for selective hydrogenation of furfural to furfuryl alcohol in water. The nanosheets with an average thickness of about 3 nm were synthesized by a simple and green method through thermal oxidation etching of bulk g-C3N4 in air. Combined with the unique feature of nitrogen richness and locally conjugated structure, the g-C3N4 nanosheets with a high surface area of 142 m(2) g(-1) were demonstrated to be an excellent supports for loading small-size Pt nanoparticles. Superior furfural hydrogenation activity in water with complete conversion of furfural and high selectivity of furfuryl alcohol (>99%) was observed for g-C3N4 nanosheets supported Pt catalysts. The large specific surface area, uniform dispersion of Pt nanoparticles and the stronger furfural adsorption ability of nanosheets contributed to the considerable catalytic performance. The reusability tests showed that the novel Pt catalyst could maintain high activity and stability in the furfural hydrogenation reaction.

Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

PubMed

Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

2016-02-26

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

Highly selective hydrogenation of furfural to furfuryl alcohol over Pt nanoparticles supported on g-C3N4 nanosheets catalysts in water

NASA Astrophysics Data System (ADS)

Chen, Xiufang; Zhang, Ligang; Zhang, Bo; Guo, Xingcui; Mu, Xindong

2016-06-01

Graphitic carbon nitride nanosheets were investigated for developing effective Pt catalyst supports for selective hydrogenation of furfural to furfuryl alcohol in water. The nanosheets with an average thickness of about 3 nm were synthesized by a simple and green method through thermal oxidation etching of bulk g-C3N4 in air. Combined with the unique feature of nitrogen richness and locally conjugated structure, the g-C3N4 nanosheets with a high surface area of 142 m2 g-1 were demonstrated to be an excellent supports for loading small-size Pt nanoparticles. Superior furfural hydrogenation activity in water with complete conversion of furfural and high selectivity of furfuryl alcohol (>99%) was observed for g-C3N4 nanosheets supported Pt catalysts. The large specific surface area, uniform dispersion of Pt nanoparticles and the stronger furfural adsorption ability of nanosheets contributed to the considerable catalytic performance. The reusability tests showed that the novel Pt catalyst could maintain high activity and stability in the furfural hydrogenation reaction.

Highly selective hydrogenation of furfural to furfuryl alcohol over Pt nanoparticles supported on g-C3N4 nanosheets catalysts in water

PubMed Central

Chen, Xiufang; Zhang, Ligang; Zhang, Bo; Guo, Xingcui; Mu, Xindong

2016-01-01

Graphitic carbon nitride nanosheets were investigated for developing effective Pt catalyst supports for selective hydrogenation of furfural to furfuryl alcohol in water. The nanosheets with an average thickness of about 3 nm were synthesized by a simple and green method through thermal oxidation etching of bulk g-C3N4 in air. Combined with the unique feature of nitrogen richness and locally conjugated structure, the g-C3N4 nanosheets with a high surface area of 142 m2 g−1 were demonstrated to be an excellent supports for loading small-size Pt nanoparticles. Superior furfural hydrogenation activity in water with complete conversion of furfural and high selectivity of furfuryl alcohol (>99%) was observed for g-C3N4 nanosheets supported Pt catalysts. The large specific surface area, uniform dispersion of Pt nanoparticles and the stronger furfural adsorption ability of nanosheets contributed to the considerable catalytic performance. The reusability tests showed that the novel Pt catalyst could maintain high activity and stability in the furfural hydrogenation reaction. PMID:27328834

Crystallization using reverse micelles and water-in-oil microemulsion systems: the highly selective tool for the purification of organic compounds from complex mixtures.

PubMed

Kljajic, Alen; Bester-Rogac, Marija; Klobcar, Andrej; Zupet, Rok; Pejovnik, Stane

2013-02-01

The active pharmaceutical ingredient orlistat is usually manufactured using a semi-synthetic procedure, producing crude product and complex mixtures of highly related impurities with minimal side-chain structure variability. It is therefore crucial for the overall success of industrial/pharmaceutical application to develop an effective purification process. In this communication, we present the newly developed water-in-oil reversed micelles and microemulsion system-based crystallization process. Physiochemical properties of the presented crystallization media were varied through surfactants and water composition, and the impact on efficiency was measured through final variation of these two parameters. Using precisely defined properties of the dispersed water phase in crystallization media, a highly efficient separation process in terms of selectivity and yield was developed. Small-angle X-ray scattering, high-performance liquid chromatography, mass spectrometry, and scanning electron microscopy were used to monitor and analyze the separation processes and orlistat products obtained. Typical process characteristics, especially selectivity and yield in regard to reference examples, were compared and discussed. Copyright © 2012 Wiley Periodicals, Inc.

A comparison of small-area estimation techniques to estimate selected stand attributes using LiDAR-derived auxiliary variables

Treesearch

Michael E. Goerndt; Vicente J. Monleon; Hailemariam Temesgen

2011-01-01

One of the challenges often faced in forestry is the estimation of forest attributes for smaller areas of interest within a larger population. Small-area estimation (SAE) is a set of techniques well suited to estimation of forest attributes for small areas in which the existing sample size is small and auxiliary information is available. Selected SAE methods were...

Initial small mammal responses to alternative pine regeneration methods in Arkansas and Oklahoma: preliminary findings

Treesearch

Ronald E. Thill; Roger W. Perry; Nancy E. Koerth; Philip A. Tappe; David G. Peitz

2004-01-01

Abstract - We studied winter small mammal communities in the Ouachita Mountains of west-central Arkansas and eastern Oklahoma using Sherman live traps in four replications of four regeneration treatments (clearcut/plant, shelterwood, single-tree selection, and group selection), plus four mature, untreated "controls." Data on relative small...

Palladium-tin catalysts for the direct synthesis of H 2O 2 with high selectivity

DOE PAGES

Freakley, Simon J.; He, Qian; Harrhy, Jonathan H.; ...

2016-02-25

The direct synthesis of hydrogen peroxide (H 2O 2 ) from H 2 and O 2 represents a potentially atom-efficient alternative to the current industrial indirect process. We show that the addition of tin to palladium catalysts coupled with an appropriate heat treatment cycle switches off the sequential hydrogenation and decomposition reactions, enabling selectivities of >95% toward H 2O 2 . This effect arises from a tin oxide surface layer that encapsulates small Pd-rich particles while leaving larger Pd-Sn alloy particles exposed. In conclusion, we show that this effect is a general feature for oxide-supported Pd catalysts containing an appropriatemore » second metal oxide component, and we set out the design principles for producing high-selectivity Pd-based catalysts for direct H 2O 2 production that do not contain gold.« less

Mechanism of secondary recrystallization of Goss grains in grain-oriented electrical steel

NASA Astrophysics Data System (ADS)

Hayakawa, Yasuyuki

2017-12-01

Since its invention by Goss in 1934, grain-oriented (GO) electrical steel has been widely used as a core material in transformers. GO exhibits a grain size of over several millimeters attained by secondary recrystallization during high-temperature final batch annealing. In addition to the unusually large grain size, the crystal direction in the rolling direction is aligned with <001>, which is the easy magnetization axis of α-iron. Secondary recrystallization is the phenomenon in which a certain very small number of {110}<001> (Goss) grains grow selectively (about one in 106 primary grains) at the expense of many other primary recrystallized grains. The question of why the Goss orientation is exclusively selected during secondary recrystallization has long been a main research subject in this field. The general criterion for secondary recrystallization is a small and uniform primary grain size, which is achieved through the inhibition of normal grain growth by fine precipitates called inhibitors. This paper describes several conceivable mechanisms of secondary recrystallization of Goss grains mainly based on the selective growth model.

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

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

Jenson, Justin M.; Ryan, Jeremy A.; Grant, Robert A.

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry,more » relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.« less

Quantitation of cocaine and cocaethylene in small volumes of rat whole blood using gas chromatography-mass spectrometry.

PubMed

Burdick, J D; Boni, R L; Fochtman, F W

1997-05-01

A simple solid phase extraction (SPE) technique combined with gas chromatography-mass spectrometry (GC/MS) operated in selected ion monitoring (SIM) mode is described for quantitation of cocaine and cocaethylene in small samples (250 microliters) of rat whole blood. Use of (N-[2H3C])-cocaine and (N-[2H3C])-cocaethylene internal standards resulted in high sensitivity and selectivity for this analytical method. Analysis was performed using a Hewlett-Packard 5890 GC equipped with a 7673A Automatic Liquid Sampler linked to a Hewlett-Packard 5972 Mass Selective Detector. Separation of analytes was accomplished on a cross-linked methyl silicone gum capillary column (Ultra 1: 12m x 0.2mm (i.d.) x 0.33 microns). Linearity was established over a wide range of concentrations (5.0-2000.0 ng ml-1) with good precision. Limits of detection (LOD) were 1.0 and 2.0 ng ml-1 for cocaine and cocaethylene, respectively. This analytical method was designed for use in pharmacokinetic experiments studying the formation of cocaethylene following ethanol pretreatment in rats administered cocaine.

Mechanism of secondary recrystallization of Goss grains in grain-oriented electrical steel

PubMed Central

Hayakawa, Yasuyuki

2017-01-01

Abstract Since its invention by Goss in 1934, grain-oriented (GO) electrical steel has been widely used as a core material in transformers. GO exhibits a grain size of over several millimeters attained by secondary recrystallization during high-temperature final batch annealing. In addition to the unusually large grain size, the crystal direction in the rolling direction is aligned with <001>, which is the easy magnetization axis of α-iron. Secondary recrystallization is the phenomenon in which a certain very small number of {110}<001> (Goss) grains grow selectively (about one in 106 primary grains) at the expense of many other primary recrystallized grains. The question of why the Goss orientation is exclusively selected during secondary recrystallization has long been a main research subject in this field. The general criterion for secondary recrystallization is a small and uniform primary grain size, which is achieved through the inhibition of normal grain growth by fine precipitates called inhibitors. This paper describes several conceivable mechanisms of secondary recrystallization of Goss grains mainly based on the selective growth model. PMID:28804524

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

PubMed Central

Jenson, Justin M; Ryan, Jeremy A; Grant, Robert A; Letai, Anthony; Keating, Amy E

2017-01-01

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors. DOI: http://dx.doi.org/10.7554/eLife.25541.001 PMID:28594323

Mechanism of secondary recrystallization of Goss grains in grain-oriented electrical steel.

PubMed

Hayakawa, Yasuyuki

2017-01-01

Since its invention by Goss in 1934, grain-oriented (GO) electrical steel has been widely used as a core material in transformers. GO exhibits a grain size of over several millimeters attained by secondary recrystallization during high-temperature final batch annealing. In addition to the unusually large grain size, the crystal direction in the rolling direction is aligned with <001>, which is the easy magnetization axis of α-iron. Secondary recrystallization is the phenomenon in which a certain very small number of {110}<001> (Goss) grains grow selectively (about one in 10 6 primary grains) at the expense of many other primary recrystallized grains. The question of why the Goss orientation is exclusively selected during secondary recrystallization has long been a main research subject in this field. The general criterion for secondary recrystallization is a small and uniform primary grain size, which is achieved through the inhibition of normal grain growth by fine precipitates called inhibitors. This paper describes several conceivable mechanisms of secondary recrystallization of Goss grains mainly based on the selective growth model.

Are heritability and selection related to population size in nature? Meta-analysis and conservation implications.

PubMed

Wood, Jacquelyn L A; Yates, Matthew C; Fraser, Dylan J

2016-06-01

It is widely thought that small populations should have less additive genetic variance and respond less efficiently to natural selection than large populations. Across taxa, we meta-analytically quantified the relationship between adult census population size (N) and additive genetic variance (proxy: h (2)) and found no reduction in h (2) with decreasing N; surveyed populations ranged from four to one million individuals (1735 h (2) estimates, 146 populations, 83 species). In terms of adaptation, ecological conditions may systematically differ between populations of varying N; the magnitude of selection these populations experience may therefore also differ. We thus also meta-analytically tested whether selection changes with N and found little evidence for systematic differences in the strength, direction or form of selection with N across different trait types and taxa (7344 selection estimates, 172 populations, 80 species). Collectively, our results (i) indirectly suggest that genetic drift neither overwhelms selection more in small than in large natural populations, nor weakens adaptive potential/h (2) in small populations, and (ii) imply that natural populations of varying sizes experience a variety of environmental conditions, without consistently differing habitat quality at small N. However, we caution that the data are currently insufficient to determine whether some small populations may retain adaptive potential definitively. Further study is required into (i) selection and genetic variation in completely isolated populations of known N, under-represented taxonomic groups, and nongeneralist species, (ii) adaptive potential using multidimensional approaches and (iii) the nature of selective pressures for specific traits.

Examining small molecule: HIV RNA interactions using arrayed imaging reflectometry

NASA Astrophysics Data System (ADS)

Chaimayo, Wanaruk; Miller, Benjamin L.

2014-03-01

Human Immunodeficiency Virus (HIV) has been the subject of intense research for more than three decades as it causes an uncurable disease: Acquired Immunodeficiency Syndrome, AIDS. In the pursuit of a medical treatment, RNAtargeted small molecules are emerging as promising targets. In order to understand the binding kinetics of small molecules and HIV RNA, association (ka) and dissociation (kd) kinetic constants must be obtained, ideally for a large number of sequences to assess selectivity. We have developed Aqueous Array Imaged Reflectometry (Aq-AIR) to address this challenge. Using a simple light interference phenomenon, Aq-AIR provides real-time high-throughput multiplex capabilities to detect binding of targets to surface-immobilized probes in a label-free microarray format. The second generation of Aq-AIR consisting of high-sensitivity CCD camera and 12-μL flow cell was fabricated. The system performance was assessed by real-time detection of MBNL1-(CUG)10 and neomycin B - HIV RNA bindings. The results establish this second-generation Aq-AIR to be able to examine small molecules binding to RNA sequences specific to HIV.

When bigger is not better: selection against large size, high condition and fast growth in juvenile lemon sharks.

PubMed

Dibattista, J D; Feldheim, K A; Gruber, S H; Hendry, A P

2007-01-01

Selection acting on large marine vertebrates may be qualitatively different from that acting on terrestrial or freshwater organisms, but logistical constraints have thus far precluded selection estimates for the former. We overcame these constraints by exhaustively sampling and repeatedly recapturing individuals in six cohorts of juvenile lemon sharks (450 age-0 and 255 age-1 fish) at an enclosed nursery site (Bimini, Bahamas). Data on individual size, condition factor, growth rate and inter-annual survival were used to test the 'bigger is better', 'fatter is better' and 'faster is better' hypotheses of life-history theory. For age-0 sharks, selection on all measured traits was weak, and generally acted against large size and high condition. For age-1 sharks, selection was much stronger, and consistently acted against large size and fast growth. These results suggest that selective pressures at Bimini may be constraining the evolution of large size and fast growth, an observation that fits well with the observed small size and low growth rate of juveniles at this site. Our results support those of some other recent studies in suggesting that bigger/fatter/faster is not always better, and may often be worse.

Carbon nanotubes-based chemiresistive immunosensor for small molecules: detection of nitroaromatic explosives.

PubMed

Park, Miso; Cella, Lakshmi N; Chen, Wilfred; Myung, Nosang V; Mulchandani, Ashok

2010-12-15

In recent years, there has been a growing focus on use of one-dimensional (1-D) nanostructures, such as carbon nanotubes and nanowires, as transducer elements for label-free chemiresistive/field-effect transistor biosensors as they provide label-free and high sensitivity detection. While research to-date has elucidated the power of carbon nanotubes- and other 1-D nanostructure-based field effect transistors immunosensors for large charged macromolecules such as proteins and viruses, their application to small uncharged or charged molecules has not been demonstrated. In this paper we report a single-walled carbon nanotubes (SWNTs)-based chemiresistive immunosensor for label-free, rapid, sensitive and selective detection of 2,4,6-trinitrotoluene (TNT), a small molecule. The newly developed immunosensor employed a displacement mode/format in which SWNTs network forming conduction channel of the sensor was first modified with trinitrophenyl (TNP), an analog of TNT, and then ligated with the anti-TNP single chain antibody. Upon exposure to TNT or its derivatives the bound antibodies were displaced producing a large change, several folds higher than the noise, in the resistance/conductance of SWNTs giving excellent limit of detection, sensitivity and selectivity. The sensor detected between 0.5 ppb and 5000 ppb TNT with good selectivity to other nitroaromatic explosives and demonstrated good accuracy for monitoring TNT in untreated environmental water matrix. We believe this new displacement format can be easily generalized to other one-dimensional nanostructure-based chemiresistive immuno/affinity-sensors for detecting small and/or uncharged molecules of interest in environmental monitoring and health care. Copyright © 2010 Elsevier B.V. All rights reserved.

[Crystal structure of SMU.2055 protein from Streptococcus mutans and its small molecule inhibitors design and selection].

PubMed

Xiaodan, Chen; Xiurong, Zhan; Xinyu, Wu; Chunyan, Zhao; Wanghong, Zhao

2015-04-01

The aim of this study is to analyze the three-dimensional crystal structure of SMU.2055 protein, a putative acetyltransferase from the major caries pathogen Streptococcus mutans (S. mutans). The design and selection of the structure-based small molecule inhibitors are also studied. The three-dimensional crystal structure of SMU.2055 protein was obtained by structural genomics research methods of gene cloning and expression, protein purification with Ni²⁺-chelating affinity chromatography, crystal screening, and X-ray diffraction data collection. An inhibitor virtual model matching with its target protein structure was set up using computer-aided drug design methods, virtual screening and fine docking, and Libdock and Autodock procedures. The crystal of SMU.2055 protein was obtained, and its three-dimensional crystal structure was analyzed. This crystal was diffracted to a resolution of 0.23 nm. It belongs to orthorhombic space group C222(1), with unit cell parameters of a = 9.20 nm, b = 9.46 nm, and c = 19.39 nm. The asymmetric unit contained four molecules, with a solvent content of 56.7%. Moreover, five small molecule compounds, whose structure matched with that of the target protein in high degree, were designed and selected. Protein crystallography research of S. mutans SMU.2055 helps to understand the structures and functions of proteins from S. mutans at the atomic level. These five compounds may be considered as effective inhibitors to SMU.2055. The virtual model of small molecule inhibitors we built will lay a foundation to the anticaries research based on the crystal structure of proteins.

Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.

PubMed

Ikegami, Tohru; Tanaka, Nobuo

2016-06-12

Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.

Urea transporter proteins as targets for small-molecule diuretics.

PubMed

Esteva-Font, Cristina; Anderson, Marc O; Verkman, Alan S

2015-02-01

Conventional diuretics such as furosemide and thiazides target salt transporters in kidney tubules, but urea transporters (UTs) have emerged as alternative targets. UTs are a family of transmembrane channels expressed in a variety of mammalian tissues, in particular the kidney. UT knockout mice and humans with UT mutations exhibit reduced maximal urinary osmolality, demonstrating that UTs are necessary for the concentration of urine. Small-molecule screening has identified potent and selective inhibitors of UT-A, the UT protein expressed in renal tubule epithelial cells, and UT-B, the UT protein expressed in vasa recta endothelial cells. Data from UT knockout mice and from rodents administered UT inhibitors support the diuretic action of UT inhibition. The kidney-specific expression of UT-A1, together with high selectivity of the small-molecule inhibitors, means that off-target effects of such small-molecule drugs should be minimal. This Review summarizes the structure, expression and function of UTs, and looks at the evidence supporting the validity of UTs as targets for the development of salt-sparing diuretics with a unique mechanism of action. UT-targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.

Analytic theory for the selection of 2-D needle crystal at arbitrary Peclet number

NASA Technical Reports Server (NTRS)

Tanveer, Saleh

1989-01-01

An accurate analytic theory is presented for the velocity selection of a two-dimensional needle crystal for arbitrary Peclet number for small values of the surface tension parameter. The velocity selection is caused by the effect of transcendentally small terms which are determined by analytic continuation to the complex plane and analysis of nonlinear equations. The work supports the general conclusion of previous small Peclet number analytical results of other investigators, though there are some discrepancies in details. It also addresses questions raised on the validity of selection theory owing to assumptions made on shape corrections at large distances from the tip.

Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411.

PubMed

Holmboe, Sif; Hansen, Pernille Lund; Thisgaard, Helge; Block, Ines; Müller, Carolin; Langkjær, Niels; Høilund-Carlsen, Poul Flemming; Olsen, Birgitte Brinkmann; Mollenhauer, Jan

2017-01-01

Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somatostatin receptor 2 and nucleolin are known to be overexpressed by various cancer types, which have elicited comprehensive efforts to explore their therapeutic utilization. Here, we evaluated somatostatin receptor 2 targeting and nucleolin targeting for therapeutic delivery to cancer stem cells from lung cancer. Nucleolin is expressed highly but not selectively, while somatostatin receptor 2 is expressed selectively but not highly by cancer cells. The non-small cell lung cancer cell lines A549 and H1299, displayed average levels of both surface molecules as judged based on analysis of a larger cell line panel. H1299 compared to A549 cells showed significantly elevated sphere-forming capacity, indicating higher cancer stem cell content, thus qualifying as suitable test system. Nucleolin-targeting 57Co-DOTA-AS1411 aptamer showed efficient internalization by cancer cells and, remarkably, at even higher efficiency by cancer stem cells. In contrast, somatostatin receptor 2 expression levels were not sufficiently high in H1299 cells to confer efficient uptake by either non-cancer stem cells or cancer stem cells. The data provides indication that the nucleolin-targeting AS1411 aptamer might be used for therapeutic delivery to non-small cell lung cancer stem cells.

Why are most aquatic plants widely distributed? Dispersal, clonal growth and small-scale heterogeneity in a stressful environment

NASA Astrophysics Data System (ADS)

Santamaría, Luis

2002-06-01

Non-marine aquatic vascular plants generally show broad distributional ranges. Climatic factors seem to have limited effects on their distributions, besides the determination of major disjunctions (tropical-temperate-subarctic). Dispersal should have been frequent enough to assure the quick colonisation of extensive areas following glacial retreat, but dispersal limitation is still apparent in areas separated by geographic barriers. Aquatic vascular plants also show limited taxonomic differentiation and low within-species genetic variation. Variation within populations is particularly low, but variation among populations seems to be relatively high, mainly due to the persistence of long-lived clones. Ecotypic differentiation is often related to factors that constrain clonal reproduction (salinity and ephemeral inundation). Inland aquatic habitats are heterogeneous environments, but this heterogeneity largely occurs at relatively small scales (within waterbodies and among neighbouring ones). They also represent a stressful environment for plants, characterised by low carbon availability, shaded conditions, sediment anoxia, mechanical damage by currents and waves, significant restrictions to sexual reproduction, and sometimes also osmotic stress and limited nutrient supply. I propose that the generality of broad distributions and low differentiation among the inland aquatic flora is best explained by a combination of: (1) selection for stress-tolerant taxa with broad tolerance ranges. (2) The selective advantages provided by clonal growth and multiplication, which increases plant tolerance to stress, genet survivorship and population viability. (3) Long-distance dispersal of sexual propagules and high local dispersal of asexual clones. (4) The generality of broad plastic responses, promoted by the combination of clonal growth, high local dispersal, small-scale spatial heterogeneity and temporal variability.

Generative model selection using a scalable and size-independent complex network classifier

NASA Astrophysics Data System (ADS)

Motallebi, Sadegh; Aliakbary, Sadegh; Habibi, Jafar

2013-12-01

Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree for model selection. Our proposed method, which is named "Generative Model Selection for Complex Networks," outperforms existing methods with respect to accuracy, scalability, and size-independence.

A novel strategy for selection of allosteric ribozymes yields RiboReporter™ sensors for caffeine and aspartame

PubMed Central

Ferguson, Alicia; Boomer, Ryan M.; Kurz, Markus; Keene, Sara C.; Diener, John L.; Keefe, Anthony D.; Wilson, Charles; Cload, Sharon T.

2004-01-01

We have utilized in vitro selection technology to develop allosteric ribozyme sensors that are specific for the small molecule analytes caffeine or aspartame. Caffeine- or aspartame-responsive ribozymes were converted into fluorescence-based RiboReporter™ sensor systems that were able to detect caffeine or aspartame in solution over a concentration range from 0.5 to 5 mM. With read-times as short as 5 min, these caffeine- or aspartame-dependent ribozymes function as highly specific and facile molecular sensors. Interestingly, successful isolation of allosteric ribozymes for the analytes described here was enabled by a novel selection strategy that incorporated elements of both modular design and activity-based selection methods typically used for generation of catalytic nucleic acids. PMID:15026535

An Attempt of Formalizing the Selection Parameters for Settlements Generalization in Small-Scales

NASA Astrophysics Data System (ADS)

Karsznia, Izabela

2014-12-01

The paper covers one of the most important problems concerning context-sensitive settlement selection for the purpose of the small-scale maps. So far, no formal parameters for small-scale settlements generalization have been specified, hence the problem seems to be an important and innovative challenge. It is also crucial from the practical point of view as it is necessary to develop appropriate generalization algorithms for the purpose of the General Geographic Objects Database generalization which is the essential Spatial Data Infrastructure component in Poland. The author proposes and verifies quantitative generalization parameters for the purpose of the settlement selection process in small-scale maps. The selection of settlements was carried out in two research areas - in Lower Silesia and Łódź Province. Based on the conducted analysis appropriate contextual-sensitive settlements selection parameters have been defined. Particular effort has been made to develop a methodology of quantitative settlements selection which would be useful in the automation processes and that would make it possible to keep specifics of generalized objects unchanged.

An Exemplary Program for Occupational Preparation in Selected Agricultural and Industrial Activities for Small High Schools in Utah. An Integrated Shop Program.

ERIC Educational Resources Information Center

Wasden, Jed W.

Many educational problems center around vocational education--its place in the total educational program, its relation to academic education, when vocational education should be started, and who should participate. Vocational education, the alternative to college preparatory programs, is frequently rejected and more often misunderstood by…

Theory and Practice: How Filming "Learning in the Real World" Helps Students Make the Connection

ERIC Educational Resources Information Center

Commander, Nannette Evans; Ward, Teresa E.; Zabrucky, Karen M.

