Development of very small-diameter, inductively coupled magnetized plasma device

NASA Astrophysics Data System (ADS)

Kuwahara, D.; Mishio, A.; Nakagawa, T.; Shinohara, S.

2013-10-01

In order to miniaturize a high-density, inductively coupled magnetized plasma or helicon plasma to be applied to, e.g., an industrial application and an electric propulsion field, small helicon device has been developed. The specifications of this device along with the experimental results are described. We have succeeded in generating high-density (˜1019 m-3) plasmas using quartz tubes with very small diameters of 10 and 20 mm, with a radio frequency power ˜1200 and 700 W, respectively, in the presence of the magnetic field less than 1 kG.

Development of very small-diameter, inductively coupled magnetized plasma device.

PubMed

Kuwahara, D; Mishio, A; Nakagawa, T; Shinohara, S

2013-10-01

In order to miniaturize a high-density, inductively coupled magnetized plasma or helicon plasma to be applied to, e.g., an industrial application and an electric propulsion field, small helicon device has been developed. The specifications of this device along with the experimental results are described. We have succeeded in generating high-density (~10(19) m(-3)) plasmas using quartz tubes with very small diameters of 10 and 20 mm, with a radio frequency power ~1200 and 700 W, respectively, in the presence of the magnetic field less than 1 kG.

A Highly Specific Gold Nanoprobe for Live-Cell Single-Molecule Imaging

NASA Astrophysics Data System (ADS)

Leduc, Cécile; Si, Satyabrata; Gautier, Jérémie; Soto-Ribeiro, Martinho; Wehrle-Haller, Bernhard; Gautreau, Alexis; Giannone, Grégory; Cognet, Laurent; Lounis, Brahim

2013-04-01

Single molecule tracking in live cells is the ultimate tool to study subcellular protein dynamics, but it is often limited by the probe size and photostability. Due to these issues, long-term tracking of proteins in confined and crowded environments, such as intracellular spaces, remains challenging. We have developed a novel optical probe consisting of 5-nm gold nanoparticles functionalized with a small fragment of camelid antibodies that recognize widely used GFPs with a very high affinity, which we call GFP-nanobodies. These small gold nanoparticles can be detected and tracked using photothermal imaging for arbitrarily long periods of time. Surface and intracellular GFP-proteins were effectively labeled even in very crowded environments such as adhesion sites and cytoskeletal structures both in vitro and in live cell cultures. These nanobody-coated gold nanoparticles are probes with unparalleled capabilities; small size, perfect photostability, high specificity, and versatility afforded by combination with the vast existing library of GFP-tagged proteins.

A 45-Amino-Acid Scaffold Mined from the PDB for High-Affinity Ligand Engineering.

PubMed

Kruziki, Max A; Bhatnagar, Sumit; Woldring, Daniel R; Duong, Vandon T; Hackel, Benjamin J

2015-07-23

Small protein ligands can provide superior physiological distribution compared with antibodies, and improved stability, production, and specific conjugation. Systematic evaluation of the PDB identified a scaffold to push the limits of small size and robust evolution of stable, high-affinity ligands: 45-residue T7 phage gene 2 protein (Gp2) contains an α helix opposite a β sheet with two adjacent loops amenable to mutation. De novo ligand discovery from 10(8) mutants and directed evolution toward four targets yielded target-specific binders with affinities as strong as 200 ± 100 pM, Tms from 65 °C ± 3 °C to 80°C ± 1 °C, and retained activity after thermal denaturation. For cancer targeting, a Gp2 domain for epidermal growth factor receptor was evolved with 18 ± 8 nM affinity, receptor-specific binding, and high thermal stability with refolding. The efficiency of evolving new binding function and the size, affinity, specificity, and stability of evolved domains render Gp2 a uniquely effective ligand scaffold. Copyright © 2015 Elsevier Ltd. All rights reserved.

Small and mid-sized carnivores

Treesearch

Steven W. Buskirk; William J. Zielinski

2003-01-01

Small and mid-sized carnivores of western forests represent an ecologically diverse and influential guild of forest vertebrates. They comprise over a dozen species with varied life histories and habitat associations, highly species-specific responses to human-caused habitat change, and varied conservation status across western North America. Forested habitats fulfill...

Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis.

PubMed

Bauer, Paige V; Duca, Frank A; Waise, T M Zaved; Dranse, Helen J; Rasmussen, Brittany A; Puri, Akshita; Rasti, Mozhgan; O'Brien, Catherine A; Lam, Tony K T

2018-03-06

Long-chain acyl-CoA synthetase (ACSL)-dependent upper small intestinal lipid metabolism activates pre-absorptive pathways to regulate metabolic homeostasis, but whether changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid pre-absorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs pre-absorptive fatty acid sensing and reduces upper small intestinal Lactobacillus gasseri levels and ACSL3 expression. Transplantation of healthy upper small intestinal microbiota to high-fat-fed rodents restores L. gasseri levels and fatty acid sensing via increased ACSL3 expression, while L. gasseri probiotic administration to non-transplanted high-fat-fed rodents is sufficient to restore upper small intestinal ACSL3 expression and fatty acid sensing. In summary, we unveil a glucoregulatory role of upper small intestinal L. gasseri that impacts an ACSL3-dependent glucoregulatory fatty acid-sensing pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

Principle and design of small-sized and high-definition x-ray machine

NASA Astrophysics Data System (ADS)

Zhao, Anqing

2010-10-01

The paper discusses the circuit design and working principles of VMOS PWM type 75KV10mA high frequency X-ray machine. The system mainly consists of silicon controlled rectifier, VMOS tube PWM type high-frequency and highvoltage inverter circuit, filament inverter circuit, high-voltage rectifier filter circuit and as X-ray tube. The working process can be carried out under the control of a single-chip microcomputer. Due to the small size and high resolution in imaging, the X-ray machine is mostly adopted for emergent medical diagnosis and specific circumstances where nondestructive tests are conducted.

Scaling of Ion Thrusters to Low Power

NASA Technical Reports Server (NTRS)

Patterson, Michael J.; Grisnik, Stanley P.; Soulas, George C.

1998-01-01

Analyses were conducted to examine ion thruster scaling relationships in detail to determine performance limits, and lifetime expectations for thruster input power levels below 0.5 kW. This was motivated by mission analyses indicating the potential advantages of high performance, high specific impulse systems for small spacecraft. The design and development status of a 0.1-0.3 kW prototype small thruster and its components are discussed. Performance goals include thruster efficiencies on the order of 40% to 54% over a specific impulse range of 2000 to 3000 seconds, with a lifetime in excess of 8000 hours at full power. Thruster technologies required to achieve the performance and lifetime targets are identified.

Spacecraft/Rover Hybrids for the Exploration of Small Solar System Bodies. [NASA NIAC Phase I Study

NASA Technical Reports Server (NTRS)

Pavone, Marco; Castillo-Rogez, Julie C.; Hoffman, Jeffrey A.; Nesnas, Issa A. D.

2012-01-01

This study investigated a novel mission architecture for the systematic and affordable in-situ exploration of small Solar System bodies. Specifically, a mother spacecraft would deploy over the surface of a small body one, or several, spacecraft/rover hybrids, which are small, multi-faceted enclosed robots with internal actuation and external spikes. They would be capable of 1) long excursions (by hopping), 2) short traverses to specific locations (through a sequence of controlled tumbles), and 3) high-altitude, attitude-controlled ballistic flight (akin to spacecraft flight). Their control would rely on synergistic operations with the mother spacecraft (where most of hybrids' perception and localization functionalities would be hosted), which would make the platforms minimalistic and, in turn, the entire mission architecture affordable.

A universal TaqMan-based RT-PCR protocol for cost-efficient detection of small noncoding RNA.

PubMed

Jung, Ulrike; Jiang, Xiaoou; Kaufmann, Stefan H E; Patzel, Volker

2013-12-01

Several methods for the detection of RNA have been developed over time. For small RNA detection, a stem-loop reverse primer-based protocol relying on TaqMan RT-PCR has been described. This protocol requires an individual specific TaqMan probe for each target RNA and, hence, is highly cost-intensive for experiments with small sample sizes or large numbers of different samples. We describe a universal TaqMan-based probe protocol which can be used to detect any target sequence and demonstrate its applicability for the detection of endogenous as well as artificial eukaryotic and bacterial small RNAs. While the specific and the universal probe-based protocol showed the same sensitivity, the absolute sensitivity of detection was found to be more than 100-fold lower for both than previously reported. In subsequent experiments, we found previously unknown limitations intrinsic to the method affecting its feasibility in determination of mature template RISC incorporation as well as in multiplexing. Both protocols were equally specific in discriminating between correct and incorrect small RNA targets or between mature miRNA and its unprocessed RNA precursor, indicating the stem-loop RT-primer, but not the TaqMan probe, triggers target specificity. The presented universal TaqMan-based RT-PCR protocol represents a cost-efficient method for the detection of small RNAs.

SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement.

PubMed

Sun, Bo; Li, Yifan; Liu, Lizhi; Chen, Zhaohui; Ling, Li; Yang, Fei; Liu, Jiexiao; Liu, Hong; Huang, Xusheng

2018-05-01

Purpose/aim of the study: To date, there are no validated screening scales for small fibre neuropathy. This study investigated the small-fibre neuropathy and the symptom inventory questionnaire as well as the small fibre neuropathy screening list for small fibre neuropathy diagnosis. Fifty-five patients were divided into small fibre neuropathy and mixed fibre damage groups. Relevant scales, nerve conduction studies and skin biopsies were performed. Relationships between the intraepidermal nerve fibre density and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined. Compared with healthy Chinese participants, 20 patients were diagnosed with small fibre neuropathy. Intraepidermal nerve fibre density was moderately and highly correlated with the small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list, respectively. The diagnostic values were moderate and high for the small fibre neuropathy-symptom inventory questionnaire (cut-off value = 5, sensitivity = 80%, specificity = 81.8%) and small fibre neuropathy screening list (cut-off value = 8, sensitivity = 94.1%, specificity = 90.9%), respectively. There were no significant differences in the visual analogue scale between the small fibre neuropathy group, mixed small and large fibre neuropathy group, pure large fibre neuropathy group and the normal group. Small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list represent potential small fibre neuropathy screening tools. Abbreviations EMG electromyography ENA anti-extractable nuclear antigens ESR erythrocyte sedimentation rate IENFD intraepidermal nerve fibre density IGT impaired glucose tolerance NCS nerve conduction studies NDS neuropathy disability score OGTT oral glucose tolerance test PGP protein gene product PN peripheral neuropathy ROC receiver operating characteristic curve ROC-AUC area under the ROC curve SFN small fibre neuropathy SFN-SIQ small-fibre neuropathy and symptom inventory questionnaire SFNSL small fibre neuropathy screening list VAS visual analogue scale WHO World Health Organization.

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.

Insight into small RNA abundance and expression in high- and low-temperature stress response using deep sequencing in Arabidopsis.

PubMed

Baev, Vesselin; Milev, Ivan; Naydenov, Mladen; Vachev, Tihomir; Apostolova, Elena; Mehterov, Nikolay; Gozmanva, Mariyana; Minkov, Georgi; Sablok, Gaurav; Yahubyan, Galina

2014-11-01

Small RNA profiling and assessing its dependence on changing environmental factors have expanded our understanding of the transcriptional and post-transcriptional regulation of plant stress responses. Insufficient data have been documented earlier to depict the profiling of small RNA classes in temperature-associated stress which has a wide implication for climate change biology. In the present study, we report a comparative assessment of the genome-wide profiling of small RNAs in Arabidopsis thaliana using two conditional responses, induced by high- and low-temperature. Genome-wide profiling of small RNAs revealed an abundance of 21 nt small RNAs at low temperature, while high temperature showed an abundance of 21 nt and 24 nt small RNAs. The two temperature treatments altered the expression of a specific subset of mature miRNAs and displayed differential expression of a number of miRNA isoforms (isomiRs). Comparative analysis demonstrated that a large number of protein-coding genes can give rise to differentially expressed small RNAs following temperature shifts. Low temperature caused accumulation of small RNAs, corresponding to the sense strand of a number of cold-responsive genes. In contrast, high temperature stimulated the production of small RNAs of both polarities from genes encoding functionally diverse proteins. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system.

PubMed

Zeilinger, Markus; Dumanic, Monika; Pichler, Florian; Budinsky, Lubos; Wadsak, Wolfgang; Pallitsch, Katharina; Spreitzer, Helmut; Lanzenberger, Rupert; Hacker, Marcus; Mitterhauser, Markus; Philippe, Cécile

2017-08-14

The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

Small-molecule control of protein function through Staudinger reduction

NASA Astrophysics Data System (ADS)

Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander

2016-11-01

Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

PubMed

Chen, Han-Kuang; Pemberton, Richard

2016-01-08

We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

Reversible and long-term immobilization in a hydrogel-microbead matrix for high-resolution imaging of Caenorhabditis elegans and other small organisms

PubMed Central

Cornaglia, Matteo; Krishnamani, Gopalan; Zhang, Jingwei; Mouchiroud, Laurent; Lehnert, Thomas; Auwerx, Johan; Gijs, Martin A. M.

2018-01-01

The nematode Caenorhabditis elegans is an important model organism for biomedical research and genetic studies relevant to human biology and disease. Such studies are often based on high-resolution imaging of dynamic biological processes in the worm body tissues, requiring well-immobilized and physiologically active animals in order to avoid movement-related artifacts and to obtain meaningful biological information. However, existing immobilization methods employ the application of either anesthetics or servere physical constraints, by using glue or specific microfluidic on-chip mechanical structures, which in some cases may strongly affect physiological processes of the animals. Here, we immobilize C. elegans nematodes by taking advantage of a biocompatible and temperature-responsive hydrogel-microbead matrix. Our gel-based immobilization technique does not require a specific chip design and enables fast and reversible immobilization, thereby allowing successive imaging of the same single worm or of small worm populations at all development stages for several days. We successfully demonstrated the applicability of this method in challenging worm imaging contexts, in particular by applying it for high-resolution confocal imaging of the mitochondrial morphology in worm body wall muscle cells and for the long-term quantification of number and size of specific protein aggregates in different C. elegans neurodegenerative disease models. Our approach was also suitable for immobilizing other small organisms, such as the larvae of the fruit fly Drosophila melanogaster and the unicellular parasite Trypanosoma brucei. We anticipate that this versatile technique will significantly simplify biological assay-based longitudinal studies and long-term observation of small model organisms. PMID:29509812

[Importance of occupational medicine problem on small and medium scale business enterprises].

PubMed

Fasikov, R M; Stepanov, E G

2008-01-01

First stage of hygienic and psychosocial studies on evaluating the conditions, work specification and health state of small and medium scale business enterprise workers is finished. Findings are that psychosocial factors of work process are highly significant for those workers, and locomotor disorders (backaches) are leaders in morbidity structure among those workers.

Characterization of Human Salivary Extracellular RNA by Next-generation Sequencing.

PubMed

Li, Feng; Kaczor-Urbanowicz, Karolina Elżbieta; Sun, Jie; Majem, Blanca; Lo, Hsien-Chun; Kim, Yong; Koyano, Kikuye; Liu Rao, Shannon; Young Kang, So; Mi Kim, Su; Kim, Kyoung-Mee; Kim, Sung; Chia, David; Elashoff, David; Grogan, Tristan R; Xiao, Xinshu; Wong, David T W

2018-04-23

It was recently discovered that abundant and stable extracellular RNA (exRNA) species exist in bodily fluids. Saliva is an emerging biofluid for biomarker development for noninvasive detection and screening of local and systemic diseases. Use of RNA-Sequencing (RNA-Seq) to profile exRNA is rapidly growing; however, no single preparation and analysis protocol can be used for all biofluids. Specifically, RNA-Seq of saliva is particularly challenging owing to high abundance of bacterial contents and low abundance of salivary exRNA. Given the laborious procedures needed for RNA-Seq library construction, sequencing, data storage, and data analysis, saliva-specific and optimized protocols are essential. We compared different RNA isolation methods and library construction kits for long and small RNA sequencing. The role of ribosomal RNA (rRNA) depletion also was evaluated. The miRNeasy Micro Kit (Qiagen) showed the highest total RNA yield (70.8 ng/mL cell-free saliva) and best small RNA recovery, and the NEBNext library preparation kits resulted in the highest number of detected human genes [5649-6813 at 1 reads per kilobase RNA per million mapped (RPKM)] and small RNAs [482-696 microRNAs (miRNAs) and 190-214 other small RNAs]. The proportion of human RNA-Seq reads was much higher in rRNA-depleted saliva samples (41%) than in samples without rRNA depletion (14%). In addition, the transfer RNA (tRNA)-derived RNA fragments (tRFs), a novel class of small RNAs, were highly abundant in human saliva, specifically tRF-4 (4%) and tRF-5 (15.25%). Our results may help in selection of the best adapted methods of RNA isolation and small and long RNA library constructions for salivary exRNA studies. © 2018 American Association for Clinical Chemistry.

Wafer-scale pixelated detector system

DOEpatents

Fahim, Farah; Deptuch, Grzegorz; Zimmerman, Tom

2017-10-17

A large area, gapless, detection system comprises at least one sensor; an interposer operably connected to the at least one sensor; and at least one application specific integrated circuit operably connected to the sensor via the interposer wherein the detection system provides high dynamic range while maintaining small pixel area and low power dissipation. Thereby the invention provides methods and systems for a wafer-scale gapless and seamless detector systems with small pixels, which have both high dynamic range and low power dissipation.

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.

Mapping the Medical Literature for High Quality Studies and Reviews for Age-specific Clinical Specialties

PubMed Central

Stevens, Adrienne L.; Wilczynski, Nancy L.; McKibbon, K. Ann; Haynes, R. Brian

2001-01-01

Objective: To identify a journal subset that publishes reports of high quality studies and reviews relating to age-specific clinical specialties, such as pediatrics and geriatrics. Design: Handsearch of 172 journals using explicit criteria to determine methodologic quality for generating evidence for clinical practice. Main outcome measure: Frequency of high quality articles and their top yielding journals. Results: Between 17% and 33% of articles published in age-specific specialties are of high quality for clinical use. Top yielding journals for the specialties ranged from 16 to 130. Conclusion: Handsearch of the clinical literature for the year 2000 reveals that high quality articles for some age-specific specialties are concentrated in a small subset of journals (eg, obstetrics), whereas articles for other specialties are widely scattered among a large number of journals (eg, adult medicine).

Immune Centroids Over-Sampling Method for Multi-Class Classification

DTIC Science & Technology

2015-05-22

recognize to specific antigens . The response of a receptor to an antigen can activate its hosting B-cell. Activated B-cell then proliferates and...modifying N.K. Jerne’s theory. The theory states that in a pre-existing group of lympho- cytes ( specifically B cells), a specific antigen only...the clusters of each small class, which have high data density, called global immune centroids over-sampling (denoted as Global-IC). Specifically

Automatic detection of oesophageal intubation based on ventilation pressure waveforms shows high sensitivity and specificity in patients with pulmonary disease.

PubMed

Kalmar, Alain F; Absalom, Anthony; Rombouts, Pieter; Roets, Jelle; Dewaele, Frank; Verdonck, Pascal; Stemerdink, Arjanne; Zijlstra, Jan G; Monsieurs, Koenraad G

2016-08-01

Unrecognised endotracheal tube misplacement in emergency intubations has a reported incidence of up to 17%. Current detection methods have many limitations restricting their reliability and availability in these circumstances. There is therefore a clinical need for a device that is small enough to be practical in emergency situations and that can detect oesophageal intubation within seconds. In a first reported evaluation, we demonstrated an algorithm based on pressure waveform analysis, able to determine tube location with high reliability in healthy patients. The aim of this study was to validate the specificity of the algorithm in patients with abnormal pulmonary compliance, and to demonstrate the reliability of a newly developed small device that incorporates the technology. Intubated patients with mild to moderate lung injury, admitted to intensive care were included in the study. The device was connected to the endotracheal tube, and three test ventilations were performed in each patient. All diagnostic data were recorded on PC for subsequent specificity/sensitivity analysis. A total of 105 ventilations in 35 patients with lung injury were analysed. With the threshold D-value of 0.1, the system showed a 100% sensitivity and specificity to diagnose tube location. The algorithm retained its specificity in patients with decreased pulmonary compliance. We also demonstrated the feasibility to integrate sensors and diagnostic hardware in a small, portable hand-held device for convenient use in emergency situations. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

PubMed Central

Moon, Chan Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2012-01-01

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals are dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 Tesla. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies. PMID:22960251

Enzyme specificity under dynamic control

NASA Astrophysics Data System (ADS)

Ota, Nobuyuki; Agard, David A.

2002-03-01

The contributions of conformational dynamics to substrate specificity have been examined by the application of principal component analysis to molecular dynamics trajectories of alpha-lytic protease. The wild-type alpha-lytic protease is highly specific for substrates with small hydrophobic side chains at the specificity pocket, while the Met190Ala binding pocket mutant has a much broader specificity, actively hydrolyzing substrates ranging from Ala to Phe. We performed a principal component analysis using 1-nanosecond molecular dynamics simulations using solvent boundary condition. We found that the walls of the wild-type substrate binding pocket move in tandem with one another, causing the pocket size to remain fixed so that only small substrates are recognized. In contrast, the M190A mutant shows uncoupled movement of the binding pocket walls, allowing the pocket to sample both smaller and larger sizes, which appears to be the cause of the observed broad specificity. The results suggest that the protein dynamics of alpha-lytic protease may play a significant role in defining the patterns of substrate specificity.

FPGA-Based Smart Sensor for Online Displacement Measurements Using a Heterodyne Interferometer

PubMed Central

Vera-Salas, Luis Alberto; Moreno-Tapia, Sandra Veronica; Garcia-Perez, Arturo; de Jesus Romero-Troncoso, Rene; Osornio-Rios, Roque Alfredo; Serroukh, Ibrahim; Cabal-Yepez, Eduardo

2011-01-01

The measurement of small displacements on the nanometric scale demands metrological systems of high accuracy and precision. In this context, interferometer-based displacement measurements have become the main tools used for traceable dimensional metrology. The different industrial applications in which small displacement measurements are employed requires the use of online measurements, high speed processes, open architecture control systems, as well as good adaptability to specific process conditions. The main contribution of this work is the development of a smart sensor for large displacement measurement based on phase measurement which achieves high accuracy and resolution, designed to be used with a commercial heterodyne interferometer. The system is based on a low-cost Field Programmable Gate Array (FPGA) allowing the integration of several functions in a single portable device. This system is optimal for high speed applications where online measurement is needed and the reconfigurability feature allows the addition of different modules for error compensation, as might be required by a specific application. PMID:22164040

Highly conserved small subunit residues influence rubisco large subunit catalysis.

PubMed

Genkov, Todor; Spreitzer, Robert J

2009-10-30

The chloroplast enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of photosynthetic CO(2) fixation. With a deeper understanding of its structure-function relationships and competitive inhibition by O(2), it may be possible to engineer an increase in agricultural productivity and renewable energy. The chloroplast-encoded large subunits form the active site, but the nuclear-encoded small subunits can also influence catalytic efficiency and CO(2)/O(2) specificity. To further define the role of the small subunit in Rubisco function, the 10 most conserved residues in all small subunits were substituted with alanine by transformation of a Chlamydomonas reinhardtii mutant that lacks the small subunit gene family. All the mutant strains were able to grow photosynthetically, indicating that none of the residues is essential for function. Three of the substitutions have little or no effect (S16A, P19A, and E92A), one primarily affects holoenzyme stability (L18A), and the remainder affect catalysis with or without some level of associated structural instability (Y32A, E43A, W73A, L78A, P79A, and F81A). Y32A and E43A cause decreases in CO(2)/O(2) specificity. Based on the x-ray crystal structure of Chlamydomonas Rubisco, all but one (Glu-92) of the conserved residues are in contact with large subunits and cluster near the amino- or carboxyl-terminal ends of large subunit alpha-helix 8, which is a structural element of the alpha/beta-barrel active site. Small subunit residues Glu-43 and Trp-73 identify a possible structural connection between active site alpha-helix 8 and the highly variable small subunit loop between beta-strands A and B, which can also influence Rubisco CO(2)/O(2) specificity.

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.

Exploring aligned-carbon-nanotubes@polyaniline arrays on household Al as supercapacitors.

PubMed

Huang, Fan; Lou, Fengliu; Chen, De

2012-05-01

Herein, we demonstrate a new approach towards the construction of supercapacitors consisting of carbon nanotubes (CNTs) and conducting polymers (ECPs) with high specific power, high specific energy, and stable cycling performance through a 3D design of a thin film of polyaniline (PANI) on an aligned small carbon nanotube (ACNT) array on household Al foils. The thin-film strategy is used to fully exploit the specific capacitance of PANI, and obtain regular pores, strong interaction between PANI and CNTs, and reduced electrical resistance for the electrodes. A facile process is developed to fabricate a highly flexible supercapacitor using this binder-free composite on household Al foil as the current collector. It exhibits high specific energy of 18.9 Wh kg(-1) , high maximum specific power of 11.3 kW kg(-1) of the active material in an aqueous electrolyte at 1.0 A g(-1) , and excellent rate performance and cycling stability. A high specific energy of 72.4 Wh kg(-1) , a high maximum specific power of 24.9 kW kg(-1) , and a good cycling performance of the active material are obtained in an organic electrolyte. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of variable specific heat on energy transfer in a high-temperature supersonic channel flow

NASA Astrophysics Data System (ADS)

Chen, Xiaoping; Li, Xiaopeng; Dou, Hua-Shu; Zhu, Zuchao

2018-05-01

An energy transfer mechanism in high-temperature supersonic turbulent flow for variable specific heat (VSH) condition through turbulent kinetic energy (TKE), mean kinetic energy (MKE), turbulent internal energy (TIE) and mean internal energy (MIE) is proposed. The similarities of energy budgets between VSH and constant specific heat (CSH) conditions are investigated by introducing a vibrational energy excited degree and considering the effects of fluctuating specific heat. Direct numerical simulation (DNS) of temporally evolving high-temperature supersonic turbulent channel flow is conducted at Mach number 3.0 and Reynolds number 4800 combined with a constant dimensional wall temperature 1192.60 K for VSH and CSH conditions to validate the proposed energy transfer mechanism. The differences between the terms in the two kinetic energy budgets for VSH and CSH conditions are small; however, the magnitude of molecular diffusion term for VSH condition is significantly smaller than that for CSH condition. The non-negligible energy transfer is obtained after neglecting several small terms of diffusion, dissipation and compressibility related. The non-negligible energy transfer involving TIE includes three processes, in which energy can be gained from TKE and MIE and lost to MIE. The same non-negligible energy transfer through TKE, MKE and MIE is observed for both the conditions.

A Compact, Flexible, High Channel Count DAQ Built From Off-the-Shelf Components

DOE PAGES

Heffner, M.; Riot, V.; Fabris, L.

2013-06-01

Medium to large channel count detectors are usually faced with a few unattractive options for data acquisition (DAQ). Small to medium sized TPC experiments, for example, can be too small to justify the high expense and long development time of application specific integrated circuit (ASIC) development. In some cases an experiment can piggy-back on a larger experiment and the associated ASIC development, but this puts the time line of development out of the hands of the smaller experiment. Another option is to run perhaps thousands of cables to rack mounted equipment, which is clearly undesirable. The development of commercial high-speedmore » high-density FPGAs and ADCs combined with the small discrete components and robotic assembly open a new option that scales to tens of thousands of channels and is only slightly larger than ASICs using off-the-shelf components.« less

Light-Activated Staudinger–Bertozzi Ligation within Living Animals

PubMed Central

Shah, Lisa; Laughlin, Scott T.; Carrico, Isaac S.

2016-01-01

The ability to regulate small molecule chemistry in vivo will enable new avenues of exploration in imaging and pharmacology. However, realization of these goals will require reactions with high specificity and precise control. Here we demonstrate photocontrol over the highly specific Staudinger–Bertozzi ligation in vitro and in vivo. Our simple approach, photocaging the key phosphine atom, allows for the facile production of reagents with photochemistry that can be engineered for specific applications. The resulting compounds, which are both stable and efficiently activated, enable the spatial labeling of metabolically introduced azides in vitro and on live zebrafish. PMID:27010217

Innovations in biomedical nanoengineering: nanowell array biosensor.

PubMed

Seo, YoungTae; Jeong, Sunil; Lee, JuKyung; Choi, Hak Soo; Kim, Jonghan; Lee, HeaYeon

2018-01-01

Nanostructured biosensors have pioneered biomedical engineering by providing highly sensitive analyses of biomolecules. The nanowell array (NWA)-based biosensing platform is particularly innovative, where the small size of NWs within the array permits extremely profound sensing of a small quantity of biomolecules. Undoubtedly, the NWA geometry of a gently-sloped vertical wall is critical for selective docking of specific proteins without capillary resistances, and nanoprocessing has contributed to the fabrication of NWA electrodes on gold substrate such as molding process, e-beam lithography, and krypton-fluoride (KrF) stepper semiconductor method. The Lee group at the Mara Nanotech has established this NW-based biosensing technology during the past two decades by engineering highly sensitive electrochemical sensors and providing a broad range of detection methods from large molecules (e.g., cells or proteins) to small molecules (e.g., DNA and RNA). Nanosized gold dots in the NWA enhance the detection of electrochemical biosensing to the range of zeptomoles in precision against the complementary target DNA molecules. In this review, we discuss recent innovations in biomedical nanoengineering with a specific focus on novel NWA-based biosensors. We also describe our continuous efforts in achieving a label-free detection without non-specific binding while maintaining the activity and stability of immobilized biomolecules. This research can lay the foundation of a new platform for biomedical nanoengineering systems.

Innovations in biomedical nanoengineering: nanowell array biosensor

NASA Astrophysics Data System (ADS)

Seo, YoungTae; Jeong, Sunil; Lee, JuKyung; Choi, Hak Soo; Kim, Jonghan; Lee, HeaYeon

2018-04-01

Nanostructured biosensors have pioneered biomedical engineering by providing highly sensitive analyses of biomolecules. The nanowell array (NWA)-based biosensing platform is particularly innovative, where the small size of NWs within the array permits extremely profound sensing of a small quantity of biomolecules. Undoubtedly, the NWA geometry of a gently-sloped vertical wall is critical for selective docking of specific proteins without capillary resistances, and nanoprocessing has contributed to the fabrication of NWA electrodes on gold substrate such as molding process, e-beam lithography, and krypton-fluoride (KrF) stepper semiconductor method. The Lee group at the Mara Nanotech has established this NW-based biosensing technology during the past two decades by engineering highly sensitive electrochemical sensors and providing a broad range of detection methods from large molecules (e.g., cells or proteins) to small molecules (e.g., DNA and RNA). Nanosized gold dots in the NWA enhance the detection of electrochemical biosensing to the range of zeptomoles in precision against the complementary target DNA molecules. In this review, we discuss recent innovations in biomedical nanoengineering with a specific focus on novel NWA-based biosensors. We also describe our continuous efforts in achieving a label-free detection without non-specific binding while maintaining the activity and stability of immobilized biomolecules. This research can lay the foundation of a new platform for biomedical nanoengineering systems.