2012-01-01

This article describes an assignment, titled "Learning in the Real World," designed for graduate students in a learning theory course. Students work in small groups to create high quality audio-visual films that present "real learning" through interviews and/or observations of learners. Students select topics relevant to theories we are discussing…

Working with Street Children. Selected Case-Studies from Africa, Asia and Latin America. Youth Plus Series.

ERIC Educational Resources Information Center

International Catholic Child Bureau, Geneva (Switzerland).

Governments have traditionally left the plight of street children and working children, who by some counts number over 100 million, to individuals and nongovernmental organizations, including many religious organizations. As a result, there are a multitude of small, uncoordinated, but highly effective projects throughout the world concentrated in…

“AmaRosa,” a red skinned, red fleshed fingerling with high phytonutrient value

USDA-ARS?s Scientific Manuscript database

AmaRosa is a mid season specialty potato with red skin and red flesh. This selection is unique among commercially available potato varieties in that plants set a large number of smooth, small, fingerling-shaped tubers with red skin and red flesh. AmaRosa tubers have higher total anthocyanin and hyd...

Woodland salamander and small mammal responses to alternative silvicultural practices in the Southern Appalachians of North Carolina

Treesearch

W. Mark Ford; Michael A. Menzel; Timothy S. McCay; Jonathan W. Gassett; Joshua Laerm

2000-01-01

The effects of 2 years post-treatment of group selection and 2-aged timber harvests on woodland salamanders and mammals were assessed on stands in high elevation, southern Appalachian northern red oak (Quercus rubra)-flame azalea (Rhododendron calendulaceum) communities, in the Nantahala National Forest. We collected 4 salamander...

Revolution in Higher Education: How a Small Band of Innovators Will Make College Accessible and Affordable

ERIC Educational Resources Information Center

DeMillo, Richard A.

2015-01-01

Colleges and universities have become increasingly costly, and, except for a handful of highly selective, elite institutions, unresponsive to twenty-first-century needs. But for the past few years, technology-fueled innovation has begun to transform higher education, introducing new ways to disseminate knowledge and better ways to learn--all at…

Evolution of high mobility group nucleosome-binding proteins and its implications for vertebrate chromatin specialization.

PubMed

González-Romero, Rodrigo; Eirín-López, José M; Ausió, Juan

2015-01-01

High mobility group (HMG)-N proteins are a family of small nonhistone proteins that bind to nucleosomes (N). Despite the amount of information available on their structure and function, there is an almost complete lack of information on the molecular evolutionary mechanisms leading to their exclusive differentiation. In the present work, we provide evidence suggesting that HMGN lineages constitute independent monophyletic groups derived from a common ancestor prior to the diversification of vertebrates. Based on observations of the functional diversification across vertebrate HMGN proteins and on the extensive silent nucleotide divergence, our results suggest that the long-term evolution of HMGNs occurs under strong purifying selection, resulting from the lineage-specific functional constraints of their different protein domains. Selection analyses on independent lineages suggest that their functional specialization was mediated by bursts of adaptive selection at specific evolutionary times, in a small subset of codons with functional relevance-most notably in HMGN1, and in the rapidly evolving HMGN5. This work provides useful information to our understanding of the specialization imparted on chromatin metabolism by HMGNs, especially on the evolutionary mechanisms underlying their functional differentiation in vertebrates. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genomic complexity and dynamics of clonal evolution in childhood acute myeloid leukemia studied with whole-exome sequencing.

PubMed

Masetti, Riccardo; Castelli, Ilaria; Astolfi, Annalisa; Bertuccio, Salvatore Nicola; Indio, Valentina; Togni, Marco; Belotti, Tamara; Serravalle, Salvatore; Tarantino, Giuseppe; Zecca, Marco; Pigazzi, Martina; Basso, Giuseppe; Pession, Andrea; Locatelli, Franco

2016-08-30

Despite significant improvement in treatment of childhood acute myeloid leukemia (AML), 30% of patients experience disease recurrence, which is still the major cause of treatment failure and death in these patients. To investigate molecular mechanisms underlying relapse, we performed whole-exome sequencing of diagnosis-relapse pairs and matched remission samples from 4 pediatric AML patients without recurrent cytogenetic alterations. Candidate driver mutations were selected for targeted deep sequencing at high coverage, suitable to detect small subclones (0.12%). BiCEBPα mutation was found to be stable and highly penetrant, representing a separate biological and clinical entity, unlike WT1 mutations, which were extremely unstable. Among the mutational patterns underlying relapse, we detected the acquisition of proliferative advantage by signaling activation (PTPN11 and FLT3-TKD mutations) and the increased resistance to apoptosis (hyperactivation of TYK2). We also found a previously undescribed feature of AML, consisting of a hypermutator phenotype caused by SETD2 inactivation. The consequent accumulation of new mutations promotes the adaptability of the leukemia, contributing to clonal selection. We report a novel ASXL3 mutation characterizing a very small subclone (<1%) present at diagnosis and undergoing expansion (60%) at relapse. Taken together, these findings provide molecular clues for designing optimal therapeutic strategies, in terms of target selection, adequate schedule design and reliable response-monitoring techniques.

Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors

PubMed Central

Smith, Aaron L.; Freeman, Sara M.; Stehouwer, Jeffery S.; Inoue, Kiyoshi; Voll, Ronald J.; Young, Larry J.; Goodman, Mark M.

2013-01-01

Compounds 1–4 were synthesized and investigated for selectivity and potency for the oxytocin receptor (OTR) to determine their viability as radioactive ligands. Binding assays determined 1–4 to have high binding affinity for both the human and rodent OTR and also have high selectivity for the human OTR over human vasopressin V1a receptors (V1aR). Inadequate selectivity for OTR over V1aR was found for rodent receptors in all four compounds. The radioactive (C-11, F-18, and I-125) derivatives of 1–4 were synthesized and investigated for use as autoradiography and positron emission tomography (PET) ligands. Receptor autoradiography performed with [125I]1 and [125I]2 on rodent brain slices provided the first small molecule radioligand images of the OTR and V1aR. Biodistribution studies determined [125I]1 and [125I]2 were adequate for in vivo peripheral investigations, but not for central investigations due to low uptake within the brain. A biodistribution study with [18F]3 suggested brain uptake occurred slowly over time. PET imaging studies with [18F]3 and [11C]4 using a rat model provided insufficient uptake in the brain over a 90 and 45 min scan times respectively to merit further investigations in non-human primates. PMID:22425346

Diuresis and reduced urinary osmolality in rats produced by small-molecule UT-A-selective urea transport inhibitors.

PubMed

Esteva-Font, Cristina; Cil, Onur; Phuan, Puay-Wah; Su, Tao; Lee, Sujin; Anderson, Marc O; Verkman, A S

2014-09-01

Urea transport (UT) proteins of the UT-A class are expressed in epithelial cells in kidney tubules, where they are required for the formation of a concentrated urine by countercurrent multiplication. Here, using a recently developed high-throughput assay to identify UT-A inhibitors, a screen of 50,000 synthetic small molecules identified UT-A inhibitors of aryl-thiazole, γ-sultambenzosulfonamide, aminocarbonitrile butene, and 4-isoxazolamide chemical classes. Structure-activity analysis identified compounds that inhibited UT-A selectively by a noncompetitive mechanism with IC50 down to ∼1 μM. Molecular modeling identified putative inhibitor binding sites on rat UT-A. To test compound efficacy in rats, formulations and administration procedures were established to give therapeutic inhibitor concentrations in blood and urine. We found that intravenous administration of an indole thiazole or a γ-sultambenzosulfonamide at 20 mg/kg increased urine output by 3-5-fold and reduced urine osmolality by ∼2-fold compared to vehicle control rats, even under conditions of maximum antidiuresis produced by 1-deamino-8-D-arginine vasopressin (DDAVP). The diuresis was reversible and showed urea > salt excretion. The results provide proof of concept for the diuretic action of UT-A-selective inhibitors. UT-A inhibitors are first in their class salt-sparing diuretics with potential clinical indications in volume-overload edemas and high-vasopressin-associated hyponatremias. © FASEB.

Insights to primitive replication derived from structures of small oligonucleotides

NASA Technical Reports Server (NTRS)

Smith, G. K.; Fox, G. E.

1995-01-01

Available information on the structure of small oligonucleotides is surveyed. It is observed that even small oligomers typically exhibit defined structures over a wide range of pH and temperature. These structures rely on a plethora of non-standard base-base interactions in addition to the traditional Watson-Crick pairings. Stable duplexes, though typically antiparallel, can be parallel or staggered and perfect complementarity is not essential. These results imply that primitive template directed reactions do not require high fidelity. Hence, the extensive use of Watson-Crick complementarity in genes rather than being a direct consequence of the primitive condensation process, may instead reflect subsequent selection based on the advantage of accuracy in maintaining the primitive genetic machinery once it arose.

Gravitational lensing in a cold dark matter universe

NASA Technical Reports Server (NTRS)

Narayan, Ramesh; White, Simon D. M.

1988-01-01

Gravitational lensing due to mass condensations in a biased cold dark matter (CDM) universe is investigated using the Press-Schechter (1974) theory with density fluctuation amplitudes taken from previous N-body work. Under the critical assumption that CDM haloes have small core radii, a distribution of image angular separations for high-z lensed quasars with a peak at about 1 arcsec and a half-width of a factor of about 10. Allowing for selection effects at small angular separations, this is in good agreement with the observed separations. The estimated frequency of lensing is somewhat lower than that observed, but the discrepancy can be removed by invoking amplification bias and by making a small upward adjustment to the density fluctuation amplitudes assumed in the CDM model.

Detection of small human cerebral cortical lesions with MRI under different levels of Gaussian smoothing: applications in epilepsy

NASA Astrophysics Data System (ADS)

Cantor-Rivera, Diego; Goubran, Maged; Kraguljac, Alan; Bartha, Robert; Peters, Terry

2010-03-01

The main objective of this study was to assess the effect of smoothing filter selection in Voxel-Based Morphometry studies on structural T1-weighted magnetic resonance images. Gaussian filters of 4 mm, 8 mm or 10 mm Full Width at High Maximum are commonly used, based on the assumption that the filter size should be at least twice the voxel size to obtain robust statistical results. The hypothesis of the presented work was that the selection of the smoothing filter influenced the detectability of small lesions in the brain. Mesial Temporal Sclerosis associated to Epilepsy was used as the case to demonstrate this effect. Twenty T1-weighted MRIs from the BrainWeb database were selected. A small phantom lesion was placed in the amygdala, hippocampus, or parahippocampal gyrus of ten of the images. Subsequently the images were registered to the ICBM/MNI space. After grey matter segmentation, a T-test was carried out to compare each image containing a phantom lesion with the rest of the images in the set. For each lesion the T-test was repeated with different Gaussian filter sizes. Voxel-Based Morphometry detected some of the phantom lesions. Of the three parameters considered: location,size, and intensity; it was shown that location is the dominant factor for the detection of the lesions.

A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

PubMed

Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

2015-12-01

Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

Low-Power, Chip-Scale, Carbon Dioxide Gas Sensors for Spacesuit Monitoring

NASA Technical Reports Server (NTRS)

Rani, Asha; Shi, Chen; Thomson, Brian; Debnath, Ratan; Wen, Boamei; Motayed, Abhishek; Chullen, Cinda

2018-01-01

N5 Sensors, Inc. through a Small Business Technology Transfer (STTR) contract award has been developing ultra-small, low-power carbon dioxide (CO2) gas sensors, suited for monitoring CO2 levels inside NASA spacesuits. Due to the unique environmental conditions within the spacesuits, such as high humidity, large temperature swings, and operating pressure swings, measurement of key gases relevant to astronaut's safety and health such as(CO2), is quite challenging. Conventional non-dispersive infrared absorption based CO2 sensors present challenges inside the spacesuits due to size, weight, and power constraints, along with the ability to sense CO2 in a high humidity environment. Unique chip-scale, nanoengineered chemiresistive gas-sensing architecture has been developed for this application, which can be operated in a typical space-suite environmental conditions. Unique design combining the selective adsorption properties of the nanophotocatalytic clusters of metal-oxides and metals, provides selective detection of CO2 in high relative humidity conditions. All electronic design provides a compact and low-power solution, which can be implemented for multipoint detection of CO2 inside the spacesuits. This paper will describe the sensor architecture, development of new photocatalytic material for better sensor response, and advanced structure for better sensitivity and shorter response times.

The 3'UTR of nanos2 directs enrichment in the germ cell lineage of the sea urchin.

PubMed

Oulhen, Nathalie; Yoshida, Takaya; Yajima, Mamiko; Song, Jia L; Sakuma, Tetsushi; Sakamoto, Naoaki; Yamamoto, Takashi; Wessel, Gary M

2013-05-01

Nanos is a translational regulator required for the survival and maintenance of primordial germ cells during embryogenesis. Three nanos homologs are present in the genome of the sea urchin Strongylocentrotus purpuratus (Sp), and each nanos mRNA accumulates specifically in the small micromere (sMic) lineage. We found that a highly conserved element in the 3' UTR of nanos2 is sufficient for reporter expression selectively in the sMic lineage: microinjection into a Sp fertilized egg of an RNA that contains the GFP open reading frame followed by Sp nanos2 3'UTR leads to selective reporter enrichment in the small micromeres in blastulae. The same result was seen with nanos2 from the sea urchin Hemicentrotus pulcherrimus (Hp). In both species, the 5'UTR alone is not sufficient for the sMic localization but it always increased the sMic reporter enrichment when present with the 3'UTR. We defined an element conserved between Hp and Sp in the nanos2 3'UTR which is necessary and sufficient for protein enrichment in the sMic, and refer to it as GNARLE (Global Nanos Associated RNA Lability Element). We also found that the nanos2 3'UTR is essential for the selective RNA retention in the small micromeres; GNARLE is required but not sufficient for this process. These results show that a combination of selective RNA retention and translational control mechanisms instills nanos accumulation uniquely in the sMic lineage. Copyright © 2013 Elsevier Inc. All rights reserved.

The 3’UTR of Nanos2 directs enrichment in the germ cell lineage of the sea urchin

PubMed Central

Oulhen, Nathalie; Yoshida, Takaya; Yajima, Mamiko; Song, Jia; Sakuma, Tetsushi; Sakamoto, Naoaki; Yamamoto, Takashi; Wessel, Gary M.

2013-01-01

Nanos is a translational regulator required for the survival and maintenance of primordial germ cells during embryogenesis. Three nanos homologs are present in the genome of the sea urchin Strongylocentrotus purpuratus (Sp), and each nanos mRNA accumulates specifically in the small micromere (sMic) lineage. We found that a highly conserved element in the 3’ UTR of nanos2 is sufficient for reporter expression selectively in the sMic lineage: microinjection into a Sp fertilized egg of an RNA that contains the GFP open reading frame followed by Sp nanos2 3’UTR leads to selective reporter enrichment in the small micromeres in blastulae. The same result was seen with nanos2 from the sea urchin Hemicentrotus pulcherrimus (Hp). In both species, the 5’UTR alone is not sufficient for the sMic localization but it always increased the sMic reporter enrichment when present with the 3’UTR. We defined an element conserved between Hp and Sp in the nanos2 3’UTR which is necessary and sufficient for protein enrichment in the sMic, and refer to it as GNARLE (Global Nanos Associated RNA Lability Element). We also found that the nanos2 3’UTR is essential for the selective RNA retention in the small micromeres; GNARLE is required but not sufficient for this process. These results show that a combination of selective RNA retention and translational control mechanisms instills nanos accumulation uniquely in the sMic lineage. PMID:23357540

Photoinduced Electron Transfer Based Ion Sensing within an Optical Fiber

PubMed Central

Englich, Florian V.; Foo, Tze Cheung; Richardson, Andrew C.; Ebendorff-Heidepriem, Heike; Sumby, Christopher J.; Monro, Tanya M.

2011-01-01

We combine suspended-core microstructured optical fibers with the photoinduced electron transfer (PET) effect to demonstrate a new type of fluorescent optical fiber-dip sensing platform for small volume ion detection. A sensor design based on a simple model PET-fluoroionophore system and small core microstructured optical fiber capable of detecting sodium ions is demonstrated. The performance of the dip sensor operating in a high sodium concentration regime (925 ppm Na+) and for lower sodium concentration environments (18.4 ppm Na+) is explored and future approaches to improving the sensor’s signal stability, sensitivity and selectivity are discussed. PMID:22163712

Optimal marker-assisted selection to increase the effective size of small populations.

PubMed

Wang, J

2001-02-01

An approach to the optimal utilization of marker and pedigree information in minimizing the rates of inbreeding and genetic drift at the average locus of the genome (not just the marked loci) in a small diploid population is proposed, and its efficiency is investigated by stochastic simulations. The approach is based on estimating the expected pedigree of each chromosome by using marker and individual pedigree information and minimizing the average coancestry of selected chromosomes by quadratic integer programming. It is shown that the approach is much more effective and much less computer demanding in implementation than previous ones. For pigs with 10 offspring per mother genotyped for two markers (each with four alleles at equal initial frequency) per chromosome of 100 cM, the approach can increase the average effective size for the whole genome by approximately 40 and 55% if mating ratios (the number of females mated with a male) are 3 and 12, respectively, compared with the corresponding values obtained by optimizing between-family selection using pedigree information only. The efficiency of the marker-assisted selection method increases with increasing amount of marker information (number of markers per chromosome, heterozygosity per marker) and family size, but decreases with increasing genome size. For less prolific species, the approach is still effective if the mating ratio is large so that a high marker-assisted selection pressure on the rarer sex can be maintained.

Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.

PubMed

Rahm, Fredrik; Viklund, Jenny; Trésaugues, Lionel; Ellermann, Manuel; Giese, Anja; Ericsson, Ulrika; Forsblom, Rickard; Ginman, Tobias; Günther, Judith; Hallberg, Kenth; Lindström, Johan; Persson, Lars Boukharta; Silvander, Camilla; Talagas, Antoine; Díaz-Sáez, Laura; Fedorov, Oleg; Huber, Kilian V M; Panagakou, Ioanna; Siejka, Paulina; Gorjánácz, Mátyás; Bauser, Marcus; Andersson, Martin

2018-03-22

Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.

Little Evidence That Time in Child Care Causes Externalizing Problems During Early Childhood in Norway

PubMed Central

Zachrisson, Henrik Daae; Dearing, Eric; Lekhal, Ratib; Toppelberg, Claudio O.

2012-01-01

Associations between maternal reports of hours in child care and children’s externalizing problems at 18 and 36 months of age were examined in a population-based Norwegian sample (n = 75,271). Within a sociopolitical context of homogenously high-quality child care, there was little evidence that high quantity of care causes externalizing problems. Using conventional approaches to handling selection bias and listwise deletion for substantial attrition in this sample, more hours in care predicted higher problem levels, yet with small effect sizes. The finding, however, was not robust to using multiple imputation for missing values. Moreover, when sibling and individual fixed-effects models for handling selection bias were used, no relation between hours and problems was evident. PMID:23311645

Prioritized LT Codes

NASA Technical Reports Server (NTRS)

Woo, Simon S.; Cheng, Michael K.

2011-01-01

The original Luby Transform (LT) coding scheme is extended to account for data transmissions where some information symbols in a message block are more important than others. Prioritized LT codes provide unequal error protection (UEP) of data on an erasure channel by modifying the original LT encoder. The prioritized algorithm improves high-priority data protection without penalizing low-priority data recovery. Moreover, low-latency decoding is also obtained for high-priority data due to fast encoding. Prioritized LT codes only require a slight change in the original encoding algorithm, and no changes at all at the decoder. Hence, with a small complexity increase in the LT encoder, an improved UEP and low-decoding latency performance for high-priority data can be achieved. LT encoding partitions a data stream into fixed-sized message blocks each with a constant number of information symbols. To generate a code symbol from the information symbols in a message, the Robust-Soliton probability distribution is first applied in order to determine the number of information symbols to be used to compute the code symbol. Then, the specific information symbols are chosen uniform randomly from the message block. Finally, the selected information symbols are XORed to form the code symbol. The Prioritized LT code construction includes an additional restriction that code symbols formed by a relatively small number of XORed information symbols select some of these information symbols from the pool of high-priority data. Once high-priority data are fully covered, encoding continues with the conventional LT approach where code symbols are generated by selecting information symbols from the entire message block including all different priorities. Therefore, if code symbols derived from high-priority data experience an unusual high number of erasures, Prioritized LT codes can still reliably recover both high- and low-priority data. This hybrid approach decides not only "how to encode" but also "what to encode" to achieve UEP. Another advantage of the priority encoding process is that the majority of high-priority data can be decoded sooner since only a small number of code symbols are required to reconstruct high-priority data. This approach increases the likelihood that high-priority data is decoded first over low-priority data. The Prioritized LT code scheme achieves an improvement in high-priority data decoding performance as well as overall information recovery without penalizing the decoding of low-priority data, assuming high-priority data is no more than half of a message block. The cost is in the additional complexity required in the encoder. If extra computation resource is available at the transmitter, image, voice, and video transmission quality in terrestrial and space communications can benefit from accurate use of redundancy in protecting data with varying priorities.

The Grassmannian Atlas: A General Framework for Exploring Linear Projections of High-Dimensional Data

DOE PAGES

Liu, S.; Bremer, P. -T; Jayaraman, J. J.; ...

2016-06-04

Linear projections are one of the most common approaches to visualize high-dimensional data. Since the space of possible projections is large, existing systems usually select a small set of interesting projections by ranking a large set of candidate projections based on a chosen quality measure. However, while highly ranked projections can be informative, some lower ranked ones could offer important complementary information. Therefore, selection based on ranking may miss projections that are important to provide a global picture of the data. Here, the proposed work fills this gap by presenting the Grassmannian Atlas, a framework that captures the global structuresmore » of quality measures in the space of all projections, which enables a systematic exploration of many complementary projections and provides new insights into the properties of existing quality measures.« less

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

Honorio, J.; Goldstein, R.; Honorio, J.

We propose a simple, well grounded classification technique which is suited for group classification on brain fMRI data sets that have high dimensionality, small number of subjects, high noise level, high subject variability, imperfect registration and capture subtle cognitive effects. We propose threshold-split region as a new feature selection method and majority voteas the classification technique. Our method does not require a predefined set of regions of interest. We use average acros ssessions, only one feature perexperimental condition, feature independence assumption, and simple classifiers. The seeming counter-intuitive approach of using a simple design is supported by signal processing and statisticalmore » theory. Experimental results in two block design data sets that capture brain function under distinct monetary rewards for cocaine addicted and control subjects, show that our method exhibits increased generalization accuracy compared to commonly used feature selection and classification techniques.« less

Walk the Line: The Development of Route Selection Standards for Spent Nuclear Fuel and High-level Radioactive Waste in the United States - 13519

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

Dilger, Fred; Halstead, Robert J.; Ballard, James D.

2013-07-01

Although storage facilities for spent nuclear fuel (SNF) and high-level radioactive waste (HLRW) are widely dispersed throughout the United States, these materials are also relatively concentrated in terms of geographic area. That is, the impacts of storage occur in a very small geographic space. Once shipments begin to a national repository or centralized interim storage facility, the impacts of SNF and HLRW will become more geographically distributed, more publicly visible, and almost certainly more contentious. The selection of shipping routes will likely be a major source of controversy. This paper describes the development of procedures, regulations, and standards for themore » selection of routes used to ship spent nuclear fuel and high-level radioactive waste in the United States. The paper begins by reviewing the circumstances around the development of HM-164 routing guidelines. The paper discusses the significance of New York City versus the Department of Transportation and application of HM-164. The paper describes the methods used to implement those regulations. The paper will also describe the current HM-164 designated routes and will provide a summary data analysis of their characteristics. This analysis will reveal the relatively small spatial scale of the effects of HM 164. The paper will then describe subsequent developments that have affected route selection for these materials. These developments include the use of 'representative routes' found in the Department of Energy (DOE) 2008 Supplemental Environmental Impact Statement for the formerly proposed Yucca Mountain geologic repository. The paper will describe recommendations related to route selection found in the National Academy of Sciences 2006 report Going the Distance, as well as recommendations found in the 2012 Final Report of the Blue Ribbon Commission on America's Nuclear Future. The paper will examine recently promulgated federal regulations (HM-232) for selection of rail routes for hazardous materials transport. The paper concludes that while the HM 164 regime is sufficient for certain applications, it does not provide an adequate basis for a national plan to ship spent nuclear fuel and high-level radioactive waste to centralized storage and disposal facilities over a period of 30 to 50 years. (authors)« less

Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

PubMed Central

Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

2015-01-01

Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

Surface stress sensor based on MEMS Fabry-Perot interferometer with high wavelength selectivity for label-free biosensing

NASA Astrophysics Data System (ADS)

Takahashi, Toshiaki; Hizawa, Takeshi; Misawa, Nobuo; Taki, Miki; Sawada, Kazuaki; Takahashi, Kazuhiro

2018-05-01

We have developed a surface stress sensor based on a microelectromechanical Fabry-Perot interferometer with high wavelength selectivity by using Au half-mirrors, for highly sensitive label-free biosensing. When the target molecule is adsorbed by the antigen-antibody reaction onto a movable membrane with a thin Au film, which acts as an upper mirror of the optical interferometer, the amount of deflection of the movable membrane deflected by the change in surface stress can be detected with high sensitivity. To improve the signal at the small membrane deflection region of this biosensor resulting in detection of low concentration molecules, by integrating 50 nm-thick Au half-mirrors, the wavelength selectivity of the optical interferometer has been successfully improved 6.6 times. Furthermore, the peak shift in the reflection spectrum due to the adsorption of bovine serum albumin (BSA) antigen with a concentration of 10 ng ml-l by the antigen-antibody reaction was spectroscopically measured on the fabricated optical interferometer, and the deflection amount of the movable membrane after 10 min treatment was 2.4 times larger than that of nonspecific adsorption with the avidin molecules. This result indicated that the proposed sensor can be used for selective detection of low-concentration target antigen molecules.

Monitoring/Verification using DMS: TATP Example

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

Stephan Weeks, Kevin Kyle, Manuel Manard

Field-rugged and field-programmable differential mobility spectrometry (DMS) networks provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. CBE sensor motes used in conjunction with automated fast gas chromatography with DMS detection (GC/DMS) verification instrumentation integrated into situational operations-management systems can be readily deployed and optimized for changing application scenarios. The feasibility of developing selective DMS motes for a “smart dust” sampling approach with guided, highly selective, fast GC/DMS verification analysis is a compelling approach to minimize or prevent the illegal use of explosives or chemical and biologicalmore » materials. DMS is currently one of the foremost emerging technologies for field separation and detection of gas-phase chemical species. This is due to trace-level detection limits, high selectivity, and small size. Fast GC is the leading field analytical method for gas phase separation of chemical species in complex mixtures. Low-thermal-mass GC columns have led to compact, low-power field systems capable of complete analyses in 15–300 seconds. A collaborative effort optimized a handheld, fast GC/DMS, equipped with a non-rad ionization source, for peroxide-based explosive measurements.« less

Monitoring/Verification Using DMS: TATP Example

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

Kevin Kyle; Stephan Weeks

Field-rugged and field-programmable differential mobility spectrometry (DMS) networks provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. CBE sensor motes used in conjunction with automated fast gas chromatography with DMS detection (GC/DMS) verification instrumentation integrated into situational operationsmanagement systems can be readily deployed and optimized for changing application scenarios. The feasibility of developing selective DMS motes for a “smart dust” sampling approach with guided, highly selective, fast GC/DMS verification analysis is a compelling approach to minimize or prevent the illegal use of explosives or chemical and biologicalmore » materials. DMS is currently one of the foremost emerging technologies for field separation and detection of gas-phase chemical species. This is due to trace-level detection limits, high selectivity, and small size. GC is the leading analytical method for the separation of chemical species in complex mixtures. Low-thermal-mass GC columns have led to compact, low-power field systems capable of complete analyses in 15–300 seconds. A collaborative effort optimized a handheld, fast GC/DMS, equipped with a non-rad ionization source, for peroxide-based explosive measurements.« less

Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment.

PubMed

Sheng, Zheya; Pettersson, Mats E; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

2015-10-01

Artificial selection provides a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions where allele-frequencies have diverged during selection. To avoid false positive signatures of selection, it is necessary to show that a sweep affects a selected trait before it can be considered adaptive. Here, we confirm candidate, genome-wide distributed selective sweeps originating from the standing genetic variation in a long-term selection experiment on high and low body weight of chickens. Using an intercross between the two divergent chicken lines, 16 adaptive selective sweeps were confirmed based on their association with the body weight at 56 days of age. Although individual additive effects were small, the fixation for alternative alleles across the loci contributed at least 40 % of the phenotypic difference for the selected trait between these lines. The sweeps contributed about half of the additive genetic variance present within and between the lines after 40 generations of selection, corresponding to a considerable portion of the additive genetic variance of the base population. Long-term, single-trait, bi-directional selection in the Virginia chicken lines has resulted in a gradual response to selection for extreme phenotypes without a drastic reduction in the genetic variation. We find that fixation of several standing genetic variants across a highly polygenic genetic architecture made a considerable contribution to long-term selection response. This provides new fundamental insights into the dynamics of standing genetic variation during long-term selection and adaptation.

Parameters selection in gene selection using Gaussian kernel support vector machines by genetic algorithm.

PubMed

Mao, Yong; Zhou, Xiao-Bo; Pi, Dao-Ying; Sun, You-Xian; Wong, Stephen T C

2005-10-01

In microarray-based cancer classification, gene selection is an important issue owing to the large number of variables and small number of samples as well as its non-linearity. It is difficult to get satisfying results by using conventional linear statistical methods. Recursive feature elimination based on support vector machine (SVM RFE) is an effective algorithm for gene selection and cancer classification, which are integrated into a consistent framework. In this paper, we propose a new method to select parameters of the aforementioned algorithm implemented with Gaussian kernel SVMs as better alternatives to the common practice of selecting the apparently best parameters by using a genetic algorithm to search for a couple of optimal parameter. Fast implementation issues for this method are also discussed for pragmatic reasons. The proposed method was tested on two representative hereditary breast cancer and acute leukaemia datasets. The experimental results indicate that the proposed method performs well in selecting genes and achieves high classification accuracies with these genes.

Analysis of high load dampers

NASA Technical Reports Server (NTRS)

Bhat, S. T.; Buono, D. F.; Hibner, D. H.

1981-01-01

High load damping requirements for modern jet engines are discussed. The design of damping systems which could satisfy these requirements is also discusseed. In order to evaluate high load damping requirements, engines in three major classes were studied; large transport engines, small general aviation engines, and military engines. Four damper concepts applicable to these engines were evaluated; multi-ring, cartridge, curved beam, and viscous/friction. The most promising damper concept was selected for each engine and performance was assessed relative to conventional dampers and in light of projected damping requirements for advanced jet engines.

High Q-factor metasurfaces based on miniaturized asymmetric single split resonators

NASA Astrophysics Data System (ADS)

Al-Naib, Ibraheem A. I.; Jansen, Christian; Koch, Martin

2009-04-01

We introduce asymmetric single split rectangular resonators as bandstop metasurfaces, which exhibit very high Q-factors in combination with low passband losses and a small electrical footprint. The effect of the degree of asymmetry on the frequency response is thoroughly studied. Furthermore, complementary structures, which feature a bandpass behavior, were derived by applying Babinet's principle and investigated with regards to their transmission characteristics. In future, asymmetric single split rectangular resonators could provide efficient unit cells for frequency selective surface devices, such as thin-film sensors or high performance filters.

Small jets in radio-loud hot DOGs

NASA Astrophysics Data System (ADS)

Lonsdale, C. J.; Whittle, M.; Trapp, A.; Patil, P.; Lonsdale, C. J.; Thorp, R.; Lacy, M.; Kimball, A. E.; Blain, A.; Jones, S.; Kim, M.

2016-02-01

We address the impact of young radio jets on the ISM and star formation in a sample of radiatively efficient, highly obscured, radio AGN with look back times that place them near the peak of the galaxy and BH building era, z˜ 1-3. By selecting systems with a high mid-infrared (MIR) luminosity we aim to identify radiatively efficient (``quasar-mode'' or ``radiative-mode") AGN in a peak fueling phase, and by selecting compact radio sources we favor young or re-generated radio jets which are confined within the hosts. By selecting AGN which are very red through the optical-MIR we favor highly obscured systems likely to have been recently merger-triggered and still in the pre-blow-out phase of AGN feedback into the surrounding ISM. ALMA imaging at 345 GHz of 49 sources has revealed that they are accretion dominated, relative to star formation, with luminosities reaching 1014 L⊙. Extensive VLA imaging at 8-10 GHz in both A-array and B-array for 155 sources reveals that the majority of these powerful radio systems are compact on < 2-5 kpc scales while some have resolved structures on 3-25 kpc scales, and a small number have giant radio lobes on hundreds of kpc scales. The majority of the GHz range radio SEDs are typical of optically thin synchrotron, however for the 34 sources with data at more than 2 frequencies, 40 % are likely to be CSS, GPS, or HFP sources. VLBA imaging of 62 sources reveals varied morphologies, from unresolved sources to complex multicomponent 1-10 mas scale structures. Data from ALMA, VLA, and VLBA

Miniature spectrally selective dosimeter

NASA Technical Reports Server (NTRS)

Adams, R. R.; Macconochie, I. O.; Poole, B. D., Jr. (Inventor)

1980-01-01

A miniature spectrally selective dosimeter capable of measuring selected bandwidths of radiation exposure on small mobile areas is described. This is achieved by the combination of photovoltaic detectors, electrochemical integrators (E-cells) and filters in a small compact case which can be easily attached in close proximity to and substantially parallel to the surface being measured. In one embodiment two photovoltaic detectors, two E-cells, and three filters are packaged in a small case with attaching means consisting of a safety pin. In another embodiment, two detectors, one E-cell, three filters are packaged in a small case with attaching means consisting of a clip to clip over a side piece of an eye glass frame.

Oligo-branched peptides for tumor targeting: from magic bullets to magic forks.

PubMed

Falciani, Chiara; Pini, Alessandro; Bracci, Luisa

2009-02-01

Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents. We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides. Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules.

Feature weight estimation for gene selection: a local hyperlinear learning approach

PubMed Central

2014-01-01

Background Modeling high-dimensional data involving thousands of variables is particularly important for gene expression profiling experiments, nevertheless,it remains a challenging task. One of the challenges is to implement an effective method for selecting a small set of relevant genes, buried in high-dimensional irrelevant noises. RELIEF is a popular and widely used approach for feature selection owing to its low computational cost and high accuracy. However, RELIEF based methods suffer from instability, especially in the presence of noisy and/or high-dimensional outliers. Results We propose an innovative feature weighting algorithm, called LHR, to select informative genes from highly noisy data. LHR is based on RELIEF for feature weighting using classical margin maximization. The key idea of LHR is to estimate the feature weights through local approximation rather than global measurement, which is typically used in existing methods. The weights obtained by our method are very robust in terms of degradation of noisy features, even those with vast dimensions. To demonstrate the performance of our method, extensive experiments involving classification tests have been carried out on both synthetic and real microarray benchmark datasets by combining the proposed technique with standard classifiers, including the support vector machine (SVM), k-nearest neighbor (KNN), hyperplane k-nearest neighbor (HKNN), linear discriminant analysis (LDA) and naive Bayes (NB). Conclusion Experiments on both synthetic and real-world datasets demonstrate the superior performance of the proposed feature selection method combined with supervised learning in three aspects: 1) high classification accuracy, 2) excellent robustness to noise and 3) good stability using to various classification algorithms. PMID:24625071

A TiS2 nanosheet enhanced fluorescence polarization biosensor for ultra-sensitive detection of biomolecules

NASA Astrophysics Data System (ADS)

Li, Xiang; Ding, Xuelian; Li, Yongfang; Wang, Linsong; Fan, Jing

2016-05-01

Development of new strategies for the sensitive and selective detection of ultra-low concentrations of specific cancer markers is of great importance for assessing cancer therapeutics due to its crucial role in early clinical diagnoses and biomedical applications. In this work, we have developed two types of fluorescence polarization (FP) amplification assay strategies for the detection of biomolecules by using TiS2 as a FP enhancer and Zn2+-dependent self-hydrolyzing deoxyribozymes as catalysts to realize enzyme-catalyzed target-recycling signal amplification. One approach is based on the terminal protection of small-molecule-linked DNA, in which biomolecular binding to small molecules in DNA-small-molecule chimeras can protect the conjugated DNA from degradation by exonuclease I (Exo I); the other approach is based on the terminal protection of biomolecular bound aptamer DNA, in which biomolecules directly bound to the single strand aptamer DNA can protect the ssDNA from degradation by Exo I. We select folate receptor (FR) and thrombin (Tb) as model analytes to verify the current concept. It is shown that under optimized conditions, our strategies exhibit high sensitivity and selectivity for the quantification of FR and Tb with low detection limits (0.003 ng mL-1 and 0.01 pM, respectively). Additionally, this strategy is a simple ``mix and detect'' approach, and does not require any separation steps. This biosensor is also utilized in the analysis of real biological samples, the results agree well with those obtained by the enzyme-linked immunosorbent assay (ELISA).Development of new strategies for the sensitive and selective detection of ultra-low concentrations of specific cancer markers is of great importance for assessing cancer therapeutics due to its crucial role in early clinical diagnoses and biomedical applications. In this work, we have developed two types of fluorescence polarization (FP) amplification assay strategies for the detection of biomolecules by using TiS2 as a FP enhancer and Zn2+-dependent self-hydrolyzing deoxyribozymes as catalysts to realize enzyme-catalyzed target-recycling signal amplification. One approach is based on the terminal protection of small-molecule-linked DNA, in which biomolecular binding to small molecules in DNA-small-molecule chimeras can protect the conjugated DNA from degradation by exonuclease I (Exo I); the other approach is based on the terminal protection of biomolecular bound aptamer DNA, in which biomolecules directly bound to the single strand aptamer DNA can protect the ssDNA from degradation by Exo I. We select folate receptor (FR) and thrombin (Tb) as model analytes to verify the current concept. It is shown that under optimized conditions, our strategies exhibit high sensitivity and selectivity for the quantification of FR and Tb with low detection limits (0.003 ng mL-1 and 0.01 pM, respectively). Additionally, this strategy is a simple ``mix and detect'' approach, and does not require any separation steps. This biosensor is also utilized in the analysis of real biological samples, the results agree well with those obtained by the enzyme-linked immunosorbent assay (ELISA). Electronic supplementary information (ESI) available: Tables S1-S4, Scheme S1, Fig. S1-S10. See DOI: 10.1039/c6nr00946h

Selection of the simplest RNA that binds isoleucine

PubMed Central

LOZUPONE, CATHERINE; CHANGAYIL, SHANKAR; MAJERFELD, IRENE; YARUS, MICHAEL

2003-01-01

We have identified the simplest RNA binding site for isoleucine using selection-amplification (SELEX), by shrinking the size of the randomized region until affinity selection is extinguished. Such a protocol can be useful because selection does not necessarily make the simplest active motif most prominent, as is often assumed. We find an isoleucine binding site that behaves exactly as predicted for the site that requires fewest nucleotides. This UAUU motif (16 highly conserved positions; 27 total), is also the most abundant site in successful selections on short random tracts. The UAUU site, now isolated independently at least 63 times, is a small asymmetric internal loop. Conserved loop sequences include isoleucine codon and anticodon triplets, whose nucleotides are required for amino acid binding. This reproducible association between isoleucine and its coding sequences supports the idea that the genetic code is, at least in part, a stereochemical residue of the most easily isolated RNA–amino acid binding structures. PMID:14561881

Voluntary strategy suppresses the positive impact of preferential selection in prisoner’s dilemma

NASA Astrophysics Data System (ADS)

Sun, Lei; Lin, Pei-jie; Chen, Ya-shan

2014-11-01

Impact of aspiration is ubiquitous in social and biological disciplines. In this work, we try to explore the impact of such a trait on voluntary prisoners’ dilemma game via a selection parameter w. w=0 returns the traditional version of random selection. For positive w, the opponent of high payoff will be selected; while negative w means that the partner of low payoff will be chosen. We find that for positive w, cooperation will be greatly promoted in the interval of small b, at variance cooperation is inhibited with large b. For negative w, cooperation is fully restrained, irrespective of b value. It is found that the positive impact of preferential selection is suppressed by the voluntary strategy in prisoner’s dilemma. These observations can be supported by the spatial patterns. Our work may shed light on the emergence and persistence of cooperation with voluntary participation in social dilemma.

TINAGL1 and B3GALNT1 are potential therapy target genes to suppress metastasis in non-small cell lung cancer

PubMed Central

2014-01-01

Background Non-small cell lung cancer (NSCLC) remains lethal despite the development of numerous drug therapy technologies. About 85% to 90% of lung cancers are NSCLC and the 5-year survival rate is at best still below 50%. Thus, it is important to find drugable target genes for NSCLC to develop an effective therapy for NSCLC. Results Integrated analysis of publically available gene expression and promoter methylation patterns of two highly aggressive NSCLC cell lines generated by in vivo selection was performed. We selected eleven critical genes that may mediate metastasis using recently proposed principal component analysis based unsupervised feature extraction. The eleven selected genes were significantly related to cancer diagnosis. The tertiary protein structure of the selected genes was inferred by Full Automatic Modeling System, a profile-based protein structure inference software, to determine protein functions and to specify genes that could be potential drug targets. Conclusions We identified eleven potentially critical genes that may mediate NSCLC metastasis using bioinformatic analysis of publically available data sets. These genes are potential target genes for the therapy of NSCLC. Among the eleven genes, TINAGL1 and B3GALNT1 are possible candidates for drug compounds that inhibit their gene expression. PMID:25521548

Design and Discovery of N -(2-Methyl-5'-morpholino-6'-((tetrahydro-2 H -pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers

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

Nishiguchi, Gisele A.; Rico, Alice; Tanner, Huw

RAS oncogenes have been implicated in >30% of human cancers, all representing high unmet medical need. The exquisite dependency on CRAF kinase in KRAS mutant tumors has been established in genetically engineered mouse models and human tumor cells. To date, many small molecule approaches are under investigation to target CRAF, yet kinase-selective and cellular potent inhibitors remain challenging to identify. Herein, we describe 14 (RAF709) [Aversa, Biaryl amide compounds as kinase inhibitors and their preparation. WO 2014151616, 2014], a selective B/C RAF inhibitor, which was developed through a hypothesis-driven approach focusing on drug-like properties. A key challenge encountered in themore » medicinal chemistry campaign was maintaining a balance between good solubility and potent cellular activity (suppression of pMEK and proliferation) in KRAS mutant tumor cell lines. We investigated the small molecule crystal structure of lead molecule 7 and hypothesized that disruption of the crystal packing would improve solubility, which led to a change from N-methylpyridone to a tetrahydropyranyl oxy-pyridine derivative. 14 proved to be soluble, kinase selective, and efficacious in a KRAS mutant xenograft model.« less

On Galactic Density Modeling in the Presence of Dust Extinction

NASA Astrophysics Data System (ADS)

Bovy, Jo; Rix, Hans-Walter; Green, Gregory M.; Schlafly, Edward F.; Finkbeiner, Douglas P.

2016-02-01

Inferences about the spatial density or phase-space structure of stellar populations in the Milky Way require a precise determination of the effective survey volume. The volume observed by surveys such as Gaia or near-infrared spectroscopic surveys, which have good coverage of the Galactic midplane region, is highly complex because of the abundant small-scale structure in the three-dimensional interstellar dust extinction. We introduce a novel framework for analyzing the importance of small-scale structure in the extinction. This formalism demonstrates that the spatially complex effect of extinction on the selection function of a pencil-beam or contiguous sky survey is equivalent to a low-pass filtering of the extinction-affected selection function with the smooth density field. We find that the angular resolution of current 3D extinction maps is sufficient for analyzing Gaia sub-samples of millions of stars. However, the current distance resolution is inadequate and needs to be improved by an order of magnitude, especially in the inner Galaxy. We also present a practical and efficient method for properly taking the effect of extinction into account in analyses of Galactic structure through an effective selection function. We illustrate its use with the selection function of red-clump stars in APOGEE using and comparing a variety of current 3D extinction maps.

Iridium clusters in KLTL zeolite: Structure and catalytic selectivity for n-hexane aromatization

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

Triantafillou, N.D.; Miller, J.T.; Gates, B.C.

Catalysts consisting of Ir clusters in zeolite KLTL were prepared by reduction of [Ir(NH{sub 3}){sub 5}Cl]Cl{sub 2} in the zeolite with H{sub 2} at temperatures 300 or 500{degrees}C. The catalysts were tested for reactions of n-hexane and H{sub 2} at 400, 440 and 480{degrees}C and were characterized by temperature-programmed reduction, hydrogen chemisorption, transmission electron microscopy, infrared spectroscopy of adsorbed CO, and extended X-ray absorption fine structure spectroscopy. The clusters consist of 4 to 6 Ir atoms on average and are sufficiently small to reside within the pores of the zeolite. The infrared spectra characteristic of terminal CO suggest that themore » support environment is slightly basic and that the Ir clusters are electron rich relative to the bulk metal. Notwithstanding the small cluster size, the support basicity, and the confining geometry of the LTL zeolite pore structure, the catalytic performance is similar to those of other Ir catalysts, with a poor selectivity for aromatization and a high selectivity for hydrogenolysis. These results are consistent with the inference that the principal requirements for selective naphtha aromatization catalysts are both a nonacidic support and a metal with a low hydrogenolsis activity, i.e., Pt. 47 refs., 6 figs., 3 tabs.« less

Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

PubMed

Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

2013-01-21

The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

Automatic extraction and processing of small RNAs on a multi-well/multi-channel (M&M) chip.

PubMed

Zhong, Runtao; Flack, Kenneth; Zhong, Wenwan

2012-12-07

The study of the regulatory roles in small RNAs can be accelerated by techniques that permit simple, low-cost, and rapid extraction of small RNAs from a small number of cells. In order to ensure highly specific and sensitive detection, the extracted RNAs should be free of the background nucleic acids and present stably in a small volume. To meet these criteria, we designed a multi-well/multi-channel (M&M) chip to carry out automatic and selective isolation of small RNAs via solid-phase extraction (SPE), followed by reverse-transcription (RT) to convert them to the more stable cDNAs in a final volume of 2 μL. Droplets containing buffers for RNA binding, washing, and elution were trapped in microwells, which were connected by one channel, and suspended in mineral oil. The silica magnetic particles (SMPs) for SPE were moved along the channel from well to well, i.e. in between droplets, by a fixed magnet and a translation stage, allowing the nucleic acid fragments to bind to the SMPs, be washed, and then be eluted for RT reaction within 15 minutes. RNAs shorter than 63 nt were selectively enriched from cell lysates, with recovery comparable to that of a commercial kit. Physical separation of the droplets on our M&M chip allowed the usage of multiple channels for parallel processing of multiple samples. It also permitted smooth integration with on-chip RT-PCR, which simultaneously detected the target microRNA, mir-191, expressed in fewer than 10 cancer cells. Our results have demonstrated that the M&M chip device is a valuable and cost-saving platform for studying small RNA expression patterns in a limited number of cells with reasonable sample throughput.

A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models

NASA Astrophysics Data System (ADS)

Li, Lin; Zhang, Cheng-Wu; Chen, Grace Y. J.; Zhu, Biwei; Chai, Chou; Xu, Qing-Hua; Tan, Eng-King; Zhu, Qing; Lim, Kah-Leong; Yao, Shao Q.

2014-02-01

The unusually high MAO-B activity consistently observed in Parkinson’s disease (PD) patients has been proposed as a biomarker; however, this has not been realized due to the lack of probes suitable for MAO-B-specific detection in live cells/tissues. Here we report the first two-photon, small molecule fluorogenic probe (U1) that enables highly sensitive/specific and real-time imaging of endogenous MAO-B activities across biological samples. We also used U1 to confirm the reported inverse relationship between parkin and MAO-B in PD models. With no apparent toxicity, U1 may be used to monitor MAO-B activities in small animals during disease development. In clinical samples, we find elevated MAO-B activities only in B lymphocytes (not in fibroblasts), hinting that MAO-B activity in peripheral blood cells might be an accessible biomarker for rapid detection of PD. Our results provide important starting points for using small molecule imaging techniques to explore MAO-B at the organism level.

A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson's disease models.

PubMed

Li, Lin; Zhang, Cheng-Wu; Chen, Grace Y J; Zhu, Biwei; Chai, Chou; Xu, Qing-Hua; Tan, Eng-King; Zhu, Qing; Lim, Kah-Leong; Yao, Shao Q

2014-01-01

The unusually high MAO-B activity consistently observed in Parkinson's disease (PD) patients has been proposed as a biomarker; however, this has not been realized due to the lack of probes suitable for MAO-B-specific detection in live cells/tissues. Here we report the first two-photon, small molecule fluorogenic probe (U1) that enables highly sensitive/specific and real-time imaging of endogenous MAO-B activities across biological samples. We also used U1 to confirm the reported inverse relationship between parkin and MAO-B in PD models. With no apparent toxicity, U1 may be used to monitor MAO-B activities in small animals during disease development. In clinical samples, we find elevated MAO-B activities only in B lymphocytes (not in fibroblasts), hinting that MAO-B activity in peripheral blood cells might be an accessible biomarker for rapid detection of PD. Our results provide important starting points for using small molecule imaging techniques to explore MAO-B at the organism level.

Progress and issues for high-speed vertical cavity surface emitting lasers

NASA Astrophysics Data System (ADS)

Lear, Kevin L.; Al-Omari, Ahmad N.

2007-02-01

Extrinsic electrical, thermal, and optical issues rather than intrinsic factors currently constrain the maximum bandwidth of directly modulated vertical cavity surface emitting lasers (VCSELs). Intrinsic limits based on resonance frequency, damping, and K-factor analysis are summarized. Previous reports are used to compare parasitic circuit values and electrical 3dB bandwidths and thermal resistances. A correlation between multimode operation and junction heating with bandwidth saturation is presented. The extrinsic factors motivate modified bottom-emitting structures with no electrical pads, small mesas, copper plated heatsinks, and uniform current injection. Selected results on high speed quantum well and quantum dot VCSELs at 850 nm, 980 nm, and 1070 nm are reviewed including small-signal 3dB frequencies up to 21.5 GHz and bit rates up to 30 Gb/s.

CUBES Project Support

NASA Technical Reports Server (NTRS)

Jenkins, Kenneth T., Jr.

2012-01-01

CUBES stands for Creating Understanding and Broadening Education through Satellites. The goal of the project is to allow high school students to build a small satellite, or CubeSat. Merritt Island High School (MIHS) was selected to partner with NASA, and California Polytechnic State University (Cal-Poly}, to build a CubeSat. The objective of the mission is to collect flight data to better characterize maximum predicted environments inside the CubeSat launcher, Poly-Picosatellite Orbital Deplorer (P-POD), while attached to the launch vehicle. The MIHS CubeSat team will apply to the NASA CubeSat Launch Initiative, which provides opportunities for small satellite development teams to secure launch slots on upcoming expendable launch vehicle missions. The MIHS team is working to achieve a test launch, or proof of concept flight aboard a suborbital launch vehicle in early 2013.

Ecological context of the evolution of self-pollination in Clarkia xantiana: population size, plant communities, and reproductive assurance.

PubMed

Moeller, David A; Geber, Monica A

2005-04-01

The repeated evolutionary transition from outcrossing to self-pollination in flowering plants has been suggested to occur because selfing provides reproductive assurance. Reports from biogeographical and ecological surveys indicate that selfing taxa are often associated with stressful and ephemeral environments, situations in which plant abundance is low (e.g., Baker's law) and with novel plant communities, however experimental tests of ecological hypotheses are few. In this study, we examined the ecological context of selection on mating system traits (herkogamy and protandry) in a California annual, Clarkia xantiana, where natural selfing populations differ from outcrossing populations in that they are often of small size or low density and occur mainly outside the range of pollinator-sharing congeners. We constructed artificial populations of plants with broad genetic variation in floral traits and manipulated two ecological factors, plant population size, and the presence versus absence of pollinator-sharing congeners, in the center of the geographic range of outcrossing populations. We found evidence for context-dependent selection on herkogamy and protandry via female fitness in which reduced traits, which promote autonomous selfing, were favored in small populations isolated from congeners whereas selection was comparatively weak in large populations or when congeners were present. In small, isolated populations, the fertility of plants with low herkogamy or protandry was elevated by 66% and 58%, respectively, compared to those with high herkogamy or protandry. The presence of pollinator-sharing congeners augmented bee visitation rates to C. xantiana flowers by 47% for all bees and by 93% for pollen specialists. By facilitating pollinator visitation, congeners mitigated selection on mating system traits in small populations, where outcross mating success is often low (the Allee effect). We also found support for the hypothesis that pollinator availability directly influenced variation in the strength of selection on herkogamy among populations. The striking parallels between our experimental results and patterns of variation in ecological factors across the geographic range of outcrossing and selfing populations suggest that reproductive assurance may play a central role in directing mating system evolution in C. xantiana.