The Effect of the Student Success Skills Small Group Counseling Intervention on Factors Associated with Dropout Potential in High School

ERIC Educational Resources Information Center

Weinstein, Jodie

2013-01-01

The focus of this study is to add to the outcome research on effective school counseling interventions and to specifically evaluate the effectiveness of the Student Success Skills (SSS) small group intervention with students identified as having drop out potential in the 9th grade. This study analyzed two years of pre-existing, non-identifiable…

Tests of Rock Cores Scott Study Area, Missouri

DTIC Science & Technology

1970-05-01

porphyry with some granodiorite and small amounts of dolomite, acid metavolcanics, and dark gray volcanic breccia. Specific gravity, * Schmidt...petrographically identified as predominantly rhyolite and dacite porphyry with some granodiorite and small amounts of dolomite, acid metavolcanics, and dark...exhibit- ing little, if any, hysteresis. 9. Direct and indirect tensile strengths exhibited by tne rhyro- lite and dacite porphyry and granite are very high

Purple Pelisse: A specialty fingerling potato with purple skin and flesh and medium specific gravity

USDA-ARS?s Scientific Manuscript database

Purple Pelisse is a specialty fingerling potato with purple skin and dark purple flesh. It has medium maturity and sets a large number of smooth, small, fingerling-shaped tubers. The tubers have medium specific gravity and high levels of antioxidants. This potato variety is mainly intended for the f...

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications.

PubMed

Stockwell, B R; Haggarty, S J; Schreiber, S L

1999-02-01

Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.

A dynamic model for generating actuator specifications for small arms barrel active stabilization

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan; Lavigna, Chris

2006-03-01

Due to stresses encountered in combat, it is known that soldier marksmanship noticeably decreases regardless of prior training. Active stabilization systems in small arms have potential to address this problem to increase soldier survivability and mission effectiveness. The key to success is proper actuator design, but this is highly dependent on proper specification which is challenging due to the human/weapon interaction. This paper presents a generic analytical dynamic model which is capable of defining the necessary actuation specifications for a wide range of small arms platforms. The model is unique because it captures the human interface--shoulder and arm--that introduces the jitter disturbance in addition to the geometry, inertial properties and active stabilization stiffness of the small arms platform. Because no data to date is available for actual shooter-induced disturbance in field conditions, a method is given using the model to back-solve from measured shooting range variability data the disturbance amplitude information relative to the input source (arm or shoulder). As examples of the applicability of the model to various small arms systems, two different weapon systems were investigated: the M24 sniper weapon and the M16 assault rifle. In both cases, model based simulations provided valuable insight into impact on the actuation specifications (force, displacement, phase, frequency) due to the interplay of the human-weapon-active stabilization interface including the effect of shooter-disturbance frequency, disturbance location (shoulder vs. arm), and system parameters (stiffness, barrel rotation).

Occurrence of small Hsd plasmids in Salmonella typhi, Shigella boydii, and Escherichia coli.

PubMed Central

Yoshida, Y; Mise, K

1986-01-01

The natural occurrence of small Hsd (host specificity for DNA) plasmids was demonstrated in restriction endonuclease-producing strains of Salmonella typhi, Shigella boydii, and Escherichia coli. The five Hsd plasmids isolated were between 5.0 and 12.2 kilobases long. The copy number of all the Hsd plasmids was high (more than 10 copies per cell). Introduction of these small plasmids into E. coli strain 0 drastically lowered the efficiency of plating of the lambda.0 phages (the efficiency of plating was less than 5 X 10(-5) PFU-1). High restriction endonuclease activities were detected in the Hsd plasmid-positive strains because of the elevated copy numbers of the hsdR+ gene. The advantages of using E. coli strains containing the small Hsd plasmids for purification of type II restriction endonucleases are discussed. Images PMID:3003023

Advanced 35 W Free-Piston Stirling Engine for Space Power Applications

NASA Astrophysics Data System (ADS)

Wood, J. Gary; Lane, Neill

2003-01-01

This paper presents the projected performance and overall design characteristics of a high efficiency, low mass 35 W free-piston Stirling engine design. Overall (engine plus linear alternator) thermodynamic performance greater than 50% of Carnot, with a specific power close to 100 W/kg appears to be a reasonable goal at this small power level. Supporting test data and analysis results from exiting engines are presented. Design implications of high specific power in relatively low power engines is presented and discussed.

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

Heffner, M.; Riot, V.; Fabris, L.

Medium to large channel count detectors are usually faced with a few unattractive options for data acquisition (DAQ). Small to medium sized TPC experiments, for example, can be too small to justify the high expense and long development time of application specific integrated circuit (ASIC) development. In some cases an experiment can piggy-back on a larger experiment and the associated ASIC development, but this puts the time line of development out of the hands of the smaller experiment. Another option is to run perhaps thousands of cables to rack mounted equipment, which is clearly undesirable. The development of commercial high-speedmore » high-density FPGAs and ADCs combined with the small discrete components and robotic assembly open a new option that scales to tens of thousands of channels and is only slightly larger than ASICs using off-the-shelf components.« less

May the Best Molecule Win: Competition ESI Mass Spectrometry

PubMed Central

Laughlin, Sarah; Wilson, W. David

2015-01-01

Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences. PMID:26501262

Rational design of tetraphenylethylene-based luminescent down-shifting molecules: photophysical studies and photovoltaic applications in a CdTe solar cell from small to large units.

PubMed

Li, Yilin; Li, Zhipeng; Ablekim, Tursunjan; Ren, Tianhui; Dong, Wen-Ji

2014-12-21

A rational design strategy of novel fluorophores for luminescent down-shifting (LDS) application was proposed and tested in this paper. Three new fluorophores (1a-c) with specific intramolecular charge transfer (ICT) and aggregation-induced emission (AIE) characteristics were synthesized as LDS molecules for increasing the output short circuit current density (Jsc) of a CdTe solar cell. Photophysical studies of their solution and solid states, and photovoltaic measurements of their PMMA solid films applied on a CdTe solar cell suggested that the specific spectroscopic properties and Jsc enhancement effects of these molecules were highly related to their chemical structures. The Jsc enhancement effects of these fluorophores were measured on both a CdTe small cell and a large panel. An increase in the output Jsc by as high as 5.69% for a small cell and 8.88% for a large panel was observed. Compared to a traditional LDS molecule, Y083, these fluorophores exhibited more superior capabilities of LDS.

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

Rund, D.; Cohen, T.; Filon, D.

{beta}-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the {beta}-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of {beta}-thalassemia-the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered. Four of the mutations are unique to Kurdish Jews and have not been discovered inmore » any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews. The authors traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. They conclude that several evolutionary mechanisms contributed to the evolution of {beta}-thalassemia in this small ethnic isolate.« less

Repeat Prostate Biopsy Practice Patterns in a Statewide Quality Improvement Collaborative.

PubMed

Burks, Frank N; Hu, Jonathan C; Telang, Dinesh; Liu, Alice; Hawken, Scott; Montgomery, Zack; Linsell, Susan; Montie, James E; Miller, David C; Ghani, Khurshid R

2017-08-01

We examined rebiopsies in MUSIC (Michigan Urological Surgery Improvement Collaborative) to understand adherence to guidelines recommending repeat prostate biopsy in patients with multifocal high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. We analyzed data on men undergoing repeat biopsy, practice patterns and cancer detection rates. Multivariate regression modeling was used to calculate the proportion of patients undergoing rebiopsy. We used claims data to validate the treatment classification in MUSIC. To understand reasons for not performing rebiopsy we reviewed records of a sample of patients with atypical small acinar proliferation. We identified 5,375 men with a negative biopsy, of whom 411 (7.6%) underwent repeat biopsy. In 718 men with high grade prostatic intraepithelial neoplasia, 350 with atypical small acinar proliferation and 587 with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone at initial biopsy the rebiopsy rate was 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients with rebiopsy in each practice ranged from 0% to 17.2% (p <0.001). The overall cancer detection rate at rebiopsy was 39.3%. It was highest after atypical small acinar proliferation (adjusted probability 0.39, 95% CI 0.30-0.48), and after high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation (adjusted probability 0.50, 95% CI 0.35-0.65). The greatest Gleason 7 or greatest detection rate of 41.1% was found in patients with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation. Chart review revealed that 45.5% of patients with atypical small acinar proliferation underwent prostate specific antigen testing instead of rebiopsy while 36% failed to undergo rebiopsy despite a recommendation. Rebiopsy rates vary in Michigan practices with relatively low use in men with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone. Quality improvement strategies should target patients with atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia as they have the highest likelihood of cancer detection. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

PubMed

Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

2003-01-01

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we strongly suggest that the final interpretation of the results from this assay be viewed in light of the other features of the case, including clinical history, histology, and immunohistochemistry, by the diagnostic pathologist. Additional studies such as FISH may be useful in clarifying the nature of equivocal or unexpected results.

KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting

NASA Astrophysics Data System (ADS)

Wrobel, Eva; Rothenberg, Ina; Krisp, Christoph; Hundt, Franziska; Fraenzel, Benjamin; Eckey, Karina; Linders, Joannes T. M.; Gallacher, David J.; Towart, Rob; Pott, Lutz; Pusch, Michael; Yang, Tao; Roden, Dan M.; Kurata, Harley T.; Schulze-Bahr, Eric; Strutz-Seebohm, Nathalie; Wolters, Dirk; Seebohm, Guiscard

2016-10-01

Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors.

Quantum oscillations in the heavy-fermion compound YbPtBi

DOE PAGES

Mun, E.; Bud'ko, S. L.; Lee, Y.; ...

2015-08-01

We present quantum oscillations observed in the heavy-fermion compound YbPtBi in magnetic fields far beyond its field-tuned, quantum critical point. Quantum oscillations are observed in magnetic fields as low as 60 kOe at 60 mK and up to temperatures as high as 3 K, which confirms the very high quality of the samples as well as the small effective mass of the conduction carriers far from the quantum critical point. Although the electronic specific heat coefficient of YbPtBi reaches ~7.4 J/molK 2 in zero field, which is one of the highest effective mass values among heavy-fermion systems, we suppress itmore » quickly by an applied magnetic field. The quantum oscillations were used to extract the quasiparticle effective masses of the order of the bare electron mass, which is consistent with the behavior observed in specific heat measurements. Furthermore, such small effective masses at high fields can be understood by considering the suppression of Kondo screening.« less

Reactive Oxygen Species Produced by Prostate Cancer Cells Cause Castrate-Resistant Cell Growth by Inducing B-cell Lymphotoxin Release

DTIC Science & Technology

2013-06-01

data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...Gaussia luciferase reconstitution, high throughput screen, small molecule inhibitors, human prostate carcinoma cells, pharmacokinetcs, prostate cancer...cells. The increase in ROS levels is probably due to an induction of a polyamine oxidation pathway and specific small molecule inhibitors of this

Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

NASA Technical Reports Server (NTRS)

Zhang, Xiang (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Ellman, Jonathan A. (Inventor); Sun, Cheng (Inventor)

2014-01-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

DOEpatents

Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

2014-04-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Aptamer-mediated 'turn-off/turn-on' nanozyme activity of gold nanoparticles for kanamycin detection.

PubMed

Sharma, Tarun Kumar; Ramanathan, Rajesh; Weerathunge, Pabudi; Mohammadtaheri, Mahsa; Daima, Hemant Kumar; Shukla, Ravi; Bansal, Vipul

2014-12-28

A new ultrafast and highly sensitive 'turn-off/turn-on' biosensing approach that combines the intrinsic peroxidase-like activity of gold nanoparticles (GNPs) with the high affinity and specificity of a ssDNA aptamer is presented for the efficient detection of a model small molecule kanamycin.

Numerical viscosity and resolution of high-order weighted essentially nonoscillatory schemes for compressible flows with high Reynolds numbers.

PubMed

Zhang, Yong-Tao; Shi, Jing; Shu, Chi-Wang; Zhou, Ye

2003-10-01

A quantitative study is carried out in this paper to investigate the size of numerical viscosities and the resolution power of high-order weighted essentially nonoscillatory (WENO) schemes for solving one- and two-dimensional Navier-Stokes equations for compressible gas dynamics with high Reynolds numbers. A one-dimensional shock tube problem, a one-dimensional example with parameters motivated by supernova and laser experiments, and a two-dimensional Rayleigh-Taylor instability problem are used as numerical test problems. For the two-dimensional Rayleigh-Taylor instability problem, or similar problems with small-scale structures, the details of the small structures are determined by the physical viscosity (therefore, the Reynolds number) in the Navier-Stokes equations. Thus, to obtain faithful resolution to these small-scale structures, the numerical viscosity inherent in the scheme must be small enough so that the physical viscosity dominates. A careful mesh refinement study is performed to capture the threshold mesh for full resolution, for specific Reynolds numbers, when WENO schemes of different orders of accuracy are used. It is demonstrated that high-order WENO schemes are more CPU time efficient to reach the same resolution, both for the one-dimensional and two-dimensional test problems.

Printing Proteins as Microarrays for High-Throughput Function Determination

NASA Astrophysics Data System (ADS)

MacBeath, Gavin; Schreiber, Stuart L.

2000-09-01

Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

2015-02-01

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay. Electronic supplementary information (ESI) available: Fig. S1-S4. See DOI: 10.1039/c4nr05200e

Privileged structures: efficient chemical "navigators" toward unexplored biologically relevant chemical spaces.

PubMed

Kim, Jonghoon; Kim, Heejun; Park, Seung Bum

2014-10-22

In the search for new therapeutic agents for currently incurable diseases, attention has turned to traditionally "undruggable" targets, and collections of drug-like small molecules with high diversity and quality have become a prerequisite for new breakthroughs. To generate such collections, the diversity-oriented synthesis (DOS) strategy was developed, which aims to populate new chemical space with drug-like compounds containing a high degree of molecular diversity. The resulting DOS-derived libraries have been of great value for the discovery of various bioactive small molecules and therapeutic agents, and thus DOS has emerged as an essential tool in chemical biology and drug discovery. However, the key challenge has become how to design and synthesize drug-like small-molecule libraries with improved biological relevancy as well as maximum molecular diversity. This Perspective presents the development of privileged substructure-based DOS (pDOS), an efficient strategy for the construction of polyheterocyclic compound libraries with high biological relevancy. We envisioned the specific interaction of drug-like small molecules with certain biopolymers via the incorporation of privileged substructures into polyheterocyclic core skeletons. The importance of privileged substructures such as benzopyran, pyrimidine, and oxopiperazine in rigid skeletons was clearly demonstrated through the discovery of bioactive small molecules and the subsequent identification of appropriate target biomolecule using a method called "fluorescence difference in two-dimensional gel electrophoresis". Focusing on examples of pDOS-derived bioactive compounds with exceptional specificity, we discuss the capability of privileged structures to serve as chemical "navigators" toward biologically relevant chemical spaces. We also provide an outlook on chemical biology research and drug discovery using biologically relevant compound libraries constructed by pDOS, biology-oriented synthesis, or natural product-inspired DOS.

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.

Initiating Growth Of Crystals Away From Container Walls

NASA Technical Reports Server (NTRS)

Kroes, Roger L.; Reiss, Donald A.; Lehoczky, Sandor L.

1991-01-01

Nucleation controlled to obtain better crystals. In technique proposed specifically for growing large protein crystals in microgravity (where no thermal convection), small region of high supersaturation created by injection of hot concentrated solution or by use of cold probe. Crystals nucleate preferably in this small region. Also conceivable technique applied on Earth to crystallizations in melts and solutions sufficiently viscous to suppress convection to extent necessary to prevent cooling-induced nucleation in undesired sites.

Small Sample Reactivity Measurements in the RRR/SEG Facility: Reanalysis using TRIPOLI-4

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

Hummel, Andrew; Palmiotti, Guiseppe

2016-08-01

This work involved reanalyzing the RRR/SEG integral experiments performed at the Rossendorf facility in Germany throughout the 1970s and 80s. These small sample reactivity worth measurements were carried out using the pile oscillator technique for many different fission products, structural materials, and standards. The coupled fast-thermal system was designed such that the measurements would provide insight into elemental data, specifically the competing effects between neutron capture and scatter. Comparing the measured to calculated reactivity values can then provide adjustment criteria to ultimately improve nuclear data for fast reactor designs. Due to the extremely small reactivity effects measured (typically less thanmore » 1 pcm) and the specific heterogeneity of the core, the tool chosen for this analysis was TRIPOLI-4. This code allows for high fidelity 3-dimensional geometric modeling, and the most recent, unreleased version, is capable of exact perturbation theory.« less

A High-Throughput Processor for Flight Control Research Using Small UAVs

NASA Technical Reports Server (NTRS)

Klenke, Robert H.; Sleeman, W. C., IV; Motter, Mark A.

2006-01-01

There are numerous autopilot systems that are commercially available for small (<100 lbs) UAVs. However, they all share several key disadvantages for conducting aerodynamic research, chief amongst which is the fact that most utilize older, slower, 8- or 16-bit microcontroller technologies. This paper describes the development and testing of a flight control system (FCS) for small UAV s based on a modern, high throughput, embedded processor. In addition, this FCS platform contains user-configurable hardware resources in the form of a Field Programmable Gate Array (FPGA) that can be used to implement custom, application-specific hardware. This hardware can be used to off-load routine tasks such as sensor data collection, from the FCS processor thereby further increasing the computational throughput of the system.

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.

Literature-Based Workshops for Language Arts: Ideas for Active Learning Grades K-2.

ERIC Educational Resources Information Center

Morrison, Kathy; Dittrich, Tina

This book is intended for teachers who want to integrate high-quality children's literature into the language arts curriculum. The illustrated book provides a host of small-group workshops for children in kindergarten through second grade, planned around storybooks they love. Each workshop suggested in the book is geared to specific High/Scope…

Immigration and Resiliency: Unpacking the Experiences of High School Students from Cape Verde and Ethiopia

ERIC Educational Resources Information Center

Hersi, Afra Ahmed

2011-01-01

This article explores the complex factors, both individual and social, that contribute to the resiliency and academic achievement of six adolescent African immigrant students from Cape Verde and Ethiopia who were enrolled in a small high school in the United States. The school was designed specifically for recent adolescent immigrant students.…

Recovery and purification of spanish high oleate peanut ‘AT-9899’

USDA-ARS?s Scientific Manuscript database

“AT-9899” developed in Golden Peanut Company in 2002 is a Spanish market type peanut. It has spreading growth habit and mid maturity. Due to high level of oleate and small seed size, it is grown specifically for confectionery market in the USA and Mexico. However, from the time of development and re...

Recovery and Purification of Spanish High Oleate Peanut ‘AT-9899’

USDA-ARS?s Scientific Manuscript database

“AT-9899” developed in Golden Peanut Company in 2002 is a Spanish market type peanut. It has spreading growth habit and mid maturity. Due to high level of oleate and small seed size, it is grown specifically for confectionery market in the USA and Mexico. However, from the time of development and ...

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

Embedded Volttron specification - benchmarking small footprint compute device for Volttron

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

Sanyal, Jibonananda; Fugate, David L.; Woodworth, Ken

An embedded system is a small footprint computing unit that typically serves a specific purpose closely associated with measurements and control of hardware devices. These units are designed for reasonable durability and operations in a wide range of operating conditions. Some embedded systems support real-time operations and can demonstrate high levels of reliability. Many have failsafe mechanisms built to handle graceful shutdown of the device in exception conditions. The available memory, processing power, and network connectivity of these devices are limited due to the nature of their specific-purpose design and intended application. Industry practice is to carefully design the softwaremore » for the available hardware capability to suit desired deployment needs. Volttron is an open source agent development and deployment platform designed to enable researchers to interact with devices and appliances without having to write drivers themselves. Hosting Volttron on small footprint embeddable devices enables its demonstration for embedded use. This report details the steps required and the experience in setting up and running Volttron applications on three small footprint devices: the Intel Next Unit of Computing (NUC), the Raspberry Pi 2, and the BeagleBone Black. In addition, the report also details preliminary investigation of the execution performance of Volttron on these devices.« less

Site-Specific Bioorthogonal Labeling for Fluorescence Imaging of Intracellular Proteins in Living Cells.

PubMed

Peng, Tao; Hang, Howard C

2016-11-02

Over the past years, fluorescent proteins (e.g., green fluorescent proteins) have been widely utilized to visualize recombinant protein expression and localization in live cells. Although powerful, fluorescent protein tags are limited by their relatively large sizes and potential perturbation to protein function. Alternatively, site-specific labeling of proteins with small-molecule organic fluorophores using bioorthogonal chemistry may provide a more precise and less perturbing method. This approach involves site-specific incorporation of unnatural amino acids (UAAs) into proteins via genetic code expansion, followed by bioorthogonal chemical labeling with small organic fluorophores in living cells. While this approach has been used to label extracellular proteins for live cell imaging studies, site-specific bioorthogonal labeling and fluorescence imaging of intracellular proteins in live cells is still challenging. Herein, we systematically evaluate site-specific incorporation of diastereomerically pure bioorthogonal UAAs bearing stained alkynes or alkenes into intracellular proteins for inverse-electron-demand Diels-Alder cycloaddition reactions with tetrazine-functionalized fluorophores for live cell labeling and imaging in mammalian cells. Our studies show that site-specific incorporation of axial diastereomer of trans-cyclooct-2-ene-lysine robustly affords highly efficient and specific bioorthogonal labeling with monosubstituted tetrazine fluorophores in live mammalian cells, which enabled us to image the intracellular localization and real-time dynamic trafficking of IFITM3, a small membrane-associated protein with only 137 amino acids, for the first time. Our optimized UAA incorporation and bioorthogonal labeling conditions also enabled efficient site-specific fluorescence labeling of other intracellular proteins for live cell imaging studies in mammalian cells.

Positional Differences in External On-Field Load During Specific Drill Classifications Over a Professional Rugby League Preseason.

PubMed

Cummins, Cloe; McLean, Blake; Halaki, Mark; Orr, Rhonda

2017-07-01

To quantify the external training loads of positional groups in preseason training drills. Thirty-three elite rugby league players were categorized into 1 of 4 positional groups: outside backs (n = 9), adjustables (n = 9), wide-running forwards (n = 9), and hit-up forwards (n = 6). Data for 8 preseason weeks were collected using microtechnology devices. Training drills were classified based on drill focus: speed and agility, conditioning, and generic and positional skills. Total, high-speed, and very-high-speed distance decreased across the preseason in speed and agility (moderate, small, and small, respectively), conditioning (large, large, and small) and generic skills (large, large, and large). The duration of speed and generic skills also decreased (77% and 48%, respectively). This was matched by a concomitant increase in total distance (small), high-speed running (small), very-high-speed running (moderate), and 2-dimensional (2D) BodyLoad (small) demands in positional skills. In positional skills, hit-up forwards (1240 ± 386 m) completed less very-high-speed running than outside backs (2570 ± 1331 m) and adjustables (2121 ± 1163 m). Hit-up forwards (674 ± 253 AU) experienced greater 2D BodyLoad demands than outside backs (432 ± 230 AU, P = .034). In positional drills, hit-up forwards experienced greater relative 2D BodyLoad demands than outside backs (P = .015). Conversely, outside backs experienced greater relative high- (P = .007) and very-high-speed-running (P < .001) demands than hit-up forwards. Significant differences were observed in training loads between positional groups during positional skills but not in speed and agility, conditioning, and generic skills. This work also highlights the importance of different external-load parameters to adequately quantify workload across different positional groups.

Magnetic relaxometry as applied to sensitive cancer detection and localization

DOE PAGES

De Haro, Leyma P.; Karaulanov, Todor; Vreeland, Erika C.; ...

2015-06-02

Abstract Here we describe superparamagnetic relaxometry (SPMR), a technology that utilizes highly sensitive magnetic sensors and superparamagnetic nanoparticles for cancer detection. Using SPMR, we sensitively and specifically detect nanoparticles conjugated to biomarkers for various types of cancer. SPMR offers high contrast In SPMR measurements, a brief magnetizing pulse is used to align superparamagnetic nanoparticles of a discrete size. Following the pulse, an array of superconducting quantum interference detectors (SQUID) sensors detect the decaying magnetization field. NP size is chosen so that, when bound, the induced field decays in seconds. They are functionalized with specific biomarkers and incubated with cancer cellsmore » As a result, superparamagnetic NPs developed here have small size dispersion. Cell incubation studies measure specificity for different cell lines and antibodies with very high contrast.« less

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.

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.

GENETIC ADAPTATION TO CHRONIC CONTAMINANT EXPOSURE BY A SMALL ESTUARINE FISH

EPA Science Inventory

Investigations of the non-migratory fish species Fundulus heteroclitus indigenous to a highly chemically contaminated site is providing novel insights into stressor costs and adaptive strategies. Specifically, we are studying an abundant and persistent population of F. heterocli...

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.

"Egg-Box"-Assisted Fabrication of Porous Carbon with Small Mesopores for High-Rate Electric Double Layer Capacitors.

PubMed

Kang, Danmiao; Liu, Qinglei; Gu, Jiajun; Su, Yishi; Zhang, Wang; Zhang, Di

2015-11-24

Here we report a method to fabricate porous carbon with small mesopores around 2-4 nm by simple activation of charcoals derived from carbonization of seaweed consisting of microcrystalline domains formed by the "egg-box" model. The existence of mesopores in charcoals leads to a high specific surface area up to 3270 m(2) g(-1), with 95% surface area provided by small mesopores. This special pore structure shows high adaptability when used as electrode materials for an electric double layer capacitor, especially at high charge-discharge rate. The gravimetric capacitance values of the porous carbon are 425 and 210 F g(-1) and volumetric capacitance values are 242 and 120 F cm(-3) in 1 M H2SO4 and 1 M TEA BF4/AN, respectively. The capacitances even remain at 280 F g(-1) (160 F cm(-3)) at 100 A g(-1) and 156 F g(-1) (90 F cm(-3)) at 50 A g(-1) in the aqueous and organic electrolytes, demonstrating excellent high-rate capacitive performance.

Meta-assessment of bias in science

PubMed Central

Fanelli, Daniele; Costas, Rodrigo; Ioannidis, John P. A.

2017-01-01

Numerous biases are believed to affect the scientific literature, but their actual prevalence across disciplines is unknown. To gain a comprehensive picture of the potential imprint of bias in science, we probed for the most commonly postulated bias-related patterns and risk factors, in a large random sample of meta-analyses taken from all disciplines. The magnitude of these biases varied widely across fields and was overall relatively small. However, we consistently observed a significant risk of small, early, and highly cited studies to overestimate effects and of studies not published in peer-reviewed journals to underestimate them. We also found at least partial confirmation of previous evidence suggesting that US studies and early studies might report more extreme effects, although these effects were smaller and more heterogeneously distributed across meta-analyses and disciplines. Authors publishing at high rates and receiving many citations were, overall, not at greater risk of bias. However, effect sizes were likely to be overestimated by early-career researchers, those working in small or long-distance collaborations, and those responsible for scientific misconduct, supporting hypotheses that connect bias to situational factors, lack of mutual control, and individual integrity. Some of these patterns and risk factors might have modestly increased in intensity over time, particularly in the social sciences. Our findings suggest that, besides one being routinely cautious that published small, highly-cited, and earlier studies may yield inflated results, the feasibility and costs of interventions to attenuate biases in the literature might need to be discussed on a discipline-specific and topic-specific basis. PMID:28320937

Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

PubMed

Mueller, Ralf S; Olivry, Thierry

2017-08-30

The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3

PubMed Central

Subramanian, Shoba; Hardt, Markus; Choe, Youngchool; Niles, Richard K.; Johansen, Eric B.; Legac, Jennifer; Gut, Jiri; Kerr, Iain D.; Craik, Charles S.; Rosenthal, Philip J.

2009-01-01

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P1 – P4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P2 position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent 18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents. PMID:19357776

Peregrine: A rapid and unbiased method to produce strand-specific RNA-Seq libraries from small quantities of starting material.

PubMed

Langevin, Stanley A; Bent, Zachary W; Solberg, Owen D; Curtis, Deanna J; Lane, Pamela D; Williams, Kelly P; Schoeniger, Joseph S; Sinha, Anupama; Lane, Todd W; Branda, Steven S

2013-04-01

Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows.

Gene expression analysis using a highly sensitive DNA microarray for colorectal cancer screening.

PubMed

Koga, Yoshikatsu; Yamazaki, Nobuyoshi; Takizawa, Satoko; Kawauchi, Junpei; Nomura, Osamu; Yamamoto, Seiichiro; Saito, Norio; Kakugawa, Yasuo; Otake, Yosuke; Matsumoto, Minori; Matsumura, Yasuhiro

2014-01-01

Half of all patients with small, right-sided, non-metastatic colorectal cancer (CRC) have negative results for the fecal occult blood test (FOBT). In the present study, the usefulness of CRC screening with a highly sensitive DNA microarray was evaluated in comparison with that by FOBT using fecal samples. A total of 53 patients with CRC and 61 healthy controls were divided into "training" and "validation sets". For the gene profiling, total RNA extracted from 0.5 g of feces was hybridized to a highly sensitive DNA chip. The expressions of 43 genes were significantly higher in the patients with CRC than in healthy controls (p<0.05). In the training set, the sensitivity and specificity of the DNA chip assay using six genes were 85.4% and 85.2%, respectively. On the other hand, in the validation set, the sensitivity and specificity of the DNA chip assay were 85.2% and 85.7%, respectively. The sensitivities of the DNA chip assay were higher than those of FOBT in cases of the small, right-sided, early-CRC, tumor invading up to the muscularis propria (i.e. surface tumor) subgroups. In particular, the sensitivities of the DNA chip assay in the surface tumor and early-CRC subgroups were significantly higher than those of FOBT (p=0.023 and 0.019, respectively.). Gene profiling assay using a highly sensitive DNA chip was more effective than FOBT at detecting patients with small, right-sided, surface tumor, and early-stage CRC.

A high fidelity real-time simulation of a small turboshaft engine

NASA Technical Reports Server (NTRS)

Ballin, Mark G.

1988-01-01

A high-fidelity component-type model and real-time digital simulation of the General Electric T700-GE-700 turboshaft engine were developed for use with current generation real-time blade-element rotor helicopter simulations. A control system model based on the specification fuel control system used in the UH-60A Black Hawk helicopter is also presented. The modeling assumptions and real-time digital implementation methods particular to the simulation of small turboshaft engines are described. The validity of the simulation is demonstrated by comparison with analysis-oriented simulations developed by the manufacturer, available test data, and flight-test time histories.

Ligand binding by repeat proteins: natural and designed

PubMed Central

Grove, Tijana Z; Cortajarena, Aitziber L; Regan, Lynne

2012-01-01

Repeat proteins contain tandem arrays of small structural motifs. As a consequence of this architecture, they adopt non-globular, extended structures that present large, highly specific surfaces for ligand binding. Here we discuss recent advances toward understanding the functional role of this unique modular architecture. We showcase specific examples of natural repeat proteins interacting with diverse ligands and also present examples of designed repeat protein–ligand interactions. PMID:18602006

Diagnostic accuracy of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging of small renal masses in real practice: sensitivity and specificity according to subjective radiologic interpretation.

PubMed

Kim, Jae Heon; Sun, Hwa Yeon; Hwang, Jiyoung; Hong, Seong Sook; Cho, Yong Jin; Doo, Seung Whan; Yang, Won Jae; Song, Yun Seob

2016-10-12

The aim of this study was to investigate the diagnostic accuracy of contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of small renal masses in real practice. Contrast-enhanced CT and MRI were performed between February 2008 and February 2013 on 68 patients who had suspected small (≤4 cm) renal cell carcinoma (RCC) based on ultrasonographic measurements. CT and MRI radiographs were reviewed, and the findings of small renal masses were re-categorized into five dichotomized scales by the same two radiologists who had interpreted the original images. Receiver operating characteristics curve analysis was performed, and sensitivity and specificity were determined. Among the 68 patients, 60 (88.2 %) had RCC and eight had benign disease. The diagnostic accuracy rates of contrast-enhanced CT and MRI were 79.41 and 88.23 %, respectively. Diagnostic accuracy was greater when using contrast-enhanced MRI because too many masses (67.6 %) were characterized as "4 (probably solid cancer) or 5 (definitely solid cancer)." The sensitivity of contrast-enhanced CT and MRI for predicting RCC were 79.7 and 88.1 %, respectively. The specificities of contrast-enhanced CT and MRI for predicting RCC were 44.4 and 33.3 %, respectively. Fourteen diagnoses (20.5 %) were missed or inconsistent compared with the final pathological diagnoses. One appropriate nephroureterectomy and five unnecessary percutaneous biopsies were performed for RCC. Seven unnecessary partial nephrectomies were performed for benign disease. Although contrast-enhanced CT and MRI showed high sensitivity for detecting small renal masses, specificity remained low.