Fluid Mechanics and Heat Transfer of Liquid Precursor Droplets Injected into High-Temperature Plasmas

NASA Astrophysics Data System (ADS)

Basu, Saptarshi; Jordan, Eric H.; Cetegen, Baki M.

2008-03-01

Thermo-physical processes in liquid ceramic precursor droplets in plasma were modeled. Models include aerodynamic droplet break-up, droplet transport, as well as heat and mass transfer within individual droplets. Droplet size, solute concentration, and plasma temperature effects are studied. Results are discussed with the perspective of selecting processing conditions and injection parameters to obtain certain types of coating microstructures. Small droplets (<5 microns) are found to undergo volumetric precipitation and coating deposition with small unpyrolized material. Droplets can be made to undergo shear break-up by reducing surface tension and small droplets promote volumetric precipitation. Small particles reach substrate as molten splats resulting in denser coatings. Model predicts that larger droplets (>5 microns) tend to surface precipitate-forming shells with liquid core. They may be subjected to internal pressurization leading to shattering of shells and secondary atomization of liquid within. They arrive at the substrate as broken shells and unpyrolized material.

Influence of collector heat capacity and internal conditions of heat exchanger on cool-down process of small gas liquefier

NASA Astrophysics Data System (ADS)

Saberimoghaddam, Ali; Bahri Rasht Abadi, Mohammad Mahdi

2018-01-01

Joule-Thomson cooling systems are commonly used in gas liquefaction. In small gas liquefiers, transient cool-down time is high. Selecting suitable conditions for cooling down process leads to decrease in time and cost. In the present work, transient thermal behavior of Joule-Thomson cooling system including counter current helically coiled tube in tube heat exchanger, expansion valve, and collector was studied using experimental tests and simulations. The experiments were performed using small gas liquefier and nitrogen gas as working fluid. The heat exchanger was thermally studied by experimental data obtained from a small gas liquefier. In addition, the simulations were performed using experimental data as variable boundary conditions. A comparison was done between presented and conventional methods. The effect of collector heat capacity and convection heat transfer coefficient inside the tubes on system performance was studied using temperature profiles along the heat exchanger.

Implementing Technology with Industrial Community: The SBIR Example

NASA Technical Reports Server (NTRS)

Ghuman, Parminder

2005-01-01

The Earth-Sun system Technology Office (ESTO) works with Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs to supplement its own technology development program. The SBIR/STTR program is a highly competitive program that encourages small business to explore their technological potential to fulfill technology needs identified by ESTO. SBIR program has three phases. The Phase 1 contracts last for 6 months with a maximum funding of $70,000, and Phase 2 contracts last for 24 months with a maximum funding of $600,000. For Phase 3, the small business must find funding in the private sector or other non-SBIR federal agency funding. During this phase ESTO evaluates Phase 2 graduates and selects those that need to be further developed for airborne or spaceflight demonstration and provides funding. This paper will discuss the all three phases in and role of ESTO in this program.

Application-Dedicated Selection of Filters (ADSF) using covariance maximization and orthogonal projection.

PubMed

Hadoux, Xavier; Kumar, Dinesh Kant; Sarossy, Marc G; Roger, Jean-Michel; Gorretta, Nathalie

2016-05-19

Visible and near-infrared (Vis-NIR) spectra are generated by the combination of numerous low resolution features. Spectral variables are thus highly correlated, which can cause problems for selecting the most appropriate ones for a given application. Some decomposition bases such as Fourier or wavelet generally help highlighting spectral features that are important, but are by nature constraint to have both positive and negative components. Thus, in addition to complicating the selected features interpretability, it impedes their use for application-dedicated sensors. In this paper we have proposed a new method for feature selection: Application-Dedicated Selection of Filters (ADSF). This method relaxes the shape constraint by enabling the selection of any type of user defined custom features. By considering only relevant features, based on the underlying nature of the data, high regularization of the final model can be obtained, even in the small sample size context often encountered in spectroscopic applications. For larger scale deployment of application-dedicated sensors, these predefined feature constraints can lead to application specific optical filters, e.g., lowpass, highpass, bandpass or bandstop filters with positive only coefficients. In a similar fashion to Partial Least Squares, ADSF successively selects features using covariance maximization and deflates their influences using orthogonal projection in order to optimally tune the selection to the data with limited redundancy. ADSF is well suited for spectroscopic data as it can deal with large numbers of highly correlated variables in supervised learning, even with many correlated responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Diet and feeding strategies of mesopelagic fishes in the western Mediterranean

NASA Astrophysics Data System (ADS)

Bernal, Ainhoa; Olivar, M. Pilar; Maynou, Francesc; Fernández de Puelles, M. Luz

2015-06-01

Myctophids, gonostomatids and sternoptychids are the most abundant teleosteans worldwide and constitute an important assemblage of the mesopelagic ecosystem, functioning as vehicles of energy and matter through trophic webs. This study concentrates on the trophic ecology of the most abundant mesopelagic fishes of the western Mediterranean (WM) based on stomach content analysis. The myctophids (in this study: Benthosema glaciale, Ceratoscopelus maderensis, Lobianchia dofleini, Myctophum punctatum, Hygophum benoiti, Hygophum hygomii, Lampanyctus crocodilus, Lampanyctus pusillus and Notoscopelus elongatus) perform extensive diel migrations across the water column, between the surface to as deep as 1000 m, interacting with plankton and micronekton at multiple depths, and generally feeding in the epipelagic layers at night. In contrast, the gonostomatids Cyclothone braueri, Cyclothone pygmaea, and the sternoptychid Argyropelecus hemigymnus remain below epipelagic layers, feeding at different times throughout the day and night. The diet composition, trophic niche breadth and prey selectivity of 11 of these fish species were determined for juvenile and adult individuals from two surveys performed in December 2009 and July 2010 in the western Mediterranean Sea. The number of prey items varied among species, e.g. Myctophum punctatum was the species with the highest feeding intensity, reaching ca. 700 prey items in a stomach, whereas the mean number of prey in Cyclothone braueri was low (usually 1 or 2 prey per stomach). A dietary shift towards larger prey was evident from juveniles to the largest and oldest adult individuals, despite trophic niche breadths did not increase with body length for any of these mesopelagic species. The diets of the small gonostomatids, sternoptychid and early juveniles of myctophids were dominated by non-calanoid copepods, ostracods, and other small zooplankton, whereas medium-sized myctophids, e.g. L. dofleini or H. benoiti, preyed mainly on calanoids. The oldest stages of L. crocodilus and N. elongatus fed mostly on macrozooplankton and micronekton. There was high diet overlap among mesopelagic fish species and strong heterogeneity in diet composition at intraspecific level. Nevertheless, some species showed certain degree of segregation of food resources, determined by the developmental stage or spatial distribution, and positive selection towards particular prey items. The Chesson's electivity index showed that L. dofleini, N. elongatus, L. crocodilus and L. pusillus preyed selectively on euphausiids; B. glaciale was selective on the calanoid genus Pleuromamma, and C. maderensis preferred to feed on larvaceans in autumn. The two congeneric species of Hygophum consumed a high number of food items, but H. hygomii showed positive selection for euphausiids, whilst H. benoiti preferred small corycaeid copepods. Overall, the main trophic difference among mesopelagic fishes in the WM was observed between the small non-migratory species that do not evidence a diel rhythm, feeding during both day- and night-time on small zooplankton, and the largest-sized myctophids, which fed on meso- and macrozooplankton and, more occasionally, on small fishes. Mediterranean midwater fishes can be characterised by the adoption of mixed feeding strategies, with varying degrees of specialisation on different prey types that allow flexibility in a changeable environment.

Morphological MRI characteristics of recent small subcortical infarcts.

PubMed

Gattringer, Thomas; Eppinger, Sebastian; Pinter, Daniela; Pirpamer, Lukas; Berghold, Andrea; Wünsch, Gerit; Ropele, Stefan; Wardlaw, Joanna M; Enzinger, Christian; Fazekas, Franz

2015-10-01

New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown. To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables. We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection. Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging did not influence lesion metrics or the distribution of recent small subcortical infarcts. Our study confirms the recent neuroimaging criteria for recent small subcortical infarcts as a practical concept. Definitions of the maximal axial and longitudinal diameter have a significant impact on the frequency and distribution of selected infarcts, which has to be considered for future studies. © 2015 World Stroke Organization.

Protein Complex Production from the Drug Discovery Standpoint.

PubMed

Moarefi, Ismail

2016-01-01

Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

Realization and performance of cryogenic selection mechanisms

NASA Astrophysics Data System (ADS)

Aitink-Kroes, Gabby; Bettonvil, Felix; Kragt, Jan; Elswijk, Eddy; Tromp, Niels

2014-07-01

Within Infra-Red large wavelength bandwidth instruments the use of mechanisms for selection of observation modes, filters, dispersing elements, pinholes or slits is inevitable. The cryogenic operating environment poses several challenges to these cryogenic mechanisms; like differential thermal shrinkage, physical property change of materials, limited use of lubrication, high feature density, limited space etc. MATISSE the mid-infrared interferometric spectrograph and imager for ESO's VLT interferometer (VLTI) at Paranal in Chile coherently combines the light from 4 telescopes. Within the Cold Optics Bench (COB) of MATISSE two concepts of selection mechanisms can be distinguished based on the same design principles: linear selection mechanisms (sliders) and rotating selection mechanisms (wheels).Both sliders and wheels are used at a temperature of 38 Kelvin. The selection mechanisms have to provide high accuracy and repeatability. The sliders/wheels have integrated tracks that run on small, accurately located, spring loaded precision bearings. Special indents are used for selection of the slider/wheel position. For maximum accuracy/repeatability the guiding/selection system is separated from the actuation in this case a cryogenic actuator inside the cryostat. The paper discusses the detailed design of the mechanisms and the final realization for the MATISSE COB. Limited lifetime and performance tests determine accuracy, warm and cold and the reliability/wear during life of the instrument. The test results and further improvements to the mechanisms are discussed.

Validation and extraction of molecular-geometry information from small-molecule databases.

PubMed

Long, Fei; Nicholls, Robert A; Emsley, Paul; Graǽulis, Saulius; Merkys, Andrius; Vaitkus, Antanas; Murshudov, Garib N

2017-02-01

A freely available small-molecule structure database, the Crystallography Open Database (COD), is used for the extraction of molecular-geometry information on small-molecule compounds. The results are used for the generation of new ligand descriptions, which are subsequently used by macromolecular model-building and structure-refinement software. To increase the reliability of the derived data, and therefore the new ligand descriptions, the entries from this database were subjected to very strict validation. The selection criteria made sure that the crystal structures used to derive atom types, bond and angle classes are of sufficiently high quality. Any suspicious entries at a crystal or molecular level were removed from further consideration. The selection criteria included (i) the resolution of the data used for refinement (entries solved at 0.84 Å resolution or higher) and (ii) the structure-solution method (structures must be from a single-crystal experiment and all atoms of generated molecules must have full occupancies), as well as basic sanity checks such as (iii) consistency between the valences and the number of connections between atoms, (iv) acceptable bond-length deviations from the expected values and (v) detection of atomic collisions. The derived atom types and bond classes were then validated using high-order moment-based statistical techniques. The results of the statistical analyses were fed back to fine-tune the atom typing. The developed procedure was repeated four times, resulting in fine-grained atom typing, bond and angle classes. The procedure will be repeated in the future as and when new entries are deposited in the COD. The whole procedure can also be applied to any source of small-molecule structures, including the Cambridge Structural Database and the ZINC database.

Unlocking the Gates: How and Why Leading Universities Are Opening up Access to Their Courses

ERIC Educational Resources Information Center

Walsh, Taylor

2011-01-01

Over the past decade, a small revolution has taken place at some of the world's leading universities, as they have started to provide free access to undergraduate course materials--including syllabi, assignments, and lectures--to anyone with an Internet connection. Yale offers high-quality audio and video recordings of a careful selection of…

Gender Differences in Promotion Experiences at Two Elite Private Liberal Arts Colleges in the United States

ERIC Educational Resources Information Center

Berheide, Catherine White; Christenson, Lisa; Linden, Rena; Bray, Una

2013-01-01

In colleges and universities throughout the United States, women are underrepresented at the rank of full professor. This national pattern holds true at two highly selective small private liberal arts colleges in the Northeast, one formerly a men's college and the other formerly a women's college. Analysis of personnel data at the former women's…

Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

PubMed

Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.

PubMed

Tran, Tuan; Disney, Matthew D

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.

Identifying the Preferred RNA Motifs and Chemotypes that Interact by Probing Millions of Combinations

PubMed Central

Tran, Tuan; Disney, Matthew D.

2012-01-01

RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (amongst a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole, and pyridinium chemotypes allow for specific recognition of RNA motifs. Since targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses. PMID:23047683

Monitoring of fluvial transport in small upland catchments - methods and preliminary results

NASA Astrophysics Data System (ADS)

Janicki, Grzegorz; Rodzik, Jan; Chabudziński, Łukasz; Franczak, Łukasz; Siłuch, Marcin; Stępniewski, Krzysztof; Dyer, Jamie L.; Kołodziej, Grzegorz; Maciejewska, Ewa

2014-06-01

In April 2011 a study was initiated, financed from resources of the Polish National Science Centre, entitled: ‘Rainstorm prediction and mathematic modelling of their environmental and social-economical effects’ (No. NN/306571640). The study, implemented by a Polish-American team, covers meteorological research, including: (1) monitoring of single cell storms developing in various synoptic situations, (2) detection of their movement courses, and (3) estimation of parameters of their rain field. Empirical studies, including hydrological and geomorphological measurements, are conducted in objects researched thoroughly in physiographic terms (experimental catchments) in the Lublin region (SE Poland), distinguished by high frequency of occurrence of the events described. For comparative purposes, studies are also carried out on selected model areas in the lower course of the Mississippi River valley (USA), in a region with high frequency of summer rainstorms. For detailed studies on sediment transport processes during rainstorm events, catchments of low hydrological rank and their sub-catchments in a cascade system were selected. For the basic, relatively uniform geomorpho logical units distinguished this way, erosion and deposition balance of material transported was determined. The aim of work was to determine influence of weather condition on fluvial transport rate in small catchment with low hydrological order

Female mate choice by chemical signals in a semi-terrestrial crab

NASA Astrophysics Data System (ADS)

Sal Moyano, María Paz; Silva, Paola; Luppi, Tomás; Gavio, María Andrea

2014-01-01

Information about the roles of both sexes in pair formation is required to better understand the mechanisms involved in sexual selection. Mate choice could depend on the courtship behavior, involving chemical, tactile and visual signals. We determined if Neohelice granulata mate choice is based on female or male choice, considering visual and chemical with contact and without contact signals between partners and different categories of individuals: receptive and unreceptive females; and large, small, mated or unmated males. Experiments showed that mate selection was based on receptive female's choice using chemical signals, but not visual ones. Since copulation occurs during high and low tides, water-borne chemical signals would be preferentially used during high tide, while contact ones during low tide. Females preferred large and unmated males, while males did not seem to recognize receptive females using chemical neither visual signals. Females were capable of detecting the presence of the chemical signals released by large and unmated males, but not its amount. It is proposed that small and mated males are probably releasing different types of chemical signals, not attractive to females, or that they are not emitting any signal.

Delineation of clinical target volume for postoperative radiotherapy in stage IIIA-pN2 non-small-cell lung cancer.

PubMed

Jing, Xuquan; Meng, Xue; Sun, Xindong; Yu, Jinming

2016-01-01

With the high locoregional relapse rate and the improvement of radiation technology, postoperative radiotherapy (PORT) has been widely used in the treatment of completely resected stage IIIA-pN2 non-small-cell lung cancer (NSCLC). However, there is still no definitive consensus on clinical target volume for the pN2 subgroup. This review will discuss how to delineate the clinical target volume (CTV) for pN2 subgroups of IIIA-N2 NSCLC based on the published literature and to investigate the optimal PORT CTV in this cohort of patients. Besides overall survival (OS), locoregional recurrence (LR), and radiotherapy-related toxicity of this subset of the population in the modern PORT era, selection of proper patients will also be considered in this review. In summary, it is appropriate to include involved lymph node stations and uninvolved stations at high risk in PORT CTV for patients with pN2 disease when PORT is administered. PORT can reduce LR and has the potential to improve OS. In the current era of modern radiation technology, PORT can be administered safely with well-tolerated toxicity. Clinicopathological characteristics may be helpful in selecting proper candidates for PORT.

A novel orally available small molecule that inhibits hepatitis B virus expression.

PubMed

Mueller, Henrik; Wildum, Steffen; Luangsay, Souphalone; Walther, Johanna; Lopez, Anaïs; Tropberger, Philipp; Ottaviani, Giorgio; Lu, Wenzhe; Parrott, Neil John; Zhang, Jitao David; Schmucki, Roland; Racek, Tomas; Hoflack, Jean-Christophe; Kueng, Erich; Point, Floriane; Zhou, Xue; Steiner, Guido; Lütgehetmann, Marc; Rapp, Gianna; Volz, Tassilo; Dandri, Maura; Yang, Song; Young, John A T; Javanbakht, Hassan

2018-03-01

The hallmarks of chronic HBV infection are a high viral load (HBV DNA) and even higher levels (>100-fold in excess of virions) of non-infectious membranous particles containing the tolerogenic viral S antigen (HBsAg). Currently, standard treatment effectively reduces viremia but only rarely results in a functional cure (defined as sustained HBsAg loss). There is an urgent need to identify novel therapies that reduce HBsAg levels and restore virus-specific immune responsiveness in patients. We report the discovery of a novel, potent and orally bioavailable small molecule inhibitor of HBV gene expression (RG7834). RG7834 antiviral characteristics and selectivity against HBV were evaluated in HBV natural infection assays and in a urokinase-type plasminogen activator/severe combined immunodeficiency humanized mouse model of HBV infection, either alone or in combination with entecavir. Unlike nucleos(t)ide therapies, which reduce viremia but do not lead to an effective reduction in HBV antigen expression, RG7834 significantly reduced the levels of viral proteins (including HBsAg), as well as lowering viremia. Consistent with its proposed mechanism of action, time course RNA-seq analysis revealed a fast and selective reduction in HBV mRNAs in response to RG7834 treatment. Furthermore, oral treatment of HBV-infected humanized mice with RG7834 led to a mean HBsAg reduction of 1.09 log 10 compared to entecavir, which had no significant effect on HBsAg levels. Combination of RG7834, entecavir and pegylated interferon α-2a led to significant reductions of both HBV DNA and HBsAg levels in humanized mice. We have identified a novel oral HBV viral gene expression inhibitor that blocks viral antigen and virion production, that is highly selective for HBV, and has a unique antiviral profile that is clearly differentiated from nucleos(t)ide analogues. We discovered a novel small molecule viral expression inhibitor that is highly selective for HBV and unlike current therapy inhibits the expression of viral proteins by specifically reducing HBV mRNAs. RG7834 can therefore potentially provide anti-HBV benefits and increase HBV cure rates, by direct reduction of viral agents needed to complete the viral life cycle, as well as a reduction of viral agents involved in evasion of the host immune responses. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Microhabitat of small mammals at ground and understorey levels in a deciduous, southern Atlantic forest.

PubMed

Melo, Geruza L; Miotto, Barbara; Peres, Brisa; Cáceres, Nilton C

2013-01-01

Each animal species selects specific microhabitats for protection, foraging, or micro-climate. To understand the distribution patterns of small mammals on the ground and in the understorey, we investigated the use of microhabitats by small mammals in a deciduous forest of southern Brazil. Ten trap stations with seven capture points were used to sample the following microhabitats: liana, fallen log, ground litter, terrestrial ferns, simple-trunk tree, forked tree, and Piper sp. shrubs. Seven field phases were conducted, each for eight consecutive days, from September 2006 through January 2008. Four species of rodents (Akodon montensis, Sooretamys angouya, Oligoryzomys nigripes and Mus musculus) and two species of marsupials (Didelphis albiventris and Gracilinanus microtarsus) were captured. Captured species presented significant differences on their microhabitat use (ANOVA, p = 0.003), particularly between ground and understorey sites. Akodon montensis selected positively terrestrial ferns and trunks, S. angouya selected lianas, D. albiventris selected fallen trunks and Piper sp., and G. microtarsus choose tree trunks and lianas. We demonstrated that the local small-mammal assemblage does select microhabitats, with different types of associations between species and habitats. Besides, there is a strong evidence of habitat selection in order to diminish predation.

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups.

PubMed

Martin, Adam D; Wojciechowski, Jonathan P; Robinson, Andrew B; Heu, Celine; Garvey, Christopher J; Ratcliffe, Julian; Waddington, Lynne J; Gardiner, James; Thordarson, Pall

2017-03-08

Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy.

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology

PubMed Central

Galdeano, Carles; Ciulli, Alessio

2017-01-01

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity. PMID:27193077

Generative model selection using a scalable and size-independent complex network classifier

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

Motallebi, Sadegh, E-mail: motallebi@ce.sharif.edu; Aliakbary, Sadegh, E-mail: aliakbary@ce.sharif.edu; Habibi, Jafar, E-mail: jhabibi@sharif.edu

2013-12-15

Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree formore » model selection. Our proposed method, which is named “Generative Model Selection for Complex Networks,” outperforms existing methods with respect to accuracy, scalability, and size-independence.« less

Dietary change of the rock lobster Jasus lalandii after an ‘invasive’ geographic shift: Effects of size, density and food availability

NASA Astrophysics Data System (ADS)

Haley, C. N.; Blamey, L. K.; Atkinson, L. J.; Branch, G. M.

2011-06-01

During the 1990s the rock lobster Jasus lalandii shifted its focus of distribution south-eastwards along the coast of South Africa, to establish a dense population in an area where it was previously rare. This coincided with a marked decrease in the sea urchin Parechinus angulosus, a preferred prey item of J. lalandii and a vital source of shelter for juveniles of the abalone Haliotis midae. The range expansion of lobsters has thus economic and ecological ripple effects. We determined the diets of small (50-65 mm carapace length) and large (>69 mm CL) rock lobsters from gut content analyses, and compared them between three 'lobster invaded' sites and three adjacent 'non-invaded' sites where densities are still low. At the non-invaded sites, diets were collectively heterogeneous but the dietary breadth of individual lobsters was narrow (in contradiction to generally accepted ecological theory), and the lobsters fed mainly on large, individual, mobile, high-energy prey such as sea urchins and large winkles. Conversely, at invaded sites where lobster densities were high, they consumed predominantly small, colonial or sessile low-energy prey such as sponges, barnacles and foliar algae, and the diet was significantly more uniform among individuals, but broader within individuals. This was a direct result of the contrasting benthic community structure of the two areas, and consequent prey availability - itself caused by differences in intensity of rock-lobster predation. Cannibalism was unexpectedly greater at non-invaded sites, possibly as a result of lobsters being larger there. The diet of small and large lobsters also differed significantly. Large rock lobsters predominantly consumed large individual prey such as lobsters, urchins and crabs, while small rock lobsters ate mainly colonial, sessile prey such as sponges and barnacles, and small prey such as tiny winkles and crustaceans. Dietary selectivity indices revealed that algae and sponges were negatively selected (avoided) in non-invaded areas but positively or neutrally selected in invaded areas. These dietary differences have important ramifications not only for the lobster populations but also for the structure and functioning of the radically different communities that have developed in invaded areas, reflecting a regime shift induced by lobster predation.

The structure of XIAP BIR2: understanding the selectivity of the BIR domains

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

Lukacs, Christine, E-mail: cmlukacs230@gmail.com; Belunis, Charles; Crowther, Robert

2013-09-01

The high-resolution crystal structures of apo and peptide-bound XIAP BIR2 are presented and compared with BIR3 structures to understand their selectivity. This crystal system can be used to determine the structures of BIR2–inhibitor complexes. XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain–caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3–caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2–caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized;more » peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2–tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.« less

An efficient and high-throughput protocol for Agrobacterium-mediated transformation based on phosphomannose isomerase positive selection in Japonica rice (Oryza sativa L.).

PubMed

Duan, Yongbo; Zhai, Chenguang; Li, Hao; Li, Juan; Mei, Wenqian; Gui, Huaping; Ni, Dahu; Song, Fengshun; Li, Li; Zhang, Wanggen; Yang, Jianbo

2012-09-01

A number of Agrobacterium-mediated rice transformation systems have been developed and widely used in numerous laboratories and research institutes. However, those systems generally employ antibiotics like kanamycin and hygromycin, or herbicide as selectable agents, and are used for the small-scale experiments. To address high-throughput production of transgenic rice plants via Agrobacterium-mediated transformation, and to eliminate public concern on antibiotic markers, we developed a comprehensive efficient protocol, covering from explant preparation to the acquisition of low copy events by real-time PCR analysis before transplant to field, for high-throughput production of transgenic plants of Japonica rice varieties Wanjing97 and Nipponbare using Escherichia coli phosphomannose isomerase gene (pmi) as a selectable marker. The transformation frequencies (TF) of Wanjing97 and Nipponbare were achieved as high as 54.8 and 47.5%, respectively, in one round of selection of 7.5 or 12.5 g/L mannose appended with 5 g/L sucrose. High-throughput transformation from inoculation to transplant of low copy events was accomplished within 55-60 days. Moreover, the Taqman assay data from a large number of transformants showed 45.2% in Wanjing97 and 31.5% in Nipponbare as a low copy rate, and the transformants are fertile and follow the Mendelian segregation ratio. This protocol facilitates us to perform genome-wide functional annotation of the open reading frames and utilization of the agronomically important genes in rice under a reduced public concern on selectable markers. We describe a comprehensive protocol for large scale production of transgenic Japonica rice plants using non-antibiotic selectable agent, at simplified, cost- and labor-saving manners.