Deep skin structural and microcirculation imaging with extended-focus OCT

NASA Astrophysics Data System (ADS)

Blatter, Cedric; Grajciar, Branislav; Huber, Robert; Leitgeb, Rainer A.

2012-02-01

We present an extended focus OCT system for dermatologic applications that maintains high lateral resolution over a large depth range by using Bessel beam illumination. More, Bessel beams exhibit a self-reconstruction property that is particularly useful to avoid shadowing from surface structures such as hairs. High lateral resolution and high-speed measurement, thanks to a rapidly tuning swept source, allows not only for imaging of small skin structures in depth but also for comprehensive visualization of the small capillary network within the human skin in-vivo. We use this information for studying temporal vaso-responses to hypothermia. In contrast to other perfusion imaging methods such as laser Doppler imaging (LDI), OCT gives specific access to vascular responses in different vascular beds in depth.

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

Ryan Hruska

Currently, small Unmanned Aerial Vehicles (UAVs) are primarily used for capturing and down-linking real-time video. To date, their role as a low-cost airborne platform for capturing high-resolution, georeferenced still imagery has not been fully utilized. On-going work within the Unmanned Vehicle Systems Program at the Idaho National Laboratory (INL) is attempting to exploit this small UAV-acquired, still imagery potential. Initially, a UAV-based still imagery work flow model was developed that includes initial UAV mission planning, sensor selection, UAV/sensor integration, and imagery collection, processing, and analysis. Components to support each stage of the work flow are also being developed. Critical tomore » use of acquired still imagery is the ability to detect changes between images of the same area over time. To enhance the analysts’ change detection ability, a UAV-specific, GIS-based change detection system called SADI or System for Analyzing Differences in Imagery is under development. This paper will discuss the associated challenges and approaches to collecting still imagery with small UAVs. Additionally, specific components of the developed work flow system will be described and graphically illustrated using varied examples of small UAV-acquired still imagery.« less

Detection of disease specific sialoglycoconjugate specific antibodies in bronchoalveolar lavage fluid of non-small cell lung cancer patients.

PubMed

Mehta, Sangeeta; Chhetra, Rakhee; Srinivasan, Radhika; Sharma, Suresh C; Behera, Digambar; Ghosh, Sujata

2010-07-01

In this study, we report the presence of significantly higher level of GM3 specific IgG antibodies (IgG(TL)) in the bronchoalveolar lavage fluid obtained from tumor bearing lung of non-small cell lung cancer (NSCLC) patients as compared to other non-neoplastic controls. The antibodies were isolated using DEAE-cellulose anion exchange chromatography and molecular weight of the subunits of IgG(TL) was confirmed in SDS-PAGE. IgG(TL) revealed high specificity to GM3 and the IgG distribution was confined to IgG1. Furthermore, IgG(TL) showed strong reactivity with NSCLC cell lines as well as the tissue biopsies and cells obtained from fine needle aspirations of NSCLC patients. A 66 kDa membrane glycoprotein of NSCLC cell lines was found to interact specifically with IgG(TL), the intensity of which was drastically reduced in presence of GM3. Further, binding of Maackia amurensis agglutinin [specific for NeuAcalpha(2-->3)Gal unit , the same disaccharide unit also known to be present in GM3] to the 66 kDa band confirmed it to be a sialoglycoprotein in nature. IgG(TL) could not show any reactivity to alkaline borohydrate treated or periodate oxidised membrane fractions, suggesting the probable involvement of the carbohydrate moiety of the 66 kDa glycoprotein in the interaction with IgG(TL). Thus, the 66 kDa sialoglycoprotein seems to be the NSCLC specific sialoglycoconjugate. Taken together, IgG(TL) antibodies may have the potential to serve as a unique probe for detail investigation of NSCLC specific cell surface sialoglycoconjugate. Further, due to high specificity of IgG(TL) to GM3, it may be possible to develop a simple alternative diagnostic approach (GM3-ELISA) for NSCLC.

Wave rotor-enhanced gas turbine engines

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Scott, Jones M.; Paxson, Daniel E.

1995-01-01

The benefits of wave rotor-topping in small (400 to 600 hp-class) and intermediate (3000 to 4000 hp-class) turboshaft engines, and large (80,000 to 100,000 lb(sub f)-class) high bypass ratio turbofan engines are evaluated. Wave rotor performance levels are calculated using a one-dimensional design/analysis code. Baseline and wave rotor-enhanced engine performance levels are obtained from a cycle deck in which the wave rotor is represented as a burner with pressure gain. Wave rotor-toppings is shown to significantly enhance the specific fuel consumption and specific power of small and intermediate size turboshaft engines. The specific fuel consumption of the wave rotor-enhanced large turbofan engine can be reduced while operating at significantly reduced turbine inlet temperature. The wave rotor-enhanced engine is shown to behave off-design like a conventional engine. Discussion concerning the impact of the wave rotor/gas turbine engine integration identifies tenable technical challenges.

Application of CHESS single-bounce capillaries at synchrotron beamlines

NASA Astrophysics Data System (ADS)

Huang, R.; Szebenyi, T.; Pfeifer, M.; Woll, A.; Smilgies, D.-M.; Finkelstein, K.; Dale, D.; Wang, Y.; Vila-Comamala, J.; Gillilan, R.; Cook, M.; Bilderback, D. H.

2014-03-01

Single-bounce capillaries are achromatic X-ray focusing optics that can provide efficient and high demagnification focusing with large numerical apertures. Capillary fabrication at CHESS can be customized according to specific application requirements. Exemplary applications are reviewed in this paper, as well as recent progress on condensers for high-resolution transmission X-ray microscopy and small focal size capillaries.

Selecting, Acquiring, and Using Small Molecule Libraries for High-Throughput Screening

PubMed Central

Dandapani, Sivaraman; Rosse, Gerard; Southall, Noel; Salvino, Joseph M.; Thomas, Craig J.

2015-01-01

The selection, acquisition and use of high quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs. Screening libraries continue to evolve as researchers gain a greater appreciation of the suitability of small molecules for specific biological targets, processes and environments. The decisions surrounding the make-up of any given small molecule library is informed by a multitude of variables and opinions vary on best-practices. The fitness of any collection relies upon upfront filtering to avoiding problematic compounds, assess appropriate physicochemical properties, install the ideal level of structural uniqueness and determine the desired extent of molecular complexity. These criteria are under constant evaluation and revision as academic and industrial organizations seek out collections that yield ever improving results from their screening portfolios. Practical questions including cost, compound management, screening sophistication and assay objective also play a significant role in the choice of library composition. This overview attempts to offer advice to all organizations engaged in small molecule screening based upon current best practices and theoretical considerations in library selection and acquisition. PMID:26705509

Selecting, Acquiring, and Using Small Molecule Libraries for High-Throughput Screening.

PubMed

Dandapani, Sivaraman; Rosse, Gerard; Southall, Noel; Salvino, Joseph M; Thomas, Craig J

The selection, acquisition and use of high quality small molecule libraries for screening is an essential aspect of drug discovery and chemical biology programs. Screening libraries continue to evolve as researchers gain a greater appreciation of the suitability of small molecules for specific biological targets, processes and environments. The decisions surrounding the make-up of any given small molecule library is informed by a multitude of variables and opinions vary on best-practices. The fitness of any collection relies upon upfront filtering to avoiding problematic compounds, assess appropriate physicochemical properties, install the ideal level of structural uniqueness and determine the desired extent of molecular complexity. These criteria are under constant evaluation and revision as academic and industrial organizations seek out collections that yield ever improving results from their screening portfolios. Practical questions including cost, compound management, screening sophistication and assay objective also play a significant role in the choice of library composition. This overview attempts to offer advice to all organizations engaged in small molecule screening based upon current best practices and theoretical considerations in library selection and acquisition.

Statistical context shapes stimulus-specific adaptation in human auditory cortex

PubMed Central

Henry, Molly J.; Fromboluti, Elisa Kim; McAuley, J. Devin

2015-01-01

Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity. PMID:25652920

SPAR: small RNA-seq portal for analysis of sequencing experiments.

PubMed

Kuksa, Pavel P; Amlie-Wolf, Alexandre; Katanic, Živadin; Valladares, Otto; Wang, Li-San; Leung, Yuk Yee

2018-05-04

The introduction of new high-throughput small RNA sequencing protocols that generate large-scale genomics datasets along with increasing evidence of the significant regulatory roles of small non-coding RNAs (sncRNAs) have highlighted the urgent need for tools to analyze and interpret large amounts of small RNA sequencing data. However, it remains challenging to systematically and comprehensively discover and characterize sncRNA genes and specifically-processed sncRNA products from these datasets. To fill this gap, we present Small RNA-seq Portal for Analysis of sequencing expeRiments (SPAR), a user-friendly web server for interactive processing, analysis, annotation and visualization of small RNA sequencing data. SPAR supports sequencing data generated from various experimental protocols, including smRNA-seq, short total RNA sequencing, microRNA-seq, and single-cell small RNA-seq. Additionally, SPAR includes publicly available reference sncRNA datasets from our DASHR database and from ENCODE across 185 human tissues and cell types to produce highly informative small RNA annotations across all major small RNA types and other features such as co-localization with various genomic features, precursor transcript cleavage patterns, and conservation. SPAR allows the user to compare the input experiment against reference ENCODE/DASHR datasets. SPAR currently supports analyses of human (hg19, hg38) and mouse (mm10) sequencing data. SPAR is freely available at https://www.lisanwanglab.org/SPAR.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications

PubMed Central

Laurencin, Cato T.; Ashe, Keshia M.; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H.

2014-01-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. Common limitations with protein growth factors are high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host. New strategies for bone regeneration that obviate these problems can have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. PMID:24508820

No evidence of infection or exposure to Highly Pathogenic Avian Influenzas in peridomestic wildlife on an affected poultry facility

USGS Publications Warehouse

Grear, Daniel A.; Dusek, Robert J.; Walsh, Daniel P.; Hall, Jeffrey S.

2017-01-01

We evaluated the potential transmission of avian influenza viruses (AIV) in wildlife species in three settings in association with an outbreak at a poultry facility: 1) small birds and small mammals on a poultry facility that was affected with highly pathogenic AIV (HPAIV) in April 2015; 2) small birds and small mammals on a nearby poultry facility that was unaffected by HPAIV; and 3) small birds, small mammals, and waterfowl in a nearby natural area. We live-captured small birds and small mammals and collected samples from hunter-harvested waterfowl to test for active viral shedding and evidence of exposure (serum antibody) to AIV and the H5N2 HPAIV that affected the poultry facility. We detected no evidence of shedding or specific antibody to AIV in small mammals and small birds 5 mo after depopulation of the poultry. We detected viral shedding and exposure to AIV in waterfowl and estimated approximately 15% viral shedding and 60% antibody prevalence. In waterfowl, we did not detect shedding or exposure to the HPAIV that affected the poultry facility. We also conducted camera trapping around poultry carcass depopulation composting barns and found regular visitation by four species of medium-sized mammals. We provide preliminary data suggesting that peridomestic wildlife were not an important factor in the transmission of AIV during the poultry outbreak, nor did small birds and mammals in natural wetland settings show wide evidence of AIV shedding or exposure, despite the opportunity for exposure.

NO EVIDENCE OF INFECTION OR EXPOSURE TO HIGHLY PATHOGENIC AVIAN INFLUENZAS IN PERIDOMESTIC WILDLIFE ON AN AFFECTED POULTRY FACILITY.

PubMed

Grear, Daniel A; Dusek, Robert J; Walsh, Daniel P; Hall, Jeffrey S

2017-01-01

We evaluated the potential transmission of avian influenza viruses (AIV) in wildlife species in three settings in association with an outbreak at a poultry facility: 1) small birds and small mammals on a poultry facility that was affected with highly pathogenic AIV (HPAIV) in April 2015; 2) small birds and small mammals on a nearby poultry facility that was unaffected by HPAIV; and 3) small birds, small mammals, and waterfowl in a nearby natural area. We live-captured small birds and small mammals and collected samples from hunter-harvested waterfowl to test for active viral shedding and evidence of exposure (serum antibody) to AIV and the H5N2 HPAIV that affected the poultry facility. We detected no evidence of shedding or specific antibody to AIV in small mammals and small birds 5 mo after depopulation of the poultry. We detected viral shedding and exposure to AIV in waterfowl and estimated approximately 15% viral shedding and 60% antibody prevalence. In waterfowl, we did not detect shedding or exposure to the HPAIV that affected the poultry facility. We also conducted camera trapping around poultry carcass depopulation composting barns and found regular visitation by four species of medium-sized mammals. We provide preliminary data suggesting that peridomestic wildlife were not an important factor in the transmission of AIV during the poultry outbreak, nor did small birds and mammals in natural wetland settings show wide evidence of AIV shedding or exposure, despite the opportunity for exposure.

Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

PubMed Central

De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

2013-01-01

SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

PubMed

Miettinen, M

1981-03-01

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

Towards a high sensitivity small animal PET system based on CZT detectors (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abbaszadeh, Shiva; Levin, Craig

2017-03-01

Small animal positron emission tomography (PET) is a biological imaging technology that allows non-invasive interrogation of internal molecular and cellular processes and mechanisms of disease. New PET molecular probes with high specificity are under development to target, detect, visualize, and quantify subtle molecular and cellular processes associated with cancer, heart disease, and neurological disorders. However, the limited uptake of these targeted probes leads to significant reduction in signal. There is a need to advance the performance of small animal PET system technology to reach its full potential for molecular imaging. Our goal is to assemble a small animal PET system based on CZT detectors and to explore methods to enhance its photon sensitivity. In this work, we reconstruct an image from a phantom using a two-panel subsystem consisting of six CZT crystals in each panel. For image reconstruction, coincidence events with energy between 450 and 570 keV were included. We are developing an algorithm to improve sensitivity of the system by including multiple interaction events.

High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

PubMed

Lorenz, Daniel A; Song, James M; Garner, Amanda L

2015-01-21

MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

Tissue-specific mutation accumulation in human adult stem cells during life

NASA Astrophysics Data System (ADS)

Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Roerink, Sophie; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Martincorena, Inigo; Mokry, Michal; Wiegerinck, Caroline L.; Middendorp, Sabine; Sato, Toshiro; Schwank, Gerald; Nieuwenhuis, Edward E. S.; Verstegen, Monique M. A.; van der Laan, Luc J. W.; de Jonge, Jeroen; Ijzermans, Jan N. M.; Vries, Robert G.; van de Wetering, Marc; Stratton, Michael R.; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben

2016-10-01

The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.

Identification of high-specificity H-NS binding site in LEE5 promoter of enteropathogenic Esherichia coli (EPEC).

PubMed

Bhat, Abhay Prasad; Shin, Minsang; Choy, Hyon E

2014-07-01

Histone-like nucleoid structuring protein (H-NS) is a small but abundant protein present in enteric bacteria and is involved in compaction of the DNA and regulation of the transcription. Recent reports have suggested that H-NS binds to a specific AT rich DNA sequence than to intrinsically curved DNA in sequence independent manner. We detected two high-specificity H-NS binding sites in LEE5 promoter of EPEC centered at -110 and -138, which were close to the proposed consensus H-NS binding motif. To identify H-NS binding sequence in LEE5 promoter, we took a random mutagenesis approach and found the mutations at around -138 were specifically defective in the regulation by H-NS. It was concluded that H-NS exerts maximum repression via the specific sequence at around -138 and subsequently contacts a subunit of RNAP through oligomerization.

High fat diet impairs the function of glucagon-like peptide-1 producing L-cells.

PubMed

Richards, Paul; Pais, Ramona; Habib, Abdella M; Brighton, Cheryl A; Yeo, Giles S H; Reimann, Frank; Gribble, Fiona M

2016-03-01

Glucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. Transgenic mouse models were utilized in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. Two weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L-cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post-prandial signaling, which could impact on insulin secretion and satiety. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

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

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Development of a 0.014-inch magnetic resonance imaging guidewire.

PubMed

Qiu, Bensheng; Karmarkar, Parag; Brushett, Chris; Gao, Fabao; Kon, Ryan; Kar, Sourav; Atalar, Ergin; Yang, Xiaoming

2005-04-01

The purpose of this study was to develop a standard 0.014-inch intravascular magnetic resonance imaging guidewire (MRIG), a coaxial cable with an extension of the inner conductor, specifically designed for use in the small vessels. After a theoretical analysis, the 0.014-inch MRIG was built by plating/cladding highly electrically conductive materials, silver or gold, over the inside and outside of the coaxial conductors. The conductors were made of superelastic, nonmagnetic, biocompatible materials, Nitinol or MP35N. Then, in comparison with a previously designed 0.032-inch MRIG, the performance of the new 0.014-inch MRIG in vitro and in vivo was successfully evaluated. This study represents the initial work to confirm the critical role of highly conductive and superelastic materials in building such small-size MRIGs, which are expected to generate high-resolution MR imaging of vessel walls/plaques and guide endovascular interventional procedures in the small vessels, such as the coronary arteries. Copyright 2005 Wiley-Liss, Inc.

Design criteria for a high energy Compton Camera and possible application to targeted cancer therapy

NASA Astrophysics Data System (ADS)

Conka Nurdan, T.; Nurdan, K.; Brill, A. B.; Walenta, A. H.

2015-07-01

The proposed research focuses on the design criteria for a Compton Camera with high spatial resolution and sensitivity, operating at high gamma energies and its possible application for molecular imaging. This application is mainly on the detection and visualization of the pharmacokinetics of tumor targeting substances specific for particular cancer sites. Expected high resolution (< 0.5 mm) permits monitoring the pharmacokinetics of labeled gene constructs in vivo in small animals with a human tumor xenograft which is one of the first steps in evaluating the potential utility of a candidate gene. The additional benefit of high sensitivity detection will be improved cancer treatment strategies in patients based on the use of specific molecules binding to cancer sites for early detection of tumors and identifying metastasis, monitoring drug delivery and radionuclide therapy for optimum cell killing at the tumor site. This new technology can provide high resolution, high sensitivity imaging of a wide range of gamma energies and will significantly extend the range of radiotracers that can be investigated and used clinically. The small and compact construction of the proposed camera system allows flexible application which will be particularly useful for monitoring residual tumor around the resection site during surgery. It is also envisaged as able to test the performance of new drug/gene-based therapies in vitro and in vivo for tumor targeting efficacy using automatic large scale screening methods.

VHDL Modeling and Simulation of a Digital Image Synthesizer for Countering ISAR

DTIC Science & Technology

2003-06-01

This thesis discusses VHDL modeling and simulation of a full custom Application Specific Integrated Circuit (ASIC) for a Digital Image Synthesizer...necessary for a given application . With such a digital method, it is possible for a small ship to appear as large as an aircraft carrier or any high...INTRODUCTION TO DIGITAL IMAGE SYNTHESIZER (DIS) A. BACKGROUND The Digital Image Synthesizer (DIS) is an Application Specific Integrated Circuit

Identification and Characterization of a Suite of Tumor Targeting Peptides for Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

McGuire, Michael J.; Gray, Bethany Powell; Li, Shunzi; Cupka, Dorothy; Byers, Lauren Averett; Wu, Lei; Rezaie, Shaghayegh; Liu, Ying-Horng; Pattisapu, Naveen; Issac, James; Oyama, Tsukasa; Diao, Lixia; Heymach, John V.; Xie, Xian-Jin; Minna, John D.; Brown, Kathlynn C.

2014-03-01

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The peptides show distinct binding profiles across 40 NSCLC cell lines and do not bind normal bronchial epithelial cell lines. Binding of specific peptides correlates with onco-genotypes and activation of particular pathways, such as EGFR signaling, suggesting the peptides may serve as surrogate markers. Multimerization of the peptides results in cell binding affinities between 0.0071-40 nM. The peptides home to tumors in vivo and bind to patient tumor samples. This is the first comprehensive biopanning for isolation of high affinity peptidic ligands for a single cancer type and expands the diversity of NSCLC targeting ligands.

Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions

PubMed Central

Kagan, Valerian E.; Wipf, Peter; Stoyanovsky, Detcho; Greenberger, Joel S.; Borisenko, Grigory; Belikova, Natalia A.; Yanamala, Naveena; Samhan Arias, Alejandro K.; Tungekar, Muhammad A.; Jiang, Jianfei; Tyurina, Yulia Y.; Ji, Jing; Klein-Seetharaman, Judith; Pitt, Bruce R.; Shvedova, Anna A; Bayır, Hülya

2009-01-01

Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader-sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants. PMID:19716396

D Imaging for Museum Artefacts: a Portable Test Object for Heritage and Museum Documentation of Small Objects

NASA Astrophysics Data System (ADS)

Hess, M.; Robson, S.

2012-07-01

3D colour image data generated for the recording of small museum objects and archaeological finds are highly variable in quality and fitness for purpose. Whilst current technology is capable of extremely high quality outputs, there are currently no common standards or applicable guidelines in either the museum or engineering domain suited to scientific evaluation, understanding and tendering for 3D colour digital data. This paper firstly explains the rationale towards and requirements for 3D digital documentation in museums. Secondly it describes the design process, development and use of a new portable test object suited to sensor evaluation and the provision of user acceptance metrics. The test object is specifically designed for museums and heritage institutions and includes known surface and geometric properties which support quantitative and comparative imaging on different systems. The development for a supporting protocol will allow object reference data to be included in the data processing workflow with specific reference to conservation and curation.

Identification and Characterization of a Suite of Tumor Targeting Peptides for Non-Small Cell Lung Cancer

PubMed Central

McGuire, Michael J.; Gray, Bethany Powell; Li, Shunzi; Cupka, Dorothy; Byers, Lauren Averett; Wu, Lei; Rezaie, Shaghayegh; Liu, Ying-Horng; Pattisapu, Naveen; Issac, James; Oyama, Tsukasa; Diao, Lixia; Heymach, John V.; Xie, Xian-Jin; Minna, John D.; Brown, Kathlynn C.

2014-01-01

Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging is dependent on increasing the number of high affinity, tumor-specific ligands. Towards this goal, we biopanned three phage-displayed peptide libraries on a series of well-defined human non-small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The peptides show distinct binding profiles across 40 NSCLC cell lines and do not bind normal bronchial epithelial cell lines. Binding of specific peptides correlates with onco-genotypes and activation of particular pathways, such as EGFR signaling, suggesting the peptides may serve as surrogate markers. Multimerization of the peptides results in cell binding affinities between 0.0071–40 nM. The peptides home to tumors in vivo and bind to patient tumor samples. This is the first comprehensive biopanning for isolation of high affinity peptidic ligands for a single cancer type and expands the diversity of NSCLC targeting ligands. PMID:24670678

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

PubMed

Laurencin, Cato T; Ashe, Keshia M; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H

2014-06-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

A high-throughput microRNA expression profiling system.

PubMed

Guo, Yanwen; Mastriano, Stephen; Lu, Jun

2014-01-01

As small noncoding RNAs, microRNAs (miRNAs) regulate diverse biological functions, including physiological and pathological processes. The expression and deregulation of miRNA levels contain rich information with diagnostic and prognostic relevance and can reflect pharmacological responses. The increasing interest in miRNA-related research demands global miRNA expression profiling on large numbers of samples. We describe here a robust protocol that supports high-throughput sample labeling and detection on hundreds of samples simultaneously. This method employs 96-well-based miRNA capturing from total RNA samples and on-site biochemical reactions, coupled with bead-based detection in 96-well format for hundreds of miRNAs per sample. With low-cost, high-throughput, high detection specificity, and flexibility to profile both small and large numbers of samples, this protocol can be adapted in a wide range of laboratory settings.

Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

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

Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman

2005-08-01

To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudalmore » and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two (12%) patients, invasive carcinoma was diagnosed at US-guided biopsy (9 mm each at pathologic examination). CONCLUSION: High-resolution breast-specific scintimammography can depict small (<1-cm), mammographically occult, nonpalpable lesions in women at increased risk for breast cancer not otherwise identified at mammography or physical examination.« less

An apparent cluster of aplastic anemia in a small population of teenagers.

PubMed

Linet, M S; Tielsch, J M; Markowitz, J A; Sensenbrenner, L L; McCaffrey, L D; Warm, S G; Vanderslice, S F; Morgan, W F; Bearden, J D; Szklo, M

1985-04-01

Four teenagers with severe aplastic anemia, initially diagnosed and evaluated over a seven-year period at The Johns Hopkins Bone Marrow Transplant Unit, Baltimore, were residents of the same small town in South Carolina. Estimated annual incidence for that age group in the town, based on the four cases, was 100 times the expected rate. All four of the teenagers had attended one of two junior high schools. An exploratory survey of all high-school students, comparing risk factors of those who had attended the "affected" junior high school with those who had attended the "unaffected" junior high school, showed no associations with exposure to glue, paint or varnishes, pesticides, history of hepatitis or infectious mononucleosis, or use of chloramphenicol or other suspected drugs. Weak associations were found between the affected junior high school and employment in the textile industry and in agriculture (specifically peach orchards).

A Dual-Specific Targeting Approach Based on the Simultaneous Recognition of Duplex and Quadruplex Motifs.

PubMed

Nguyen, Thi Quynh Ngoc; Lim, Kah Wai; Phan, Anh Tuân

2017-09-20

Small-molecule ligands targeting nucleic acids have been explored as potential therapeutic agents. Duplex groove-binding ligands have been shown to recognize DNA in a sequence-specific manner. On the other hand, quadruplex-binding ligands exhibit high selectivity between quadruplex and duplex, but show limited discrimination between different quadruplex structures. Here we propose a dual-specific approach through the simultaneous application of duplex- and quadruplex-binders. We demonstrated that a quadruplex-specific ligand and a duplex-specific ligand can simultaneously interact at two separate binding sites of a quadruplex-duplex hybrid harbouring both quadruplex and duplex structural elements. Such a dual-specific targeting strategy would combine the sequence specificity of duplex-binders and the strong binding affinity of quadruplex-binders, potentially allowing the specific targeting of unique quadruplex structures. Future research can be directed towards the development of conjugated compounds targeting specific genomic quadruplex-duplex sites, for which the linker would be highly context-dependent in terms of length and flexibility, as well as the attachment points onto both ligands.

Small RNA populations revealed by blocking rRNA fragments in Drosophila melanogaster reproductive tissues

PubMed Central

Dalmay, Tamas

2018-01-01

RNA interference (RNAi) is a complex and highly conserved regulatory mechanism mediated via small RNAs (sRNAs). Recent technical advances in high throughput sequencing have enabled an increasingly detailed analysis of sRNA abundances and profiles in specific body parts and tissues. This enables investigations of the localized roles of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, variation in the proportions of non-coding RNAs in the samples being compared can hinder these analyses. Specific tissues may vary significantly in the proportions of fragments of longer non-coding RNAs (such as ribosomal RNA or transfer RNA) present, potentially reflecting tissue-specific differences in biological functions. For example, in Drosophila, some tissues contain a highly abundant 30nt rRNA fragment (the 2S rRNA) as well as abundant 5’ and 3’ terminal rRNA fragments. These can pose difficulties for the construction of sRNA libraries as they can swamp the sequencing space and obscure sRNA abundances. Here we addressed this problem and present a modified “rRNA blocking” protocol for the construction of high-definition (HD) adapter sRNA libraries, in D. melanogaster reproductive tissues. The results showed that 2S rRNAs targeted by blocking oligos were reduced from >80% to < 0.01% total reads. In addition, the use of multiple rRNA blocking oligos to bind the most abundant rRNA fragments allowed us to reveal the underlying sRNA populations at increased resolution. Side-by-side comparisons of sequencing libraries of blocked and non-blocked samples revealed that rRNA blocking did not change the miRNA populations present, but instead enhanced their abundances. We suggest that this rRNA blocking procedure offers the potential to improve the in-depth analysis of differentially expressed sRNAs within and across different tissues. PMID:29474379

Small indels induced by CRISPR/Cas9 in the 5' region of microRNA lead to its depletion and Drosha processing retardance.

PubMed

Jiang, Qian; Meng, Xing; Meng, Lingwei; Chang, Nannan; Xiong, Jingwei; Cao, Huiqing; Liang, Zicai

2014-01-01

MicroRNA knockout by genome editing technologies is promising. In order to extend the application of the technology and to investigate the function of a specific miRNA, we used CRISPR/Cas9 to deplete human miR-93 from a cluster by targeting its 5' region in HeLa cells. Various small indels were induced in the targeted region containing the Drosha processing site and seed sequences. Interestingly, we found that even a single nucleotide deletion led to complete knockout of the target miRNA with high specificity. Functional knockout was confirmed by phenotype analysis. Furthermore, de novo microRNAs were not found by RNA-seq. Nevertheless, expression of the pri-microRNAs was increased. When combined with structural analysis, the data indicated that biogenesis was impaired. Altogether, we showed that small indels in the 5' region of a microRNA result in sequence depletion as well as Drosha processing retard.

Flexible and Lightweight Fuel Cell with High Specific Power Density.

PubMed

Ning, Fandi; He, Xudong; Shen, Yangbin; Jin, Hehua; Li, Qingwen; Li, Da; Li, Shuping; Zhan, Yulu; Du, Ying; Jiang, Jingjing; Yang, Hui; Zhou, Xiaochun

2017-06-27

Flexible devices have been attracting great attention recently due to their numerous advantages. But the energy densities of current energy sources are still not high enough to support flexible devices for a satisfactory length of time. Although proton exchange membrane fuel cells (PEMFCs) do have a high-energy density, traditional PEMFCs are usually too heavy, rigid, and bulky to be used in flexible devices. In this research, we successfully invented a light and flexible air-breathing PEMFC by using a new design of PEMFC and a flexible composite electrode. The flexible air-breathing PEMFC with 1 × 1 cm 2 working area can be as light as 0.065 g and as thin as 0.22 mm. This new PEMFC exhibits an amazing specific volume power density as high as 5190 W L -1 , which is much higher than traditional (air-breathing) PEMFCs. Also outstanding is that the flexible PEMFC retains 89.1% of its original performance after being bent 600 times, and it retains its original performance after being dropped five times from a height of 30 m. Moreover, the research has demonstrated that when stacked, the flexible PEMFCs are also useful in mobile applications such as mobile phones. Therefore, our research shows that PEMFCs can be made light, flexible, and suitable for applications in flexible devices. These innovative flexible PEMFCs may also notably advance the progress in the PEMFC field, because flexible PEMFCs can achieve high specific power density with small size, small volume, low weight, and much lower cost; they are also much easier to mass produce.

Comparative Genomics Analysis of Streptococcus Isolates from the Human Small Intestine Reveals their Adaptation to a Highly Dynamic Ecosystem

PubMed Central

Van den Bogert, Bartholomeus; Boekhorst, Jos; Herrmann, Ruth; Smid, Eddy J.; Zoetendal, Erwin G.; Kleerebezem, Michiel

2013-01-01

The human small-intestinal microbiota is characterised by relatively large and dynamic Streptococcus populations. In this study, genome sequences of small-intestinal streptococci from S. mitis, S. bovis, and S. salivarius species-groups were determined and compared with those from 58 Streptococcus strains in public databases. The Streptococcus pangenome consists of 12,403 orthologous groups of which 574 are shared among all sequenced streptococci and are defined as the Streptococcus core genome. Genome mining of the small-intestinal streptococci focused on functions playing an important role in the interaction of these streptococci in the small-intestinal ecosystem, including natural competence and nutrient-transport and metabolism. Analysis of the small-intestinal Streptococcus genomes predicts a high capacity to synthesize amino acids and various vitamins as well as substantial divergence in their carbohydrate transport and metabolic capacities, which is in agreement with observed physiological differences between these Streptococcus strains. Gene-specific PCR-strategies enabled evaluation of conservation of Streptococcus populations in intestinal samples from different human individuals, revealing that the S. salivarius strains were frequently detected in the small-intestine microbiota, supporting the representative value of the genomes provided in this study. Finally, the Streptococcus genomes allow prediction of the effect of dietary substances on Streptococcus population dynamics in the human small-intestine. PMID:24386196

A High-efficiency, Small, Solid-state Laser for Pyrotechnic Ignition

NASA Technical Reports Server (NTRS)

Yang, L. C.; Menichelli, V. J.

1973-01-01

A completely self-contained, small, neodymium laser has been designed and demonstrated for use in a pyrotechnic ignition system. A nominal 16 J of laser energy (1.06 micron wavelength, 1-ms duration) was achieved in a rectangular 10.5-X 15.1-X 25.4-cm package weighting 5.14 kg. This high energy-to-weight ratio is encouraging for laser applications in which specific energy efficiency (energy per unit weight or volume) is important. The laser design concepts are described, and some results on pyrotechnic ignition are given. Some details on a laser currently under construction, which will be 1/8 the size of the above laser, are included.

Development and prospect of unmanned aerial vehicles for agricultural production management

USDA-ARS?s Scientific Manuscript database

Unmanned aerial vehicles have been developed and applied to support agricultural production management. Compared to piloted aircrafts, an Unmanned Aerial Vehicle (UAV) can focus on small crop fields in lower flight altitude than regular airplanes to perform site-specific management with high precisi...

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.

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.

Biological Evaluation of 99mTc-HYNIC-EDDA/tricine-(Ser)-D4 Peptide for Tumor Targeting.

PubMed

Kazemi, Ziba; Zahmatkesh, Mona Haddad; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2017-08-24

D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice. This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection. This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Vogel, John P.

The goal of this project was to apply high-throughput, non-destructive phenotyping (phenomics) to collections of natural variants and induced mutants of the model grass Brachypodium distachyon and characterize a small subset of that material in detail. B. distachyon is well suited to this phenomic approach because its small size and rapid generation time allow researchers to grow many plants under carefully controlled conditions. In addition, the simple diploid genetics, high quality genome sequence and existence of numerous experimental tools available for B. distachyon allow us to rapidly identify genes affecting specific phenotypes. Our phenomic analysis revealed great diversity in biofuel-relevantmore » traits like growth rate, biomass and photosynthetic rate. This clearly demonstrated the feasibility of applying a phenomic approach to the model grass B. distachyon. We also demonstrated the utility of B. distachyon for studying mature root system, something that is virtually impossible to do with biomass crops. We showed tremendous natural variation in root architecture that can potentially be used to design crops with superior nutrient and water harvesting capability. Finally, we demonstrated the speed with which we can link specific genes to specific phenotypes by studying two mutants in detail. Importantly, in both cases, the specific biological lessons learned were grass-specific and could not have been learned from a dicot model system. Furthermore, one of the genes affects cell wall integrity and thus may be a useful target in the context of biomass crop improvement. Ultimately, all this information can be used to accelerate the creation of improved biomass crops.« less

The Small Aircraft Transportation System (SATS): Research Collaborations with the NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Tarry, Scott E.; Bowen, Brent D.; Nickerson, Jocelyn S.

2002-01-01

The aviation industry is an integral part of the world s economy. Travelers have consistently chosen aviation as their mode of transportation as it is reliable, time efficient and safe. The out- dated Hub and Spoke system, coupled with high demand, has led to delays, cancellations and gridlock. NASA is developing innovative solutions to these and other air transportation problems. This research is being conducted through partnerships with federal agencies, industry stakeholders, and academia, specifically the University of Nebraska at Omaha. Each collaborator is pursuing the NASA General Aviation Roadmap through their involvement in the expansion of the Small Aircraft Transportation System (SATS). SATS will utilize technologically advanced small aircraft to transport travelers to and from rural and isolated communities. Additionally, this system will provide a safe alternative to the hub and spoke system, giving more time to more people through high-speed mobility and increased accessibility.

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.

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.

Statistical context shapes stimulus-specific adaptation in human auditory cortex.

PubMed

Herrmann, Björn; Henry, Molly J; Fromboluti, Elisa Kim; McAuley, J Devin; Obleser, Jonas

2015-04-01

Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity. Copyright © 2015 the American Physiological Society.

Protein Scaffolding for Small Molecule Catalysts

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

Baker, David

We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematicallymore » modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.« less

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy.

PubMed

Wüstemann, Till; Haberkorn, Uwe; Babich, John; Mier, Walter

2018-05-17

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels. © 2018 Wiley Periodicals, Inc.

Role of the Small Intestine in Developmental Programming: Impact of Maternal Nutrition on the Dam and Offspring123

PubMed Central

Meyer, Allison M; Caton, Joel S

2016-01-01

Small-intestinal growth and function are critical for optimal animal growth and health and play a major role in nutrient digestion and absorption, energy and nutrient expenditure, and immunological competence. During fetal and perinatal development, the small intestine is affected by the maternal environment and nutrient intake. In ruminants, altered small-intestinal mass, villi morphology, hypertrophy, hyperplasia, vascularity, and gene expression have been observed as a result of poor gestational nutrition or intrauterine growth restriction. Although many of these data come from fetal stages, data have also demonstrated that nutrition during mid- and late gestation affects lamb small-intestinal growth, vascularity, digestive enzyme activity, and gene expression at 20 and 180 d of age as well. The small intestine is known to be a highly plastic tissue, changing with nutrient intake and physiological state even in adulthood, and the maternal small intestine adapts to pregnancy and advancing gestation. In ruminants, the growth, vascularity, and gene expression of the maternal small intestine also adapt to the nutritional plane and specific nutrient intake such as high selenium during pregnancy. These changes likely alter both pre- and postnatal nutrient delivery to offspring. More research is necessary to better understand the role of the offspring and maternal small intestines in whole-animal responses to developmental programming, but programming of this plastic tissue seems to play a dynamic role in gestational nutrition impacts on the whole animal. PMID:27180380

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D

2017-03-22

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.

Defining RNA–Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA

PubMed Central

2017-01-01

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif–small molecule interactions identified via selection. Named High Throughput Structure–Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif–small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule–RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs. PMID:28386598

Resource Use in Small Island States: Material Flows in Iceland and Trinidad and Tobago, 1961-2008.

PubMed

Krausmann, Fridolin; Richter, Regina; Eisenmenger, Nina

2014-04-01

Iceland and Trinidad and Tobago are small open, high-income island economies with very specific resource-use patterns. This article presents a material flow analysis (MFA) for the two countries covering a time period of nearly five decades. Both countries have a narrow domestic resource base, their economy being largely based on the exploitation of one or two key resources for export production. In the case of Trinidad and Tobago, the physical economy is dominated by oil and natural gas extraction and petrochemical industries, whereas Iceland's economy for centuries has been based on fisheries. More recently, abundant hydropower and geothermal heat were the basis for the establishment of large export-oriented metal processing industries, which fully depend on imported raw materials and make use of domestic renewable electricity. Both countries are highly dependent on these natural resources and vulnerable to overexploitation and price developments. We show how the export-oriented industries lead to high and growing levels of per capita material and energy use and carbon dioxide emissions resulting from large amounts of processing wastes and energy consumption in production processes. The example of small open economies with an industrial production system focused on few, but abundant, key resources and of comparatively low complexity provides interesting insights of how resource endowment paired with availability or absence of infrastructure and specific institutional arrangements drives domestic resource-use patterns. This also contributes to a better understanding and interpretation of MFA indicators, such as domestic material consumption.

Resource Use in Small Island States

PubMed Central

Krausmann, Fridolin; Richter, Regina; Eisenmenger, Nina

2014-01-01

Iceland and Trinidad and Tobago are small open, high-income island economies with very specific resource-use patterns. This article presents a material flow analysis (MFA) for the two countries covering a time period of nearly five decades. Both countries have a narrow domestic resource base, their economy being largely based on the exploitation of one or two key resources for export production. In the case of Trinidad and Tobago, the physical economy is dominated by oil and natural gas extraction and petrochemical industries, whereas Iceland's economy for centuries has been based on fisheries. More recently, abundant hydropower and geothermal heat were the basis for the establishment of large export-oriented metal processing industries, which fully depend on imported raw materials and make use of domestic renewable electricity. Both countries are highly dependent on these natural resources and vulnerable to overexploitation and price developments. We show how the export-oriented industries lead to high and growing levels of per capita material and energy use and carbon dioxide emissions resulting from large amounts of processing wastes and energy consumption in production processes. The example of small open economies with an industrial production system focused on few, but abundant, key resources and of comparatively low complexity provides interesting insights of how resource endowment paired with availability or absence of infrastructure and specific institutional arrangements drives domestic resource-use patterns. This also contributes to a better understanding and interpretation of MFA indicators, such as domestic material consumption. PMID:25505367

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Business Education: The Creative Approaches of Three Small High Schools.

ERIC Educational Resources Information Center

Rawers, Lois J.

1983-01-01

To encourage the schools to train students in broad and flexible occupational competencies rather than specific job skills, the Oregon Department of Education has promoted the cluster concept of vocational education. Of the 14 occupational clusters identified as being economically significant in Oregon, business competencies in the accounting,…

Small Learning Communities Meet School-to-Work: Whole-School Restructuring for Urban Comprehensive High Schools. Report No. 31.

ERIC Educational Resources Information Center

Legters, Nettie E.

This report describes specific reform practices schools are implementing to realize the vision set forth in the National Association of Secondary School Principals document, "Breaking Ranks," which calls for changes in curriculum, instruction, assessment, school organization, professional development, community partnerships, and…

Roles of small RNAs in plant disease resistance.

PubMed

Yang, Li; Huang, Hai

2014-10-01

The interaction between plants and pathogens represents a dynamic competition between a robust immune system and efficient infectious strategies. Plant innate immunity is composed of complex and highly regulated molecular networks, which can be triggered by the perception of either conserved or race-specific pathogenic molecular signatures. Small RNAs are emerging as versatile regulators of plant development, growth and response to biotic and abiotic stresses. They act in different tiers of plant immunity, including the pathogen-associated molecular pattern-triggered and the effector-triggered immunity. On the other hand, pathogens have evolved effector molecules to suppress or hijack the host small RNA pathways. This leads to an arms race between plants and pathogens at the level of small RNA-mediated defense. Here, we review recent advances in small RNA-mediated defense responses and discuss the challenging questions in this area. © 2014 Institute of Botany, Chinese Academy of Sciences.

Large- and small-size advantages in sneaking behaviour in the dusky frillgoby Bathygobius fuscus.

PubMed

Takegaki, Takeshi; Kaneko, Takashi; Matsumoto, Yukio

2012-04-01

Sneaking tactic, a male alternative reproductive tactic involving sperm competition, is generally adopted by small individuals because of its inconspicuousness. However, large size has an advantage when competition occurs between sneakers for fertilization of eggs. Here, we suggest that both large- and small-size advantages of sneaker males are present within the same species. Large sneaker males of the dusky frillgoby Bathygobius fuscus showed a high success rate in intruding into spawning nests because of their advantage in competition among sneaker males in keeping a suitable position to sneak, whereas small sneakers had few chances to sneak. However, small sneaker males were able to stay in the nests longer than large sneaker males when they succeeded in sneak intrusion. This suggests the possibility of an increase in their paternity. The findings of these size-specific behavioural advantages may be important in considering the evolution of size-related reproductive traits.

Large- and small-size advantages in sneaking behaviour in the dusky frillgoby Bathygobius fuscus

NASA Astrophysics Data System (ADS)

Takegaki, Takeshi; Kaneko, Takashi; Matsumoto, Yukio

2012-04-01

Sneaking tactic, a male alternative reproductive tactic involving sperm competition, is generally adopted by small individuals because of its inconspicuousness. However, large size has an advantage when competition occurs between sneakers for fertilization of eggs. Here, we suggest that both large- and small-size advantages of sneaker males are present within the same species. Large sneaker males of the dusky frillgoby Bathygobius fuscus showed a high success rate in intruding into spawning nests because of their advantage in competition among sneaker males in keeping a suitable position to sneak, whereas small sneakers had few chances to sneak. However, small sneaker males were able to stay in the nests longer than large sneaker males when they succeeded in sneak intrusion. This suggests the possibility of an increase in their paternity. The findings of these size-specific behavioural advantages may be important in considering the evolution of size-related reproductive traits.

High-definition vs. standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.

PubMed

Longcroft-Wheaton, G; Brown, J; Cowlishaw, D; Higgins, B; Bhandari, P

2012-10-01

The resolution of endoscopes has increased in recent years. Modern Fujinon colonoscopes have a charge-coupled device (CCD) pixel density of 650,000 pixels compared with the 410,000 pixel CCD in standard-definition scopes. Acquiring high-definition scopes represents a significant capital investment and their clinical value remains uncertain. The aim of the current study was to investigate the impact of high-definition endoscopes on the in vivo histology prediction of colonic polyps. Colonoscopy procedures were performed using Fujinon colonoscopes and EPX-4400 processor. Procedures were randomized to be performed using either a standard-definition EC-530 colonoscope or high-definition EC-530 and EC-590 colonoscopes. Polyps of <10 mm were assessed using both white light imaging (WLI) and flexible spectral imaging color enhancement (FICE), and the predicted diagnosis was recorded. Polyps were removed and sent for histological analysis by a pathologist who was blinded to the endoscopic diagnosis. The predicted diagnosis was compared with the histology to calculate the accuracy, sensitivity, and specificity of in vivo assessment using either standard or high-definition scopes. A total of 293 polyps of <10 mm were examined–150 polyps using the standard-definition colonoscope and 143 polyps using high-definition colonoscopes. There was no difference in sensitivity, specificity or accuracy between the two scopes when WLI was used (standard vs. high: accuracy 70% [95% CI 62–77] vs. 73% [95% CI 65–80]; P=0.61). When FICE was used, high-definition colonoscopes showed a sensitivity of 93% compared with 83% for standard-definition colonoscopes (P=0.048); specificity was 81% and 82%, respectively. There was no difference between high- and standard-definition colonoscopes when white light was used, but FICE significantly improved the in vivo diagnosis of small polyps when high-definition scopes were used compared with standard definition.

Portable SERS sensor for malachite green and other small dye molecules

NASA Astrophysics Data System (ADS)

Qiu, Suyan; Zhao, Fusheng; Li, Jingting; Shih, Wei-Chuan

2017-02-01

Sensitive detection of specific chemicals on site can be extremely powerful in many fields. Owing to its molecular fingerprinting capability, surface-enhanced Raman scattering has been one of the technological contenders. In this paper, we describe the novel use of DNA topological nanostructure on nanoporous gold nanoparticle (NPG-NP) array chip for chemical sensing. NPG-NP features large surface area and high-density plasmonic field enhancement known as "hotspots". Hence, NPG-NP array chip has found many applications in nanoplasmonic sensor development. This technique can provide novel label-free molecular sensing capability and enables high sensitivity and specificity detection using a portable Raman spectrometer.

Recent Progress in Aptamer-Based Functional Probes for Bioanalysis and Biomedicine.

PubMed

Zhang, Huimin; Zhou, Leiji; Zhu, Zhi; Yang, Chaoyong

2016-07-11

Nucleic acid aptamers are short synthetic DNA or RNA sequences that can bind to a wide range of targets with high affinity and specificity. In recent years, aptamers have attracted increasing research interest due to their unique features of high binding affinity and specificity, small size, excellent chemical stability, easy chemical synthesis, facile modification, and minimal immunogenicity. These properties make aptamers ideal recognition ligands for bioanalysis, disease diagnosis, and cancer therapy. This review highlights the recent progress in aptamer selection and the latest applications of aptamer-based functional probes in the fields of bioanalysis and biomedicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Demonstrations of Deployable Systems for Robotic Precursor Missions

NASA Technical Reports Server (NTRS)

Dervan, J.; Johnson, L.; Lockett, T.; Carr, J.; Boyd, D.

2017-01-01

NASA is developing thin-film based, deployable propulsion, power, and communication systems for small spacecraft that serve as enabling technologies for exploration of the solar system. By leveraging recent advancements in thin films, photovoltaics, deployment systems, and miniaturized electronics, new mission-level capabilities will be demonstrated aboard small spacecraft enabling a new generation of frequent, inexpensive, and highly capable robotic precursor missions with goals extensible to future human exploration. Specifically, thin-film technologies are allowing the development and use of solar sails for propulsion, small, lightweight photovoltaics for power, and omnidirectional antennas for communication as demonstrated by recent advances on the Near Earth Asteroid (NEA) Scout and Lightweight Integrated Solar Array and anTenna (LISA-T) projects.

Weak localization of electromagnetic waves and opposition phenomena exhibited by high-albedo atmosphereless solar system objects.

PubMed

Mishchenko, Michael I; Rosenbush, Vera K; Kiselev, Nikolai N

2006-06-20

The totality of new and previous optical observations of a class of high-albedo solar system objects at small phase angles reveals a unique combination of extremely narrow brightness and polarization features centered at exactly the opposition. The specific morphological parameters of these features provide an almost unequivocal evidence that they are caused by the renowned effect of coherent backscattering.

Real-Time Polymerase Chain Reaction for Detection of Schistosoma DNA in Small-Volume Urine Samples Reflects Focal Distribution of Urogenital Schistosomiasis in Primary School Girls in KwaZulu Natal, South Africa

PubMed Central

Pillay, Pavitra; Taylor, Myra; Zulu, Siphosenkosi G.; Gundersen, Svein G.; Verweij, Jaco J.; Hoekstra, Pytsje; Brienen, Eric A. T.; Kleppa, Elisabeth; Kjetland, Eyrun F.; van Lieshout, Lisette

2014-01-01

Schistosoma haematobium eggs and Schistosoma DNA levels were measured in urine samples from 708 girls recruited from 18 randomly sampled primary schools in South Africa. Microscopic analysis of two 10-mL urine subsamples collected on three consecutive days confirmed high day-to-day variation; 103 (14.5%) girls had positive results at all six examinations, and at least one positive sample was seen in 225 (31.8%) girls. Schistosoma-specific DNA, which was measured in a 200-μL urine subsample by using real-time polymerase chain reaction, was detected in 180 (25.4%) cases, and levels of DNA corresponded significantly with average urine egg excretion. In concordance with microscopic results, polymerase chain reaction results were significantly associated with history of gynecologic symptoms and confirmed highly focal distribution of urogenital schistosomiasis. Parasite-specific DNA detection has a sensitivity comparable to single urine microscopy and could be used as a standardized high-throughput procedure to assess distribution of urogenital schistosomiasis in relatively large study populations by using small sample volumes. PMID:24470560

Galaxy And Mass Assembly (GAMA): the connection between metals, specific SFR and H I gas in galaxies: the Z-SSFR relation

NASA Astrophysics Data System (ADS)

Lara-López, M. A.; Hopkins, A. M.; López-Sánchez, A. R.; Brough, S.; Colless, M.; Bland-Hawthorn, J.; Driver, S.; Foster, C.; Liske, J.; Loveday, J.; Robotham, A. S. G.; Sharp, R. G.; Steele, O.; Taylor, E. N.

2013-06-01

We study the interplay between gas phase metallicity (Z), specific star formation rate (SSFR) and neutral hydrogen gas (H I) for galaxies of different stellar masses. Our study uses spectroscopic data from Galaxy and Mass Assembly and Sloan Digital Sky Survey (SDSS) star-forming galaxies, as well as H I detection from the Arecibo Legacy Fast Arecibo L-band Feed Array (ALFALFA) and Galex Arecibo SDSS Survey (GASS) public catalogues. We present a model based on the Z-SSFR relation that shows that at a given stellar mass, depending on the amount of gas, galaxies will follow opposite behaviours. Low-mass galaxies with a large amount of gas will show high SSFR and low metallicities, while low-mass galaxies with small amounts of gas will show lower SSFR and high metallicities. In contrast, massive galaxies with a large amount of gas will show moderate SSFR and high metallicities, while massive galaxies with small amounts of gas will show low SSFR and low metallicities. Using ALFALFA and GASS counterparts, we find that the amount of gas is related to those drastic differences in Z and SSFR for galaxies of a similar stellar mass.

Comparison of super-high-energy-propulsion-systems based on metallic hydrogen propellant for ES to LEO space transportation

NASA Technical Reports Server (NTRS)

Thierschmann, M.

1990-01-01

The application is studied of metallic H2 as a rocket propellant, which contains a specific energy of about 52 kcal/g in theory yielding a maximum specific impulse of 1700 s. With the convincing advantage of having a density 14 times that of conventional liquid H2/liquid O2 propellants, metallic H2 could satisfy the demands of advanced launch vehicle propulsion for the next millennium. Provided that there is an atomic metallic state of H2, and that this state is metastable at ambient pressure, which still is not proven, the results are given of the study of some important areas, which concern the production of metallic H2, the combustion, chamber cooling, and storage. The results show that the use of metallic H2 as rocket propellant could lead to revolutionary changes in space vehicle philosophy toward small size, small weight, and high performance single stage to orbit systems. The use of high metallic H2 mass fractions results in a dramatic reduction of required propellant volume, while gas temperatures in the combustion chamber exceed 5000 K. Furthermore, it follows, that H2 (liquid or slush) is the most favorable candidate as working fluid. Jet generated noise due to high exhaust velocities could be a problem.

Diversity of human copy number variation and multicopy genes.

PubMed

Sudmant, Peter H; Kitzman, Jacob O; Antonacci, Francesca; Alkan, Can; Malig, Maika; Tsalenko, Anya; Sampas, Nick; Bruhn, Laurakay; Shendure, Jay; Eichler, Evan E

2010-10-29

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

Multi-Plane High Speed Balancing Techniques and the Use of a High Specific Stiffness Ti-Borsic Material for Vibration Control.

DTIC Science & Technology

1980-02-01

maneuver conditions, and transmit the net axial thrust force between the turbine and fan sections due to pressure and aero dynamic gas loads . 49 Lm...stiffness composite material shaft. Both~~ balancing demonstration and the composite shaft design ad as their objective the management of small turbofan ...CONFIGURATIONS 99 LIST OF ILLUSTRATIONS Figure Title Page 1 High Speed Balancing Program Schedule 4 2 Teledyne CAE Model 471-11DX Turbofan Engine

The Rationale behind Small Food Store Interventions in Low-Income Urban Neighborhoods: Insights from New Orleans1–3

PubMed Central

Bodor, J. Nicholas; Ulmer, Vanessa M.; Futrell Dunaway, Lauren; Farley, Thomas A.; Rose, Donald

2010-01-01

Environmental approaches to the obesity problem in the US have garnered favor due to growing evidence that changes to the environment are at the root of the epidemic. Low-income urban neighborhoods, where obesity rates are disproportionately high, typically lack supermarkets yet have a high density of small food stores. This may increase the risk for unhealthy diets and obesity for neighborhood residents, because small stores carry mostly energy-dense foods and few fruits and vegetables. This paper pulls together various studies and pilot work conducted in New Orleans to explore the rationale behind small store interventions. Many low-income residents in New Orleans live within walking distance of small food stores and shop at them frequently. Marketing research has documented that changes to in-store shelf space and displays of specific foods affect the sales of these foods. Initiatives in New Orleans and elsewhere have demonstrated some success with improving healthy food availability in small stores, and an intercept survey of customers at small stores suggests that customers would purchase more fruits and vegetables if available. Efforts to encourage small store operators to offer a healthier mix of foods may, in the end, depend on the profitability of such changes. Evidence from a typical small store in New Orleans indicates that a greater percentage of gross profits come from snack foods and beverages than from fruits and vegetables. More research is needed to better understand the financial operations of small food stores and whether altering the mix of foods is economically feasible. PMID:20410086

The rationale behind small food store interventions in low-income urban neighborhoods: insights from New Orleans.

PubMed

Bodor, J Nicholas; Ulmer, Vanessa M; Dunaway, Lauren Futrell; Farley, Thomas A; Rose, Donald

2010-06-01

Environmental approaches to the obesity problem in the US have garnered favor due to growing evidence that changes to the environment are at the root of the epidemic. Low-income urban neighborhoods, where obesity rates are disproportionately high, typically lack supermarkets yet have a high density of small food stores. This may increase the risk for unhealthy diets and obesity for neighborhood residents, because small stores carry mostly energy-dense foods and few fruits and vegetables. This paper pulls together various studies and pilot work conducted in New Orleans to explore the rationale behind small store interventions. Many low-income residents in New Orleans live within walking distance of small food stores and shop at them frequently. Marketing research has documented that changes to in-store shelf space and displays of specific foods affect the sales of these foods. Initiatives in New Orleans and elsewhere have demonstrated some success with improving healthy food availability in small stores, and an intercept survey of customers at small stores suggests that customers would purchase more fruits and vegetables if available. Efforts to encourage small store operators to offer a healthier mix of foods may, in the end, depend on the profitability of such changes. Evidence from a typical small store in New Orleans indicates that a greater percentage of gross profits come from snack foods and beverages than from fruits and vegetables. More research is needed to better understand the financial operations of small food stores and whether altering the mix of foods is economically feasible.

Toward Generalization of Iterative Small Molecule Synthesis

PubMed Central

Lehmann, Jonathan W.; Blair, Daniel J.; Burke, Martin D.

2018-01-01

Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach. PMID:29696152

Small RNA profiling in two Brassica napus cultivars identifies microRNAs with oil production- and development-correlated expression and new small RNA classes.

PubMed

Zhao, Ying-Tao; Wang, Meng; Fu, San-Xiong; Yang, Wei-Cai; Qi, Cun-Kou; Wang, Xiu-Jie

2012-02-01

MicroRNAs (miRNAs) and small interfering RNAs are important regulators of plant development and seed formation, yet their population and abundance in the oil crop Brassica napus are still not well understood, especially at different developmental stages and among cultivars with varied seed oil contents. Here, we systematically analyzed the small RNA expression profiles of Brassica napus seeds at early embryonic developmental stages in high-oil-content and low-oil-content B. napus cultivars, both cultured in two environments. A total of 50 conserved miRNAs and 9 new miRNAs were identified, together with some new miRNA targets. Expression analysis revealed some miRNAs with varied expression levels in different seed oil content cultivars or at different embryonic developmental stages. A large number of 23-nucleotide small RNAs with specific nucleotide composition preferences were also identified, which may present new classes of functional small RNAs.

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.

Insights from Smart Meters: Ramp-Up, Dependability, and Short-Term Persistence of Savings from Home Energy Reports

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

Todd, A.; Perry, M.; Smith, B.

2015-04-01

Smart meters, smart thermostats, and other new technologies provide previously unavailable high-frequency and location-specific energy usage data. Many utilities are now able to capture real-time, customer-specific hourly interval usage data for a large proportion of their residential and small commercial customers. These vast, constantly growing streams of rich data (or big data) have the potential to provide novel insights into key policy questions about how people make energy decisions.

Optimization of the performance of the polymerase chain reaction in silicon-based microstructures.

PubMed Central

Taylor, T B; Winn-Deen, E S; Picozza, E; Woudenberg, T M; Albin, M

1997-01-01

We have demonstrated the ability to perform real-time homogeneous, sequence specific detection of PCR products in silicon microstructures. Optimal design/ processing result in equivalent performance (yield and specificity) for high surface-to-volume silicon structures as compared to larger volume reactions in polypropylene tubes. Amplifications in volumes as small as 0.5 microl and thermal cycling times reduced as much as 5-fold from that of conventional systems have been demonstrated for the microstructures. PMID:9224619

Effect of wrinkles on the surface area of graphene: toward the design of nanoelectronics.

PubMed

Qin, Zhao; Taylor, Michael; Hwang, Mary; Bertoldi, Katia; Buehler, Markus J

2014-11-12

Graphene has attracted intense attention to the use in extreme applications. However, its small thickness facilitates wrinkle formation, and it is not clear how such structural change affects its area-specific capacitance. Herein, we combine molecular dynamics and continuum mechanics-based simulations to study the changes in surface area induced by wrinkles. We find that the high specific surface area of graphene can only be affected up to 2% regardless of loading conditions, geometry, and defects.

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quantifying domain-ligand affinities and specificities by high-throughput holdup assay

PubMed Central

Vincentelli, Renaud; Luck, Katja; Poirson, Juline; Polanowska, Jolanta; Abdat, Julie; Blémont, Marilyne; Turchetto, Jeremy; Iv, François; Ricquier, Kevin; Straub, Marie-Laure; Forster, Anne; Cassonnet, Patricia; Borg, Jean-Paul; Jacob, Yves; Masson, Murielle; Nominé, Yves; Reboul, Jérôme; Wolff, Nicolas; Charbonnier, Sebastian; Travé, Gilles

2015-01-01

Many protein interactions are mediated by small linear motifs interacting specifically with defined families of globular domains. Quantifying the specificity of a motif requires measuring and comparing its binding affinities to all its putative target domains. To this aim, we developed the high-throughput holdup assay, a chromatographic approach that can measure up to a thousand domain-motif equilibrium binding affinities per day. Extracts of overexpressed domains are incubated with peptide-coated resins and subjected to filtration. Binding affinities are deduced from microfluidic capillary electrophoresis of flow-throughs. After benchmarking the approach on 210 PDZ-peptide pairs with known affinities, we determined the affinities of two viral PDZ-binding motifs derived from Human Papillomavirus E6 oncoproteins for 209 PDZ domains covering 79% of the human PDZome. We obtained exquisite sequence-dependent binding profiles, describing quantitatively the PDZome recognition specificity of each motif. This approach, applicable to many categories of domain-ligand interactions, has a wide potential for quantifying the specificities of interactomes. PMID:26053890

Standardized methods for the production of high specific-activity zirconium-89

PubMed Central

Holland, Jason P.; Sheh, Yiauchung; Lewis, Jason S.

2009-01-01

Zirconium-89 is an attractive metallo-radionuclide for use in immunoPET due to the favorable decay characteristics. Standardized methods for the routine production and isolation of high purity and high specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52 ± 0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available 89Y-foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [89Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of 89Zr was found to be in the range 5.28 – 13.43 mCi/μg (470 – 1195 Ci/mmol) of zirconium. New methods for the facile production of [89Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min. at room temperature and in vitro stability measurements confirmed that [89Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal PET imaging studies have demonstrated that free 89Zr(IV) ions administered as [89Zr]Zr-chloride accumulate in the liver whilst [89Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immunoPET imaging of 89Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in both basic science and clinical investigations. PMID:19720285

The Unknown Oldowan: ~1.7-Million-Year-Old Standardized Obsidian Small Tools from Garba IV, Melka Kunture, Ethiopia

PubMed Central

2015-01-01

The Oldowan Industrial Complex has long been thought to have been static, with limited internal variability, embracing techno-complexes essentially focused on small-to-medium flake production. The flakes were rarely modified by retouch to produce small tools, which do not show any standardized pattern. Usually, the manufacture of small standardized tools has been interpreted as a more complex behavior emerging with the Acheulean technology. Here we report on the ~1.7 Ma Oldowan assemblages from Garba IVE-F at Melka Kunture in the Ethiopian highland. This industry is structured by technical criteria shared by the other East African Oldowan assemblages. However, there is also evidence of a specific technical process never recorded before, i.e. the systematic production of standardized small pointed tools strictly linked to the obsidian exploitation. Standardization and raw material selection in the manufacture of small tools disappear at Melka Kunture during the Lower Pleistocene Acheulean. This proves that 1) the emergence of a certain degree of standardization in tool-kits does not reflect in itself a major step in cultural evolution; and that 2) the Oldowan knappers, when driven by functional needs and supported by a highly suitable raw material, were occasionally able to develop specific technical solutions. The small tool production at ~1.7 Ma, at a time when the Acheulean was already emerging elsewhere in East Africa, adds to the growing amount of evidence of Oldowan techno-economic variability and flexibility, further challenging the view that early stone knapping was static over hundreds of thousands of years. PMID:26690569

The Unknown Oldowan: ~1.7-Million-Year-Old Standardized Obsidian Small Tools from Garba IV, Melka Kunture, Ethiopia.