Effect of Two-Step Metal Organic Chemical Vapor Deposition Growth on Quality, Diameter and Density of InAs Nanowires on Si (111) Substrate

NASA Astrophysics Data System (ADS)

Yu, Hung Wei; Anandan, Deepak; Hsu, Ching Yi; Hung, Yu Chih; Su, Chun Jung; Wu, Chien Ting; Kakkerla, Ramesh Kumar; Ha, Minh Thien Huu; Huynh, Sa Hoang; Tu, Yung Yi; Chang, Edward Yi

2018-02-01

High-density (˜ 80/um2) vertical InAs nanowires (NWs) with small diameters (˜ 28 nm) were grown on bare Si (111) substrates by means of two-step metal organic chemical vapor deposition. There are two critical factors in the growth process: (1) a critical nucleation temperature for a specific In molar fraction (approximately 1.69 × 10-5 atm) is the key factor to reduce the size of the nuclei and hence the diameter of the InAs NWs, and (2) a critical V/III ratio during the 2nd step growth will greatly increase the density of the InAs NWs (from 45 μm-2 to 80 μm-2) and at the same time keep the diameter small. The high-resolution transmission electron microscopy and selected area diffraction patterns of InAs NWs grown on Si exhibit a Wurtzite structure and no stacking faults. The observed longitudinal optic peaks in the Raman spectra were explained in terms of the small surface charge region width due to the small NW diameter and the increase of the free electron concentration, which was consistent with the TCAD program simulation of small diameter (< 40 nm) InAs NWs.

Lake warming favours small-sized planktonic diatom species

PubMed Central

Winder, Monika; Reuter, John E.; Schladow, S. Geoffrey

2008-01-01

Diatoms contribute to a substantial portion of primary production in the oceans and many lakes. Owing to their relatively heavy cell walls and high nutrient requirements, planktonic diatoms are expected to decrease with climate warming because of reduced nutrient redistribution and increasing sinking velocities. Using a historical dataset, this study shows that diatoms were able to maintain their biovolume with increasing stratification in Lake Tahoe over the last decades; however, the diatom community structure changed. Increased stratification and reduced nitrogen to phosphorus ratios selected for small-celled diatoms, particularly within the Cyclotella genus. An empirical model showed that a shift in phytoplankton species composition and cell size was consistent within different depth strata, indicating that altered nutrient concentrations were not responsible for the change. The increase in small-celled species was sufficient to decrease the average diatom size and thus sinking velocity, which strongly influences energy transfer through the food web and carbon cycling. Our results show that within the diverse group of diatoms, small-sized species with a high surface area to volume ratio were able to adapt to a decrease in mixing intensity, supporting the hypotheses that abiotic drivers affect the size structure of planktonic communities and that warmer climate favours small-sized diatom cells. PMID:18812287

Boronic Acid Functionalized Au Nanoparticles for Selective MicroRNA Signal Amplification in Fiber-Optic Surface Plasmon Resonance Sensing System.

PubMed

Qian, Siyu; Lin, Ming; Ji, Wei; Yuan, Huizhen; Zhang, Yang; Jing, Zhenguo; Zhao, Jianzhang; Masson, Jean-François; Peng, Wei

2018-05-25

MicroRNA (miRNA) regulates gene expression and plays a fundamental role in multiple biological processes. However, if both single-stranded RNA and DNA can bind with capture DNA on the sensing surface, selectively amplifying the complementary RNA signal is still challenging for researchers. Fiber-optic surface plasmon resonance (SPR) sensors are small, accurate, and convenient tools for monitoring biological interaction. In this paper, we present a high sensitivity microRNA detection technique using phenylboronic acid functionalized Au nanoparticles (PBA-AuNPs) in fiber-optic SPR sensing systems. Due to the inherent difficulty directly detecting the hybridized RNA on the sensing surface, the PBA-AuNPs were used to selectively amplify the signal of target miRNA. The result shows that the method has high selectivity and sensitivity for miRNA, with a detection limit at 2.7 × 10 -13 M (0.27 pM). This PBA-AuNPs amplification strategy is universally applicable for RNA detection with various sensing technologies, such as surface-enhanced Raman spectroscopy and electrochemistry, among others.

Similarity selection and the evolution of sex: revisiting the red queen.

PubMed

Agrawal, Aneil F

2006-08-01

For over 25 years, many evolutionary ecologists have believed that sexual reproduction occurs because it allows hosts to change genotypes each generation and thereby evade their coevolving parasites. However, recent influential theoretical analyses suggest that, though parasites can select for sex under some conditions, they often select against it. These models assume that encounters between hosts and parasites are completely random. Because of this assumption, the fitness of a host depends only on its own genotype ("genotypic selection"). If a host is even slightly more likely to encounter a parasite transmitted by its mother than expected by random chance, then the fitness of a host also depends on its genetic similarity to its mother ("similarity selection"). A population genetic model is presented here that includes both genotypic and similarity selection, allowing them to be directly compared in the same framework. It is shown that similarity selection is a much more potent force with respect to the evolution of sex than is genotypic selection. Consequently, similarity selection can drive the evolution of sex even if it is much weaker than genotypic selection with respect to fitness. Examination of explicit coevolutionary models reveals that even a small degree of mother-offspring parasite transmission can cause parasites to favor sex rather than oppose it. In contrast to previous predictions, the model shows that weakly virulent parasites are more likely to favor sex than are highly virulent ones. Parasites have figured prominently in discussions of the evolution of sex, but recent models suggest that parasites often select against sex rather than for it. With the inclusion of small and realistic exposure biases, parasites are much more likely to favor sex. Though parasites alone may not provide a complete explanation for sex, the results presented here expand the potential for parasites to contribute to the maintenance of sex rather than act against it.

Interplay of Metalloligand and Organic Ligand to Tune Micropores within Isostructural Mixed-Metal Organic Frameworks (M MOFs) for Their Highly Selective Separation of Chiral and Achiral Small Molecules

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

Madhab, Das; He, Yabing; Kim, Jaheon

2012-01-01

Four porous isostructural mixed-metal-organic frameworks (M'MOFs) have been synthesized and structurally characterized. The pores within these M'MOFs are systematically tuned by the interplay of both the metalloligands and organic ligands which have enabled us not only to direct their highly selective separation of chiral alcohols 1-phenylethanol (PEA), 2-butanol (BUT), and 2-pentanol (2-PEN) with the highest ee up to 82.4% but also to lead highly selective separation of achiral C{sub 2}H{sub 2}/C{sub 2}H{sub 4} separation. The potential application of these M'MOFs for the fixed bed pressure swing adsorption (PSA) separation of C{sub 2}H{sub 2}/C{sub 2}H{sub 4} has been further examined andmore » compared by the transient breakthrough simulations in which the purity requirement of 40 ppm in the outlet gas can be readily fulfilled by the fixed bed M'MOF-4a adsorber at ambient conditions.« less

Son preference and sex-selective abortion in China: informing policy options.

PubMed

Zhou, Chi; Wang, Xiao Lei; Zhou, Xu Dong; Hesketh, Therese

2012-06-01

There is growing evidence in China that son preference is on the decline, but the sex ratio at birth is still the highest in the world at around 120 male births to 100 females. The aim of the study was to explore attitudes towards gender preference among people of reproductive age, to determine the reasons why the sex ratio is persistently high, and to inform policy options. We conducted in-depth interviews with 212 individuals who aged from 18 to 39 in rural and urban areas of three provinces: Yunnan, Guizhou and Zhejiang. We show that while son preference has weakened considerably, it has not disappeared. The sex ratio remains high, because of this small minority of individuals, who still choose sex-selective abortion to ensure male offsprings. Intensive local policy interventions have been successful in reducing the sex ratio in some areas and these should be disseminated widely. In addition, the law forbidding sex selection should be actively enforced, and the One Child Policy should be relaxed in some areas, to reduce the disproportionately high sex ratio in the second order births.

Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation.

PubMed

Danquah, Welbeck; Meyer-Schwesinger, Catherine; Rissiek, Björn; Pinto, Carolina; Serracant-Prat, Arnau; Amadi, Miriam; Iacenda, Domenica; Knop, Jan-Hendrik; Hammel, Anna; Bergmann, Philine; Schwarz, Nicole; Assunção, Joana; Rotthier, Wendy; Haag, Friedrich; Tolosa, Eva; Bannas, Peter; Boué-Grabot, Eric; Magnus, Tim; Laeremans, Toon; Stortelers, Catelijne; Koch-Nolte, Friedrich

2016-11-23

Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5'-triphosphate released by damaged cells, initiates a proinflammatory signaling cascade, including release of cytokines, such as interleukin-1β (IL-1β). To further explore its function, we generated and characterized nanobodies against mouse P2X7 that effectively blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and ameliorated experimental glomerulonephritis and allergic contact dermatitis. We also generated nanobody Dano1, which specifically inhibited human P2X7. In endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL-1β release than small-molecule P2X7 antagonists currently in clinical development. Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7. Copyright © 2016, American Association for the Advancement of Science.

A statistical approach to selecting and confirming validation targets in -omics experiments

PubMed Central

2012-01-01

Background Genomic technologies are, by their very nature, designed for hypothesis generation. In some cases, the hypotheses that are generated require that genome scientists confirm findings about specific genes or proteins. But one major advantage of high-throughput technology is that global genetic, genomic, transcriptomic, and proteomic behaviors can be observed. Manual confirmation of every statistically significant genomic result is prohibitively expensive. This has led researchers in genomics to adopt the strategy of confirming only a handful of the most statistically significant results, a small subset chosen for biological interest, or a small random subset. But there is no standard approach for selecting and quantitatively evaluating validation targets. Results Here we present a new statistical method and approach for statistically validating lists of significant results based on confirming only a small random sample. We apply our statistical method to show that the usual practice of confirming only the most statistically significant results does not statistically validate result lists. We analyze an extensively validated RNA-sequencing experiment to show that confirming a random subset can statistically validate entire lists of significant results. Finally, we analyze multiple publicly available microarray experiments to show that statistically validating random samples can both (i) provide evidence to confirm long gene lists and (ii) save thousands of dollars and hundreds of hours of labor over manual validation of each significant result. Conclusions For high-throughput -omics studies, statistical validation is a cost-effective and statistically valid approach to confirming lists of significant results. PMID:22738145

In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels – mirage or pot of gold?

PubMed Central

Bon, Robin S; Beech, David J

2013-01-01

The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7). These proteins generate channels for calcium and sodium ion entry. They are relevant to many mammalian cell types including acinar gland cells, adipocytes, astrocytes, cardiac myocytes, cochlea hair cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, keratinocytes, leukocytes, mast cells, mesangial cells, neurones, osteoblasts, osteoclasts, platelets, podocytes, smooth muscle cells, skeletal muscle and tumour cells. There are broad-ranging positive roles of the channels in cell adhesion, migration, proliferation, survival and turning, vascular permeability, hypertrophy, wound-healing, hypo-adiponectinaemia, angiogenesis, neointimal hyperplasia, oedema, thrombosis, muscle endurance, lung hyper-responsiveness, glomerular filtration, gastrointestinal motility, pancreatitis, seizure, innate fear, motor coordination, saliva secretion, mast cell degranulation, cancer cell drug resistance, survival after myocardial infarction, efferocytosis, hypo-matrix metalloproteinase, vasoconstriction and vasodilatation. Known small molecule stimulators of the channels include hyperforin, genistein and rosiglitazone, but there is more progress with inhibitors, some of which have promising potency and selectivity. The inhibitors include 2-aminoethoxydiphenyl borate, 2-aminoquinolines, 2-aminothiazoles, fatty acids, isothiourea derivatives, naphthalene sulfonamides, N-phenylanthranilic acids, phenylethylimidazoles, piperazine/piperidine analogues, polyphenols, pyrazoles and steroids. A few of these agents are starting to be useful as tools for determining the physiological and pathophysiological functions of TRPC channels. We suggest that the pursuit of small molecule modulators for TRPC channels is important but that it requires substantial additional effort and investment before we can reap the rewards of highly potent and selective pharmacological modulators. PMID:23763262

Selective epitaxy using the gild process

DOEpatents

Weiner, Kurt H.

1992-01-01

The present invention comprises a method of selective epitaxy on a semiconductor substrate. The present invention provides a method of selectively forming high quality, thin GeSi layers in a silicon circuit, and a method for fabricating smaller semiconductor chips with a greater yield (more error free chips) at a lower cost. The method comprises forming an upper layer over a substrate, and depositing a reflectivity mask which is then removed over selected sections. Using a laser to melt the unmasked sections of the upper layer, the semiconductor material in the upper layer is heated and diffused into the substrate semiconductor material. By varying the amount of laser radiation, the epitaxial layer is formed to a controlled depth which may be very thin. When cooled, a single crystal epitaxial layer is formed over the patterned substrate. The present invention provides the ability to selectively grow layers of mixed semiconductors over patterned substrates such as a layer of Ge.sub.x Si.sub.1-x grown over silicon. Such a process may be used to manufacture small transistors that have a narrow base, heavy doping, and high gain. The narrowness allows a faster transistor, and the heavy doping reduces the resistance of the narrow layer. The process does not require high temperature annealing; therefore materials such as aluminum can be used. Furthermore, the process may be used to fabricate diodes that have a high reverse breakdown voltage and a low reverse leakage current.

Popularity and user diversity of online objects

NASA Astrophysics Data System (ADS)

Wang, Jia-Hua; Guo, Qiang; Yang, Kai; Zhang, Yi-Lu; Han, Jingti; Liu, Jian-Guo

2016-11-01

The popularity has been widely used to describe the object property of online user-object bipartite networks regardless of the user characteristics. In this paper, we introduce a measurement namely user diversity to measure diversity of users who select or rate one type of objects by using the information entropy. We empirically calculate the user diversity of objects with specific degree for both MovieLens and Diggs data sets. The results indicate that more types of users select normal-degree objects than those who select large-degree and small-degree objects. Furthermore, small-degree objects are usually selected by large-degree users while large-degree objects are usually selected by small-degree users. Moreover, we define 15% objects of smallest degrees as unpopular objects and 10% ones of largest degrees as popular objects. The timestamp is introduced to help further analyze the evolution of user diversity of popular objects and unpopular objects. The dynamic analysis shows that as objects become popular gradually, they are more likely accepted by small-degree users but lose attention among the large-degree users.

Analytic theory for the selection of Saffman-Taylor fingers in the presence of thin film effects

NASA Technical Reports Server (NTRS)

Tanveer, S.

1990-01-01

The present analytic theory for the width selection of Saffman-Taylor (1958) fingers in the presence of the thin film effect establishes that, in the limit of a small capillary number and a small gap-to-width ratio, fingers whose relative width is smaller than 1/2 are possible. It is established that a fully nonlinear analysis is required for this problem in order to obtain even the correct (and rather preliminary) scaling law. The way in which the selection rule for arbitrary small capillary number is obtainable is also presented.

Properties of different selection signature statistics and a new strategy for combining them.

PubMed

Ma, Y; Ding, X; Qanbari, S; Weigend, S; Zhang, Q; Simianer, H

2015-11-01

Identifying signatures of recent or ongoing selection is of high relevance in livestock population genomics. From a statistical perspective, determining a proper testing procedure and combining various test statistics is challenging. On the basis of extensive simulations in this study, we discuss the statistical properties of eight different established selection signature statistics. In the considered scenario, we show that a reasonable power to detect selection signatures is achieved with high marker density (>1 SNP/kb) as obtained from sequencing, while rather small sample sizes (~15 diploid individuals) appear to be sufficient. Most selection signature statistics such as composite likelihood ratio and cross population extended haplotype homozogysity have the highest power when fixation of the selected allele is reached, while integrated haplotype score has the highest power when selection is ongoing. We suggest a novel strategy, called de-correlated composite of multiple signals (DCMS) to combine different statistics for detecting selection signatures while accounting for the correlation between the different selection signature statistics. When examined with simulated data, DCMS consistently has a higher power than most of the single statistics and shows a reliable positional resolution. We illustrate the new statistic to the established selective sweep around the lactase gene in human HapMap data providing further evidence of the reliability of this new statistic. Then, we apply it to scan selection signatures in two chicken samples with diverse skin color. Our analysis suggests that a set of well-known genes such as BCO2, MC1R, ASIP and TYR were involved in the divergent selection for this trait.

High energy density propulsion systems and small engine dynamometer

NASA Astrophysics Data System (ADS)

Hays, Thomas

2009-07-01

Scope and Method of Study. This study investigates all possible methods of powering small unmanned vehicles, provides reasoning for the propulsion system down select, and covers in detail the design and production of a dynamometer to confirm theoretical energy density calculations for small engines. Initial energy density calculations are based upon manufacturer data, pressure vessel theory, and ideal thermodynamic cycle efficiencies. Engine tests are conducted with a braking type dynamometer for constant load energy density tests, and show true energy densities in excess of 1400 WH/lb of fuel. Findings and Conclusions. Theory predicts lithium polymer, the present unmanned system energy storage device of choice, to have much lower energy densities than other conversion energy sources. Small engines designed for efficiency, instead of maximum power, would provide the most advantageous method for powering small unmanned vehicles because these engines have widely variable power output, loss of mass during flight, and generate rotational power directly. Theoretical predictions for the energy density of small engines has been verified through testing. Tested values up to 1400 WH/lb can be seen under proper operating conditions. The implementation of such a high energy density system will require a significant amount of follow-on design work to enable the engines to tolerate the higher temperatures of lean operation. Suggestions are proposed to enable a reliable, small-engine propulsion system in future work. Performance calculations show that a mature system is capable of month long flight times, and unrefueled circumnavigation of the globe.

Three Small-Receptive-Field Ganglion Cells in the Mouse Retina Are Distinctly Tuned to Size, Speed, and Object Motion

PubMed Central

Jacoby, Jason

2017-01-01

Retinal ganglion cells (RGCs) are frequently divided into functional types by their ability to extract and relay specific features from a visual scene, such as the capacity to discern local or global motion, direction of motion, stimulus orientation, contrast or uniformity, or the presence of large or small objects. Here we introduce three previously uncharacterized, nondirection-selective ON–OFF RGC types that represent a distinct set of feature detectors in the mouse retina. The three high-definition (HD) RGCs possess small receptive-field centers and strong surround suppression. They respond selectively to objects of specific sizes, speeds, and types of motion. We present comprehensive morphological characterization of the HD RGCs and physiological recordings of their light responses, receptive-field size and structure, and synaptic mechanisms of surround suppression. We also explore the similarities and differences between the HD RGCs and a well characterized RGC with a comparably small receptive field, the local edge detector, in response to moving objects and textures. We model populations of each RGC type to study how they differ in their performance tracking a moving object. These results, besides introducing three new RGC types that together constitute a substantial fraction of mouse RGCs, provide insights into the role of different circuits in shaping RGC receptive fields and establish a foundation for continued study of the mechanisms of surround suppression and the neural basis of motion detection. SIGNIFICANCE STATEMENT The output cells of the retina, retinal ganglion cells (RGCs), are a diverse group of ∼40 distinct neuron types that are often assigned “feature detection” profiles based on the specific aspects of the visual scene to which they respond. Here we describe, for the first time, morphological and physiological characterization of three new RGC types in the mouse retina, substantially augmenting our understanding of feature selectivity. Experiments and modeling show that while these three “high-definition” RGCs share certain receptive-field properties, they also have distinct tuning to the size, speed, and type of motion on the retina, enabling them to occupy different niches in stimulus space. PMID:28100743

Sage-grouse habitat selection during winter in Alberta

USGS Publications Warehouse

Carpenter, Jennifer L.; Aldridge, Cameron L.; Boyce, Mark S.

2010-01-01

Greater sage-grouse (Centrocercus urophasianus) are dependent on sagebrush (Artemisia spp.) for food and shelter during winter, yet few studies have assessed winter habitat selection, particularly at scales applicable to conservation planning. Small changes to availability of winter habitats have caused drastic reductions in some sage-grouse populations. We modeled winter habitat selection by sage-grouse in Alberta, Canada, by using a resource selection function. Our purpose was to 1) generate a robust winter habitat-selection model for Alberta sage-grouse; 2) spatially depict habitat suitability in a Geographic Information System to identify areas with a high probability of selection and thus, conservation importance; and 3) assess the relative influence of human development, including oil and gas wells, in landscape models of winter habitat selection. Terrain and vegetation characteristics, sagebrush cover, anthropogenic landscape features, and energy development were important in top Akaike's Information Criterionselected models. During winter, sage-grouse selected dense sagebrush cover and homogenous less rugged areas, and avoided energy development and 2-track truck trails. Sage-grouse avoidance of energy development highlights the need for comprehensive management strategies that maintain suitable habitats across all seasons. ?? 2010 The Wildlife Society.

Editorial highlighting and highly cited papers

NASA Astrophysics Data System (ADS)

Antonoyiannakis, Manolis

Editorial highlighting-the process whereby journal editors select, at the time of publication, a small subset of papers that are ostensibly of higher quality, importance or interest-is by now a widespread practice among major scientific journal publishers. Depending on the venue, and the extent to which editorial resources are invested in the process, highlighted papers appear as News & Views, Research Highlights, Perspectives, Editors' Choice, IOP Select, Editors' Summary, Spotlight on Optics, Editors' Picks, Viewpoints, Synopses, Editors' Suggestions, etc. Here, we look at the relation between highlighted papers and highly influential papers, which we define at two levels: having received enough citations to be among the (i) top few percent of their journal, and (ii) top 1% of all physics papers. Using multiple linear regression and multilevel regression modeling we examine the parameters associated with highly influential papers. We briefly comment on cause and effect relationships between citedness and highlighting of papers.

Highχ block copolymers for directed self-assembly patterning without the need for topcoat or solvent annealing

NASA Astrophysics Data System (ADS)

Xu, Kui; Hockey, Mary Ann; Calderas, Eric; Guerrero, Douglas; Sweat, Daniel; Fiehler, Jeffrey

2017-03-01

High-χ block copolymers for directed self-assembly (DSA) patterning that do not need topcoat or solvent annealing have been developed. A variety of functionalities have been successfully added into the block copolymers, such as balanced surface energy between the polymer blocks, outstandingly high χ, tunable glass transition temperature (Tg), and selective crosslinking. Perpendicular orientation control, as desired for patterning, of the block copolymers can be simply achieved by thermal annealing due to the equal surface energy of the polymer blocks at the annealing temperatures, which allows avoiding solvent annealing or top-coat. The χ value can be tuned up to achieve L0 as low as 8-10 nm for lamellar-structured block copolymers and hole/pillar size as small as 5-6 nm for cylinder-structured block copolymers. The Tg of the block copolymers can be tuned to improve the kinetics of thermal annealing by enhancing the polymer chain mobility. Block-selective crosslinking facilitates the pattern transfer by mitigating pattern collapse during wet etching and improving oxygen plasma etching selectivity between the polymer blocks. This paper provides an introductory review of our high-χ block copolymer materials with various functionalities for achieving improved DSA performance.

Biotinylated Rh(III) complexes in engineered streptavidin for accelerated asymmetric C-H activation.

PubMed

Hyster, Todd K; Knörr, Livia; Ward, Thomas R; Rovis, Tomislav

2012-10-26

Enzymes provide an exquisitely tailored chiral environment to foster high catalytic activities and selectivities, but their native structures are optimized for very specific biochemical transformations. Designing a protein to accommodate a non-native transition metal complex can broaden the scope of enzymatic transformations while raising the activity and selectivity of small-molecule catalysis. Here, we report the creation of a bifunctional artificial metalloenzyme in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C-H) activation. The coupling of benzamides and alkenes to access dihydroisoquinolones proceeds with up to nearly a 100-fold rate acceleration compared with the activity of the isolated rhodium complex and enantiomeric ratios as high as 93:7.

Best kept secrets ... Source Data Systems, Inc. (SDS).

PubMed

Andrew, W F

1991-03-01

The SDS/MEDNET system is a cost-effective option for small- to medium-size hospitals (up to 400 beds). The parameter-driven system lets users control operations with only occasional SDS assistance. A full application set, available for modular selection to reduce upfront costs while facilitating steady growth and protecting client investment, is adaptable to multi-facility environments. The industry-standard, Intel-based multi-user processors, network communications and protocols assure high efficiency, low-cost solutions independent of any one hardware vendor. Sustained growth in both client base and product offerings point to a high level of responsiveness and healthcare industry commitment. Corporate emphasis on user involvement and open systems integration assures clients of leading-edge capabilities. SDS/MEDNET will be a strong contender in selected marketing environments.

A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis

PubMed Central

2011-01-01

Introduction Janus kinase 2 (JAK2) is involved in the downstream activation of signal transducer and activator of transcription 3 (STAT3) and STAT5 and is responsible for transducing signals for several proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), including interleukin (IL)-6, interferon γ (IFNγ) and IL-12. In this paper, we describe the efficacy profile of CEP-33779, a highly selective, orally active, small-molecule inhibitor of JAK2 evaluated in two mouse models of RA. Methods Collagen antibody-induced arthritis (CAIA) and collagen type II (CII)-induced arthritis (CIA) were established before the oral administration of a small-molecule JAK2 inhibitor, CEP-33779, twice daily at 10 mg/kg, 30 mg/kg, 55 mg/kg or 100 mg/kg over a period of 4 to 8 weeks. Results Pharmacodynamic inhibition of JAK2 reduced mean paw edema and clinical scores in both CIA and CAIA models of arthritis. Reduction in paw cytokines (IL-12, IFNγ and tumor necrosis factor α) and serum cytokines (IL-12 and IL-2) correlated with reduced spleen CII-specific T helper 1 cell frequencies as measured by ex vivo IFNγ enzyme-linked immunosorbent spot assay. Both models demonstrated histological evidence of disease amelioration upon treatment (for example, reduced matrix erosion, subchondral osteolysis, pannus formation and synovial inflammation) and reduced paw phosphorylated STAT3 levels. No changes in body weight or serum anti-CII autoantibody titers were observed in either RA model. Conclusions This study demonstrates the utility of using a potent and highly selective, orally bioavailable JAK2 inhibitor for the treatment of RA. Using a selective inhibitor of JAK2 rather than pan-JAK inhibitors avoids the potential complication of immunosuppression while targeting critical signaling pathways involved in autoimmune disease progression. PMID:21510883

Selective imaging of cathepsin L in breast cancer by fluorescent activity-based probes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04303a

PubMed Central

Rut, Wioletta; Vizovisek, Matej; Groborz, Katarzyna; Kasperkiewicz, Paulina; Finlay, Darren; Vuori, Kristiina; Turk, Dusan; Turk, Boris; Salvesen, Guy S.