PubMed

Gallotti, Rosalia; Mussi, Margherita

2015-01-01

The Oldowan Industrial Complex has long been thought to have been static, with limited internal variability, embracing techno-complexes essentially focused on small-to-medium flake production. The flakes were rarely modified by retouch to produce small tools, which do not show any standardized pattern. Usually, the manufacture of small standardized tools has been interpreted as a more complex behavior emerging with the Acheulean technology. Here we report on the ~1.7 Ma Oldowan assemblages from Garba IVE-F at Melka Kunture in the Ethiopian highland. This industry is structured by technical criteria shared by the other East African Oldowan assemblages. However, there is also evidence of a specific technical process never recorded before, i.e. the systematic production of standardized small pointed tools strictly linked to the obsidian exploitation. Standardization and raw material selection in the manufacture of small tools disappear at Melka Kunture during the Lower Pleistocene Acheulean. This proves that 1) the emergence of a certain degree of standardization in tool-kits does not reflect in itself a major step in cultural evolution; and that 2) the Oldowan knappers, when driven by functional needs and supported by a highly suitable raw material, were occasionally able to develop specific technical solutions. The small tool production at ~1.7 Ma, at a time when the Acheulean was already emerging elsewhere in East Africa, adds to the growing amount of evidence of Oldowan techno-economic variability and flexibility, further challenging the view that early stone knapping was static over hundreds of thousands of years.

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

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

Kim, Sun Young; Song, Kyung-A; Samsung Biomedical Research Institute

Highlights: Black-Right-Pointing-Pointer Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. Black-Right-Pointing-Pointer A small molecule and a peptide as EBNA1 dimerization inhibitors identified. Black-Right-Pointing-Pointer Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. Black-Right-Pointing-Pointer Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation.more » In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-J{kappa} binding to the J{kappa} site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with EBNA1 in vitro, and repressed EBNA1-dependent transcription in vivo. Collectively, this study describes two novel inhibitors of EBNA1 dimerization. This study demonstrates that EBNA1 homodimerization can be effectively targeted by a small molecule or peptide.« less

High-throughput spectral and lifetime-based FRET screening in living cells to identify small-molecule effectors of SERCA

PubMed Central

Schaaf, Tory M.; Peterson, Kurt C.; Grant, Benjamin D.; Bawaskar, Prachi; Yuen, Samantha; Li, Ji; Muretta, Joseph M.; Gillispie, Gregory D.; Thomas, David D.

2017-01-01

A robust high-throughput screening (HTS) strategy has been developed to discover small-molecule effectors targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA), based on a fluorescence microplate reader that records both the nanosecond decay waveform (lifetime mode) and the complete emission spectrum (spectral mode), with high precision and speed. This spectral unmixing plate reader (SUPR) was used to screen libraries of small molecules with a fluorescence resonance energy transfer (FRET) biosensor expressed in living cells. Ligand binding was detected by FRET associated with structural rearrangements of green (GFP, donor) and red (RFP, acceptor) fluorescent proteins fused to the cardiac-specific SERCA2a isoform. The results demonstrate accurate quantitation of FRET along with high precision of hit identification. Fluorescence lifetime analysis resolved SERCA’s distinct structural states, providing a method to classify small-molecule chemotypes on the basis of their structural effect on the target. The spectral analysis was also applied to flag interference by fluorescent compounds. FRET hits were further evaluated for functional effects on SERCA’s ATPase activity via both a coupled-enzyme assay and a FRET-based calcium sensor. Concentration-response curves indicated excellent correlation between FRET and function. These complementary spectral and lifetime FRET detection methods offer an attractive combination of precision, speed, and resolution for HTS. PMID:27899691

Quantitative Comparison of Minimum Inductance and Minimum Power Algorithms for the Design of Shim Coils for Small Animal Imaging

PubMed Central

HUDSON, PARISA; HUDSON, STEPHEN D.; HANDLER, WILLIAM B.; SCHOLL, TIMOTHY J.; CHRONIK, BLAINE A.

2010-01-01

High-performance shim coils are required for high-field magnetic resonance imaging and spectroscopy. Complete sets of high-power and high-performance shim coils were designed using two different methods: the minimum inductance and the minimum power target field methods. A quantitative comparison of shim performance in terms of merit of inductance (ML) and merit of resistance (MR) was made for shim coils designed using the minimum inductance and the minimum power design algorithms. In each design case, the difference in ML and the difference in MR given by the two design methods was <15%. Comparison of wire patterns obtained using the two design algorithms show that minimum inductance designs tend to feature oscillations within the current density; while minimum power designs tend to feature less rapidly varying current densities and lower power dissipation. Overall, the differences in coil performance obtained by the two methods are relatively small. For the specific case of shim systems customized for small animal imaging, the reduced power dissipation obtained when using the minimum power method is judged to be more significant than the improvements in switching speed obtained from the minimum inductance method. PMID:20411157

Development of an oligonucleotide probe for Aureobasidium pullulans based on the small-subunit rRNA gene.

PubMed Central

Li, S; Cullen, D; Hjort, M; Spear, R; Andrews, J H

1996-01-01

Aureobasidium pullulans, a cosmopolitan yeast-like fungus, colonizes leaf surfaces and has potential as a biocontrol agent of pathogens. To assess the feasibility of rRNA as a target for A. pullulans-specific oligonucleotide probes, we compared the nucleotide sequences of the small-subunit rRNA (18S) genes of 12 geographically diverse A. pullulans strains. Extreme sequence conservation was observed. The consensus A. pullulans sequence was compared with other fungal sequences to identify potential probes. A 21-mer probe which hybridized to the 12 A. pullulans strains but not to 98 other fungi, including 82 isolates from the phylloplane, was identified. A 17-mer highly specific for Cladosporium herbarum was also identified. These probes have potential in monitoring and quantifying fungi in leaf surface and other microbial communities. PMID:8633850

Proteoform-specific protein binding of small molecules in complex matrices

USDA-ARS?s Scientific Manuscript database

Characterizing the specific binding between protein targets and small molecules is critically important for drug discovery. Conventional assays require isolation and purification of small molecules from complex matrices through multistep chromatographic fractionation, which may alter their original ...

Transition metal mediated transformations of small molecules

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

Sen, Ayusman

Catalysis at metal centers is of great scientific, as well as practical, importance because of the high efficiency, high specificity, and low energy demands often associated with such systems. The two major themes of our research are (a) the design of metal-based systems for the synthesis of novel classes of polymers and (b) the identification of new metal-catalyzed systems for the conversion of biomass to fuels and chemicals, and related “green” chemical processes.

VirusDetect: An automated pipeline for efficient virus discovery using deep sequencing of small RNAs

USDA-ARS?s Scientific Manuscript database

Accurate detection of viruses in plants and animals is critical for agriculture production and human health. Deep sequencing and assembly of virus-derived siRNAs has proven to be a highly efficient approach for virus discovery. However, to date no computational tools specifically designed for both k...

Transformative Parents: Facilitating Transformative Experiences and Interest with a Parent Involvement Intervention

ERIC Educational Resources Information Center

Heddy, Benjamin C.; Sinatra, Gale M.

2017-01-01

This study reports the implementation of a parental involvement intervention coupled with small group discussions aimed at facilitating transformative experiences (TEs) in science courses (biology and chemistry) in an all-girls middle and high school. Specifically, the goal was to generate parental involvement, TE, and interest. Analyses showed…

Cognitive Behavioral Treatment for Recurrent Binge Eating in Adolescent Girls: A Pilot Trial

ERIC Educational Resources Information Center

DeBar, Lynn L.; Wilson, G. Terence; Yarborough, Bobbi Jo; Burns, Beryl; Oyler, Barbara; Hildebrandt, Tom; Clarke, Gregory N.; Dickerson, John; Striegel, Ruth H.

2013-01-01

There is a need for treatment interventions to address the high prevalence of disordered eating throughout adolescence and early adulthood. We developed an adolescent-specific manualized CBT protocol to treat female adolescents with recurrent binge eating and tested its efficacy in a small, pilot randomized controlled trial. We present lessons…

Two methods for increased specificity and sensitivity in loop-mediated isothermal amplification

USDA-ARS?s Scientific Manuscript database

The technique of loop-mediated isothermal amplification (LAMP) utilizes 4 (or 6) primers targeting 6 (or 8) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used leads to an in...

A Cell Based Assay To Identify Neuroprotective Molecules for the Treatment of Amyotrophic Lateral Sclerosis

DTIC Science & Technology

This project on ALS stems from our findings that rodent astrocytes expressing mutated SOD1 kill specifically spinal primary and embryonic mouse stem...identifying the toxic factor, the topic of this project is to search for neuroprotective small molecules by using ourcell-based model of ALS for high

Purple Pelisse: a specialty fingerling potato with purple skin and purple flesh

USDA-ARS?s Scientific Manuscript database

Purple Pelisse is a specialty fingerling potato with purple skin and dark purple flesh. It has medium maturity and sets a large number of smooth, small, fingerling-shaped tubers. The tubers have medium specific gravity and high levels of antioxidants. This potato variety is mainly intended for the f...

Adopted Children: A Question of Identity

ERIC Educational Resources Information Center

Mahmood, Samina; Visser, John

2015-01-01

This article draws upon a study completed in a specific school in Bangalore where most children enter at the pre-school level and continue till high school. While the particular children in the study constitute a small number--four--it was observed that questions of identity mainly arose when they started questioning the circumstances behind their…

Small high cooling power space cooler

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

Nguyen, T. V.; Raab, J.; Durand, D.

The small High Efficiency pulse tube Cooler (HEC) cooler, that has been produced and flown on a number of space infrared instruments, was originally designed to provide cooling of 10 W @ 95 K. It achieved its goal with >50% margin when limited by the 180 W output ac power of its flight electronics. It has also been produced in 2 stage configurations, typically for simultaneously cooling of focal planes to temperatures as low as 35 K and optics at higher temperatures. The need for even higher cooling power in such a low mass cryocooler is motivated by the adventmore » of large focal plane arrays. With the current availability at NGAS of much larger power cryocooler flight electronics, reliable long term operation in space with much larger cooling powers is now possible with the flight proven 4 kg HEC mechanical cooler. Even though the single stage cooler design can be re-qualified for those larger input powers without design change, we redesigned both the linear and coaxial version passive pulse tube cold heads to re-optimize them for high power cooling at temperatures above 130 K while rejecting heat to 300 K. Small changes to the regenerator packing, the re-optimization of the tuned inertance and no change to the compressor resulted in the increased performance at 150 K. The cooler operating at 290 W input power achieves 35 W@ 150 K corresponding to a specific cooling power at 150 K of 8.25 W/W and a very high specific power of 72.5 W/Kg. At these powers the cooler still maintains large stroke, thermal and current margins. In this paper we will present the measured data and the changes to this flight proven cooler that were made to achieve this increased performance.« less

Single-cell RNA-sequencing reveals a distinct population of proglucagon-expressing cells specific to the mouse upper small intestine.

PubMed

Glass, Leslie L; Calero-Nieto, Fernando J; Jawaid, Wajid; Larraufie, Pierre; Kay, Richard G; Göttgens, Berthold; Reimann, Frank; Gribble, Fiona M

2017-10-01

To identify sub-populations of intestinal preproglucagon-expressing (PPG) cells producing Glucagon-like Peptide-1, and their associated expression profiles of sensory receptors, thereby enabling the discovery of therapeutic strategies that target these cell populations for the treatment of diabetes and obesity. We performed single cell RNA sequencing of PPG-cells purified by flow cytometry from the upper small intestine of 3 GLU-Venus mice. Cells from 2 mice were sequenced at low depth, and from the third mouse at high depth. High quality sequencing data from 234 PPG-cells were used to identify clusters by tSNE analysis. qPCR was performed to compare the longitudinal and crypt/villus locations of cluster-specific genes. Immunofluorescence and mass spectrometry were used to confirm protein expression. PPG-cells formed 3 major clusters: a group with typical characteristics of classical L-cells, including high expression of Gcg and Pyy (comprising 51% of all PPG-cells); a cell type overlapping with Gip-expressing K-cells (14%); and a unique cluster expressing Tph1 and Pzp that was predominantly located in proximal small intestine villi and co-produced 5-HT (35%). Expression of G-protein coupled receptors differed between clusters, suggesting the cell types are differentially regulated and would be differentially targetable. Our findings support the emerging concept that many enteroendocrine cell populations are highly overlapping, with individual cells producing a range of peptides previously assigned to distinct cell types. Different receptor expression profiles across the clusters highlight potential drug targets to increase gut hormone secretion for the treatment of diabetes and obesity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Design of the EO-1 Pulsed Plasma Thruster Attitude Control Experiment

NASA Technical Reports Server (NTRS)

Zakrzwski, Charles; Sanneman, Paul; Hunt, Teresa; Blackman, Kathie; Bauer, Frank H. (Technical Monitor)

2001-01-01

The Pulsed Plasma Thruster (PPT) Experiment on the Earth Observing 1 (EO-1) spacecraft has been designed to demonstrate the capability of a new generation PPT to perform spacecraft attitude control. The PPT is a small, self-contained pulsed electromagnetic Propulsion system capable of delivering high specific impulse (900-1200 s), very small impulse bits (10-1000 micro N-s) at low average power (less than 1 to 100 W). EO-1 has a single PPT that can produce torque in either the positive or negative pitch direction. For the PPT in-flight experiment, the pitch reaction wheel will be replaced by the PPT during nominal EO-1 nadir pointing. A PPT specific proportional-integral-derivative (PID) control algorithm was developed for the experiment. High fidelity simulations of the spacecraft attitude control capability using the PPT were conducted. The simulations, which showed PPT control performance within acceptable mission limits, will be used as the benchmark for on-orbit performance. The flight validation will demonstrate the ability of the PPT to provide precision pointing resolution. response and stability as an attitude control actuator.

Geritalk: communication skills training for geriatric and palliative medicine fellows.

PubMed

Kelley, Amy S; Back, Anthony L; Arnold, Robert M; Goldberg, Gabrielle R; Lim, Betty B; Litrivis, Evgenia; Smith, Cardinale B; O'Neill, Lynn B

2012-02-01

Expert communication is essential to high-quality care for older patients with serious illness. Although the importance of communication skills is widely recognized, formal curricula for teaching communication skills to geriatric and palliative medicine fellows is often inadequate or unavailable. The current study drew upon the educational principles and format of an evidence-based, interactive teaching method to develop an intensive communication skills training course designed specifically to address the common communication challenges that geriatric and palliative medicine fellows face. The 2-day retreat, held away from the hospital environment, included large-group overview presentations, small-group communication skills practice, and development of future skills practice commitment. Faculty received in-depth training in small-group facilitation techniques before the course. Geriatric and palliative medicine fellows were recruited to participate in the course and 100% (n = 18) enrolled. Overall satisfaction with the course was very high (mean 4.8 on a 5-point scale). After the course, fellows reported an increase in self-assessed preparedness for specific communication challenges (mean increase 1.4 on 5-point scale, P < .001). Two months after the course, fellows reported a high level of sustained skills practice (mean 4.3 on 5-point scale). In sum, the intensive communication skills program, customized for the specific needs of geriatric and palliative medicine fellows, improved fellows' self-assessed preparedness for challenging communication tasks and provided a model for ongoing deliberate practice of communication skills. © 2012, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

Geritalk: Communication Skills Training for Geriatrics and Palliative Medicine Fellows

PubMed Central

Kelley, Amy S.; Back, Anthony L.; Arnold, Robert M.; Goldberg, Gabrielle R.; Lim, Betty B.; Litrivis, Evgenia; Smith, Cardinale B.; O’Neill, Lynn B.

2011-01-01

Expert communication is essential to high quality care for older patients with serious illness. While the importance of communication skills is widely recognized, formal curricula for teaching communication skills to geriatrics and palliative medicine fellows is often inadequate or unavailable. We drew upon the educational principles and format of an evidence-based, interactive teaching method, to develop an intensive communication skills training course designed specifically to address the common communication challenges faced by geriatrics and palliative medicine fellows. The 2-day retreat, held away from the hospital environment, included large-group overview presentations, small-group communication skills practice, and development of future skills practice commitment. Faculty received in-depth training in small-group facilitation techniques prior to the course. Geriatrics and palliative medicine fellows were recruited to participate in the course and 100% (n=18) enrolled. Overall satisfaction with the course was very high (mean 4.8 on 5-point scale). Compared to before the course, fellows reported an increase in self-assessed preparedness for specific communication challenges (mean increase 1.4 on 5-point scale, p<0.01). Two months after the course, fellows reported a high level of sustained skills practice (mean 4.3 on 5-point scale). In sum, the intensive communication skills program, tailored to the specific needs of geriatrics and palliative medicine fellows, improved fellows’ self-assessed preparedness for challenging communication tasks and provided a model for ongoing deliberate practice of communication skills. PMID:22211768

Favorable effect of in-situ generated platinum in the membrane on fuel cell membrane durability

NASA Astrophysics Data System (ADS)

Macauley, Natalia; Wong, Ka Hung; Watson, Mark; Kjeang, Erik

2015-12-01

The overall lifetime of polymer electrolyte fuel cells is often determined by the membrane durability. Platinum, which may dissolve from the catalyst layers during fuel cell operation and deposit in the membrane, has been shown to have both positive and negative effects on membrane stability. In the present work, we analyze what specific conditions are required in order to reach a favorable, membrane stabilizing effect with the controlled use of platinum in the membrane. Using accelerated membrane durability testing, field operated membrane samples, and electron microscopy, we demonstrate that a high platinum concentration with specific particle shapes and sizes is essential for enhanced membrane stability. Specifically, star shaped and dendritic particles with high particle density and high surface area are shown to be preferable. These particles contain high levels of Pt(111) and are expected to have high catalytic activity toward peroxide quenching and crossover gas consumption, thereby mitigating chemical membrane degradation. On the other hand, small, dispersed cubic particles are found to have no effect or the opposite, negative effect on membrane stability.

Geothermal Money Book [Geothermal Outreach and Project Financing

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

Elizabeth Battocletti

2004-02-01

Small business lending is big business and growing. Loans under $1 million totaled $460 billion in June 2001, up $23 billion from 2000. The number of loans under $100,000 continued to grow at a rapid rate, growing by 10.1%. The dollar value of loans under $100,000 increased 4.4%; those of $100,000-$250,000 by 4.1%; and those between $250,000 and $1 million by 6.4%. But getting a loan can be difficult if a business owner does not know how to find small business-friendly lenders, how to best approach them, and the specific criteria they use to evaluate a loan application. This ismore » where the Geothermal Money Book comes in. Once a business and financing plan and financial proposal are written, the Geothermal Money Book takes the next step, helping small geothermal businesses locate and obtain financing. The Geothermal Money Book will: Explain the specific criteria potential financing sources use to evaluate a proposal for debt financing; Describe the Small Business Administration's (SBA) programs to promote lending to small businesses; List specific small-business friendly lenders for small geothermal businesses, including those which participate in SBA programs; Identify federal and state incentives which are relevant to direct use and small-scale (< 1 megawatt) power generation geothermal projects; and Provide an extensive state directory of financing sources and state financial incentives for the 19 states involved in the GeoPowering the West (GPW). GPW is a U.S. Department of Energy-sponsored activity to dramatically increase the use of geothermal energy in the western United States by promoting environmentally compatible heat and power, along with industrial growth and economic development. The Geothermal Money Book will not: Substitute for financial advice; Overcome the high exploration, development, and financing costs associated with smaller geothermal projects; Remedy the lack of financing for the exploration stage of a geothermal project; or Solve financing problems that are not related to the economic soundness of your project or are caused by things outside of your control.« less

Community composition of lacustrine small eukaryotes in hyper-eutrophic conditions in relation to top-down and bottom-up factors.

PubMed

Lepère, Cécile; Domaizon, Isabelle; Debroas, Didier

2007-09-01

Small eukaryotes (0.2-5 microm) in hyper-eutrophic conditions were described using terminal restriction fragment length polymorphism and cloning-sequencing, and were related to environmental variables both by an experimental approach and by a temporal field study. In situ analysis showed marked temporal variations in the dominant terminal restriction fragments (T-RFs), which were related to environmental variables such as nutrient concentrations and metazooplankton composition. To monitor the responses of the small-eukaryote community to top-down (absence or presence of planktivorous fish) and bottom-up (low or high nitrogen and phosphorus addition) effects, a cross-classified design mesocosm experiment was used. Depending on the type of treatment, we recorded changes in the diversity of T-RFs, as well as modifications in phylogenetic composition. Centroheliozoa and Cryptophyta were found in all types of treatment, whereas Chlorophyta were specific to enclosures receiving high nutrient loadings, and were associated either with LKM11 and 'environmental sequences'. Cercozoa and Fungi were not detected in enclosures receiving high nutrient loadings and fishes. Our results showed that resources and top-down factors are both clearly involved in shaping the structure of small eukaryotes, not only autotrophs but also heterotrophs, via complex interactions and trophic cascades within a microbial loop, notably in response to nutrient loading.

Small-scale spatial heterogeneity of ecosystem properties, microbial community composition and microbial activities in a temperate mountain forest soil.

PubMed

Štursová, Martina; Bárta, Jiří; Šantrůčková, Hana; Baldrian, Petr

2016-12-01

Forests are recognised as spatially heterogeneous ecosystems. However, knowledge of the small-scale spatial variation in microbial abundance, community composition and activity is limited. Here, we aimed to describe the heterogeneity of environmental properties, namely vegetation, soil chemical composition, fungal and bacterial abundance and community composition, and enzymatic activity, in the topsoil in a small area (36 m 2 ) of a highly heterogeneous regenerating temperate natural forest, and to explore the relationships among these variables. The results demonstrated a high level of spatial heterogeneity in all properties and revealed differences between litter and soil. Fungal communities had substantially higher beta-diversity than bacterial communities, which were more uniform and less spatially autocorrelated. In litter, fungal communities were affected by vegetation and appeared to be more involved in decomposition. In the soil, chemical composition affected both microbial abundance and the rates of decomposition, whereas the effect of vegetation was small. Importantly, decomposition appeared to be concentrated in hotspots with increased activity of multiple enzymes. Overall, forest topsoil should be considered a spatially heterogeneous environment in which the mean estimates of ecosystem-level processes and microbial community composition may confound the existence of highly specific microenvironments. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Small RNA sorting: matchmaking for Argonautes

PubMed Central

Czech, Benjamin; Hannon, Gregory J.

2013-01-01

Small RNAs directly or indirectly impact nearly every biological process in eukaryotic cells. To perform their myriad roles, not only must precise small RNA species be generated, but they must also be loaded into specific effector complexes called RNA-induced silencing complexes (RISCs). Argonaute proteins form the core of RISCs and different members of this large family have specific expression patterns, protein binding partners and biochemical capabilities. In this Review, we explore the mechanisms that pair specific small RNA strands with their partner proteins, with an eye towards the substantial progress that has been recently made in understanding the sorting of the major small RNA classes — microRNAs (miRNAs) and small interfering RNAs (siRNAs) — in plants and animals. PMID:21116305

Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis

PubMed Central

Lenoir, Olivia; Jasiek, Magali; Hénique, Carole; Guyonnet, Léa; Hartleben, Björn; Bork, Tillmann; Chipont, Anna; Flosseau, Kathleen; Bensaada, Imane; Schmitt, Alain; Massé, Jean-Marc; Souyri, Michèle; Huber, Tobias B; Tharaux, Pierre-Louis

2015-01-01

The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN. PMID:26039325

Identification and specificity studies of small-molecule ligands for SH3 protein domains.

PubMed

Inglis, Steven R; Stojkoski, Cvetan; Branson, Kim M; Cawthray, Jacquie F; Fritz, Daniel; Wiadrowski, Emma; Pyke, Simon M; Booker, Grant W

2004-10-21

The Src Homology 3 (SH3) domains are small protein-protein interaction domains that bind proline-rich sequences and mediate a wide range of cell-signaling and other important biological processes. Since deregulated signaling pathways form the basis of many human diseases, the SH3 domains have been attractive targets for novel therapeutics. High-affinity ligands for SH3 domains have been designed; however, these have all been peptide-based and no examples of entirely nonpeptide SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain as a model system for structure-based ligand design, we have identified several simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using a combination of nuclear magnetic resonance chemical shift perturbation, structure-activity relationships, and site-directed mutagenesis, the binding of these compounds at the proline-rich peptide-binding site has been characterized. The most potent of these, 2-aminoquinoline, bound with Kd = 125 microM and was able to compete for binding with a proline-rich peptide. Synthesis of 6-substituted-2-aminoquinolines resulted in ligands with up to 6-fold improved affinity over 2-aminoquinoline and enhanced specificity for the Tec SH3 domain. Therefore, 2-aminoquinolines may potentially be useful for the development of high affinity small molecule ligands for SH3 domains.

Wastewater-based epidemiology generated forensic information: Amphetamine synthesis waste and its impact on a small sewage treatment plant.

PubMed

Emke, Erik; Vughs, Dennis; Kolkman, Annemieke; de Voogt, Pim

2018-05-01

Chemical analysis of domestic wastewater can reveal the presence of illicit drugs either consumed by a population or directly discharged into the sewer system. In the search for causes of a recent malfunctioning of a small domestic wastewater treatment plant aberrantly high loads of amphetamine were observed in the influent of the plant. Direct discharges of chemical waste from illegal production sites were suspected to be the cause. Illegal manufacturing of amphetamines creates substantial amounts of chemical waste. Here we show that fly-tipping of chemical waste originating from an amphetamine synthesis in the catchment of a small sewage treatment plant resulted in failure of the treatment process. Target analysis of drugs of abuse and non-target screening using high resolution mass spectrometry provided evidence for the presence of amphetamine produced from the precursor 1-phenylpropan-2-one by the Leuckart process through specific synthesis markers. Furthermore the identity and presence of the pre-precursor 3-oxo-2-phenylbutanamide was confirmed and a route specific marker was proposed. This is the first study that demonstrates that non-target screening of wastewater can identify intermediates, impurities and by products of the synthesis routes used in illegal manufacturing of amphetamine. The profiles of chemicals thus obtained can be used in tracking productions sites within the corresponding sewer catchment. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance Evaluation of a PEM Scanner Using the NEMA NU 4—2008 Small Animal PET Standards

NASA Astrophysics Data System (ADS)

Luo, Weidong; Anashkin, Edward; Matthews, Christopher G.

2010-02-01

The recently published NEMA NU 4-2008 Standards has been specially designed for evaluating the performance of small animal PET scanners used in preclinical applications. In this paper, we report on the NU 4 performance of a clinical positron emission mammography (PEM) system. Since there are no PEM specific performance test protocols available, and the NU 2 protocol (intended for whole-body PET scanners) cannot be applied without modification due to the compact design of the PEM scanner, we decided to evaluate the NU 4 Standards as an alternative. We obtained the following results: Trans-axial spatial resolution 1.8 mm FWHM for high resolution reconstruction mode and 2.4 mm FWHM for standard resolution reconstruction mode with no significant variation within the field of view. The total system sensitivity was 0.16 cps/Bq. In image quality testing, the uniformity was found to be 3.9% STD at the standard resolution mode and 5.6% at the high resolution mode when measured with a 34 mm paddle separation. The NEMA NU 4-2008 Standards were found to be a practicable tool to evaluate the performance of the PEM scanner after some modifications to address the specifics of its detector configuration. Furthermore, the PEM scanner's in-plane spatial resolution was comparable to other small animal PET scanners with good image quality.

Using stereotactic brain atlases for small rodents and nonhuman primates for optrode array customization

NASA Astrophysics Data System (ADS)

Boutte, Ronald W.; Merlin, Sam; Griffiths, Brandon; Parry, Trent; Blair, Steve

2017-02-01

As the optogenetic field expands its need to target with high specificity only grows more crucial. This work will show a method for customizing soda-lime glass optrode arrays so that fine structures within the brains of small rodents and nonhuman primates can be optically interrogated below the outer cortical layer. An 8 × 6 array is customized for optrode length (400 μm ), optrode width (75 μm ), optrode pitch (400 μm ), backplane thickness (500 μm ), and overall form factor (3.45 mm × 2.65 mm ). The 400 μm long optrode is capable of illuminating the cortical Layer IV of rhesus macaque ( Macaca Fascicularis ) and the motor cortex of small mice ( Mus Musculus ).

Waste minimisation in a hard chromiun plating Small Medium Enterprise (SME).

PubMed

Viguri, J R; Andrés, A; Irabien, A

2002-01-01

The high potential of waste stream minimisation in the metal finishing sector justifies specific studies of Small and Medium Enterprises (SME). In this work, the minimisation options of the wastes generated in a hard chromium plating activity have been analysed. The study has been performed in a small job shop company, which works in batch mode with big pieces. A process flowsheet after connecting the unit operations and determining the process inputs (raw and secondary materials) and outputs (waste streams) has been carried out. The main properties, quantity and current management of the waste streams have been shown. The obvious lack of information has been identified and finally the waste minimisation options that could be adopted by the company have been recorded.

Current trends in nanobiosensor technology

PubMed Central

Wu, Diana; Langer, Robert S

2014-01-01

The development of tools and processes used to fabricate, measure, and image nanoscale objects has lead to a wide range of work devoted to producing sensors that interact with extremely small numbers (or an extremely small concentration) of analyte molecules. These advances are particularly exciting in the context of biosensing, where the demands for low concentration detection and high specificity are great. Nanoscale biosensors, or nanobiosensors, provide researchers with an unprecedented level of sensitivity, often to the single molecule level. The use of biomolecule-functionalized surfaces can dramatically boost the specificity of the detection system, but can also yield reproducibility problems and increased complexity. Several nanobiosensor architectures based on mechanical devices, optical resonators, functionalized nanoparticles, nanowires, nanotubes, and nanofibers have been demonstrated in the lab. As nanobiosensor technology becomes more refined and reliable, it is likely it will eventually make its way from the lab to the clinic, where future lab-on-a-chip devices incorporating an array of nanobiosensors could be used for rapid screening of a wide variety of analytes at low cost using small samples of patient material. PMID:21391305

Design of elevator control surface actuated by LIPCA for small unmanned air vehicle

NASA Astrophysics Data System (ADS)

Yoon, K. J.; Setiawan, Hery; Goo, N. S.

2006-03-01

There have been persistent interests in high performance actuators suitable for the actuation of control surfaces of small aircraft and helicopter blades and for active vibration control of aerospace and submarine structures that need high specific force and displacement. What is really needed for active actuation is a large-displacement actuator with a compact source, i.e., much higher strain. A lot of effort has been made to develop compact actuators with large displacement at a high force. One of the representative actuator is LIPCA actuator that was introduced by Yoon et al. The LIPCA design offers the advantages to be applied as actuator for the small aerial vehicle comparing with any other actuators. The weight is one of the main concerns for aerospace field, and since LIPCA has lighter weight than any other piezo-actuator thus it is suitable as actuator for small aircraft control surface. In this paper, a conceptual design of LIPCA-actuated control surface is introduced. A finite element model was constructed and analyzed to predict the deflection angle of the control surface. The hinge moment that produced by the aerodynamic forces was calculated to determine the optimum position of the hinge point, which could produce the deflection as high as possible with reasonable hinge moment. To verify the prediction, a prototype of SUAV (small unmanned air vehicle) control surface was manufactured and tested both in static condition and in the wind tunnel. The prediction and test results showed a good agreement on the control surface deflection angle.

Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

PubMed

Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

2018-01-01

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

Preclinical Evaluation of 18F-PSMA-1007, a New Prostate-Specific Membrane Antigen Ligand for Prostate Cancer Imaging.

PubMed

Cardinale, Jens; Schäfer, Martin; Benešová, Martina; Bauder-Wüst, Ulrike; Leotta, Karin; Eder, Matthias; Neels, Oliver C; Haberkorn, Uwe; Giesel, Frederik L; Kopka, Klaus

2017-03-01

In recent years, several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Some of them have had a high clinical impact on the treatment of patients with prostate cancer. However, the number of 18 F-labeled tracers addressing PSMA is still limited. Therefore, we aimed to develop a radiofluorinated molecule resembling the structure of therapeutic PSMA-617. Methods: The nonradioactive reference compound PSMA-1007 and the precursor were produced by solid-phase chemistry. The radioligand 18 F-PSMA-1007 was produced by a 2-step procedure with the prosthetic group 6- 18 F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester. The binding affinity of the ligand for PSMA and its internalization properties were evaluated in vitro with PSMA-positive LNCaP (lymph node carcinoma of the prostate) cells. Further, organ distribution studies were performed with mice bearing LNCaP and PC-3 (prostate cancer cell line; PSMA-negative) tumors. Finally, small-animal PET imaging of an LNCaP tumor-bearing mouse was performed. Results: The identified ligand had a binding affinity of 6.7 ± 1.7 nM for PSMA and an exceptionally high internalization ratio (67% ± 13%) in vitro. In organ distribution studies, high and specific tumor uptake (8.0 ± 2.4 percentage injected dose per gram) in LNCaP tumor-bearing mice was observed. In the small-animal PET experiments, LNCaP tumors were clearly visualized. Conclusion: The radiofluorinated PSMA ligand showed promising characteristics in its preclinical evaluation, and the feasibility of prostate cancer imaging was demonstrated by small-animal PET studies. Therefore, we recommend clinical transfer of the radioligand 18 F-PSMA-1007 for use as a diagnostic PET tracer in prestaging and monitoring of prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Pixelated filters for spatial imaging

NASA Astrophysics Data System (ADS)

Mathieu, Karine; Lequime, Michel; Lumeau, Julien; Abel-Tiberini, Laetitia; Savin De Larclause, Isabelle; Berthon, Jacques

2015-10-01

Small satellites are often used by spatial agencies to meet scientific spatial mission requirements. Their payloads are composed of various instruments collecting an increasing amount of data, as well as respecting the growing constraints relative to volume and mass; So small-sized integrated camera have taken a favored place among these instruments. To ensure scene specific color information sensing, pixelated filters seem to be more attractive than filter wheels. The work presented here, in collaboration with Institut Fresnel, deals with the manufacturing of this kind of component, based on thin film technologies and photolithography processes. CCD detectors with a pixel pitch about 30 μm were considered. In the configuration where the matrix filters are positioned the closest to the detector, the matrix filters are composed of 2x2 macro pixels (e.g. 4 filters). These 4 filters have a bandwidth about 40 nm and are respectively centered at 550, 700, 770 and 840 nm with a specific rejection rate defined on the visible spectral range [500 - 900 nm]. After an intense design step, 4 thin-film structures have been elaborated with a maximum thickness of 5 μm. A run of tests has allowed us to choose the optimal micro-structuration parameters. The 100x100 matrix filters prototypes have been successfully manufactured with lift-off and ion assisted deposition processes. High spatial and spectral characterization, with a dedicated metrology bench, showed that initial specifications and simulations were globally met. These excellent performances knock down the technological barriers for high-end integrated specific multi spectral imaging.

Connectome sensitivity or specificity: which is more important?

PubMed

Zalesky, Andrew; Fornito, Alex; Cocchi, Luca; Gollo, Leonardo L; van den Heuvel, Martijn P; Breakspear, Michael

2016-11-15

Connectomes with high sensitivity and high specificity are unattainable with current axonal fiber reconstruction methods, particularly at the macro-scale afforded by magnetic resonance imaging. Tensor-guided deterministic tractography yields sparse connectomes that are incomplete and contain false negatives (FNs), whereas probabilistic methods steered by crossing-fiber models yield dense connectomes, often with low specificity due to false positives (FPs). Densely reconstructed probabilistic connectomes are typically thresholded to improve specificity at the cost of a reduction in sensitivity. What is the optimal tradeoff between connectome sensitivity and specificity? We show empirically and theoretically that specificity is paramount. Our evaluations of the impact of FPs and FNs on empirical connectomes indicate that specificity is at least twice as important as sensitivity when estimating key properties of brain networks, including topological measures of network clustering, network efficiency and network modularity. Our asymptotic analysis of small-world networks with idealized modular structure reveals that as the number of nodes grows, specificity becomes exactly twice as important as sensitivity to the estimation of the clustering coefficient. For the estimation of network efficiency, the relative importance of specificity grows linearly with the number of nodes. The greater importance of specificity is due to FPs occurring more prevalently between network modules rather than within them. These spurious inter-modular connections have a dramatic impact on network topology. We argue that efforts to maximize the sensitivity of connectome reconstruction should be realigned with the need to map brain networks with high specificity. Copyright © 2016 Elsevier Inc. All rights reserved.

Recent advances in developing small molecules targeting RNA.

PubMed

Guan, Lirui; Disney, Matthew D

2012-01-20

RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small-Molecular-Target-Based Photodynamic Therapy.

PubMed

Chen, Juan-Juan; Huang, Yi-Zhen; Song, Mei-Ru; Zhang, Zhi-Hong; Xue, Jin-Ping

2017-09-21

Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC 50 values as low as 8 nm under a light dose of 1.5 J cm -2 ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High resolution climate scenarios for snowmelt modelling in small alpine catchments

NASA Astrophysics Data System (ADS)

Schirmer, M.; Peleg, N.; Burlando, P.; Jonas, T.

2017-12-01

Snow in the Alps is affected by climate change with regard to duration, timing and amount. This has implications with respect to important societal issues as drinking water supply or hydropower generation. In Switzerland, the latter received a lot of attention following the political decision to phase out of nuclear electricity production. An increasing number of authorization requests for small hydropower plants located in small alpine catchments was observed in the recent years. This situation generates ecological conflicts, while the expected climate change poses a threat to water availability thus putting at risk investments in such hydropower plants. Reliable high-resolution climate scenarios are thus required, which account for small-scale processes to achieve realistic predictions of snowmelt runoff and its variability in small alpine catchments. We therefore used a novel model chain by coupling a stochastic 2-dimensional weather generator (AWE-GEN-2d) with a state-of-the-art energy balance snow cover model (FSM). AWE-GEN-2d was applied to generate ensembles of climate variables at very fine temporal and spatial resolution, thus providing all climatic input variables required for the energy balance modelling. The land-surface model FSM was used to describe spatially variable snow cover accumulation and melt processes. The FSM was refined to allow applications at very high spatial resolution by specifically accounting for small-scale processes, such as a subgrid-parametrization of snow covered area or an improved representation of forest-snow processes. For the present study, the model chain was tested for current climate conditions using extensive observational dataset of different spatial and temporal coverage. Small-scale spatial processes such as elevation gradients or aspect differences in the snow distribution were evaluated using airborne LiDAR data. 40-year of monitoring data for snow water equivalent, snowmelt and snow-covered area for entire Switzerland was used to verify snow distribution patterns at coarser spatial and temporal scale. The ability of the model chain to reproduce current climate conditions in small alpine catchments makes this model combination an outstanding candidate to produce high resolution climate scenarios of snowmelt in small alpine catchments.

Toward an Understanding of Divergent Compound Eye Development in Drones and Workers of the Honeybee (Apis mellifera L.): A Correlative Analysis of Morphology and Gene Expression.

PubMed

Marco Antonio, David S; Hartfelder, Klaus

2017-01-01

Eye development in insects is best understood in Drosophila melanogaster, but little is known for other holometabolous insects. Combining a morphological with a gene expression analysis, we investigated eye development in the honeybee, putting emphasis on the sex-specific differences in eye size. Optic lobe development starts from an optic lobe anlage in the larval brain, which sequentially gives rise to the lobula, medulla, and lamina. The lamina differentiates in the last larval instar, when it receives optic nerve projections from the developing retina. The expression analysis focused on seven genes important for Drosophila eye development: eyes absent, sine oculis, embryonic lethal abnormal vision, minibrain, small optic lobes, epidermal growth factor receptor, and roughest. All except small optic lobes were more highly expressed in third-instar drone larvae, but then, in the fourth and fifth instar, their expression was sex-specifically modulated, showing shifts in temporal dynamics. The clearest differences were seen for small optic lobes, which is highly expressed in the developing eye of workers, and minibrain and roughest, which showed a strong expression peak coinciding with retina differentiation. A microarray analysis for optic lobe/retina complexes revealed the differential expression of several metabolism-related genes, as well as of two micro-RNAs. While we could not see major morphological differences in the developing eye structures before the pupal stage, the expression differences observed for the seven candidate genes and in the transcriptional microarray profiles indicate that molecular signatures underlying sex-specific optic lobe and retina development become established throughout the larval stages. © 2016 Wiley Periodicals, Inc.

Retrospective MicroRNA Sequencing: Complementary DNA Library Preparation Protocol Using Formalin-fixed Paraffin-embedded RNA Specimens.

PubMed

Loudig, Olivier; Liu, Christina; Rohan, Thomas; Ben-Dov, Iddo Z

2018-05-05

-Archived, clinically classified formalin-fixed paraffin-embedded (FFPE) tissues can provide nucleic acids for retrospective molecular studies of cancer development. By using non-invasive or pre-malignant lesions from patients who later develop invasive disease, gene expression analyses may help identify early molecular alterations that predispose to cancer risk. It has been well described that nucleic acids recovered from FFPE tissues have undergone severe physical damage and chemical modifications, which make their analysis difficult and generally requires adapted assays. MicroRNAs (miRNAs), however, which represent a small class of RNA molecules spanning only up to ~18-24 nucleotides, have been shown to withstand long-term storage and have been successfully analyzed in FFPE samples. Here we present a 3' barcoded complementary DNA (cDNA) library preparation protocol specifically optimized for the analysis of small RNAs extracted from archived tissues, which was recently demonstrated to be robust and highly reproducible when using archived clinical specimens stored for up to 35 years. This library preparation is well adapted to the multiplex analysis of compromised/degraded material where RNA samples (up to 18) are ligated with individual 3' barcoded adapters and then pooled together for subsequent enzymatic and biochemical preparations prior to analysis. All purifications are performed by polyacrylamide gel electrophoresis (PAGE), which allows size-specific selections and enrichments of barcoded small RNA species. This cDNA library preparation is well adapted to minute RNA inputs, as a pilot polymerase chain reaction (PCR) allows determination of a specific amplification cycle to produce optimal amounts of material for next-generation sequencing (NGS). This approach was optimized for the use of degraded FFPE RNA from specimens archived for up to 35 years and provides highly reproducible NGS data.

48 CFR 2919.202 - Specific policies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Specific policies. 2919.202 Section 2919.202 Federal Acquisition Regulations System DEPARTMENT OF LABOR SOCIOECONOMIC PROGRAMS SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS CONCERNS Policies 2919.202 Specific policies...

The Next Generation of Space Cells for Diverse Environments

NASA Technical Reports Server (NTRS)

Bailey, Sheila; Landis, Geoffrey; Raffaelle, Ryne

2002-01-01

Future science, military and commercial space missions are incredibly diverse. Military and commercial missions range from large arrays of hundreds of kilowatt to small arrays of ten watts in various Earth orbits. While science missions also have small to very large power needs there are additional unique requirements to provide power for near-sun missions and planetary exploration including orbiters, landers and rovers both to the inner planets and the outer planets with a major emphasis in the near term on Mars. These mission requirements demand cells for low intensity, low temperature applications, high intensity, high temperature applications, dusty environments and often high radiation environments. This paper discusses mission requirements, the current state of the art of space solar cells, and a variety of both evolving thin-film cells as well as new technologies that may impact the future choice of space solar cells for a specific mission application.

Does size and buoyancy affect the long-distance transport of floating debris?

NASA Astrophysics Data System (ADS)

Ryan, Peter G.

2015-08-01

Floating persistent debris, primarily made from plastic, disperses long distances from source areas and accumulates in oceanic gyres. However, biofouling can increase the density of debris items to the point where they sink. Buoyancy is related to item volume, whereas fouling is related to surface area, so small items (which have high surface area to volume ratios) should start to sink sooner than large items. Empirical observations off South Africa support this prediction: moving offshore from coastal source areas there is an increase in the size of floating debris, an increase in the proportion of highly buoyant items (e.g. sealed bottles, floats and foamed plastics), and a decrease in the proportion of thin items such as plastic bags and flexible packaging which have high surface area to volume ratios. Size-specific sedimentation rates may be one reason for the apparent paucity of small plastic items floating in the world’s oceans.

Temporal efficiency evaluation and small-worldness characterization in temporal networks

PubMed Central

Dai, Zhongxiang; Chen, Yu; Li, Junhua; Fam, Johnson; Bezerianos, Anastasios; Sun, Yu

2016-01-01

Numerous real-world systems can be modeled as networks. To date, most network studies have been conducted assuming stationary network characteristics. Many systems, however, undergo topological changes over time. Temporal networks, which incorporate time into conventional network models, are therefore more accurate representations of such dynamic systems. Here, we introduce a novel generalized analytical framework for temporal networks, which enables 1) robust evaluation of the efficiency of temporal information exchange using two new network metrics and 2) quantitative inspection of the temporal small-worldness. Specifically, we define new robust temporal network efficiency measures by incorporating the time dependency of temporal distance. We propose a temporal regular network model, and based on this plus the redefined temporal efficiency metrics and widely used temporal random network models, we introduce a quantitative approach for identifying temporal small-world architectures (featuring high temporal network efficiency both globally and locally). In addition, within this framework, we can uncover network-specific dynamic structures. Applications to brain networks, international trade networks, and social networks reveal prominent temporal small-world properties with distinct dynamic network structures. We believe that the framework can provide further insight into dynamic changes in the network topology of various real-world systems and significantly promote research on temporal networks. PMID:27682314

Temporal efficiency evaluation and small-worldness characterization in temporal networks

NASA Astrophysics Data System (ADS)

Dai, Zhongxiang; Chen, Yu; Li, Junhua; Fam, Johnson; Bezerianos, Anastasios; Sun, Yu

2016-09-01

Numerous real-world systems can be modeled as networks. To date, most network studies have been conducted assuming stationary network characteristics. Many systems, however, undergo topological changes over time. Temporal networks, which incorporate time into conventional network models, are therefore more accurate representations of such dynamic systems. Here, we introduce a novel generalized analytical framework for temporal networks, which enables 1) robust evaluation of the efficiency of temporal information exchange using two new network metrics and 2) quantitative inspection of the temporal small-worldness. Specifically, we define new robust temporal network efficiency measures by incorporating the time dependency of temporal distance. We propose a temporal regular network model, and based on this plus the redefined temporal efficiency metrics and widely used temporal random network models, we introduce a quantitative approach for identifying temporal small-world architectures (featuring high temporal network efficiency both globally and locally). In addition, within this framework, we can uncover network-specific dynamic structures. Applications to brain networks, international trade networks, and social networks reveal prominent temporal small-world properties with distinct dynamic network structures. We believe that the framework can provide further insight into dynamic changes in the network topology of various real-world systems and significantly promote research on temporal networks.

Multivariate Meta-Analysis of Brain-Mass Correlations in Eutherian Mammals

PubMed Central

Steinhausen, Charlene; Zehl, Lyuba; Haas-Rioth, Michaela; Morcinek, Kerstin; Walkowiak, Wolfgang; Huggenberger, Stefan

2016-01-01

The general assumption that brain size differences are an adequate proxy for subtler differences in brain organization turned neurobiologists toward the question why some groups of mammals such as primates, elephants, and whales have such remarkably large brains. In this meta-analysis, an extensive sample of eutherian mammals (115 species distributed in 14 orders) provided data about several different biological traits and measures of brain size such as absolute brain mass (AB), relative brain mass (RB; quotient from AB and body mass), and encephalization quotient (EQ). These data were analyzed by established multivariate statistics without taking specific phylogenetic information into account. Species with high AB tend to (1) feed on protein-rich nutrition, (2) have a long lifespan, (3) delayed sexual maturity, and (4) long and rare pregnancies with small litter sizes. Animals with high RB usually have (1) a short life span, (2) reach sexual maturity early, and (3) have short and frequent gestations. Moreover, males of species with high RB also have few potential sexual partners. In contrast, animals with high EQs have (1) a high number of potential sexual partners, (2) delayed sexual maturity, and (3) rare gestations with small litter sizes. Based on these correlations, we conclude that Eutheria with either high AB or high EQ occupy positions at the top of the network of food chains (high trophic levels). Eutheria of low trophic levels can develop a high RB only if they have small body masses. PMID:27746724

13 CFR 130.350 - Specific program responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Specific program responsibilities. 130.350 Section 130.350 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... Program policies and procedures to improve the delivery of services by SBDCs to the small business...

13 CFR 130.350 - Specific program responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Specific program responsibilities. 130.350 Section 130.350 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... Program policies and procedures to improve the delivery of services by SBDCs to the small business...

A Streamlined DNA Tool for Global Identification of Heavily Exploited Coastal Shark Species (Genus Rhizoprionodon)

PubMed Central

Pinhal, Danillo; Shivji, Mahmood S.; Nachtigall, Pedro G.; Chapman, Demian D.; Martins, Cesar

2012-01-01

Obtaining accurate species-specific landings data is an essential step toward achieving sustainable shark fisheries. Globally distributed sharpnose sharks (genus Rhizoprionodon) exhibit life-history characteristics (rapid growth, early maturity, annual reproduction) that suggests that they could be fished in a sustainable manner assuming an investment in monitoring, assessment and careful management. However, obtaining species-specific landings data for sharpnose sharks is problematic because they are morphologically very similar to one another. Moreover, sharpnose sharks may also be confused with other small sharks (either small species or juveniles of large species) once they are processed (i.e., the head and fins are removed). Here we present a highly streamlined molecular genetics approach based on seven species-specific PCR primers in a multiplex format that can simultaneously discriminate body parts from the seven described sharpnose shark species commonly occurring in coastal fisheries worldwide. The species-specific primers are based on nucleotide sequence differences among species in the nuclear ribosomal internal transcribed spacer 2 locus (ITS2). This approach also distinguishes sharpnose sharks from a wide range of other sharks (52 species) and can therefore assist in the regulation of coastal shark fisheries around the world. PMID:22496864

A streamlined DNA tool for global identification of heavily exploited coastal shark species (genus Rhizoprionodon).

PubMed

Pinhal, Danillo; Shivji, Mahmood S; Nachtigall, Pedro G; Chapman, Demian D; Martins, Cesar

2012-01-01

Obtaining accurate species-specific landings data is an essential step toward achieving sustainable shark fisheries. Globally distributed sharpnose sharks (genus Rhizoprionodon) exhibit life-history characteristics (rapid growth, early maturity, annual reproduction) that suggests that they could be fished in a sustainable manner assuming an investment in monitoring, assessment and careful management. However, obtaining species-specific landings data for sharpnose sharks is problematic because they are morphologically very similar to one another. Moreover, sharpnose sharks may also be confused with other small sharks (either small species or juveniles of large species) once they are processed (i.e., the head and fins are removed). Here we present a highly streamlined molecular genetics approach based on seven species-specific PCR primers in a multiplex format that can simultaneously discriminate body parts from the seven described sharpnose shark species commonly occurring in coastal fisheries worldwide. The species-specific primers are based on nucleotide sequence differences among species in the nuclear ribosomal internal transcribed spacer 2 locus (ITS2). This approach also distinguishes sharpnose sharks from a wide range of other sharks (52 species) and can therefore assist in the regulation of coastal shark fisheries around the world.

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.

Image quality phantom and parameters for high spatial resolution small-animal SPECT

NASA Astrophysics Data System (ADS)

Visser, Eric P.; Harteveld, Anita A.; Meeuwis, Antoi P. W.; Disselhorst, Jonathan A.; Beekman, Freek J.; Oyen, Wim J. G.; Boerman, Otto C.

2011-10-01

At present, generally accepted standards to characterize small-animal single photon emission tomographs (SPECT) do not exist. Whereas for small-animal positron emission tomography (PET), the NEMA NU 4-2008 guidelines are available, such standards are still lacking for small-animal SPECT. More specifically, a dedicated image quality (IQ) phantom and corresponding IQ parameters are absent. The structures of the existing PET IQ phantom are too large to fully characterize the sub-millimeter spatial resolution of modern multi-pinhole SPECT scanners, and its diameter will not fit into all scanners when operating in high spatial resolution mode. We therefore designed and constructed an adapted IQ phantom with smaller internal structures and external diameter, and a facility to guarantee complete filling of the smallest rods. The associated IQ parameters were adapted from NEMA NU 4. An additional parameter, effective whole-body sensitivity, was defined since this was considered relevant in view of the variable size of the field of view and the use of multiple bed positions as encountered in modern small-animal SPECT scanners. The usefulness of the phantom was demonstrated for 99mTc in a USPECT-II scanner operated in whole-body scanning mode using a multi-pinhole mouse collimator with 0.6 mm pinhole diameter.

High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer Players.

PubMed

Eniseler, Niyazi; Şahan, Çağatay; Özcan, Ilker; Dinler, Kıvanç

2017-12-01

The aim of this study was to compare the effects of high-intensity small-sided games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint ability (RSA), soccer specific endurance performance and short passing ability among junior soccer players. The junior soccer players were recruited from of a professional team (age 16.9 ± 1.1 years). The tests included the repeated-shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo-Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were randomly assigned to either the small-sided games training (SSGTG) (n = 10) or repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated-sprint training were added to the regular training sessions for two days of the regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were used to examine differences in groups and training effects. A time x training group effect was found in the improvement of short-passing ability for the smallsided games training group which showed significantly better scores than the repeated-sprint training group (p ≤ 0.05). Both groups showed similar improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high-intensity small-sided games training can be used as an effective training mode to enhance both repeated sprint ability and short-passing ability.

High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer Players

PubMed Central

Şahan, Çağatay; Özcan, Ilker; Dinler, Kıvanç

2017-01-01

Abstract The aim of this study was to compare the effects of high-intensity small-sided games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint ability (RSA), soccer specific endurance performance and short passing ability among junior soccer players. The junior soccer players were recruited from of a professional team (age 16.9 ± 1.1 years). The tests included the repeated-shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo-Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were randomly assigned to either the small-sided games training (SSGTG) (n = 10) or repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated-sprint training were added to the regular training sessions for two days of the regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were used to examine differences in groups and training effects. A time x training group effect was found in the improvement of short-passing ability for the smallsided games training group which showed significantly better scores than the repeated-sprint training group (p ≤ 0.05). Both groups showed similar improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high-intensity small-sided games training can be used as an effective training mode to enhance both repeated sprint ability and short-passing ability. PMID:29339990

Small cell sweat gland carcinoma of childhood

PubMed Central

Drut, R; Giménez, O P; Oliva, J

2005-01-01

Small cell sweat gland carcinoma appears to represent a very unusual histological type of sweat gland anlage tumour presenting in children. The differential diagnosis from other small blue cell tumours involving the skin is often difficult. The present report confirms the original observation describing two patients of 2 and 5 years of age harbouring cutaneous tumours. The histology of these lesions showed a monomorphic proliferation of small cells with a high mitotic rate and areas of necrosis. Immunohistochemically, the cells were negative for desmin, cytokeratin 7, cytokeratin 20, Cam 5.2, CD99, chromogranin, CD56, synaptophysin, and S-100, and focally positive for the pancytokeratin marker AE1/AE3, carcinoembryonic antigen (one case), and neurone specific enolase (one case). The prognosis of this type of tumour seems to be good. As more cases are added, the clinical pathological spectrum of the lesion will become better defined. PMID:16311358

Nanoparticle functionalised small-core suspended-core fibre - a novel platform for efficient sensing.

PubMed

Doherty, Brenda; Csáki, Andrea; Thiele, Matthias; Zeisberger, Matthias; Schwuchow, Anka; Kobelke, Jens; Fritzsche, Wolfgang; Schmidt, Markus A

2017-02-01

Detecting small quantities of specific target molecules is of major importance within bioanalytics for efficient disease diagnostics. One promising sensing approach relies on combining plasmonically-active waveguides with microfluidics yielding an easy-to-use sensing platform. Here we introduce suspended-core fibres containing immobilised plasmonic nanoparticles surrounding the guiding core as a concept for an entirely integrated optofluidic platform for efficient refractive index sensing. Due to the extremely small optical core and the large adjacent microfluidic channels, over two orders of magnitude of nanoparticle coverage densities have been accessed with millimetre-long sample lengths showing refractive index sensitivities of 170 nm/RIU for aqueous analytes where the fibre interior is functionalised by gold nanospheres. Our concept represents a fully integrated optofluidic sensing system demanding small sample volumes and allowing for real-time analyte monitoring, both of which are highly relevant within invasive bioanalytics, particularly within molecular disease diagnostics and environmental science.

Usability of small impact craters on small surface areas in crater count dating: Analysing examples from the Harmakhis Vallis outflow channel, Mars

NASA Astrophysics Data System (ADS)

Kukkonen, S.; Kostama, V.-P.

2018-05-01

The availability of very high-resolution images has made it possible to extend crater size-frequency distribution studies to small, deca/hectometer-scale craters. This has enabled the dating of small and young surface units, as well as recent, short-time and small-scale geologic processes that have occurred on the units. Usually, however, the higher the spatial resolution of space images is, the smaller area is covered by the images. Thus the use of single, very high-resolution images in crater count age determination may be debatable if the images do not cover the studied region entirely. Here we compare the crater count results for the floor of the Harmakhis Vallis outflow channel obtained from the images of the ConTeXt camera (CTX) and High Resolution Imaging Science Experiment (HiRISE) aboard the Mars Reconnaissance Orbiter (MRO). The CTX images enable crater counts for entire units on the Harmakhis Vallis main valley, whereas the coverage of the higher-resolution HiRISE images is limited and thus the images can only be used to date small parts of the units. Our case study shows that the crater count data based on small impact craters and small surface areas mainly correspond with the crater count data based on larger craters and more extensive counting areas on the same unit. If differences between the results were founded, they could usually be explained by the regional geology. Usually, these differences appeared when at least one cratering model age is missing from either of the crater datasets. On the other hand, we found only a few cases in which the cratering model ages were completely different. We conclude that the crater counts using small impact craters on small counting areas provide useful information about the geological processes which have modified the surface. However, it is important to remember that all the crater counts results obtained from a specific counting area always primarily represent the results from the counting area-not the whole unit. On the other hand, together with crater count results from extensive counting areas and lower-resolution images, crater counts on small counting areas but by using very high-resolution images is a very valuable tool for obtaining unique additional information about the local processes on the surface units.

Screening of the binding of small molecules to proteins by desorption electrospray ionization mass spectrometry combined with protein microarray.

PubMed

Yao, Chenxi; Wang, Tao; Zhang, Buqing; He, Dacheng; Na, Na; Ouyang, Jin

2015-11-01

The interaction between bioactive small molecule ligands and proteins is one of the important research areas in proteomics. Herein, a simple and rapid method is established to screen small ligands that bind to proteins. We designed an agarose slide to immobilize different proteins. The protein microarrays were allowed to interact with different small ligands, and after washing, the microarrays were screened by desorption electrospray ionization mass spectrometry (DESI MS). This method can be applied to screen specific protein binding ligands and was shown for seven proteins and 34 known ligands for these proteins. In addition, a high-throughput screening was achieved, with the analysis requiring approximately 4 s for one sample spot. We then applied this method to determine the binding between the important protein matrix metalloproteinase-9 (MMP-9) and 88 small compounds. The molecular docking results confirmed the MS results, demonstrating that this method is suitable for the rapid and accurate screening of ligands binding to proteins. Graphical Abstract ᅟ.

Small nucleoli are a cellular hallmark of longevity

PubMed Central

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H. Eka. D.; Müller, Roman-Ulrich; Slagboom, P. Eline; Partridge, Linda; Antebi, Adam

2017-01-01

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa. PMID:28853436

Small nucleoli are a cellular hallmark of longevity.

PubMed

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

PubMed

Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

2015-02-05

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic utility of alpha-methylacyl CoA racemase (P504S) on prostate needle biopsy.

PubMed

Jiang, Zhong; Woda, Bruce A

2004-11-01

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, was identified by the analysis of cDNA library subtraction in conjunction with high throughput microarray screening from prostate tissue and has been proven to be one of the very few biomarkers that can distinguish cancer from benign cells with high sensitivity and specificity for prostate carcinoma. It is a successful example of the translation of molecular findings into clinical practice. This review focuses on the study of AMACR (P504S) expression in small focal prostate cancer and atypical small acinar proliferation (ASAP) on needle biopsies and emphasizes the utility of AMACR (P504S) in routine surgical pathology practice. We also discuss the potential pitfalls and caveats in the interpretation of immunostaining results.

New Technology CZT Detectors for High-Energy Flare Spectroscopy: The Room Temperature Semiconductor Spectrometer for JAWSAT

NASA Technical Reports Server (NTRS)

Vestrand, W. Thomas

1999-01-01

The goal of our Room Temperature Semiconductor Spectrometer (RTeSS) project is to develop a small high-energy solar flare spectrometer employing semiconductor detectors that do not require significant cooling when used as high-energy solar flare spectrometers. Specifically, the goal is to test Cadmium Zinc Telluride (CZT) detectors with coplanar grid electrodes as x-ray and gamma-ray spectrometers and to design an experiment that can be flown as a "piggy-back" payload on a satellite mission during the next solar maximum.

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

Detector-specific correction factors in radiosurgery beams and their impact on dose distribution calculations.

PubMed

García-Garduño, Olivia A; Rodríguez-Ávila, Manuel A; Lárraga-Gutiérrez, José M

2018-01-01

Silicon-diode-based detectors are commonly used for the dosimetry of small radiotherapy beams due to their relatively small volumes and high sensitivity to ionizing radiation. Nevertheless, silicon-diode-based detectors tend to over-respond in small fields because of their high density relative to water. For that reason, detector-specific beam correction factors ([Formula: see text]) have been recommended not only to correct the total scatter factors but also to correct the tissue maximum and off-axis ratios. However, the application of [Formula: see text] to in-depth and off-axis locations has not been studied. The goal of this work is to address the impact of the correction factors on the calculated dose distribution in static non-conventional photon beams (specifically, in stereotactic radiosurgery with circular collimators). To achieve this goal, the total scatter factors, tissue maximum, and off-axis ratios were measured with a stereotactic field diode for 4.0-, 10.0-, and 20.0-mm circular collimators. The irradiation was performed with a Novalis® linear accelerator using a 6-MV photon beam. The detector-specific correction factors were calculated and applied to the experimental dosimetry data for in-depth and off-axis locations. The corrected and uncorrected dosimetry data were used to commission a treatment planning system for radiosurgery planning. Various plans were calculated with simulated lesions using the uncorrected and corrected dosimetry. The resulting dose calculations were compared using the gamma index test with several criteria. The results of this work presented important conclusions for the use of detector-specific beam correction factors ([Formula: see text] in a treatment planning system. The use of [Formula: see text] for total scatter factors has an important impact on monitor unit calculation. On the contrary, the use of [Formula: see text] for tissue-maximum and off-axis ratios has not an important impact on the dose distribution calculation by the treatment planning system. This conclusion is only valid for the combination of treatment planning system, detector, and correction factors used in this work; however, this technique can be applied to other treatment planning systems, detectors, and correction factors.