2018-01-01

Cysteine cathepsins normally function in the lysosomal degradation system where they are critical for the maintenance of cellular homeostasis and the MHC II immune response, and have been found to have major roles in several diseases and in tumor progression. Selective visualization of individual protease activity within a complex proteome is of major importance to establish their roles in both normal and tumor cells, thereby facilitating our understanding of the regulation of proteolytic networks. A generally accepted means to monitor protease activity is the use of small molecule substrates and activity-based probes. However, there are eleven human cysteine cathepsins, with a few of them displaying overlapping substrate specificity, making the development of small molecules that selectively target a single cathepsin very challenging. Here, we utilized HyCoSuL, a positional scanning substrate approach, to develop a highly-selective fluorogenic substrate and activity-based probe for monitoring cathepsin L activity in the breast cancer cell line MDA-MB-231. Use of this probe enabled us to distinguish the activity of cathepsin L from that of other cathepsins, particularly cathepsin B, which is abundant and ubiquitously expressed in normal and transformed cell types. We found that cathepsin L localization in MDA-MB-231 cells greatly overlaps with that of cathepsin B, however, several cathepsin L-rich lysosomes lacked cathepsin B activity. Overall, these studies demonstrate that HyCoSuL-derived small molecule probes are valuable tools to image cathepsin L activity in living cells. This approach thus enables evaluation of cathepsin L function in tumorigenesis and is applicable to other cysteine cathepsins. PMID:29719685

Performance Comparisons and Down Selection of Small Motors for Two-Blade Heliogyro Solar Sail 6U CubeSat

NASA Technical Reports Server (NTRS)

Wiwattananon, Peerawan; Bryant, Robert G.

2015-01-01

This report compiles a review of 130 commercial small scale motors (piezoelectric and electric motors) and almost 20 researched-type small scale piezoelectricmotors for potential use in a 2 blades Heliogyro Solar Sail 6U CubeSat. In this application, a motor and gearhead (drive system) will deploy a roll of solar sailthin film (2 um thick)accommodated in a 2U CubeSat (100 x 200 x 100 mm) housing. The application requirements are: space rated, output torque at fulldeployment of 0.8 Nm, reel speed of 3 rpm, drive system weight limited to 150 grams, diameter limited to 50 mm, and the length not to exceed 40 mm. The 50mm diameter limit was imposed as motors with larger diameters would likely weigh too much and use more space on the satellite wall. This would limit theamount of the payload. The motors performance are compared between small scale, volume within 3x102 cm3 (3x105 mm3), commercial electric DC motors,commercial piezoelectric motors, and researched-type (non-commercial) piezoelectric motors extracted from scientific and product literature. The comparisonssuggest that piezoelectric motors without a gearhead exhibit larger output torque with respect to their volume and weight and require less input power toproduce high torque. A commercially available electric motor plus a gearhead was chosen through a proposed selection process to meet the applications designrequirements.

Small Business Innovation Research. Program solicitation. Closing date: July 21, 1992

NASA Technical Reports Server (NTRS)

1992-01-01

The National Aeronautics and Space Administration (NASA) invites small businesses to submit Phase 1 proposals in response to its Small Business Innovation Research (SBIR) Program Solicitation 92-1. Firms with research or research and development capabilities (R/R&D) in science or engineering in any of the areas listed are encouraged to participate. This, the tenth annual SBIR solicitation by NASA, describes the program, identifies eligibility requirements, describes the proposal evaluation and award selection process, and provides other information to assist those interested in participating in NASA's SBIR program. It also identifies, in Section 8.0, the technical topics and subtopics in which SBIR Phase 1 proposals are solicited in 1992. These topics and subtopics cover a broad range of current NASA interests but do not necessarily include all areas in which NASA plans or currently conducts research. The NASA SBIR program seeks innovative approaches that respond to the needs, technical requirements, and new opportunities described in the subtopics. The focus is on innovation through the use of emerging technologies, novel applications of existing technologies, exploitation of scientific breakthroughs, or new capabilities or major improvements to existing technologies. NASA plans to select about 320 high-quality research or research and development proposals for Phase 1 contract awards on the basis of this Solicitation. Phase 1 contracts are normally six months in duration and funded up to $50,000, including profit. Selections will be based on the competitive merits of the offers and on NASA needs and priorities.

Reduced MHC and neutral variation in the Galápagos hawk, an island endemic

PubMed Central

2011-01-01

Background Genes at the major histocompatibility complex (MHC) are known for high levels of polymorphism maintained by balancing selection. In small or bottlenecked populations, however, genetic drift may be strong enough to overwhelm the effect of balancing selection, resulting in reduced MHC variability. In this study we investigated MHC evolution in two recently diverged bird species: the endemic Galápagos hawk (Buteo galapagoensis), which occurs in small, isolated island populations, and its widespread mainland relative, the Swainson's hawk (B. swainsoni). Results We amplified at least two MHC class II B gene copies in each species. We recovered only three different sequences from 32 Galápagos hawks, while we amplified 20 unique sequences in 20 Swainson's hawks. Most of the sequences clustered into two groups in a phylogenetic network, with one group likely representing pseudogenes or nonclassical loci. Neutral genetic diversity at 17 microsatellite loci was also reduced in the Galápagos hawk compared to the Swainson's hawk. Conclusions The corresponding loss in neutral diversity suggests that the reduced variability present at Galápagos hawk MHC class II B genes compared to the Swainson's hawk is primarily due to a founder event followed by ongoing genetic drift in small populations. However, purifying selection could also explain the low number of MHC alleles present. This lack of variation at genes involved in the adaptive immune response could be cause for concern should novel diseases reach the archipelago. PMID:21612651

Habitat Selectivity and Reliance on Live Corals for Indo-Pacific Hawkfishes (Family: Cirrhitidae).

PubMed

Coker, Darren J; Hoey, Andrew S; Wilson, Shaun K; Depczynski, Martial; Graham, Nicholas A J; Hobbs, Jean-Paul A; Holmes, Thomas H; Pratchett, Morgan S

2015-01-01

Hawkfishes (family: Cirrhitidae) are small conspicuous reef predators that commonly perch on, or shelter within, the branches of coral colonies. This study examined habitat associations of hawkfishes, and explicitly tested whether hawkfishes associate with specific types of live coral. Live coral use and habitat selectivity of hawkfishes was explored at six locations from Chagos in the central Indian Ocean extending east to Fiji in the Pacific Ocean. A total of 529 hawkfishes from seven species were recorded across all locations with 63% of individuals observed perching on, or sheltering within, live coral colonies. Five species (all except Cirrhitus pinnulatus and Cirrhitichthys oxycephalus) associated with live coral habitats. Cirrhitichthys falco selected for species of Pocillopora while Paracirrhites arcatus and P. forsteri selected for both Pocillopora and Acropora, revealing that these habitats are used disproportionately more than expected based on the local cover of these coral genera. Habitat selection was consistent across geographic locations, and species of Pocillopora were the most frequently used and most consistently selected even though this coral genus never comprised more than 6% of the total coral cover at any of the locations. Across locations, Paracirrhites arcatus and P. forsteri were the most abundant species and variation in their abundance corresponded with local patterns of live coral cover and abundance of Pocilloporid corals, respectively. These findings demonstrate the link between small predatory fishes and live coral habitats adding to the growing body of literature highlighting that live corals (especially erect branching corals) are critically important for sustaining high abundance and diversity of fishes on coral reefs.

Efficiency of multi-breed genomic selection for dairy cattle breeds with different sizes of reference population.

PubMed

Hozé, C; Fritz, S; Phocas, F; Boichard, D; Ducrocq, V; Croiseau, P

2014-01-01

Single-breed genomic selection (GS) based on medium single nucleotide polymorphism (SNP) density (~50,000; 50K) is now routinely implemented in several large cattle breeds. However, building large enough reference populations remains a challenge for many medium or small breeds. The high-density BovineHD BeadChip (HD chip; Illumina Inc., San Diego, CA) containing 777,609 SNP developed in 2010 is characterized by short-distance linkage disequilibrium expected to be maintained across breeds. Therefore, combining reference populations can be envisioned. A population of 1,869 influential ancestors from 3 dairy breeds (Holstein, Montbéliarde, and Normande) was genotyped with the HD chip. Using this sample, 50K genotypes were imputed within breed to high-density genotypes, leading to a large HD reference population. This population was used to develop a multi-breed genomic evaluation. The goal of this paper was to investigate the gain of multi-breed genomic evaluation for a small breed. The advantage of using a large breed (Normande in the present study) to mimic a small breed is the large potential validation population to compare alternative genomic selection approaches more reliably. In the Normande breed, 3 training sets were defined with 1,597, 404, and 198 bulls, and a unique validation set included the 394 youngest bulls. For each training set, estimated breeding values (EBV) were computed using pedigree-based BLUP, single-breed BayesC, or multi-breed BayesC for which the reference population was formed by any of the Normande training data sets and 4,989 Holstein and 1,788 Montbéliarde bulls. Phenotypes were standardized by within-breed genetic standard deviation, the proportion of polygenic variance was set to 30%, and the estimated number of SNP with a nonzero effect was about 7,000. The 2 genomic selection (GS) approaches were performed using either the 50K or HD genotypes. The correlations between EBV and observed daughter yield deviations (DYD) were computed for 6 traits and using the different prediction approaches. Compared with pedigree-based BLUP, the average gain in accuracy with GS in small populations was 0.057 for the single-breed and 0.086 for multi-breed approach. This gain was up to 0.193 and 0.209, respectively, with the large reference population. Improvement of EBV prediction due to the multi-breed evaluation was higher for animals not closely related to the reference population. In the case of a breed with a small reference population size, the increase in correlation due to multi-breed GS was 0.141 for bulls without their sire in reference population compared with 0.016 for bulls with their sire in reference population. These results demonstrate that multi-breed GS can contribute to increase genomic evaluation accuracy in small breeds. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An efficient route to selective bio-oxidation catalysts: an iterative approach comprising modeling, diversification, and screening, based on CYP102A1.

PubMed

Seifert, Alexander; Antonovici, Mihaela; Hauer, Bernhard; Pleiss, Jürgen

2011-06-14

Perillyl alcohol is the terminal hydroxylation product of the cheap and readily available terpene, limonene. It has high potential as an anti-tumor substance, but is of limited availability. In principle, cytochrome P450 monooxygenases, such as the self-sufficient CYP102A1, are promising catalysts for the oxidation of limonene or other inert hydrocarbons. The wild-type enzyme converts (4R)-limonene to four different oxidation products; however, terminal hydroxylation at the allylic C7 is not observed. Here we describe a generic strategy to engineer this widely used enzyme to hydroxylate exclusively the exposed, but chemically less reactive, primary C7 in the presence of other reactive positions. The approach presented here turns CYP102A1 into a highly selective catalyst with a shifted product spectra by successive rounds of modeling, the design of small focused libraries, and screening. In the first round a minimal CYP102A1 mutant library was rationally designed. It contained variants with improved or strongly shifted regio-, stereo- and chemoselectivity, compared to wild-type. From this library the variant with the highest perillyl alcohol ratio was fine-tuned by two additional rounds of molecular modeling, diversification, and screening. In total only 29 variants needed to be screened to identify the triple mutant A264V/A238V/L437F that converts (4R)-limonene to perillyl alcohol with a selectivity of 97 %. Focusing mutagenesis on a small number of relevant positions identified by computational approaches is the key for efficient screening for enzyme selectivity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis Strategies for Ultrastable Zeolite GIS Polymorphs as Sorbents for Selective Separations

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

Oleksiak, Matthew D.; Ghorbanpour, Arian; Conato, Marlon T.

Designing nanoporous zeolites with tunable physicochemical properties can substantially impact their performance in commercial applications spanning diverse areas such as adsorption, separations, catalysis, and drug delivery. Zeolite synthesis typically requires the use of an organic structure-directing agent to facilitate the formation of crystals with specific pore size and topology. Attempts to remove organics from syntheses to achieve commercially-viable methods of preparing zeolites often lead to the formation of unwanted crystal polymorphs (i.e., impurities). Here, we present an organic-free synthesis of the small-pore zeolite P (GIS framework topology) that can be selectively tailored to produce two pure polymorphs: P1 and P2.more » To this end, we developed kinetic phase diagrams that identify synthesis compositions leading to the formation of GIS (P1 and P2), as well as their structural analogues MER and PHI. Using a combination of adsorption measurements and density functional theory (DFT) calculations, we also show that both GIS polymorphs are highly selective adsorbents for H2O relative to other light gases (e.g,, H2, N2, CO2). These studies highlight the potential application of GIS materials for dehydration processes, while our findings also refute prior theoretical studies postulating that GIS-type zeolites are excellent materials for CO2 separation/sequestration. Moreover, there is an impetus for discovering novel small-pore zeolites that are shape-selective catalysts for the production of value-added chemicals (e.g., light olefins); thus, our discovery of more thermally-stable P2 opens new avenues for exploring the potential role of this material as a high-performance catalyst.« less

Self-assembled near-infrared dye nanoparticles as a selective protein sensor by activation of a dormant fluorophore.

PubMed

Anees, Palapuravan; Sreejith, Sivaramapanicker; Ajayaghosh, Ayyappanpillai

2014-09-24

Design of selective sensors for a specific analyte in blood serum, which contains a large number of proteins, small molecules, and ions, is important in clinical diagnostics. While metal and polymeric nanoparticle conjugates have been used as sensors, small molecular assemblies have rarely been exploited for the selective sensing of a protein in blood serum. Herein we demonstrate how a nonspecific small molecular fluorescent dye can be empowered to form a selective protein sensor as illustrated with a thiol-sensitive near-IR squaraine (Sq) dye (λabs= 670 nm, λem= 700 nm). The dye self-assembles to form nonfluorescent nanoparticles (Dh = 200 nm) which selectively respond to human serum albumin (HSA) in the presence of other thiol-containing molecules and proteins by triggering a green fluorescence. This selective response of the dye nanoparticles allowed detection and quantification of HSA in blood serum with a sensitivity limit of 3 nM. Notably, the Sq dye in solution state is nonselective and responds to any thiol-containing proteins and small molecules. The sensing mechanism involves HSA specific controlled disassembly of the Sq nanoparticles to the molecular dye by a noncovalent binding process and its subsequent reaction with the thiol moiety of the protein, triggering the green emission of a dormant fluorophore present in the dye. This study demonstrates the power of a self-assembled small molecular fluorophore for protein sensing and is a simple chemical tool for the clinical diagnosis of blood serum.

Neutral mutation as the source of genetic variation in life history traits.

PubMed

Brcić-Kostić, Krunoslav

2005-08-01

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.

The alternative oxidase family of Vitis vinifera reveals an attractive model to study the importance of genomic design.

PubMed

Costa, José Hélio; de Melo, Dirce Fernandes; Gouveia, Zélia; Cardoso, Hélia Guerra; Peixe, Augusto; Arnholdt-Schmitt, Birgit

2009-12-01

'Genomic design' refers to the structural organization of gene sequences. Recently, the role of intron sequences for gene regulation is being better understood. Further, introns possess high rates of polymorphism that are considered as the major source for speciation. In molecular breeding, the length of gene-specific introns is recognized as a tool to discriminate genotypes with diverse traits of agronomic interest. 'Economy selection' and 'time-economy selection' have been proposed as models for explaining why highly expressed genes typically contain small introns. However, in contrast to these theories, plant-specific selection reveals that highly expressed genes contain introns that are large. In the presented research, 'wet'Aox gene identification from grapevine is advanced by a bioinformatics approach to study the species-specific organization of Aox gene structures in relation to available expressed sequence tag (EST) data. Two Aox1 and one Aox2 gene sequences have been identified in Vitis vinifera using grapevine cultivars from Portugal and Germany. Searching the complete genome sequence data of two grapevine cultivars confirmed that V. vinifera alternative oxidase (Aox) is encoded by a small multigene family composed of Aox1a, Aox1b and Aox2. An analysis of EST distribution revealed high expression of the VvAox2 gene. A relationship between the atypical long primary transcript of VvAox2 (in comparison to other plant Aox genes) and its expression level is suggested. V. vinifera Aox genes contain four exons interrupted by three introns except for Aox1a which contains an additional intron in the 3'-UTR. The lengths of primary Aox transcripts were estimated for each gene in two V. vinifera varieties: PN40024 and Pinot Noir. In both varieties, Aox1a and Aox1b contained small introns that corresponded to primary transcript lengths ranging from 1501 to 1810 bp. The Aox2 of PN40024 (12 329 bp) was longer than that from Pinot Noir (7279 bp) because of selection against a transposable-element insertion that is 5028 bp in size. An EST database basic local alignment search tool (BLAST) search of GenBank revealed the following ESTs percentages for each gene: Aox1a (26.2%), Aox1b (11.9%) and Aox2 (61.9%). Aox1a was expressed in fruits and roots, Aox1b expression was confined to flowers and Aox2 was ubiquitously expressed. These data for V. vinifera show that atypically long Aox intron lengths are related to high levels of gene expression. Furthermore, it is shown for the first time that two grapevine cultivars can be distinguished by Aox intron length polymorphism.

Image Quality in High-resolution and High-cadence Solar Imaging

NASA Astrophysics Data System (ADS)

Denker, C.; Dineva, E.; Balthasar, H.; Verma, M.; Kuckein, C.; Diercke, A.; González Manrique, S. J.

2018-03-01

Broad-band imaging and even imaging with a moderate bandpass (about 1 nm) provides a photon-rich environment, where frame selection (lucky imaging) becomes a helpful tool in image restoration, allowing us to perform a cost-benefit analysis on how to design observing sequences for imaging with high spatial resolution in combination with real-time correction provided by an adaptive optics (AO) system. This study presents high-cadence (160 Hz) G-band and blue continuum image sequences obtained with the High-resolution Fast Imager (HiFI) at the 1.5-meter GREGOR solar telescope, where the speckle-masking technique is used to restore images with nearly diffraction-limited resolution. The HiFI employs two synchronized large-format and high-cadence sCMOS detectors. The median filter gradient similarity (MFGS) image-quality metric is applied, among others, to AO-corrected image sequences of a pore and a small sunspot observed on 2017 June 4 and 5. A small region of interest, which was selected for fast-imaging performance, covered these contrast-rich features and their neighborhood, which were part of Active Region NOAA 12661. Modifications of the MFGS algorithm uncover the field- and structure-dependency of this image-quality metric. However, MFGS still remains a good choice for determining image quality without a priori knowledge, which is an important characteristic when classifying the huge number of high-resolution images contained in data archives. In addition, this investigation demonstrates that a fast cadence and millisecond exposure times are still insufficient to reach the coherence time of daytime seeing. Nonetheless, the analysis shows that data acquisition rates exceeding 50 Hz are required to capture a substantial fraction of the best seeing moments, significantly boosting the performance of post-facto image restoration.

Enhanced parent selection algorithms in mintroute protocol

NASA Astrophysics Data System (ADS)

Kim, Ki-Il

2012-11-01

A low-rate, short-range wireless radio communication on a small device often hampers high reliability in wireless sensor networks. However, more applications are increasingly demanding high reliability. To meet this requirement, various approaches have been proposed in each viewpoint of layers. Among those, MintRoute is a well-known network layer approach to develop a new metric based on link quality for path selection towards the sink. By choosing the link with the highest measured value, it has a higher possibility to transmit a packet over the link without error. However, there are still several issues to be mentioned during operations. In this paper, we propose how to improve the MintRoute protocol through revised algorithms. They include a parent selection considering distance and level from the sink node, and a fast recovery method against failures. Simulations and analysis are performed by in order to validate the suitability of reduced end-to-end delay and fast recovery for failures, thus to enhance the reliability of communication.

Defective Carbon-Based Materials for the Electrochemical Synthesis of Hydrogen Peroxide

DOE PAGES

Chen, Shucheng; Chen, Zhihua; Siahrostami, Samira; ...

2017-10-30

Hydrogen peroxide (H 2O 2), an important industrial chemical, is currently produced through an energy-intensive anthraquinone process that is limited to large-scale facilities. Small-scale decentralized electrochemical production of H 2O 2 via a two-electron oxygen reduction reaction (ORR) offers unique opportunities for sanitization applications and the purification of drinking water. The development of inexpensive, efficient, and selective catalysts for this reaction remains a challenge. Here in this paper, we examine two different porous carbon-based electrocatalysts and show that they exhibit high selectivity for H 2O 2 under alkaline conditions. By rationally varying synthetic methods, we explore the effect of poremore » size on electrocatalytic performance. Furthermore, by means of density functional calculations, we point out the critical role of carbon defects. Our theory results show that the majority of defects in graphene are naturally selective for the two-electron reduction of O 2 to H 2O 2, and we identify the types of defects with high activity.« less

Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5′ monophosphate dehydrogenase

PubMed Central

Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Sharling, Lisa; Gollapalli, Deviprasad R.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D.

2012-01-01

Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in children and immunocompromised patients. This waterborne parasite is resistant to common methods of water treatment and therefore a prominent threat to drinking and recreation water even in countries with strong water safety systems. The drugs currently used to combat these organisms are ineffective. Genomic analysis revealed that the parasite relies solely on inosine-5′-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we report a selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high throughput screening. We performed a SAR study of these inhibitors with some analogues exhibiting high potency (IC50 < 2 nM) against CpIMPDH, excellent selectivity > 1000-fold versus human IMPDH type 2 and good stability in mouse liver microsomes. A subset of inhibitors also displayed potent antiparasitic activity in a Toxoplasma gondii model. PMID:22950983

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of small RNAs abundant in Burkholderia cenocepacia biofilms reveal putative regulators with a potential role in carbon and iron metabolism.

PubMed

Sass, Andrea; Kiekens, Sanne; Coenye, Tom

2017-11-15

Small RNAs play a regulatory role in many central metabolic processes of bacteria, as well as in developmental processes such as biofilm formation. Small RNAs of Burkholderia cenocepacia, an opportunistic pathogenic beta-proteobacterium, are to date not well characterised. To address that, we performed genome-wide transcriptome structure analysis of biofilm grown B. cenocepacia J2315. 41 unannotated short transcripts were identified in intergenic regions of the B. cenocepacia genome. 15 of these short transcripts, highly abundant in biofilms, widely conserved in Burkholderia sp. and without known function, were selected for in-depth analysis. Expression profiling showed that most of these sRNAs are more abundant in biofilms than in planktonic cultures. Many are also highly abundant in cells grown in minimal media, suggesting they are involved in adaptation to nutrient limitation and growth arrest. Their computationally predicted targets include a high proportion of genes involved in carbon metabolism. Expression and target genes of one sRNA suggest a potential role in regulating iron homoeostasis. The strategy used for this study to detect sRNAs expressed in B. cenocepacia biofilms has successfully identified sRNAs with a regulatory function.

Discovery of novel small molecule inhibitors of cardiac hypertrophy using high throughput, high content imaging

PubMed Central

Reid, Brian G.; Stratton, Matthew S.; Bowers, Samantha; Cavasin, Maria A.; Demos-Davies, Kimberley M.; Susano, Isidro; McKinsey, Timothy A.

2016-01-01

Chronic cardiac hypertrophy is maladaptive and contributes to the pathogenesis of heart failure. The objective of this study was to identify small molecule inhibitors of pathological cardiomyocyte hypertrophy. High content screening was performed with primary neonatal rat ventricular myocytes (NRVMs) cultured on 96-well plates and treated with a library of 3241 distinct small molecules. Non-toxic hit compounds that blocked hypertrophy in response to phenylephrine (PE) and phorbol myristate acetate (PMA) were identified based on their ability to reduce cell size and inhibit expression of atrial natriuretic factor (ANF), which is a biomarker of pathological cardiac hypertrophy. Many of the hit compounds are existing drugs that have not previously been evaluated for benefit in the setting of cardiovascular disease. One such compound, the anti-malarial drug artesunate, blocked left ventricular hypertrophy (LVH) and improved cardiac function in adult mice subjected to transverse aortic constriction (TAC). These findings demonstrate that phenotypic screening with primary cardiomyocytes can be used to discover anti-hypertrophic lead compounds for heart failure drug discovery. Using annotated libraries of compounds with known selectivity profiles, this screening methodology also facilitates chemical biological dissection of signaling networks that control pathological growth of the heart. PMID:27130278

The Characteristics of Extreme Erosion Events in a Small Mountainous Watershed

PubMed Central

Fang, Nu-Fang; Shi, Zhi-Hua; Yue, Ben-Jiang; Wang, Ling

2013-01-01

A large amount of soil loss is caused by a small number of extreme events that are mainly responsible for the time compression of geomorphic processes. The aim of this study was to analyze suspended sediment transport during extreme erosion events in a mountainous watershed. Field measurements were conducted in Wangjiaqiao, a small agricultural watershed (16.7 km2) in the Three Gorges Area (TGA) of China. Continuous records were used to analyze suspended sediment transport regimes and assess the sediment loads of 205 rainfall–runoff events during a period of 16 hydrological years (1989–2004). Extreme events were defined as the largest events, ranked in order of their absolute magnitude (representing the 95th percentile). Ten extreme erosion events from 205 erosion events, representing 83.8% of the total suspended sediment load, were selected for study. The results of canonical discriminant analysis indicated that extreme erosion events are characterized by high maximum flood-suspended sediment concentrations, high runoff coefficients, and high flood peak discharge, which could possibly be explained by the transport of deposited sediment within the stream bed during previous events or bank collapses. PMID:24146898

Study, selection, and preparation of solid cationic conductors. [characteristics of solid electrolytes for rechargeable high energy and high power density batteries

NASA Technical Reports Server (NTRS)

Roth, W. L.; Muller, O.

1974-01-01

Crystal chemical principles and transport theory have been used to predict structures and specific compounds which might find application as solid electrolytes in rechargeable high energy and high power density batteries operating at temperatures less than 200 C. Structures with 1-, 2-, and 3-dimensional channels were synthesized and screened by nuclear magnetic resonance, dielectric loss, and conductivity. There is significant conductivity at room temperature in some of the materials but none attain a level that is comparable to beta-alumina. Microwave and fast pulse methods were developed to measure conductivity in powders and in small crystals.