Natal movement in juvenile Atlantic salmon: a body size-dependent strategy?

Treesearch

Sigurd Einum; Anders G. Finstad; Grethe Robertsen; Keith H. Nislow; Simon McKelvey; John D. Armstrong

2012-01-01

If competitive ability depends on body size, then the optimal natal movement from areas of high local population density can also be predicted to be size-dependent. Specifically, small, competitively-inferior individuals would be expected to benefit most from moving to areas of lower local density. Here we evaluate whether individual variation in natal movement...

Antenna Technologies for NASA Applications

NASA Technical Reports Server (NTRS)

Miranda, Felix

2007-01-01

This presentation addresses the efforts being performed at GRC to develop antenna technology in support of NASA s Exploration Vision. In particular, the presentation discusses the communications architecture asset-specific data services, as well as wide area coverage, high gain, low mass deployable antennas. Phased array antennas as well as electrically small, lightweight, low power, multifunctional antennas will be also discussed.

Antenna Technologies for NASA Applications

NASA Technical Reports Server (NTRS)

Miranda, Felix A.

2006-01-01

This presentation addresses the efforts being performed at GRC to develop antenna technology in support of NASA s Exploration Vision. In particular, the presentation discusses the communications architecture asset-specific data services, as well as wide area coverage, high gain, low mass deployable antennas. Phased array antennas as well as electrically small, lightweight, low power, multifunctional antennas will be also discussed.

Circulation of Newly-Acquired Materials at the Juniata College Library.

ERIC Educational Resources Information Center

Eyman, David H.

Using circulation data to determine whether materials specifically acquired for the circulation collections of libraries at undergraduate institutions show heavy use, this study examined the first 3 years of shelf life of one year's book acquisitions at a small liberal arts college. Contrary to expectations of a high rate of use for newly acquired…

Evaluation of a Secondary School Science Program Inversion: Moving from a Traditional to a Modifified-PCB Sequence

ERIC Educational Resources Information Center

Gaubatz, Julie

2013-01-01

Studies of high-school science course sequences have been limited primarily to a small number of site-specific investigations comparing traditional science sequences (e.g., Biology-Chemistry-Physics: BCP) to various Physics First-influenced sequences (Physics-Chemistry-Biology: PCB). The present study summarizes a five-year program evaluation…

Teachers' Manual: Using Teams-Games-Tournament (TGT) in the Physical Science Classroom.

ERIC Educational Resources Information Center

Hollifield, John H.; Leavey, Marshall B.

This teacher's manual provides general and specific guidelines for use of Teams-Games-Tournaments (TGT) Physical Science Curriculum materials at the junior high-middle school level. TGT is an innovative instructional model which focuses on the learning of basic skills, information, and concepts, rewarding students in small teams rather than at the…

Social Science Elective Packages: An Independent Study Program for Grade 12.

ERIC Educational Resources Information Center

Moody, David B.

During the winter semester of 1970 a seminar was conducted for doctoral students in social studies education as a practicum in curriculum development to meet some of the special needs of the small high school, specifically the production of social science independent study packages. The packages produced were one-half Carnegie unit equivalent…

Literature-Based Workshops for Mathematics: Ideas for Active Learning Grades K-2.

ERIC Educational Resources Information Center

Morrison, Kathy; Dittrich, Tina; Claridge, Jill

This book presents ways to use high quality children's literature to plan small group workshops in mathematics for K-2 instruction. Each of the six sets of workshops is built around storybooks children love and focuses on a specific aspect of numeracy: shapes, counting, seriation, addition, money, and measurement. Each set is designed for a…

Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease intended for colon-specific drug delivery.

PubMed

Freire, Cristina; Podczeck, Fridrun; Veiga, Francisco; Sousa, João

2010-02-01

Colon-specific delivery of drugs can be achieved with dosage forms coated with biopolymers that are metabolized selectively by the colonic microflora and yet resistant to enzymatic digestion in the small intestine. The aim of this study was to study the influence of formulation factors on the performance of mixed films from high-amylose starches and Surelease((R)), applied using a spray-coating process, as potential colon-specific delivery devices. 5-Aminosalicylic acid-loaded pellets were prepared by an extrusion-spheronization process and film coated with mixtures of the starches and Surelease((R)). Optimization of the coating formulation, that is, starch-to-Surelease((R)) ratio, film-coating thickness, and type of starch, was undertaken first in enzyme-free media resembling the conditions in the stomach and small intestine. The effect of curing of the film coating on the drug release profile upon storage was also evaluated. Optimized coating formulations were further assessed for enzymatic digestibility using artificial gastric and intestinal juices containing commercially available pepsin and pancreatin or alpha-amylase from hog pancreas, respectively. Finally, drug release was assessed in fluid-simulating conditions in the colon (SCF) containing Bacillus licheniformis alpha-amylase. Film coatings comprising high-amylose starches and Surelease((R)) in a ratio of 1:2 (w/w) and film thickness of approximately 45 microm were able to withstand the chemical and enzymatic environment of the upper gastrointestinal tract, in particular, resisted degradation by the pancreatic alpha-amylases. Stability of the coatings during storage was achieved with additional curing. In SCF, these coatings were susceptible to enzymatic degradation. This study showed that high amylose starch-mixed films can be successfully used as colon-specific delivery devices. The preparation of the coating dispersions described is simple and rapid, without the need to extract the amylose component of starch.

Magnetic field configurations on thruster performance in accordance with ion beam characteristics in cylindrical Hall thruster plasmas

NASA Astrophysics Data System (ADS)

Kim, Holak; Choe, Wonho; Lim, Youbong; Lee, Seunghun; Park, Sanghoo

2017-03-01

Magnetic field configuration is critical in Hall thrusters for achieving high performance, particularly in thrust, specific impulse, efficiency, etc. Ion beam features are also significantly influenced by magnetic field configurations. In two typical magnetic field configurations (i.e., co-current and counter-current configurations) of a cylindrical Hall thruster, ion beam characteristics are compared in relation to multiply charged ions. Our study shows that the co-current configuration brings about high ion current (or low electron current), high ionization rate, and small plume angle that lead to high thruster performance.

The island rule: made to be broken?

PubMed Central

Meiri, Shai; Cooper, Natalie; Purvis, Andy

2007-01-01

The island rule is a hypothesis whereby small mammals evolve larger size on islands while large insular mammals dwarf. The rule is believed to emanate from small mammals growing larger to control more resources and enhance metabolic efficiency, while large mammals evolve smaller size to reduce resource requirements and increase reproductive output. We show that there is no evidence for the existence of the island rule when phylogenetic comparative methods are applied to a large, high-quality dataset. Rather, there are just a few clade-specific patterns: carnivores; heteromyid rodents; and artiodactyls typically evolve smaller size on islands whereas murid rodents usually grow larger. The island rule is probably an artefact of comparing distantly related groups showing clade-specific responses to insularity. Instead of a rule, size evolution on islands is likely to be governed by the biotic and abiotic characteristics of different islands, the biology of the species in question and contingency. PMID:17986433

Cycle life testing of lithium-ion batteries for small satellite LEO space missions

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

Mayer, S.T.; Feikert, J.H.; Kaschmitter, J.L.

1993-08-16

In 1990, Sony corporation announced their intention to manufacture a rechargeable lithium ion battery, based on the intercalation of lithium ions into a carbonaceous anode. The cells were first introduced for portable telephone use in June, 1991. (1) A 3.6V average cell voltage (4.1-2.75V range); (2) Excellent cycle life (1200 @ 100% DOD); (3) Good capacity retention (70% after 6 months); (4) Wide temperature range performance ({minus}20 to +60{degrees}C); (5) Excellent Discharge rate (82% capacity at 30 min. discharge rate); (6) Excellent Charge rate (100% Charge in <3 hrs); and (7) High energy density (264 W*hr/1 and 120 Whr/kg formore » ``D`` size cell. These specifications show significant promise for application of these batteries in low earth orbit (LEO) small satellites, particularly when compared to existing NiH{sub 2} and NiCd technology. The very high energy density and specific energy will reduce power system volume and weight. The wide temperature range enables simpler thermal design, particularly for new, small, high power satellites. The materials used in the lithium ion batteries are relatively inexpensive and benign, so that we expect costs to come down substantially in the future. The specified cycle life at 100% DOD is also 50% longer than most NiCds, so low DOD (depth of discharge) performance could be substantial. This study was undertaken to: (a) assess the feasibility for using lithium ion cells on small satellite LEO missions and (b) verify the claims of the manufacturer. This was accomplished by performing a detailed autopsy and various depth of discharge and rate tests on the cells. Of special interest was the cycle life performance of these cell at various depths of discharge DOD`s, to get an initial measure of the reduction in capacity fade with cycle conditions. Low DOD`s are used to extend the life of all batteries used in a space application.« less

Using lithium ion batteries in the aeromedical environment: a calculated risk?

PubMed

Haggerty, Andrew; Keogh, Sean

2015-04-01

Lithium ion batteries are increasingly utilised within helicopter emergency medical services. Their favourable chemical profile confers many desirable properties: they are small, lightweight and provide a high specific capacity (energy to weight ratio) coupled with a slow self-discharge rate, ensuring a longer functional availability for vital equipment. They are frequently used in routine medical equipment including ventilators, monitors and intravenous pumps, and in aviation specific items, such as satellite and mobile phones, VHF radios and navigation systems. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

[Specific features of 2-methyl hydroxybenzene and 3-methyl hydroxybenzene distribution in the organism of warm-blooded animals].

PubMed

Shormanov, B K; Grishenko, V K; Astashkina, A P; Elizarova, M K

2013-01-01

The present work was designed to study the specific features of 2-methyl hydroxybezene and 3-methyl hydroxybenzene distribution after intragastric administration of these toxicants to warm-blooded animals (rats). They were detected in the unmetabolized form in the internal organs and blood of the animals. The levels of 2-methyl hydroxybezene were especially high in the stomach and blood whereas the maximum content of 3-methyl hydroxybenzene was found in brain, blood, small intestines of the poisoned rats.

Analysis and evaluation for consumer goods containing NORM in Korea.

PubMed

Jang, Mee; Chung, Kun Ho; Lim, Jong Myoung; Ji, Young Yong; Kim, Chang Jong; Kang, Mun Ja

2017-08-01

We analyzed the consumer goods containing NORM by ICP-MS and evaluated the external dose. To evaluate the external dose, we assumed the small room model as irradiation scenario and calculated the specific effective dose rate using MCNPX code. The external doses for twenty goods are less than 1 mSv considering the specific effective dose rates and usage quantities. However, some of them have relatively high dose and the activity concentration limits are necessary as a screening tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

LED Systems Target Plant Growth

NASA Technical Reports Server (NTRS)

2010-01-01

To help develop technologies for growing edible biomass (food crops) in space, Kennedy Space Center partnered with Orbital Technologies Corporation (ORBITEC), of Madison, Wisconsin, through the Small Business Innovation Research (SBIR) program. One result of this research was the High Efficiency Lighting with Integrated Adaptive Control (HELIAC) system, components of which have been incorporated into a variety of agricultural greenhouse and consumer aquarium lighting features. The new lighting systems can be adapted to a specific plant species during a specific growth stage, allowing maximum efficiency in light absorption by all available photosynthetic tissues.

Small fibre neuropathy in mitochondrial diseases explored with sudoscan.

PubMed

Luigetti, Marco; Primiano, Guido; Cuccagna, Cristina; Bernardo, Daniela; Sauchelli, Donato; Vollono, Catello; Servidei, Serenella

2018-06-01

Polyneuropathy in mitochondrial diseases (MDs) is relatively common and widely investigated, but few data are instead reported about small fibres involvement. In order to investigate the involvement of small fibres in MDs we performed extensive neurophysiological test (nerve conduction studies; sympathetic skin response; sudoscan) in 27 patients with genetic diagnosis of MD (7 m.3243A > G; 4 m.8344A > G; 9 single mtDNA deletion; 7 multiple mtDNA deletions). NCS showed a polyneuropathy in 11/27 cases (41%). The incidence was very high in POLG1 (100%), m.8344A > G (75%) and m.3243A > G (43%), while only 11% of patients with single deletion had evidence of large fibres involvement. Sympathetic skin response was abnormal only in three patients (one progressive external ophthalmoplegia with single mtDNA deletion; one patient with m.3243A > G mutation; one patient with POLG1 mutation). Sudoscan revealed the presence of an autonomic small fibres dysfunction in 9/27 cases (33%), most of them (7/9) carrying a single mtDNA deletion. Sudoscan data were also confirmed in a sub-group of patients by laser evoked potentials study. Considering only patients with single mtDNA deletion 7/9 (78%) showed abnormal results at sudoscan. Small fibre neuropathy is another feature to investigate in mitochondrial diseases and seems specifically associated with the presence of single mtDNA deletion. The correct identification through specific neurophysiological tests of small fibres involvement in MDs represents another tile in this challenging diagnosis. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The use of tools for learning science in small groups

NASA Astrophysics Data System (ADS)

Valdes, Rosa Maria

2000-10-01

"Hands-on" learning through the use of tools or manipulatives representative of science concepts has long been an important component of the middle school science curriculum. However, scarce research exists on the impact of tool use on learning of science concepts, particularly on the processes involved in such learning. This study investigated how the use of tools by students engaged in small group discussion about the concept of electrical resistance and the explanations that accompany such use leads to improved understandings of the concept. Specifically, the main hypothesis of the study was that students who observe explanations by their high-ability peers accompanied by accurate tool use and who are highly engaged in these explanations would show learning gains. Videotaped interactions of students working in small groups to solve tasks on electricity were coded using scales that measured the accuracy of the tool use, the accuracy of the explanations presented, and the level of engagement of target students. The data of 48 students whose knowledge of the concept of resistance was initially low and who also were determined to be low achievers as shown by their scores on a set of pretest, was analyzed. Quantitative and qualitative analyses showed that students who observed their peers give explanations using tools and who were engaged at least moderately made gains in their understandings of resistance. Specifically, the results of regression analyses showed that both the level of accuracy of a high-ability peer's explanation and the target student's level of engagement in the explanation significantly predicted target students' outcome scores. The number of presentations offered by a high-ability peer also significantly predicted outcome scores. Case study analyses of six students found that students who improved their scores the most from pretest to posttest had high-ability peers who tended to be verbal and who gave numerous explanations, whereas students who improved the least had high-ability peers who gave no explanations at all. Important implications of this study for teaching are that (1) teachers should group students heterogeneously and should monitor students' small groups to insure that students are producing content-oriented discussion, and (2) students should be allowed to manipulate tools that allow experimentation as students build understandings and promote communication of abstract ideas.

Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells

PubMed Central

Nguyen, Minh M.; Dar, Javid A.; Ai, Junkui; Wang, Yujuan; Masoodi, Khalid Z.; Shun, Tongying; Shinde, Sunita; Camarco, Daniel P.; Hua, Yun; Huryn, Donna M.; Wilson, Gabriela Mustata; Lazo, John S.; Nelson, Joel B.; Wipf, Peter

2016-01-01

Abstract Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second-generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide. PMID:27187604

Small mammal responses to Amazonian forest islands are modulated by their forest dependence.

PubMed

Palmeirim, Ana Filipa; Benchimol, Maíra; Vieira, Marcus Vinícius; Peres, Carlos A

2018-05-01

Hydroelectric dams have induced widespread loss, fragmentation and degradation of terrestrial habitats in lowland tropical forests. Yet their ecological impacts have been widely neglected, particularly in developing countries, which are currently earmarked for exponential hydropower development. Here we assess small mammal assemblage responses to Amazonian forest habitat insularization induced by the 28-year-old Balbina Hydroelectric Dam. We sampled small mammals on 25 forest islands (0.83-1466 ha) and four continuous forest sites in the mainland to assess the overall community structure and species-specific responses to forest insularization. We classified all species according to their degree of forest-dependency using a multi-scale approach, considering landscape, patch and local habitat characteristics. Based on 65,520 trap-nights, we recorded 884 individuals of at least 22 small mammal species. Species richness was best predicted by island area and isolation, with small islands (< 15 ha) harbouring an impoverished nested subset of species (mean ± SD: 2.6 ± 1.3 species), whereas large islands (> 200 ha; 10.8 ± 1.3 species) and continuous forest sites (∞ ha; 12.5 ± 2.5 species) exhibited similarly high species richness. Forest-dependent species showed higher local extinction rates and were often either absent or persisted at low abundances on small islands, where non-forest-dependent species became hyper-abundant. Species capacity to use non-forest habitat matrices appears to dictate small mammal success in small isolated islands. We suggest that ecosystem functioning may be highly disrupted on small islands, which account for 62.7% of all 3546 islands in the Balbina Reservoir.

Subunit association of gamma-glutamyltranspeptidase of Escherichia coli K-12.

PubMed

Hashimoto, W; Suzuki, H; Nohara, S; Tachi, H; Yamamoto, K; Kumagai, H

1995-12-01

gamma-Glutamyltranspeptidase [EC 2.3.2.2] of Escherichia coli K-12 consists of one large subunit and one small subunit, which can be separated from each other by high-performance liquid chromatography. Using ion spray mass spectrometry, the masses of the large and the small subunit were determined to be 39,207 and 20,015, respectively. The large subunit exhibited no gamma-glutamyltranspeptidase activity and the small subunit had little enzymatic activity, but a mixture of the two subunits showed partial recovery of the enzymatic activity. The results of native-polyacrylamide gel electrophoresis suggested that they could partially recombine, and that the recombined dimer exhibited enzymatic activity. The gene of gamma-glutamyltranspeptidase encoded a signal peptide, and the large and small subunits in a single open reading frame in that order. Two kinds of plasmid were constructed encoding the signal peptide and either the large or the small subunit. A gamma-glutamyltranspeptidase-less mutant of E. coli K-12 was transformed with each plasmid or with both of them. The strain harboring the plasmid encoding each subunit produced a small amount of the corresponding subunit protein in the periplasmic space but exhibited no enzymatic activity. The strain transformed with both plasmids together exhibited the enzymatic activity, but its specific activity was approximately 3% of that of a strain harboring a plasmid encoding the intact structural gene. These results indicate that a portion of the separated large and small subunits can be reconstituted in vitro and exhibit the enzymatic activity, and that the expressed large and small subunits independently are able to associate in vivo and be folded into an active structure, though the specific activity of the associated subunits was much lower than that of native enzyme. This suggests that the synthesis of gamma-glutamyltranspeptidase in a single precursor polypeptide and subsequent processing are more effective to construct the intact structure of gamma-glutamyltranspeptidase than the association of the separated large and small subunits.

TandemPET-A High Resolution, Small Animal, Virtual Pinhole-Based PET Scanner: Initial Design Study

NASA Astrophysics Data System (ADS)

Raylman, Raymond R.; Stolin, Alexander V.; Martone, Peter F.; Smith, Mark F.

2016-02-01

Mice are the perhaps the most common species of rodents used in biomedical research, but many of the current generation of small animal PET scanners are non-optimal for imaging these small rodents due to their relatively low resolution. Consequently, a number of researchers have investigated the development of high-resolution scanners to address this need. In this investigation, the design of a novel, high-resolution system based on the dual-detector, virtual-pinhole PET concept was explored via Monte Carlo simulations. Specifically, this system, called TandemPET, consists of a 5 cm × 5 cm high-resolution detector made-up of a 90 × 90 array of 0.5 mm × 0.5 × 10 mm (pitch = 0.55 mm) LYSO detector elements in coincidence with a lower resolution detector consisting of a 68 × 68 array of 1.5 mm × 1.5 mm × 10 mm LYSO detector elements (total size = 10.5 cm × 10.5 cm). Analyses indicated that TandemPET's optimal geometry is to position the high-resolution detector 3 cm from the center-of-rotation, with the lower resolution detector positioned 9 cm from center. Measurements using modified NEMA NU4-2008-based protocols revealed that the spatial resolution of the system is 0.5 mm FWHM, after correction of positron range effects. Peak sensitivity is 2.1%, which is comparable to current small animal PET scanners. Images from a digital mouse brain phantom demonstrated the potential of the system for identifying important neurological structures.

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

PubMed Central

Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

2017-01-01

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

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.

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

PubMed

Arnold, Anne-Sophie; Tang, Yao Liang; Qian, Keping; Shen, Leping; Valencia, Valery; Phillips, Michael Ian; Zhang, Yuan Clare

2007-01-01

Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

Highly-wrinkled reduced graphene oxide-conductive polymer fibers for flexible fiber-shaped and interdigital-designed supercapacitors

NASA Astrophysics Data System (ADS)

Li, Bo; Cheng, Jianli; Wang, Zhuanpei; Li, Yinchuan; Ni, Wei; Wang, Bin

2018-02-01

Flexible supercapacitors have attracted great interest due to outstanding flexibility and light weight. Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) fibers have the great potential in using as electrodes for flexible supercapacitors due to the good flexibility. However, the reported conductivity and specific capacitance of these PEDOT: PSS fibers are not very high, which limit their electrochemical performances. In this work, composite fibers of reduced graphene oxide(rGO)-PEDOT: PSS with a highly-wrinkled structure on the surface and pores inside are prepared by wet spinning. The fibers with different ratios of graphene to PEDOT:PSS show a distinctly enhanced conductivity up to ca. 590 S·cm-1 and high strength up to ca. 18.4 MPa. Meanwhile, the composite fibers show an improved electrochemical performances, including a high specific areal capacitance of 131 mF cm-2 and high specific areal energy density of 4.55 μWh·cm-2. The flexible supercapacitors including fiber-shaped supercapacitors and interdigital designed supercapacitors not only could work in different bending states without obvious capacitance decay, but also have small leakage current. The interdigital design can further improve the performances of composite fibers with high capacitance and high utilization compared with traditional parallel connected structure.

A framework for optimizing micro-CT in dual-modality micro-CT/XFCT small-animal imaging system

NASA Astrophysics Data System (ADS)

Vedantham, Srinivasan; Shrestha, Suman; Karellas, Andrew; Cho, Sang Hyun

2017-09-01

Dual-modality Computed Tomography (CT)/X-ray Fluorescence Computed Tomography (XFCT) can be a valuable tool for imaging and quantifying the organ and tissue distribution of small concentrations of high atomic number materials in small-animal system. In this work, the framework for optimizing the micro-CT imaging system component of the dual-modality system is described, either when the micro-CT images are concurrently acquired with XFCT and using the x-ray spectral conditions for XFCT, or when the micro-CT images are acquired sequentially and independently of XFCT. This framework utilizes the cascaded systems analysis for task-specific determination of the detectability index using numerical observer models at a given radiation dose, where the radiation dose is determined using Monte Carlo simulations.

Management of occupational health risks in small-animal veterinary practices.

PubMed

D'Souza, Eva; Barraclough, Richard; Fishwick, David; Curran, Andrew

2009-08-01

Small-animal work is a major element of veterinary practice in the UK and may be hazardous, with high levels of work-related injuries and ill-health reported in Australia and USA. There are no studies addressing the management of occupational health risks arising from small-animal work in the UK. To investigate the sources of health and safety information used and how health and safety and 12 specific occupational health risks are managed by practices. A cross-sectional postal survey of all small-animal veterinary practices in Hampshire. A response was mandatory as this was a Health & Safety Executive (HSE) inspection activity. A total of 118 (100%) practices responded of which 93 were eligible for inclusion. Of these, 99 and 86%, respectively, were aware of the Royal College of Veterinary Surgeons (RCVS) practice standards and had British Small Animal Veterinary Association (BSAVA) staff members, while only 51% had previous contact with HSE (publications, advice and visit). Ninety per cent had health and safety policies, but only 31% had trained responsible staff in health and safety. Specific health hazards such as occupational allergens and computer use were relatively overlooked both by practices and the RCVS/BSAVA guidance available in 2002. Failings in active health risk management systems could be due to a lack of training to ensure competence in those with responsibilities. Practices rely on guidance produced by their professional bodies. Current RCVS guidance, available since 2005, has remedied some previous omissions, but further improvements are recommended.

Micro-Scale Genomic DNA Copy Number Aberrations as Another Means of Mutagenesis in Breast Cancer

PubMed Central

Chao, Hann-Hsiang; He, Xiaping; Parker, Joel S.; Zhao, Wei; Perou, Charles M.

2012-01-01

Introduction In breast cancer, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations, as shown by a previously described micro-deletion event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods We sought to identify if small regions of genomic DNA copy number changes exist by using a high density, gene-centric Comparative Genomic Hybridizations (CGH) array on cell lines and primary tumors. A custom tiling array for CGH (244,000 probes, 200 bp tiling resolution) was created to identify small regions of genomic change, which was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments were called micro-aberrations (<64 contiguous probes, ∼ 15 kb). Results Our data showed that primary tumor breast cancer genomes frequently contained many small-scale copy number gains and losses, termed micro-aberrations, most of which are undetectable using typical-density genome-wide aCGH arrays. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5′ regions of the affected genes, including the promoter region, and high frequency of micro-aberrations was associated with poor survival. Conclusion Using a high-probe-density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that can contribute to gene inactivation. These events may contribute to tumor formation through mechanisms not detected using conventional DNA copy number analyses. PMID:23284754

Constellation Pharmacology: A new paradigm for drug discovery

PubMed Central

Schmidt, Eric W.; Olivera, Baldomero M.

2015-01-01

Constellation Pharmacology is a cell-based high-content phenotypic-screening platform that utilizes subtype-selective pharmacological agents to elucidate the cell-specific combinations (“constellations”) of key signaling proteins that define specific cell types. Heterogeneous populations of native cells, in which the different individual cell types have been identified and characterized, are the foundation for this screening platform. Constellation Pharmacology is useful for screening small molecules or for deconvoluting complex mixtures of biologically-active natural products. This platform has been used to purify natural products and discover their molecular mechanisms. In the on-going development of Constellation Pharmacology, there is a positive-feedback loop between the pharmacological characterization of cell types and screening for new drug candidates. As Constellation Pharmacology is used to discover compounds with novel targeting-selectivity profiles, those new compounds then further help to elucidate the constellations of specific cell types, thereby increasing the content of this high-content platform. PMID:25562646

Study of Required Thrust Profile Determination of a Three Stages Small Launch Vehicle

NASA Astrophysics Data System (ADS)

Fariz, A.; Sasongko, R. A.; Poetro, R. E.

2018-04-01

The effect of solid rocket motor specifications, i.e. specific impulse and mass flow rate, and coast time on the thrust profile of three stages small launch vehicle is studied. Solid rocket motor specifications are collected from various small launch vehicle that had ever been in operation phase, and also from previous study. Comparison of orbital parameters shows that the radius of apocenter targeted can be approached using one combination of solid rocket motor specifications and appropriate coast time. However, the launch vehicle designed is failed to achieve the targeted orbit nor injecting the satellite to any orbit.

Ion current detector for high pressure ion sources for monitoring separations

DOEpatents

Smith, R.D.; Wahl, J.H.; Hofstadler, S.A.

1996-08-13

The present invention relates generally to any application involving the monitoring of signal arising from ions produced by electrospray or other high pressure (>100 torr) ion sources. The present invention relates specifically to an apparatus and method for the detection of ions emitted from a capillary electrophoresis (CE) system, liquid chromatography, or other small-scale separation methods. And further, the invention provides a very simple diagnostic as to the quality of the separation and the operation of an electrospray source. 7 figs.

Ion current detector for high pressure ion sources for monitoring separations

DOEpatents

Smith, Richard D.; Wahl, Jon H.; Hofstadler, Steven A.

1996-01-01

The present invention relates generally to any application involving the monitoring of signal arising from ions produced by electrospray or other high pressure (>100 torr) ion sources. The present invention relates specifically to an apparatus and method for the detection of ions emitted from a capillary electrophoresis (CE) system, liquid chromatography, or other small-scale separation methods. And further, the invention provides a very simple diagnostic as to the quality of the separation and the operation of an electrospray source.

Site-specific fab fragment biotinylation at the conserved nucleotide binding site for enhanced Ebola detection.

PubMed

Mustafaoglu, Nur; Alves, Nathan J; Bilgicer, Basar

2015-07-01

The nucleotide binding site (NBS) is a highly conserved region between the variable light and heavy chains at the Fab domains of all antibodies, and a small molecule that we identified, indole-3-butyric acid (IBA), binds specifically to this site. Fab fragment, with its small size and simple production methods compared to intact antibody, is good candidate for use in miniaturized diagnostic devices and targeted therapeutic applications. However, commonly used modification techniques are not well suited for Fab fragments as they are often more delicate than intact antibodies. Fab fragments are of particular interest for sensor surface functionalization but immobilization results in damage to the antigen binding site and greatly reduced activity due to their truncated size that allows only a small area that can bind to surfaces without impeding antigen binding. In this study, we describe an NBS-UV photocrosslinking functionalization method (UV-NBS(Biotin) in which a Fab fragment is site-specifically biotinylated with an IBA-EG11-Biotin linker via UV energy exposure (1 J/cm(2)) without affecting its antigen binding activity. This study demonstrates successful immobilization of biotinylated Ebola detecting Fab fragment (KZ52 Fab fragment) via the UV-NBS(Biotin) method yielding 1031-fold and 2-fold better antigen detection sensitivity compared to commonly used immobilization methods: direct physical adsorption and NHS-Biotin functionalization, respectively. Utilization of the UV-NBS(Biotin) method for site-specific conjugation to Fab fragment represents a proof of concept use of Fab fragment for various diagnostic and therapeutic applications with numerous fluorescent probes, affinity molecules and peptides. © 2015 Wiley Periodicals, Inc.

The pulmonary circulation of some domestic animals at high altitude

NASA Astrophysics Data System (ADS)

Anand, I.; Heath, D.; Williams, D.; Deen, M.; Ferrari, R.; Bergel, D.; Harris, P.

1988-03-01

Pulmonary haemodynamics and the histology of the pulmonary vasculature have been studied at high altitude in the yak, in interbreeds between yaks and cattle, and in domestic goats and sheep indigenous to high altitudes together with crosses between them and low-altitude strains. Cattle at high altitude had a higher pulmonary arterial pressure than cattle at low altitude. The yak and two interbreeds with cattle (dzos and stols) had a low pulmonary arterial pressure compared with cattle, while the medial thickness of the small pulmonary arteries was less than would be expected in cattle, suggesting that the yak has a low capacity for hypoxic pulmonary vasoconstriction and that this characteristic is transmitted genetically. Goats and sheep showed haemodynamic evidence of a limited response of the pulmonary circulation to high altitude, but no evidence that the high altitude breeds had lost this response. There were no measurable differences in the thickness of the media of the small pulmonary arteries between high- and low-altitude breeds of goats and sheep. All these species showed prominent intimal protrusions of muscle into the pulmonary veins but no specific effect of high altitude in this respect.

Magnetoresistive biosensors for quantitative proteomics

NASA Astrophysics Data System (ADS)

Zhou, Xiahan; Huang, Chih-Cheng; Hall, Drew A.

2017-08-01

Quantitative proteomics, as a developing method for study of proteins and identification of diseases, reveals more comprehensive and accurate information of an organism than traditional genomics. A variety of platforms, such as mass spectrometry, optical sensors, electrochemical sensors, magnetic sensors, etc., have been developed for detecting proteins quantitatively. The sandwich immunoassay is widely used as a labeled detection method due to its high specificity and flexibility allowing multiple different types of labels. While optical sensors use enzyme and fluorophore labels to detect proteins with high sensitivity, they often suffer from high background signal and challenges in miniaturization. Magnetic biosensors, including nuclear magnetic resonance sensors, oscillator-based sensors, Hall-effect sensors, and magnetoresistive sensors, use the specific binding events between magnetic nanoparticles (MNPs) and target proteins to measure the analyte concentration. Compared with other biosensing techniques, magnetic sensors take advantage of the intrinsic lack of magnetic signatures in biological samples to achieve high sensitivity and high specificity, and are compatible with semiconductor-based fabrication process to have low-cost and small-size for point-of-care (POC) applications. Although still in the development stage, magnetic biosensing is a promising technique for in-home testing and portable disease monitoring.