Efficient one-cycle affinity selection of binding proteins or peptides specific for a small-molecule using a T7 phage display pool.

PubMed

Takakusagi, Yoichi; Kuramochi, Kouji; Takagi, Manami; Kusayanagi, Tomoe; Manita, Daisuke; Ozawa, Hiroko; Iwakiri, Kanako; Takakusagi, Kaori; Miyano, Yuka; Nakazaki, Atsuo; Kobayashi, Susumu; Sugawara, Fumio; Sakaguchi, Kengo

2008-11-15

Here, we report an efficient one-cycle affinity selection using a natural-protein or random-peptide T7 phage pool for identification of binding proteins or peptides specific for small-molecules. The screening procedure involved a cuvette type 27-MHz quartz-crystal microbalance (QCM) apparatus with introduction of self-assembled monolayer (SAM) for a specific small-molecule immobilization on the gold electrode surface of a sensor chip. Using this apparatus, we attempted an affinity selection of proteins or peptides against synthetic ligand for FK506-binding protein (SLF) or irinotecan (Iri, CPT-11). An affinity selection using SLF-SAM and a natural-protein T7 phage pool successfully detected FK506-binding protein 12 (FKBP12)-displaying T7 phage after an interaction time of only 10 min. Extensive exploration of time-consuming wash and/or elution conditions together with several rounds of selection was not required. Furthermore, in the selection using a 15-mer random-peptide T7 phage pool and subsequent analysis utilizing receptor ligand contact (RELIC) software, a subset of SLF-selected peptides clearly pinpointed several amino-acid residues within the binding site of FKBP12. Likewise, a subset of Iri-selected peptides pinpointed part of the positive amino-acid region of residues from the Iri-binding site of the well-known direct targets, acetylcholinesterase (AChE) and carboxylesterase (CE). Our findings demonstrate the effectiveness of this method and general applicability for a wide range of small-molecules.

George M. Low Trophy NASA's Quality and Excellence Award, 1992. Application guidelines: Small business

NASA Technical Reports Server (NTRS)

1992-01-01

Guidelines are given for the selection of small business candidates for the George M. Low Trophy, NASA's Quality and Excellence Award, 1992. Topics covered include candidate eligibility, the selection process milestone schedule, the nomination letter, and the application report.

Reading Habits of Secondary School Teachers: A Study of Selected Secondary Schools in Addis Ababa and Dessie

ERIC Educational Resources Information Center

Hassen, Rukya

2016-01-01

This study is a small-scale study of an exploration of reading habit of high school teachers. Fifty-four teachers from five schools who teach in different schools in Addis Ababa and Dessie participated in this study. Data were collected through questionnaire and in-depth interview. The result of the study shows that reading is poorly developed…

Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

PubMed

Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

2008-12-01

Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

Light Controlled Modulation of Gene Expression by Chemical Optoepigenetic Probes

PubMed Central

Reis, Surya A.; Ghosh, Balaram; Hendricks, J. Adam; Szantai-Kis, D. Miklos; Törk, Lisa; Ross, Kenneth N.; Lamb, Justin; Read-Button, Willis; Zheng, Baixue; Wang, Hongtao; Salthouse, Christopher; Haggarty, Stephen J.; Mazitschek, Ralph

2016-01-01

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatio-temporal control. Here, we present a novel and generalizable approach, referred to as ‘Chemo-Optical Modulation of Epigenetically-regulated Transcription’ (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may translate into novel therapeutic strategies for diseases where conditional and selective epigenome modulation is required. PMID:26974814

Detection of selective sweeps in cattle using genome-wide SNP data

PubMed Central

2013-01-01

Background The domestication and subsequent selection by humans to create breeds and biological types of cattle undoubtedly altered the patterning of variation within their genomes. Strong selection to fix advantageous large-effect mutations underlying domesticability, breed characteristics or productivity created selective sweeps in which variation was lost in the chromosomal region flanking the selected allele. Selective sweeps have now been identified in the genomes of many animal species including humans, dogs, horses, and chickens. Here, we attempt to identify and characterise regions of the bovine genome that have been subjected to selective sweeps. Results Two datasets were used for the discovery and validation of selective sweeps via the fixation of alleles at a series of contiguous SNP loci. BovineSNP50 data were used to identify 28 putative sweep regions among 14 diverse cattle breeds. Affymetrix BOS 1 prescreening assay data for five breeds were used to identify 85 regions and validate 5 regions identified using the BovineSNP50 data. Many genes are located within these regions and the lack of sequence data for the analysed breeds precludes the nomination of selected genes or variants and limits the prediction of the selected phenotypes. However, phenotypes that we predict to have historically been under strong selection include horned-polled, coat colour, stature, ear morphology, and behaviour. Conclusions The bias towards common SNPs in the design of the BovineSNP50 assay led to the identification of recent selective sweeps associated with breed formation and common to only a small number of breeds rather than ancient events associated with domestication which could potentially be common to all European taurines. The limited SNP density, or marker resolution, of the BovineSNP50 assay significantly impacted the rate of false discovery of selective sweeps, however, we found sweeps in common between breeds which were confirmed using an ultra-high-density assay scored in a small number of animals from a subset of the breeds. No sweep regions were shared between indicine and taurine breeds reflecting their divergent selection histories and the very different environmental habitats to which these sub-species have adapted. PMID:23758707

Large motor units are selectively affected following a stroke.

PubMed

Lukács, M; Vécsei, L; Beniczky, S

2008-11-01

Previous studies have revealed a loss of functioning motor units in stroke patients. However, it remained unclear whether the motor units are affected randomly or in some specific pattern. We assessed whether there is a selective loss of the large (high recruitment threshold) or the small (low recruitment threshold) motor units following a stroke. Forty-five stroke patients and 40 healthy controls participated in the study. Macro-EMG was recorded from the abductor digiti minimi muscle at two levels of force output (low and high). The median macro motor unit potential (macro-MUP) amplitude on the paretic side was compared with those on the unaffected side and in the controls. In the control group and on the unaffected side, the macro-MUPs were significantly larger at the high force output than at the low one. However, on the paretic side the macro-MUPs at the high force output had the same amplitude as those recorded at the low force output. These changes correlated with the severity of the paresis. Following a stroke, there is a selective functional loss of the large, high-threshold motor units. These changes are related to the severity of the symptoms. Our findings furnish further insight into the pathophysiology of the motor deficit following a stroke.

Estimation of reference intervals from small samples: an example using canine plasma creatinine.

PubMed

Geffré, A; Braun, J P; Trumel, C; Concordet, D

2009-12-01

According to international recommendations, reference intervals should be determined from at least 120 reference individuals, which often are impossible to achieve in veterinary clinical pathology, especially for wild animals. When only a small number of reference subjects is available, the possible bias cannot be known and the normality of the distribution cannot be evaluated. A comparison of reference intervals estimated by different methods could be helpful. The purpose of this study was to compare reference limits determined from a large set of canine plasma creatinine reference values, and large subsets of this data, with estimates obtained from small samples selected randomly. Twenty sets each of 120 and 27 samples were randomly selected from a set of 1439 plasma creatinine results obtained from healthy dogs in another study. Reference intervals for the whole sample and for the large samples were determined by a nonparametric method. The estimated reference limits for the small samples were minimum and maximum, mean +/- 2 SD of native and Box-Cox-transformed values, 2.5th and 97.5th percentiles by a robust method on native and Box-Cox-transformed values, and estimates from diagrams of cumulative distribution functions. The whole sample had a heavily skewed distribution, which approached Gaussian after Box-Cox transformation. The reference limits estimated from small samples were highly variable. The closest estimates to the 1439-result reference interval for 27-result subsamples were obtained by both parametric and robust methods after Box-Cox transformation but were grossly erroneous in some cases. For small samples, it is recommended that all values be reported graphically in a dot plot or histogram and that estimates of the reference limits be compared using different methods.

A novel stable 3D luminescent uranyl complex for highly efficient and sensitive recognition of Ru3+ and biomolecules

NASA Astrophysics Data System (ADS)

Tian, Hong-Hong; Chen, Liang-Ting; Zhang, Rong-Lan; Zhao, Jian-She; Liu, Chi-Yang; Weng, Ng Seik

2018-02-01

A novel highly stable 3D luminescent uranyl coordination polymer, namely {[UO2(L)]·DMA}n (1), was assembled with uranyl salt and a glycine-derivative ligand [6-(carboxymethyl-amino)-4-oxo-4,5-dihydro-[1,3,5]triazin-2-ylamino]-acetic acid (H2L) under solvothermal reaction. Besides, It was found that complex 1 possesses excellent luminescent properties, particularly the efficient selectivity and sensitivity in the recognition of Ru3+, biomacromolecule bovine serum albumin (BSA), biological small molecules dopamine (DA), ascorbic acid (AA) and uric acid (UA) in the water solution based on a "turn-off" mechanism. Accordingly, the luminescent explorations also demonstrated that complex 1 could be acted as an efficient luminescent probe with high quenching efficiency and low detection limit for selectively detecting Ru3+ and biomolecules (DA, AA, UA and BSA). It was noted that the framework structure of complex 1 still remains highly stable after quenching, which was verified by powder X-ray diffraction (PXRD).

Highly Selective and Sensitive Self-Powered Glucose Sensor Based on Capacitor Circuit.

PubMed

Slaughter, Gymama; Kulkarni, Tanmay

2017-05-03

Enzymatic glucose biosensors are being developed to incorporate nanoscale materials with the biological recognition elements to assist in the rapid and sensitive detection of glucose. Here we present a highly sensitive and selective glucose sensor based on capacitor circuit that is capable of selectively sensing glucose while simultaneously powering a small microelectronic device. Multi-walled carbon nanotubes (MWCNTs) is chemically modified with pyrroloquinoline quinone glucose dehydrogenase (PQQ-GDH) and bilirubin oxidase (BOD) at anode and cathode, respectively, in the biofuel cell arrangement. The input voltage (as low as 0.25 V) from the biofuel cell is converted to a stepped-up power and charged to the capacitor to the voltage of 1.8 V. The frequency of the charge/discharge cycle of the capacitor corresponded to the oxidation of glucose. The biofuel cell structure-based glucose sensor synergizes the advantages of both the glucose biosensor and biofuel cell. In addition, this glucose sensor favored a very high selectivity towards glucose in the presence of competing and non-competing analytes. It exhibited unprecedented sensitivity of 37.66 Hz/mM.cm 2 and a linear range of 1 to 20 mM. This innovative self-powered glucose sensor opens new doors for implementation of biofuel cells and capacitor circuits for medical diagnosis and powering therapeutic devices.

Integrative Analysis of Cancer Diagnosis Studies with Composite Penalization

PubMed Central

Liu, Jin; Huang, Jian; Ma, Shuangge

2013-01-01

Summary In cancer diagnosis studies, high-throughput gene profiling has been extensively conducted, searching for genes whose expressions may serve as markers. Data generated from such studies have the “large d, small n” feature, with the number of genes profiled much larger than the sample size. Penalization has been extensively adopted for simultaneous estimation and marker selection. Because of small sample sizes, markers identified from the analysis of single datasets can be unsatisfactory. A cost-effective remedy is to conduct integrative analysis of multiple heterogeneous datasets. In this article, we investigate composite penalization methods for estimation and marker selection in integrative analysis. The proposed methods use the minimax concave penalty (MCP) as the outer penalty. Under the homogeneity model, the ridge penalty is adopted as the inner penalty. Under the heterogeneity model, the Lasso penalty and MCP are adopted as the inner penalty. Effective computational algorithms based on coordinate descent are developed. Numerical studies, including simulation and analysis of practical cancer datasets, show satisfactory performance of the proposed methods. PMID:24578589

XAFS investigation of polyamidoxime-bound uranyl contests the paradigm from small molecule studies

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

Mayes, Richard T.; Piechowicz, Marek; Lin, Zekai

In this study, limited resource availability and population growth have motivated interest in harvesting valuable metals from unconventional reserves, but developing selective adsorbents for this task requires structural knowledge of metal binding environments. Amidoxime polymers have been identified as the most promising platform for large-scale extraction of uranium from seawater. However, despite more than 30 years of research, the uranyl coordination environment on these adsorbents has not been positively identified. We report the first XAFS investigation of polyamidoxime-bound uranyl, with EXAFS fits suggesting a cooperative chelating model, rather than the tridentate or η 2 motifs proposed by small molecule andmore » computational studies. Samples exposed to environmental seawater also display a feature consistent with a μ 2-oxo-bridged transition metal in the uranyl coordination sphere, suggesting in situ formation of a specific binding site or mineralization of uranium on the polymer surface. These unexpected findings challenge several long-held assumptions and have significant implications for development of polymer adsorbents with high selectivity.« less

XAFS investigation of polyamidoxime-bound uranyl contests the paradigm from small molecule studies

DOE PAGES

Mayes, Richard T.; Piechowicz, Marek; Lin, Zekai; ...

2015-11-12

In this study, limited resource availability and population growth have motivated interest in harvesting valuable metals from unconventional reserves, but developing selective adsorbents for this task requires structural knowledge of metal binding environments. Amidoxime polymers have been identified as the most promising platform for large-scale extraction of uranium from seawater. However, despite more than 30 years of research, the uranyl coordination environment on these adsorbents has not been positively identified. We report the first XAFS investigation of polyamidoxime-bound uranyl, with EXAFS fits suggesting a cooperative chelating model, rather than the tridentate or η 2 motifs proposed by small molecule andmore » computational studies. Samples exposed to environmental seawater also display a feature consistent with a μ 2-oxo-bridged transition metal in the uranyl coordination sphere, suggesting in situ formation of a specific binding site or mineralization of uranium on the polymer surface. These unexpected findings challenge several long-held assumptions and have significant implications for development of polymer adsorbents with high selectivity.« less

Design, synthesis and selection of DNA-encoded small-molecule libraries.

PubMed

Clark, Matthew A; Acharya, Raksha A; Arico-Muendel, Christopher C; Belyanskaya, Svetlana L; Benjamin, Dennis R; Carlson, Neil R; Centrella, Paolo A; Chiu, Cynthia H; Creaser, Steffen P; Cuozzo, John W; Davie, Christopher P; Ding, Yun; Franklin, G Joseph; Franzen, Kurt D; Gefter, Malcolm L; Hale, Steven P; Hansen, Nils J V; Israel, David I; Jiang, Jinwei; Kavarana, Malcolm J; Kelley, Michael S; Kollmann, Christopher S; Li, Fan; Lind, Kenneth; Mataruse, Sibongile; Medeiros, Patricia F; Messer, Jeffrey A; Myers, Paul; O'Keefe, Heather; Oliff, Matthew C; Rise, Cecil E; Satz, Alexander L; Skinner, Steven R; Svendsen, Jennifer L; Tang, Lujia; van Vloten, Kurt; Wagner, Richard W; Yao, Gang; Zhao, Baoguang; Morgan, Barry A

2009-09-01

Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.

History-based route selection for reactive ad hoc routing protocols

NASA Astrophysics Data System (ADS)

Medidi, Sirisha; Cappetto, Peter

2007-04-01

Ad hoc networks rely on cooperation in order to operate, but in a resource constrained environment not all nodes behave altruistically. Selfish nodes preserve their own resources and do not forward packets not in their own self interest. These nodes degrade the performance of the network, but judicious route selection can help maintain performance despite this behavior. Many route selection algorithms place importance on shortness of the route rather than its reliability. We introduce a light-weight route selection algorithm that uses past behavior to judge the quality of a route rather than solely on the length of the route. It draws information from the underlying routing layer at no extra cost and selects routes with a simple algorithm. This technique maintains this data in a small table, which does not place a high cost on memory. History-based route selection's minimalism suits the needs the portable wireless devices and is easy to implement. We implemented our algorithm and tested it in the ns2 environment. Our simulation results show that history-based route selection achieves higher packet delivery and improved stability than its length-based counterpart.

Additive Manufacturing of Al-12Si Alloy Via Pulsed Selective Laser Melting

NASA Astrophysics Data System (ADS)

Chou, R.; Milligan, J.; Paliwal, M.; Brochu, M.

2015-03-01

Additive manufacturing (AM) of metallic materials is experiencing a research and commercialization craze in almost all industrial sectors. However, to date, AM has been limited to a small numbers of alloys. With respect to aluminum, two alloys received some attention: Al-12Si and Al-10Si-1Mg. In both cases, fully dense components have been achieved using a continuous-wave selective laser melting system. In this article, a new approach of selective laser melting using a pulsed-laser source as opposed to a continuous-wave laser is proposed. Pulse selective laser melting (P-SLM) would allow for greater control over the heat input and thus further optimization possibilities of the microstructure. P-SLM was demonstrated using the Al-12Si system. Si refinement below 200 nm was achieved throughout the component. Density up to 95% and high hardness of above 135 HV were obtained. The solidification mechanism is also explained.

Characterisation of a novel, high affinity and selective αvβ6 integrin RGD-mimetic radioligand.

PubMed

Hall, Eleanor R; Bibby, Lloyd I; Slack, Robert J

2016-10-01

The alpha-v beta-6 (αvβ6) integrin has been identified as playing a key role in the activation of transforming growth factor-β (TGFβ) that is hypothesised to be pivotal in the development of cancer and fibrotic diseases. Therefore, the αvβ6 integrin is an attractive therapeutic target for these debilitating diseases and a drug discovery programme to identify small molecule αvβ6 selective arginyl-glycinyl-aspartic acid (RGD)-mimetics was initiated within GlaxoSmithKline. The primary aim of this study was to pharmacologically characterise the binding to αvβ6 of a novel clinical candidate, compound 1, using a radiolabelled form. Radioligand binding studies were completed with [(3)H]compound 1 against the human and mouse soluble protein forms of αvβ6 to determine accurate affinity estimates and binding kinetics. The selectivity of compound 1 for the RGD integrin family was also determined using saturation binding studies (αvβ1, αvβ3, αvβ5, αvβ8, α5β1 and α8β1 integrins) and fibrinogen-induced platelet aggregation (αIIbβ3 integrin). In addition, the relationship between divalent metal cation type and concentration and αvβ6 RGD site binding was also investigated. Compound 1 has been demonstrated to bind with extremely high affinity and selectivity for the αvβ6 integrin and has the potential as a clinical tool and therapeutic for investigating the role of αvβ6 in a range of disease states both pre-clinically and clinically. In addition, this is the first study that has successfully applied radioligand binding to the RGD integrin field to accurately determine the affinity and selectivity profile of a small molecule RGD-mimetic. Copyright © 2016 Elsevier Inc. All rights reserved.

48 CFR 1419.803 - Selecting acquisitions for the 8(a) Program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Selecting acquisitions for the 8(a) Program. 1419.803 Section 1419.803 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Contracting with the Small Business Administration...

ON GALACTIC DENSITY MODELING IN THE PRESENCE OF DUST EXTINCTION

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

Bovy, Jo; Rix, Hans-Walter; Schlafly, Edward F.

Inferences about the spatial density or phase-space structure of stellar populations in the Milky Way require a precise determination of the effective survey volume. The volume observed by surveys such as Gaia or near-infrared spectroscopic surveys, which have good coverage of the Galactic midplane region, is highly complex because of the abundant small-scale structure in the three-dimensional interstellar dust extinction. We introduce a novel framework for analyzing the importance of small-scale structure in the extinction. This formalism demonstrates that the spatially complex effect of extinction on the selection function of a pencil-beam or contiguous sky survey is equivalent to amore » low-pass filtering of the extinction-affected selection function with the smooth density field. We find that the angular resolution of current 3D extinction maps is sufficient for analyzing Gaia sub-samples of millions of stars. However, the current distance resolution is inadequate and needs to be improved by an order of magnitude, especially in the inner Galaxy. We also present a practical and efficient method for properly taking the effect of extinction into account in analyses of Galactic structure through an effective selection function. We illustrate its use with the selection function of red-clump stars in APOGEE using and comparing a variety of current 3D extinction maps.« less

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars.

PubMed

Cavanagh, Colin R; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K; Sorrells, Mark E; Hayden, Matthew J; Akhunov, Eduard

2013-05-14

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat.

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars

PubMed Central

Cavanagh, Colin R.; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L.; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A.; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K.; Sorrells, Mark E.; Hayden, Matthew J.; Akhunov, Eduard

2013-01-01

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat. PMID:23630259

Development of an ultrahigh-resolution Si-PM-based dual-head GAGG coincidence imaging system

NASA Astrophysics Data System (ADS)

Yamamoto, Seiichi; Watabe, Hiroshi; Kanai, Yasukazu; Kato, Katsuhiko; Hatazawa, Jun

2013-03-01

A silicon photomultiplier (Si-PM) is a promising photodetector for high resolution PET systems due to its small channel size and high gain. Using Si-PMs, it will be possible to develop a high resolution imaging systems. For this purpose, we developed a small field-of-view (FOV) ultrahigh-resolution Si-PM-based dual-head coincidence imaging system for small animals and plant research. A new scintillator, Ce doped Gd3Al12Ga3O12 (GAGG), was selected because of its high light output and its emission wavelength matched with the Si-PM arrays and contained no radioactivity. Each coincidence imaging block detector consists of 0.5×0.5×5 mm3 GAGG pixels combined with a 0.1-mm thick reflector to form a 20×17 matrix that was optically coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) with a 1.5-mm thick light guide. The GAGG block size was 12.0×10.2 mm2. Two GAGG block detectors were positioned face to face and set on a flexible arm based detector stand. All 0.5 mm GAGG pixels in the block detectors were clearly resolved in the 2-dimensional position histogram. The energy resolution was 14.4% FWHM for the Cs-137 gamma ray. The spatial resolution was 0.7 mm FWHM measured using a 0.25 mm diameter Na-22 point source. Small animal and plant images were successfully obtained. We conclude that our developed ultrahigh-resolution Si-PM-based dual-head coincidence imaging system is promising for small animal and plant imaging research.

Analysis of gas membrane ultra-high purification of small quantities of mono-isotopic silane

DOE PAGES

de Almeida, Valmor F.; Hart, Kevin J.

2017-01-03

A small quantity of high-value, crude, mono-isotopic silane is a prospective gas for a small-scale, high-recovery, ultra-high membrane purification process. This is an unusual application of gas membrane separation for which we provide a comprehensive analysis of a simple purification model. The goal is to develop direct analytic expressions for estimating the feasibility and efficiency of the method, and guide process design; this is only possible for binary mixtures of silane in the dilute limit which is a somewhat realistic case. In addition, analytic solutions are invaluable to verify numerical solutions obtained from computer-aided methods. Hence, in this paper wemore » provide new analytic solutions for the purification loops proposed. Among the common impurities in crude silane, methane poses a special membrane separation challenge since it is chemically similar to silane. Other potential problematic compounds are: ethylene, diborane and ethane (in this order). Nevertheless, we demonstrate, theoretically, that a carefully designed membrane system may be able to purify mono-isotopic, crude silane to electronics-grade level in a reasonable amount of time and expenses. We advocate a combination of membrane materials that preferentially reject heavy impurities based on mobility selectivity, and light impurities based on solubility selectivity. We provide estimates for the purification of significant contaminants of interest. In this study, we suggest cellulose acetate and polydimethylsiloxane as examples of membrane materials on the basis of limited permeability data found in the open literature. We provide estimates on the membrane area needed and priming volume of the cell enclosure for fabrication purposes when using the suggested membrane materials. These estimates are largely theoretical in view of the absence of reliable experimental data for the permeability of silane. And finally, future extension of this work to the non-dilute limit may apply to the recovery of silane from rejected streams of natural silicon semi-conductor processes.« less

Analysis of gas membrane ultra-high purification of small quantities of mono-isotopic silane

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

de Almeida, Valmor F.; Hart, Kevin J.

A small quantity of high-value, crude, mono-isotopic silane is a prospective gas for a small-scale, high-recovery, ultra-high membrane purification process. This is an unusual application of gas membrane separation for which we provide a comprehensive analysis of a simple purification model. The goal is to develop direct analytic expressions for estimating the feasibility and efficiency of the method, and guide process design; this is only possible for binary mixtures of silane in the dilute limit which is a somewhat realistic case. In addition, analytic solutions are invaluable to verify numerical solutions obtained from computer-aided methods. Hence, in this paper wemore » provide new analytic solutions for the purification loops proposed. Among the common impurities in crude silane, methane poses a special membrane separation challenge since it is chemically similar to silane. Other potential problematic compounds are: ethylene, diborane and ethane (in this order). Nevertheless, we demonstrate, theoretically, that a carefully designed membrane system may be able to purify mono-isotopic, crude silane to electronics-grade level in a reasonable amount of time and expenses. We advocate a combination of membrane materials that preferentially reject heavy impurities based on mobility selectivity, and light impurities based on solubility selectivity. We provide estimates for the purification of significant contaminants of interest. In this study, we suggest cellulose acetate and polydimethylsiloxane as examples of membrane materials on the basis of limited permeability data found in the open literature. We provide estimates on the membrane area needed and priming volume of the cell enclosure for fabrication purposes when using the suggested membrane materials. These estimates are largely theoretical in view of the absence of reliable experimental data for the permeability of silane. And finally, future extension of this work to the non-dilute limit may apply to the recovery of silane from rejected streams of natural silicon semi-conductor processes.« less

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups

PubMed Central

Martin, Adam D.; Wojciechowski, Jonathan P.; Robinson, Andrew B.; Heu, Celine; Garvey, Christopher J.; Ratcliffe, Julian; Waddington, Lynne J.; Gardiner, James; Thordarson, Pall

2017-01-01

Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy. PMID:28272523

High aspect ratio template and method for producing same

NASA Technical Reports Server (NTRS)

Sakamoto, Jeff S. (Inventor); Weiss, James R. (Inventor); Fleurial, Jean-Pierre (Inventor); Kisor, Adam (Inventor); Tuszynski, Mark (Inventor); Stokols, Shula (Inventor); Holt, Todd Edward (Inventor); Welker, David James (Inventor); Breckon, Christopher David (Inventor)

2010-01-01

Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers.

Bidirectional selection between two classes in complex social networks.

PubMed

Zhou, Bin; He, Zhe; Jiang, Luo-Luo; Wang, Nian-Xin; Wang, Bing-Hong

2014-12-19

The bidirectional selection between two classes widely emerges in various social lives, such as commercial trading and mate choosing. Until now, the discussions on bidirectional selection in structured human society are quite limited. We demonstrated theoretically that the rate of successfully matching is affected greatly by individuals' neighborhoods in social networks, regardless of the type of networks. Furthermore, it is found that the high average degree of networks contributes to increasing rates of successful matches. The matching performance in different types of networks has been quantitatively investigated, revealing that the small-world networks reinforces the matching rate more than scale-free networks at given average degree. In addition, our analysis is consistent with the modeling result, which provides the theoretical understanding of underlying mechanisms of matching in complex networks.

Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a†

PubMed Central

Liu, Feng; Chen, Xin; Allali-Hassani, Abdellah; Quinn, Amy M.; Wasney, Gregory A.; Dong, Aiping; Barsyte, Dalia; Kozieradzki, Ivona; Senisterra, Guillermo; Chau, Irene; Siarheyeva, Alena; Kireev, Dmitri B.; Jadhav, Ajit; Herold, J. Martin; Frye, Stephen V.; Arrowsmith, Cheryl H.; Brown, Peter J.; Simeonov, Anton; Vedadi, Masoud; Jin, Jian

2010-01-01

SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as a potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first co-crystal structure of G9a with a small molecule inhibitor, was obtained. The co-crystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling. PMID:19891491

A DUAL PLATFORM FOR SELECTIVE ANALYTE ENRICHMENT AND IONIZATION IN MASS SPECTROMETRY USING APTAMER-CONJUGATED GRAPHENE OXIDE

PubMed Central

Gulbakan, Basri; Yasun, Emir; Shukoor, M. Ibrahim; Zhu, Zhi; You, Mingxu; Tan, Xiaohong; Sanchez, Hernan; Powell, David H.; Dai, Hongjie; Tan, Weihong

2010-01-01

This study demonstrates the use of aptamer-conjugated graphene oxide as an affinity extraction and detection platform for analytes from complex biological media. We have shown that cocaine and adenosine can be selectively enriched from plasma samples and that direct mass spectrometric readout can be obtained without a matrix and with greatly improved signal-to-noise ratios. The aptamer conjugated graphene oxide has clear advantages in target enrichment and in generating highly efficient ionization of target molecules for mass spectrometry. These results demonstrate the utility of the approach for analysis of small molecules in real biological samples. PMID:21090719

Detection of small-size solder ball defects through heat conduction analysis

NASA Astrophysics Data System (ADS)

Zhou, Xiuyun; Chen, Yaqiu; Lu, Xiaochuan

2018-02-01

Aiming to solve the defect detection problem of a small-size solder ball in the high density chip, heat conduction analysis based on eddy current pulsed thermography is put forward to differentiate various defects. With establishing the 3D finite element model about induction heating, defects such as cracks and void can be distinguished by temperature difference resulting from heat conduction. Furthermore, the experiment of 0.4 mm-diameter solder balls with different defects is carried out to prove that crack and void solder can be distinguished. Three kinds of crack length on a gull-wing pin are selected, including 0.24 mm, 1.2 mm, and 2.16 mm, to verify that the small defect can be discriminated. Both the simulation study and experiment result show that the heat conduction analysis method is reliable and convenient.

Practice location factors influencing South Dakota School of Medicine graduates (1977-85).

PubMed

Jarratt, L G; Leonardson, G R; Nord, W J

1989-12-01

Physician numbers and placement continue to be major health delivery concerns in the rural state of South Dakota. This study of four-year graduates (1977-1985) of the South Dakota School of Medicine looks at current factors affecting physician placement and compares placement and location selection factors to a previous study of graduates of the medical school when it was a two-year program (1969-1973). Factors influencing physicians locating in South Dakota were: closeness to their home town and or spouses' home town, residency training in small towns, payment of educational loans, medical school clerkships, time of decision, etc. Factors influencing physicians locating in rural communities (less than 5,000) were: growing up in small communities, residency training in small communities, early location decisions, payment of loans, and high medical need.

Optical air-coupled NDT system with ultra-broad frequency bandwidth (Conference Presentation)

NASA Astrophysics Data System (ADS)

Fischer, Balthasar; Rohringer, Wolfgang; Heine, Thomas

2017-05-01

We present a novel, optical ultrasound airborne acoustic testing setup exhibiting a frequency bandwidth of 1MHz in air. The sound waves are detected by a miniaturized Fabry-Pérot interferometer (2mm cavity) whilst the sender consists of a thermoacoustic emitter or a short laser pulse We discuss characterization measurements and C-scans of a selected set of samples, including Carbon fiber reinforced polymer (CFRP). The high detector sensitivity allows for an increased penetration depth. The high frequency and the small transducer dimensions lead to a compelling image resolution.

Personnel Recruitment/Selection/Induction in Small/Rural Schools.

ERIC Educational Resources Information Center

Neely, Steve

This paper provides tips and resources for the recruitment, selection, and induction of teachers and other school personnel. These materials were developed with rural and small schools in mind; some resources focus on Kansas. Means of recruitment are discussed, including internal search, referrals, college and university placement services,…

Checklist/Guide to Selecting a Small Computer.

ERIC Educational Resources Information Center

Bennett, Wilma E.

This 322-point checklist was designed to help executives make an intelligent choice when selecting a small computer for a business. For ease of use the questions have been divided into ten categories: Display Features, Keyboard Features, Printer Features, Controller Features, Software, Word Processing, Service, Training, Miscellaneous, and Costs.…

Selected Energy Management Options for Small Business and Local Government.

ERIC Educational Resources Information Center

Wert, Jonathan M.; Worthington, Barry K.

This document is a checklist of 257 energy management options for small business and local government. The energy management options are categorized under: (1) Energy management strategies; (2) Buildings; (3) Lighting; (4) Water; (5) Waste operations; (6) Equipment; (7) Transportation; and (8) Food preparation. To select options for…

Small Molecule Targeted Recruitment of a Nuclease to RNA.

PubMed

Costales, Matthew G; Matsumoto, Yasumasa; Velagapudi, Sai Pradeep; Disney, Matthew D

2018-06-06

The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion. Silencing miR-96 derepressed pro-apoptotic FOXO1 transcription factor, triggering apoptosis in breast cancer, but not healthy breast, cells. These results demonstrate that small molecules can be programmed to selectively cleave RNA via nuclease recruitment and has broad implications.

A bacterial genetic selection system for ubiquitylation cascade discovery.

PubMed

Levin-Kravets, Olga; Tanner, Neta; Shohat, Noa; Attali, Ilan; Keren-Kaplan, Tal; Shusterman, Anna; Artzi, Shay; Varvak, Alexander; Reshef, Yael; Shi, Xiaojing; Zucker, Ori; Baram, Tamir; Katina, Corine; Pilzer, Inbar; Ben-Aroya, Shay; Prag, Gali

2016-11-01

About one-third of the eukaryotic proteome undergoes ubiquitylation, but the enzymatic cascades leading to substrate modification are largely unknown. We present a genetic selection tool that utilizes Escherichia coli, which lack deubiquitylases, to identify interactions along ubiquitylation cascades. Coexpression of split antibiotic resistance protein tethered to ubiquitin and ubiquitylation target together with a functional ubiquitylation apparatus results in a covalent assembly of the resistance protein, giving rise to bacterial growth on selective media. We applied the selection system to uncover an E3 ligase from the pathogenic bacteria EHEC and to identify the epsin ENTH domain as an ultraweak ubiquitin-binding domain. The latter was complemented with a structure-function analysis of the ENTH-ubiquitin interface. We also constructed and screened a yeast fusion library, discovering Sem1 as a novel ubiquitylation substrate of Rsp5 E3 ligase. Collectively, our selection system provides a robust high-throughput approach for genetic studies of ubiquitylation cascades and for small-molecule modulator screening.

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans.

PubMed

Wilming, Niklas; Kietzmann, Tim C; Jutras, Megan; Xue, Cheng; Treue, Stefan; Buffalo, Elizabeth A; König, Peter

2017-01-01

Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans. © The Author 2017. Published by Oxford University Press.

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans

PubMed Central

Wilming, Niklas; Kietzmann, Tim C.; Jutras, Megan; Xue, Cheng; Treue, Stefan; Buffalo, Elizabeth A.; König, Peter

2017-01-01

Abstract Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans. PMID:28077512

In vitro selection of functional nucleic acids

NASA Technical Reports Server (NTRS)

Wilson, D. S.; Szostak, J. W.

1999-01-01

In vitro selection allows rare functional RNA or DNA molecules to be isolated from pools of over 10(15) different sequences. This approach has been used to identify RNA and DNA ligands for numerous small molecules, and recent three-dimensional structure solutions have revealed the basis for ligand recognition in several cases. By selecting high-affinity and -specificity nucleic acid ligands for proteins, promising new therapeutic and diagnostic reagents have been identified. Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation. The existence of such RNA enzymes supports the notion that ribozymes could have directed a primitive metabolism before the evolution of protein synthesis. New in vitro protein selection techniques should allow for a direct comparison of the frequency of ligand binding and catalytic structures in pools of random sequence polynucleotides versus polypeptides.

Advanced System Design Requirements for Large and Small Fixed-wing Aerial Application Systems for Agriculture

NASA Technical Reports Server (NTRS)

Hinely, J. T., Jr.; Boyles, R. Q., Jr.

1979-01-01

Several candidate aircraft configurations were defined over the range of 1000 to 10,000 pounds payload and evaluated over a broad spectrum of agricultural missions. From these studies, baseline design points were selected at 3200 pounds payload for the small aircraft and 7500 pounds for the large aircraft. The small baseline aircraft utilizes a single turboprop powerplant while the large aircraft utilizes two turboprop powerplants. These configurations were optimized for wing loading, aspect ratio, and power loading to provide the best mission economics in representative missions. Wing loading of 20 lb/sq ft was selected for the small aircraft and 25 lb/sq ft for the large aircraft. Aspect ratio of 8 was selected for both aircraft. It was found that a 10% reduction in engine power from the original configurations provided improved mission economics for both aircraft by reducing the cost of the turboprop. Refined configurations incorporate a 675 HP engine in the small aircraft and two 688 HP engines in the large aircraft.

Morphology and chemistry of projectile residue in small experimental impact craters

NASA Astrophysics Data System (ADS)

Horz, F.; Fechtig, H.; Janicke, J.; Schneider, E.

1983-11-01

Small-scale impact craters (5-7 mm in diameter) were produced with a light gas gun in high purity Au and Cu targets using soda lime glass (SL) and man-made basalt glass (BG) as projectiles. Maximum impact velocity was 6.4 km/s resulting in peak pressures of approximately 120-150 GPa. Copious amounts of projectile melts are preserved as thin glass liners draping the entire crater cavity; some of this liner may be lost by spallation, however. SEM investigations reveal complex surface textures including multistage flow phenomena and distinct temporal deposition sequences of small droplets. Inasmuch as some of the melts were generated at peak pressures greater than 120 GPa, these glasses represent the most severely shocked silicates recovered from laboratory experiments to date. Major element analyses reveal partial loss of alkalis; Na2O loss of 10-15 percent is observed, while K2O loss may be as high as 30-50 percent. Although the observed volatile loss in these projectile melts is significant, it still remains uncertain whether target melts produced on planetary surfaces are severely fractionated by selective volatilization processes.

The hydrodynamic principle for the caudal fin shape of small aquatic animals

NASA Astrophysics Data System (ADS)

Lee, Jeongsu; Park, Yong-Jai; Cho, Kyu-Jin; Kim, Ho-Young

2014-11-01

The shape of caudal fins of small aquatic animals is completely different from that of large cruising animals like dolphin and tuna which have high aspect-ratio lunate tail. To unveil the physical principle behind natural selection of caudal fins of small aquatic animals, here we investigate the hydrodynamics of an angularly reciprocating plate as a model for the caudal fin oscillation. We find that the thrust production of a reciprocating plate at high Strouhal numbers is dominated by generation of two distinct vortical structures associated with the acceleration and deceleration of the plate regardless of their shape. Based on our observations, we construct a scaling law to predict the thrust of the flapping plate, which agrees well with the experimental data. We then seek the optimal aspect ratio to maximize thrust and efficiency of a flapping plate for fixed flapping frequency and amplitude. Thrust is maximized for the aspect ratio of approximately 0.7. We also theoretically explain the power law behaviors of the thrust and efficiency as a function of the aspect ratio.

Faint Blue Objects at High Galactic Latitude. VIII. Performance Characteristics of the US Survey

NASA Astrophysics Data System (ADS)

Mitchell, Kenneth J.; Usher, P. D.

2004-07-01

The US survey has cataloged 3987 objects in seven high Galactic latitude fields according to their optical colors, magnitudes, and morphologies using photographic techniques. This paper analyzes the effectiveness of the survey at producing finding lists for complete samples of hot stars and quasars that exhibit blue and/or ultraviolet excess (B-UVX) relative to the colors of halo F and G subdwarf stars. A table of 599 spectroscopic identifications summarizes the spectroscopic coverage of the US objects that has been accomplished to date. In addition, some of the survey plates have been reexamined for objects missed during the original selection, and the literature has been searched for all other spectroscopically identified blue stars and quasars with z<2.2 that have been selected by other surveys within the US survey areas. These results are used to estimate empirically both the accuracy of the US survey selection boundaries (in color, morphology, and brightness) and the completeness of the resulting samples of B-UVX US objects within those boundaries. In particular, it is shown that the reliability of the US color classifications is high and that the previously derived US morphological boundary for the complete selection of unresolved quasars is accurate. The contribution of color and morphological classification errors to B-UVX sample incompleteness is therefore correspondingly small. The empirical tests indicate high levels of completeness (95+1-2%) for the samples of US quasars and hot stars isolated within the stated survey selection limits. Errata and improvements to some of the published catalog data are presented in Appendices.

Assembly of ordered contigs of cosmids selected with YACs of human chromosome 13

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

Fischer, S.G.; Cayanis, E.; Boukhgalter, B.

1994-06-01

The authors have developed an efficient method for assembling ordered cosmid contigs aligned to mega-YACs and midi-YACs (average insert sizes of 1.0 and 0.35 Mb, respectively) and used this general method to initiate high-resolution physical mapping of human chromosome 13 (Chr 13). Chr 13-enriched midi-YAC (mYAC) and mega-YAC (MYAC) sublibraries were obtained from corresponding CEPH total human YAC libraries by selecting colonies with inter-Alu PCR probes derived from Chr 13 monochromosomal cell hybrid DNA. These sublibraries were arrayed on filters at high density. In this approach, the MYAC 13 sublibrary is screened by hybridization with cytogenetically assigned Chr 13 DNAmore » probes to select one or a small subset of MYACs. Inter-Alu PCR products from each mYAC are then hybridized to the MYAC and mYAC sublibraries to identify overlapping YACs and to an arrayed Chr 13-specific cosmid library to select corresponding cosmids. The set of selected cosmids, gridded on filters at high density, is hybridized with inter-Alu PCR products from each of the overlapping YACs to identify subsets of cosmids and also with riboprobes from each cosmid of the arrayed set ({open_quotes}cosmid matrix cross-hybridization{close_quotes}). From these data, cosmid contigs are assembled by a specifically designed computer program. Application of this method generates cosmid contigs spanning the length of a MYAC with few gaps. To provide a high-resolution map, ends of cosmids are sequenced at preselected sites to position densely spaced sequence-tagged sites. 33 refs., 7 figs., 1 tab.« less

High efficiency direct detection of ions from resonance ionization of sputtered atoms

DOEpatents

Gruen, Dieter M.; Pellin, Michael J.; Young, Charles E.

1986-01-01

A method and apparatus are provided for trace and other quantitative analysis with high efficiency of a component in a sample, with the analysis involving the removal by ion or other bombardment of a small quantity of ion and neutral atom groups from the sample, the conversion of selected neutral atom groups to photoions by laser initiated resonance ionization spectroscopy, the selective deflection of the photoions for separation from original ion group emanating from the sample, and the detection of the photoions as a measure of the quantity of the component. In some embodiments, the original ion group is accelerated prior to the RIS step for separation purposes. Noise and other interference are reduced by shielding the detector from primary and secondary ions and deflecting the photoions sufficiently to avoid the primary and secondary ions.

High efficiency direct detection of ions from resonance ionization of sputtered atoms

DOEpatents

Gruen, D.M.; Pellin, M.J.; Young, C.E.

1985-01-16

A method and apparatus are provided for trace and other quantitative analysis with high efficiency of a component in a sample, with the analysis involving the removal by ion or other bombardment of a small quantity of ion and neutral atom groups from the sample, the conversion of selected neutral atom groups to photoions by laser initiated resonance ionization spectroscopy, the selective deflection of the photoions for separation from original ion group emanating from the sample, and the detection of the photoions as a measure of the quantity of the component. In some embodiments, the original ion group is accelerated prior to the RIS step for separation purposes. Noise and other interference are reduced by shielding the detector from primary and secondary ions and deflecting the photoions sufficiently to avoid the primary and secondary ions.

Fluorescent Nanomaterials for the Development of Latent Fingerprints in Forensic Sciences

PubMed Central

Li, Ming; Yu, Aoyang; Zhu, Ye

2018-01-01

This review presents an overview on the application of latent fingerprint development techniques in forensic sciences. At present, traditional developing methods such as powder dusting, cyanoacrylate fuming, chemical method, and small particle reagent method, have all been gradually compromised given their emerging drawbacks such as low contrast, sensitivity, and selectivity, as well as high toxicity. Recently, much attention has been paid to the use of fluorescent nanomaterials including quantum dots (QDs) and rare earth upconversion fluorescent nanomaterials (UCNMs) due to their unique optical and chemical properties. Thus, this review lays emphasis on latent fingerprint development based on QDs and UCNMs. Compared to latent fingerprint development by traditional methods, the new methods using fluorescent nanomaterials can achieve high contrast, sensitivity, and selectivity while showing reduced toxicity. Overall, this review provides a systematic overview on such methods. PMID:29657570

Pressure waves in liquid mercury target from pulsed heat loads and the possible way controlling their effects

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

Ni, L.; Skala, K.

1996-06-01

In ESS project liquid metals are selected as the main target for the pulsed spallation neutron source. Since the very high instantaneous energy is deposited on the heavy molten target in a very short period time, pressure waves are generated. They travel through the liquid and cause high stress in the container. Also, additional stress should be considered in the wall which is the result of direct heating of the target window. These dynamic processes were simulated with computational codes with the static response being analized first. The total resulting dynamic wall stress has been found to have exceeded themore » design stress for the selected container material. Adding a small amount of gas bubbles in the liquid could be a possible way to reduce the pressure waves.« less

[Ecological niches of sucking lice (Phthiraptera: Anoplura) and their coevolution relationship with small mammal hosts in Yunnan, China].

PubMed

Meng, Yan-Fen; Guo, Xian-Guo; Men, Xing-Yuan; Wu, Dian

2008-02-28

To investigate the ecological niches of sucking lice (Phthiraptera: Anoplura) on the body surface of small mammal hosts and the co-evolutionary relationship between lice and mammal hosts in Yunnan Province. Thirty species of small mammals were captured and used as 30 resource sequences. The distribution and composition of the dominant 22 species of sucking lice on the body surface of the 30 species small mammal hosts were analyzed as the utilization proportion for each resource sequence. The niche breadth and proportional similarity were measured. SPSS 13.0 statistical software was used for analyzing the niche overlap matrix of sucking lice by hierarchical clustering analysis, and a dendrogram was made. The niche breadth was narrow for most species of sucking louse. Among the detected species, Hoplopleura pacifica showed the widest niche breadth, but only 0.1536. Indices of niche proportional similarity of most sucking lice were relatively small from 0.0005 to 0.4695. The 22 species of sucking lice were classified into 16 niche overlap groups, by lambda = 5.5, through a hierarchical clustering analysis for the niche overlaps, and the clustering process of most sucking lice was late. The sucking lice have a high specificity for hosts, of which different species show an apparent niche divergence on host selection. The results reveal a high coevolution between sucking lice and the mammal hosts.

Butterfly survival on an isolated island by improved grip

PubMed Central

Duplouy, Anne; Hanski, Ilkka

2013-01-01

On small isolated islands, natural selection is expected to reduce the dispersal capacity of organisms, as short distances do not require a high rate of dispersal, which might lead to accidental emigration from the population. In addition, individuals foregoing the high cost of maintaining flight capacity may instead allocate resources to other functions. However, in butterflies and many other insects, flight is necessary not only for dispersal but also for most other activities. A weakly flying individual would probably do worse and have an elevated rather than reduced probability of accidental emigration. Here, we report results consistent with the hypothesis that a butterfly population on an isolated island, instead of having lost its flight capacity, has evolved better grip to resist the force of wind and to avoid being blown off the island. Our study suggests that local adaptation has occurred in this population in spite of its very small size (Ne ∼ 100), complete isolation, low genetic variation and high genetic load. PMID:23445946

Small-Molecule Solar Cells with Simultaneously Enhanced Short-Circuit Current and Fill Factor to Achieve 11% Efficiency.

PubMed

Nian, Li; Gao, Ke; Jiang, Yufeng; Rong, Qikun; Hu, Xiaowen; Yuan, Dong; Liu, Feng; Peng, Xiaobin; Russell, Thomas P; Zhou, Guofu

2017-08-01

High-efficiency small-molecule-based organic photovoltaics (SM-OPVs) using two electron donors (p-DTS(FBTTh 2 ) 2 and ZnP) with distinctively different absorption and structural features are reported. Such a combination works well and synergically improves device short-circuit current density (J sc ) to 17.99 mA cm -2 and fill factor (FF) to 77.19%, yielding a milestone efficiency of 11%. To the best of our knowledge, this is the highest power conversion efficiency reported for SM-OPVs to date and the first time to combine high J sc over 17 mA cm -2 and high FF over 77% into one SM-OPV. The strategy of using multicomponent materials, with a selecting role of balancing varied electronic and structural necessities can be an important route to further developing higher performance devices. This development is important, which broadens the dimension and versatility of existing materials without much chemistry input. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fully-reversible optical sensor for hydrogen peroxide with fast response.

PubMed

Ding, Longjiang; Chen, Siyu; Zhang, Wei; Zhang, Yinglu; Wang, Xu-Dong

2018-05-09

A fully reversible optical sensor for hydrogen peroxide with fast response is presented. The sensor was fabricated by in-situ growing ultra-small platinum nanoparticles (PtNPs) inside the pores of fibrous silica particles (KCC-1). The nanocomposite was then embedded into a hydrogel matrix and form a sensor layer, the immobilized PtNPs can catalytically convert hydrogen peroxide into molecular oxygen, which is measured via luminescent quenching based oxygen sensor underneath. Owing to the high porosity and permeability of KCC-1 and high local concentration of PtNPs, the sensor exhibits fast response (less than 1 min) and full reversibility. The measurement range of the sensor covers 1.0 μM to 10.0 mM, and very small amount of sample is required during measurement (200 μL). Because of its high stability, excellent reversibility and selectivity, and extremely fast response, the sensor could fulfill all industry requirements for real-time measurement, and fill market vacancy.

High-Throughput Screening based Identification of Small Molecule Antagonists of Integrin CD11b/CD18 Ligand Binding

PubMed Central

Faridi, Mohd Hafeez; Maiguel, Dony; Brown, Brock T.; Suyama, Eigo; Barth, Constantinos J.; Hedrick, Michael; Vasile, Stefan; Sergienko, Eduard; Schürer, Stephan; Gupta, Vineet

2010-01-01

Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique. PMID:20188705

Ground-water resources of selected high volcanic islands of Truk with emphasis on small village supplies

USGS Publications Warehouse

Takasaki, K.J.

1989-01-01

Existing water supply sources in the Truk State were assessed. The first part of the assessment includes the high islands in the Truk Lagoon and the second part includes the principal inhabited outer islands of the Truk State. The high islands in the lagoons are remnant peaks of a partly sunken volcano. Coral atolls form the periphery of the lagoon. The islands are composed of tight, massive lavas and cemented rock fragments. Although saturated, the rocks yield little water to springs or wells. Weathering causes some increase in permeability, and where the weathering is the deepest as in valleys, these materials make up the main reservoirs of groundwater. Rainfall averages about 140 inches/yr and is sufficiently persistent to provide water for drinking and cooking from small rain catchments, springs and seeps with little or no storage. This situation is not desirable because rainless periods, even short ones, cause springs, seeps, and rain barrels to go dry quickly. (USGS)

Pyranoflavones: a group of small-molecule probes for exploring the active site cavities of cytochrome P450 enzymes 1A1, 1A2, and 1B1.

PubMed

Liu, Jiawang; Taylor, Shannon F; Dupart, Patrick S; Arnold, Corey L; Sridhar, Jayalakshmi; Jiang, Quan; Wang, Yuji; Skripnikova, Elena V; Zhao, Ming; Foroozesh, Maryam

2013-05-23

Selective inhibition of P450 enzymes is the key to block the conversion of environmental procarcinogens to their carcinogenic metabolites in both animals and humans. To discover highly potent and selective inhibitors of P450s 1A1, 1A2, and 1B1, as well as to investigate active site cavities of these enzymes, 14 novel flavone derivatives were prepared as chemical probes. Fluorimetric enzyme inhibition assays were used to determine the inhibitory activities of these probes toward P450s 1A1, 1A2, 1B1, 2A6, and 2B1. A highly selective P450 1B1 inhibitor 5-hydroxy-4'-propargyloxyflavone (5H4'FPE) was discovered. Some tested compounds also showed selectivity between P450s 1A1 and 1A2. α-Naphthoflavone-like and 5-hydroxyflavone derivatives preferentially inhibited P450 1A2, while β-naphthoflavone-like flavone derivatives showed selective inhibition of P450 1A1. On the basis of structural analysis, the active site cavity models of P450 enzymes 1A1 and 1A2 were generated, demonstrating a planar long strip cavity and a planar triangular cavity, respectively.

48 CFR 42.502 - Selecting contracts for postaward orientation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the product or service to critical programs; (f) Length of the planned production cycle; (g) Extent of... status, if any, as a small business, small disadvantaged, women-owned, veteran-owned, HUBZone, or service-disabled veteran-owned small business concern; (j) Contractor's performance history with small, small...