Optimizing Decadal and Precursor Science on Small Solar System Bodies with Spacecraft/Rover Hybrids

NASA Astrophysics Data System (ADS)

Pavone, M.; Castillo, J. C.; Hoffman, J. A.; Nesnas, I. A.; Strange, N. J.

2012-12-01

In this paper we present a mission architecture for the systematic and affordable in-situ exploration of small Solar System bodies (such as asteroids, comets, and Martian moons). The proposed mission architecture stems from a paradigm-shifting approach whereby small bodies' low gravity is directly exploited in the design process, rather than being faced as a constraint. At a general level, a mother spacecraft (of the type of JPL's NEOSurveyor) would deploy on the surface of a small body one, or several, spacecraft/rover hybrids, which are small (<5Kg, ~10W), multi-faceted robots enclosing three mutually orthogonal flywheels and surrounded by external spikes (in particular, there is no external propulsion). By accelerating/decelerating the flywheels and by exploiting the low gravity environment, the hybrids would be capable of performing both long excursions (by hopping) and short traverses to specific locations (through a sequence of controlled "tumbles"). Their control would rely on synergistic operations with the mother spacecraft (where most of hybrids' perception and localization functionalities would be hosted), which would make the platforms minimalistic and in turn the entire mission architecture affordable. A fundamental aspect of this mission architecture is that the responsibility for primary science would be shared between the mothership and the hybrids, in particular, the mothership would provide broad area coverage, while the hybrid would zoom in on specific areas and conduct in-situ measurements. Specifically, in the first part of the paper we discuss the scientific rationale behind the proposed mission architecture (including traceability matrices for both the mothership and the hybrids for a number of potential targets), we present preliminary models and laboratory experiments for the hybrids, we present first-order estimates for critical subsystems (e.g., communication, power, thermal) and a preliminary study for synergistic mission operations, and we discuss high-level mission trades (including deployment strategies). In the second part, we tailor our mission architecture to the exploration of Mars' moon Phobos. The mission aims at exploring Phobos' Stickney crater, whose spectral similarities with C-type asteroids and variety of terrain properties make it a particularly interesting exploration target to address both high-priority science for the Martian system and strategic knowledge gaps for the future Human exploration of Mars.

Comparison of Activity Profiles and Physiological Demands Between International Rugby Sevens Matches and Training.

PubMed

Higham, Dean G; Pyne, David B; Anson, Judith M; Hopkins, Will G; Eddy, Anthony

2016-05-01

The specificity of contemporary training practices of international rugby sevens players is unknown. We quantified the positional group-specific activity profiles and physiological demands of on-field training activities and compared these with match demands. Twenty-two international matches and 63 rugby-specific training drills were monitored in 25 backs and 17 forwards from a national squad of male rugby sevens players over a 21-month period. Drills were classified into 3 categories: low-intensity skill refining (n = 23 drills, 560 observations), moderate- to high-intensity skill refining (n = 28 drills, 600 observations), and game simulation (n = 12 drills, 365 observations). Movement patterns (via Global Positioning System devices) and physiological load (via heart rate monitors) were recorded for all activities, and the differences between training and matches were quantified using magnitude-based inferential statistics. Distance covered in total and at ≥3.5 m·s, maximal velocity, and frequency of accelerations and decelerations were lower for forwards during competition compared with those for backs by a small but practically important magnitude. No clear positional group differences were observed for physiological load during matches. Training demands exceeded match demands only for frequency of decelerations of forwards during moderate- to high-intensity skill-refining drills and only by a small amount. Accelerations and distance covered at ≥6 m·s were closer to match values for forwards than for backs during all training activities, but training drills consistently fell below the demands of international competition. Coaches could therefore improve physical and physiological specificity by increasing the movement demands and intensity of training drills.

Potent and Specific Inhibition of Glycosidases by Small Artificial Binding Proteins (Affitins)

PubMed Central

Mechaly, Ariel E.; Obal, Gonzalo; Béhar, Ghislaine; Mouratou, Barbara; Oppezzo, Pablo; Alzari, Pedro M.; Pecorari, Frédéric

2014-01-01

Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1°C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general. PMID:24823716

Potent and specific inhibition of glycosidases by small artificial binding proteins (affitins).

PubMed

Correa, Agustín; Pacheco, Sabino; Mechaly, Ariel E; Obal, Gonzalo; Béhar, Ghislaine; Mouratou, Barbara; Oppezzo, Pablo; Alzari, Pedro M; Pecorari, Frédéric

2014-01-01

Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1°C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general.

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.

Analysis of the melon (Cucumis melo) small RNAome by high-throughput pyrosequencing

PubMed Central

2011-01-01

Background Melon (Cucumis melo L.) is a commercially important fruit crop that is cultivated worldwide. The melon research community has recently benefited from the determination of a complete draft genome sequence and the development of associated genomic tools, which have allowed us to focus on small RNAs (sRNAs). These are short, non-coding RNAs 21-24 nucleotides in length with diverse physiological roles. In plants, they regulate gene expression and heterochromatin assembly, and control protection against virus infection. Much remains to be learned about the role of sRNAs in melon. Results We constructed 10 sRNA libraries from two stages of developing ovaries, fruits and photosynthetic cotyledons infected with viruses, and carried out high-throughput pyrosequencing. We catalogued and analysed the melon sRNAs, resulting in the identification of 26 known miRNA families (many conserved with other species), the prediction of 84 melon-specific miRNA candidates, the identification of trans-acting siRNAs, and the identification of chloroplast, mitochondrion and transposon-derived sRNAs. In silico analysis revealed more than 400 potential targets for the conserved and novel miRNAs. Conclusion We have discovered and analysed a large number of conserved and melon-specific sRNAs, including miRNAs and their potential target genes. This provides insight into the composition and function of the melon small RNAome, and paves the way towards an understanding of sRNA-mediated processes that regulate melon fruit development and melon-virus interactions. PMID:21812964

Improving couples' quality of life through a Web-based prostate cancer education intervention.

PubMed

Song, Lixin; Rini, Christine; Deal, Allison M; Nielsen, Matthew E; Chang, Hao; Kinneer, Patty; Teal, Randall; Johnson, David C; Dunn, Mary W; Mark, Barbara; Palmer, Mary H

2015-03-01

To evaluate the feasibility and acceptability of a newly developed web-based, couple-oriented intervention called Prostate Cancer Education and Resources for Couples (PERC). Quantitative, qualitative, mixed-methods approach. Oncology outpatient clinics at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center at UNC–Chapel Hill. 26 patients with localized prostate cancer (PCa) and their partners. Pre- and postpilot quantitative assessments and a postpilot qualitative interview were conducted. General and PCa-specific symptoms, quality of life, psychosocial factors, PERC’s ease of use, and web activities. Improvement was shown in some PCa-specific and general symptoms (small effect sizes for patients and small-to-medium effect sizes for partners), overall quality of life, and physical and social domains of quality of life for patients (small effect sizes). Web activity data indicated high PERC use. Qualitative and quantitative analyses indicated that participants found PERC easy to use and understand,as well as engaging, of high quality, and relevant. Overall, participants were satisfied with PERC and reported that PERC improved their knowledge about symptom management and communication as a couple. PERC was a feasible, acceptable method of reducing the side effects of PCa treatment–related symptoms and improving quality of life. PERC has the potential to reduce the negative impacts of symptoms and enhance quality of life for patients with localized PCa and their partners, particularly for those who live in rural areas and have limited access to post-treatment supportive care.

Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells.

PubMed

Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C; Van Duyne, Rachel; Calvert, Valerie; Petricoin, Emanuel; Saifuddin, Mohammed; Kehn-Hall, Kylene; Kashanchi, Fatah

2015-06-01

Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high-throughput proteomic assays, we have previously identified Bruton's tyrosine kinase (BTK) as a host protein that was uniquely upregulated in the plasma membrane of human immunodeficiency virus (HIV-1)-infected T cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant upregulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells; however, new BTK protein complexes were identified and distributed in both high molecular weight (∼600 kDa) and a small molecular weight complex (∼60-120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1-infected cells using small interfering RNA (siRNA) resulted in selective death of infected, but not uninfected, cells. Using BTK-specific antibody and small-molecule inhibitors including LFM-A13 and a FDA-approved compound, ibrutinib (PCI-32765), we have found that HIV-1-infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1-infected cells are sensitive to treatments targeting BTK expressed in infected cells.

A Cu-free clickable fluorescent probe for intracellular targeting of small biomolecules.

PubMed

Yamagishi, Kento; Sawaki, Kazuaki; Murata, Atsushi; Takeoka, Shinji

2015-05-07

We synthesized a novel cyclooctyne-based clickable fluorescent probe with versatile properties such as high cell-membrane permeability and free diffusibility in the cell. Our probe "FC-DBCO" was conjugated to an azide-modified mannose via a Cu-free click reaction in living HeLa cells and displayed intracellular specific fluorescence imaging with low background signals.

Extreme Environments Test Capabilities at NASA GRC for Parker Hannifin Visit

NASA Technical Reports Server (NTRS)

Arnett, Lori

2016-01-01

The presentation includes general description on the following test facilities: Fuel Cell Testing Lab, Structural Dynamics Lab, Thermal Vacuum Test Facilities - including a description of the proposed Kinetic High Altitude Simulator concept, EMI Test Lab, and the Creek Road Cryogenic Complex - specifically the Small Multi-purpose Research Facility (SMiRF) and the Cryogenics Components Lab 7 (CCL-7).

Lithographically defined microporous carbon structures

DOEpatents

Burckel, David Bruce; Washburn, Cody M.; Polsky, Ronen; Brozik, Susan M.; Wheeler, David R.

2013-01-08

A lithographic method is used to fabricate porous carbon structures that can provide electrochemical electrodes having high surface area with uniform and controllable dimensions, providing enormous flexibility to tailor the electrodes toward specific applications. Metal nanoparticles deposited on the surface of the porous carbon electrodes exhibit ultra small dimensions with uniform size distribution. The resulting electrodes are rugged, electrically conductive and show excellent electrochemical behavior.

Activist Literacies: An Analysis of the Literacy Practices of a School-Based Human Rights Club

ERIC Educational Resources Information Center

Collin, Ross

2012-01-01

In this article, I examine the literacy practices of a high school-based human rights club. I investigate how the group engages in certain kinds of textual production to sponsor and arrange advisory sessions (school-wide meetings between teachers and small groups of students). More specifically, I consider how the club adapts school genres to…

Break-even zones for cable yarding by log size

Treesearch

Chris B. LeDoux

1984-01-01

The use of cable logging to extract small pieces of residue wood may result in low rates of production and a high cost per unit of wood produced. However, the logging manager can improve yarding productivity and break-even in cable residue removal operations by using the proper planning techniques. In this study, break-even zones for specific young-growth stands were...

Observation of giant conductance fluctuations in a protein

NASA Astrophysics Data System (ADS)

Zhang, Bintian; Song, Weisi; Pang, Pei; Zhao, Yanan; Zhang, Peiming; Csabai, István; Vattay, Gábor; Lindsay, Stuart

2017-12-01

Proteins are insulating molecular solids, yet even those containing easily reduced or oxidized centers can have single-molecule electronic conductances that are too large to account for with conventional transport theories. Here, we report the observation of remarkably high electronic conductance states in an electrochemically inactive protein, the ∼200 kD α V β 3 extracellular domain of human integrin. Large current pulses (up to nA) were observed for long durations (many ms, corresponding to many pC of charge transfer) at large gap (>5 nm) distances in an STM when the protein was bound specifically by a small peptide ligand attached to the electrodes. The effect is greatly reduced when a homologous, weakly binding protein (α 4 β 1) is used as a control. In order to overcome the limitations of the STM, the time- and voltage-dependence of the conductance were further explored using a fixed-gap (5 nm) tunneling junction device that was small enough to trap a single protein molecule at any one time. Transitions to a high conductance (∼nS) state were observed, the protein being ‘on’ for times from ms to tenths of a second. The high-conductance states only occur above ∼100 mV applied bias, and thus are not an equilibrium property of the protein. Nanoamp two-level signals indicate the specific capture of a single molecule in an electrode gap functionalized with the ligand. This offers a new approach to label-free electronic detection of single protein molecules. Electronic structure calculations yield a distribution of energy level spacings that is consistent with a recently proposed quantum-critical state for proteins, in which small fluctuations can drive transitions between localized and band-like electronic states.

Observation of Giant Conductance Fluctuations in a Protein

PubMed Central

Zhang, Bintian; Song, Weisi; Pang, Pei; Zhao, Yanan; Zhang, Peiming; Csabai, István; Vattay, Gábor; Lindsay, Stuart

2017-01-01

Proteins are insulating molecular solids, yet even those containing easily reduced or oxidized centers can have single-molecule electronic conductances that are too large to account for with conventional transport theories. Here, we report the observation of remarkably high electronic conductance states in an electrochemically-inactive protein, the ~200 kD αVβ3 extracelluar domain of human integrin. Large current pulses (up to nA) were observed for long durations (many ms, corresponding to many pC of charge transfer) at large gap (>5nm) distances in an STM when the protein was bound specifically by a small peptide ligand attached to the electrodes. The effect is greatly reduced when a homologous, weakly-binding protein (α4β1) is used as a control. In order to overcome the limitations of the STM, the time- and voltage-dependence of the conductance were further explored using a fixed-gap (5 nm) tunneling junction device that was small enough to trap a single protein molecule at any one time. Transitions to a high conductance (~ nS) state were observed, the protein being “on” for times from ms to tenths of a second. The high-conductance states only occur above ~ 100mV applied bias, and thus are not an equilibrium property of the protein. Nanoamp two-level signals indicate the specific capture of a single molecule in an electrode gap functionalized with the ligand. This offers a new approach to label-free electronic detection of single protein molecules. Electronic structure calculations yield a distribution of energy level spacings that is consistent with a recently proposed quantum-critical state for proteins, in which small fluctuations can drive transitions between localized and band-like electronic states. PMID:29552645

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

Substrate specificity of the ubiquitin and Ubl proteases

PubMed Central

Ronau, Judith A; Beckmann, John F; Hochstrasser, Mark

2016-01-01

Conjugation and deconjugation of ubiquitin and ubiquitin-like proteins (Ubls) to cellular proteins are highly regulated processes integral to cellular homeostasis. Most often, the C-termini of these small polypeptides are attached to lysine side chains of target proteins by an amide (isopeptide) linkage. Deubiquitinating enzymes (DUBs) and Ubl-specific proteases (ULPs) comprise a diverse group of proteases that recognize and remove ubiquitin and Ubls from their substrates. How DUBs and ULPs distinguish among different modifiers, or different polymeric forms of these modifiers, remains poorly understood. The specificity of ubiquitin/Ubl-deconjugating enzymes for particular substrates depends on multiple factors, ranging from the topography of specific substrate features, as in different polyubiquitin chain types, to structural elements unique to each enzyme. Here we summarize recent structural and biochemical studies that provide insights into mechanisms of substrate specificity among various DUBs and ULPs. We also discuss the unexpected specificities of non-eukaryotic proteases in these families. PMID:27012468

Overproduction, purification, and biochemical characterization of the dual specificity H1 protein phosphatase encoded by variola major virus.

PubMed

Tropea, Joseph E; Phan, Jason; Waugh, David S

2006-11-01

Smallpox, a highly contagious infectious disease caused by the variola major virus, has an overall mortality rate of about 30%. Because there currently is no specific treatment for smallpox, and the only prevention is vaccination, there is an urgent need for the development of effective antiviral drugs. The dual specificity protein phosphatase encoded by the smallpox virus (H1) is essential for the production of infectious viral particles, making it a promising molecular target for antiviral therapeutics. Here, we report the molecular cloning, overproduction, purification, and initial biochemical characterization of H1 phosphatase, thereby paving the way for the discovery of small molecule inhibitors.

Hierarchically structured Co₃O₄@Pt@MnO₂ nanowire arrays for high-performance supercapacitors.

PubMed

Xia, Hui; Zhu, Dongdong; Luo, Zhentao; Yu, Yue; Shi, Xiaoqin; Yuan, Guoliang; Xie, Jianping

2013-10-17

Here we proposed a novel architectural design of a ternary MnO2-based electrode - a hierarchical Co3O4@Pt@MnO2 core-shell-shell structure, where the complemental features of the three key components (a well-defined Co3O4 nanowire array on the conductive Ti substrate, an ultrathin layer of small Pt nanoparticles, and a thin layer of MnO2 nanoflakes) are strategically combined into a single entity to synergize and construct a high-performance electrode for supercapacitors. Owing to the high conductivity of the well-defined Co3O4 nanowire arrays, in which the conductivity was further enhanced by a thin metal (Pt) coating layer, in combination with the large surface area provided by the small MnO2 nanoflakes, the as-fabricated Co3O4@Pt@MnO2 nanowire arrays have exhibited high specific capacitances, good rate capability, and excellent cycling stability. The architectural design demonstrated in this study provides a new approach to fabricate high-performance MnO2-based nanowire arrays for constructing next-generation supercapacitors.

Hierarchically Structured Co3O4@Pt@MnO2 Nanowire Arrays for High-Performance Supercapacitors

NASA Astrophysics Data System (ADS)

Xia, Hui; Zhu, Dongdong; Luo, Zhentao; Yu, Yue; Shi, Xiaoqin; Yuan, Guoliang; Xie, Jianping

2013-10-01

Here we proposed a novel architectural design of a ternary MnO2-based electrode - a hierarchical Co3O4@Pt@MnO2 core-shell-shell structure, where the complemental features of the three key components (a well-defined Co3O4 nanowire array on the conductive Ti substrate, an ultrathin layer of small Pt nanoparticles, and a thin layer of MnO2 nanoflakes) are strategically combined into a single entity to synergize and construct a high-performance electrode for supercapacitors. Owing to the high conductivity of the well-defined Co3O4 nanowire arrays, in which the conductivity was further enhanced by a thin metal (Pt) coating layer, in combination with the large surface area provided by the small MnO2 nanoflakes, the as-fabricated Co3O4@Pt@MnO2 nanowire arrays have exhibited high specific capacitances, good rate capability, and excellent cycling stability. The architectural design demonstrated in this study provides a new approach to fabricate high-performance MnO2-based nanowire arrays for constructing next-generation supercapacitors.

An end-to-end workflow for engineering of biological networks from high-level specifications.

PubMed

Beal, Jacob; Weiss, Ron; Densmore, Douglas; Adler, Aaron; Appleton, Evan; Babb, Jonathan; Bhatia, Swapnil; Davidsohn, Noah; Haddock, Traci; Loyall, Joseph; Schantz, Richard; Vasilev, Viktor; Yaman, Fusun

2012-08-17

We present a workflow for the design and production of biological networks from high-level program specifications. The workflow is based on a sequence of intermediate models that incrementally translate high-level specifications into DNA samples that implement them. We identify algorithms for translating between adjacent models and implement them as a set of software tools, organized into a four-stage toolchain: Specification, Compilation, Part Assignment, and Assembly. The specification stage begins with a Boolean logic computation specified in the Proto programming language. The compilation stage uses a library of network motifs and cellular platforms, also specified in Proto, to transform the program into an optimized Abstract Genetic Regulatory Network (AGRN) that implements the programmed behavior. The part assignment stage assigns DNA parts to the AGRN, drawing the parts from a database for the target cellular platform, to create a DNA sequence implementing the AGRN. Finally, the assembly stage computes an optimized assembly plan to create the DNA sequence from available part samples, yielding a protocol for producing a sample of engineered plasmids with robotics assistance. Our workflow is the first to automate the production of biological networks from a high-level program specification. Furthermore, the workflow's modular design allows the same program to be realized on different cellular platforms simply by swapping workflow configurations. We validated our workflow by specifying a small-molecule sensor-reporter program and verifying the resulting plasmids in both HEK 293 mammalian cells and in E. coli bacterial cells.

Highly sensitive detection of cancer cells using femtosecond dual-wavelength near-IR two-photon imaging.

PubMed

Starkey, Jean R; Makarov, Nikolay S; Drobizhev, Mikhail; Rebane, Aleksander

2012-07-01

We describe novel imaging protocols that allow detection of small cancer cell colonies deep inside tissue phantoms with high sensitivity and specificity. We compare fluorescence excited in Styryl-9M molecules by femtosecond pulses at near IR wavelengths, where Styryl-9M shows the largest dependence of the two-photon absorption (2PA) cross section on the local environment. We show that by calculating the normalized ratio of the two-photon excited fluorescence (2PEF) intensity at 1200 nm and 1100 nm excitation wavelengths we can achieve high sensitivity and specificity for determining the location of cancer cells surrounded by normal cells. The 2PEF results showed a positive correlation with the levels of MDR1 proteins expressed by the cells, and, for high MDR1 expressors, as few as ten cancer cells could be detected. Similar high sensitivity is also demonstrated for tumor colonies induced in mouse external ears. This technique could be useful in early cancer detection, and, perhaps, also in monitoring dormant cancer deposits.

Compact Plasma Accelerator for Micropropulsion Applications

NASA Technical Reports Server (NTRS)

Foster, John E.

2001-01-01

There is a need for a low power, light-weight (compact), high specific impulse electric propulsion device to satisfy mission requirements for microsatellite (1 to 20 kg) class missions. Satisfying these requirements entails addressing the general problem of generating a sufficiently dense plasma within a relatively small volume and then accelerating it. In the work presented here, the feasibility of utilizing a magnetic cusp to generate a dense plasma over small length scales of order 1 mm is investigated. This approach could potentially mitigate scaling issues associated with conventional ion thruster plasma containment schemes. Plume and discharge characteristics were documented using a Faraday probe and a retarding potential analyzer.

Input and output compensation for the cochlear traveling wave delay in wide-band ABR recordings: implications for small acoustic tumor detection.

PubMed

Don, Manuel; Elberling, Claus; Maloff, Erin

2009-02-01

The Stacked ABR (auditory brainstem response) attempts at the output of the auditory periphery to compensate for the temporal dispersion of neural activation caused by the cochlear traveling wave in response to click stimulation. Compensation can also be made at the input by using a chirp stimulus. It has been demonstrated that the Stacked ABR is sensitive to small tumors that are often missed by standard ABR latency measures. Because a chirp stimulus requires only a single data acquisition run whereas the Stacked ABR requires six, we try to evaluate some indirect evidence justifying the use of a chirp for small tumor detection. We compared the sensitivity and specificity of different Stacked ABRs formed by aligning the derived-band ABRs according to (1) the individual's peak latencies, (2) the group mean latencies, and (3) the modeled latencies used to develop a chirp. For tumor detection with a chosen sensitivity of 95%, a relatively high specificity of 85% may be achieved with a chirp. It appears worthwhile to explore the actual use of a chirp because significantly shorter test and analysis times might be possible.

MALDI matrices for low molecular weight compounds: an endless story?

PubMed

Calvano, Cosima Damiana; Monopoli, Antonio; Cataldi, Tommaso R I; Palmisano, Francesco

2018-04-23

Since its introduction in the 1980s, matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has gained a prominent role in the analysis of high molecular weight biomolecules such as proteins, peptides, oligonucleotides, and polysaccharides. Its application to low molecular weight compounds has remained for long time challenging due to the spectral interferences produced by conventional organic matrices in the low m/z window. To overcome this problem, specific sample preparation such as analyte/matrix derivatization, addition of dopants, or sophisticated deposition technique especially useful for imaging experiments, have been proposed. Alternative approaches based on second generation (rationally designed) organic matrices, ionic liquids, and inorganic matrices, including metallic nanoparticles, have been the object of intense and continuous research efforts. Definite evidences are now provided that MALDI MS represents a powerful and invaluable analytical tool also for small molecules, including their quantification, thus opening new, exciting applications in metabolomics and imaging mass spectrometry. This review is intended to offer a concise critical overview of the most recent achievements about MALDI matrices capable of specifically address the challenging issue of small molecules analysis. Graphical abstract An ideal Book of matrices for MALDI MS of small molecules.

In situ click chemistry: from small molecule discovery to synthetic antibodies

PubMed Central

Agnew, Heather D.; Lai, Bert; Lee, Su Seong; Lim, Jaehong; Nag, Arundhati; Pitram, Suresh; Rohde, Rosemary; Heath, James R.

2013-01-01

Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents. PMID:22836343

Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

PubMed

de Almeida, Carlos E B; Alves, Lais Nascimento; Rocha, Henrique F; Cabral-Neto, Januário Bispo; Missailidis, Sotiris

2017-06-20

Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements. Copyright © 2017 Elsevier B.V. All rights reserved.

Highly sensitive and specific colorimetric detection of cancer cells via dual-aptamer target binding strategy.

PubMed

Wang, Kun; Fan, Daoqing; Liu, Yaqing; Wang, Erkang

2015-11-15

Simple, rapid, sensitive and specific detection of cancer cells is of great importance for early and accurate cancer diagnostics and therapy. By coupling nanotechnology and dual-aptamer target binding strategies, we developed a colorimetric assay for visually detecting cancer cells with high sensitivity and specificity. The nanotechnology including high catalytic activity of PtAuNP and magnetic separation & concentration plays a vital role on the signal amplification and improvement of detection sensitivity. The color change caused by small amount of target cancer cells (10 cells/mL) can be clearly distinguished by naked eyes. The dual-aptamer target binding strategy guarantees the detection specificity that large amount of non-cancer cells and different cancer cells (10(4) cells/mL) cannot cause obvious color change. A detection limit as low as 10 cells/mL with detection linear range from 10 to 10(5) cells/mL was reached according to the experimental detections in phosphate buffer solution as well as serum sample. The developed enzyme-free and cost effective colorimetric assay is simple and no need of instrument while still provides excellent sensitivity, specificity and repeatability, having potential application on point-of-care cancer diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Alterations to metabolically active bacteria in the mucosa of the small intestine predict anti-obesity and anti-diabetic activities of grape seed extract in mice.

PubMed

Griffin, Laura E; Witrick, Katherine A; Klotz, Courtney; Dorenkott, Melanie R; Goodrich, Katheryn M; Fundaro, Gabrielle; McMillan, Ryan P; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P

2017-10-18

Epidemiological and clinical studies suggest that grapes and grape-derived products may reduce the risk for chronic disease. Grape seed extract specifically has been gaining interest due to its reported ability to prevent weight gain, moderate hyperglycemia, and reduce inflammation. The purpose of this study was to examine the long-term effects of two doses of grape seed extract (10 and 100 mg kg -1 body wt per d in mice) on markers of metabolic syndrome in the context of a moderately high-fat diet. After 12 weeks, the lower dose of grape seed extract was more effective at inhibiting fat gain and improving glucose tolerance and insulin sensitivity. Neither the high fat diet nor grape seed extract altered skeletal muscle substrate metabolism. Most interestingly, when examining the profile of metabolically active microbiota in the mucosa of the small intestine, cecum, and colonic tissue, grape seed extract seemed to have the most dramatic effect on small intestinal tissue, where the population of Firmicutes was lower compared to control groups. This effect was not observed in the cecal or colonic tissues, suggesting that the main alterations to gut microbiota due to flavan-3-ol supplementation occur in the small intestine, which has not been reported previously. These findings suggest that grape seed extract can prevent early changes in glucose tolerance and alter small intestinal gut microbiota, prior to the onset of skeletal muscle metabolic derangements, when grape seed extract is consumed at a low dose in the context of a moderately high fat diet.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

PubMed Central

Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

2016-01-01

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

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

The influence of DNA degradation in formalin-fixed, paraffin-embedded (FFPE) tissue on locus-specific methylation assessment by MS-HRM.

PubMed

Daugaard, Iben; Kjeldsen, Tina E; Hager, Henrik; Hansen, Lise Lotte; Wojdacz, Tomasz K

2015-12-01

Readily accessible formalin-fixed paraffin embedded (FFPE) tissues are a highly valuable source of genetic material for molecular analyses in both research and in vitro diagnostics but frequently genetic material in those samples is highly degraded. With locus-specific methylation changes being widely investigated for use as biomarkers in various aspects of clinical disease management, we aimed to evaluate to what extent standard laboratory procedures can approximate the quality of the DNA extracted from FFPE samples prior to methylation analyses. DNA quality in 107 FFPE non-small cell lung cancer (NSCLC) samples was evaluated using spectrophotometry and gel electrophoresis. Subsequently, the quality assessment results were correlated with the results of locus specific methylation assessment with methylation sensitive high resolution melting (MS-HRM). The correlation of template quality with PCR amplification performance and HRM based methylation detection indicated a significant influence of DNA quality on PCR amplification but not on methylation assessment. In conclusion, standard laboratory procedures fairly well approximate DNA degradation of FFPE samples and DNA degradation does not seem to considerably affect locus-specific methylation assessment by MS-HRM. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevalence of tick-borne haemoparasites in small ruminants in Turkey and diagnostic sensitivity of single-PCR and RLB.

PubMed

Bilgic, Huseyin Bilgin; Bakırcı, Serkan; Kose, Onur; Unlu, Ahmet Hakan; Hacılarlıoglu, Selin; Eren, Hasan; Weir, William; Karagenc, Tulin

2017-04-27

Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria, Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the distributions of host, pathogen and vector overlap. Many of these diseases threaten livestock production and some also represent a concern to human public health. The primary aim of this study was to determine the prevalence of the above-mentioned pathogens in a large number of blood samples (n = 1979) collected from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to assess the diagnostic sensitivity of a number of species-specific polymerase chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples were screened using species-specific PCR for the presence of Theileria ovis, Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis, Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The diagnostic sensitivity of these two approaches was then compared in terms of their ability to detect single species and mixed infections. Overall, 84 and 74.43% of the small ruminants sampled were identified as hosting one or more pathogen(s) by species-specific PCR and RLB respectively. The presence of Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the first time while the presence of Babesia motasi, B. crassa and T. separata in Turkish small ruminants was confirmed using molecular methods. A high prevalence of mixed infection was evident, with PCR and RLB approaches indicating that 52.24 and 35.42% of animals were co-infected with multiple species, respectively. More than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB approach was found to be capable of detecting mixed infections with species such as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp. The results indicated that pathogens causing TBHDs are highly prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species-specific single PCR was generally higher than that of RLB. However, the latter approach was still capable of identifying a high proportion of individuals containing mixed-species infections. The use of species-specific single PCR is recommended to accurately estimate pathogen prevalence and to identify co-infected hosts.

Computational active site analysis of molecular pathways to improve functional classification of enzymes.

PubMed

Ozyurt, A Sinem; Selby, Thomas L

2008-07-01

This study describes a method to computationally assess the function of homologous enzymes through small molecule binding interaction energy. Three experimentally determined X-ray structures and four enzyme models from ornithine cyclo-deaminase, alanine dehydrogenase, and mu-crystallin were used in combination with nine small molecules to derive a function score (FS) for each enzyme-model combination. While energy values varied for a single molecule-enzyme combination due to differences in the active sites, we observe that the binding energies for the entire pathway were proportional for each set of small molecules investigated. This proportionality of energies for a reaction pathway appears to be dependent on the amino acids in the active site and their direct interactions with the small molecules, which allows a function score (FS) to be calculated to assess the specificity of each enzyme. Potential of mean force (PMF) calculations were used to obtain the energies, and the resulting FS values demonstrate that a measurement of function may be obtained using differences between these PMF values. Additionally, limitations of this method are discussed based on: (a) larger substrates with significant conformational flexibility; (b) low homology enzymes; and (c) open active sites. This method should be useful in accurately predicting specificity for single enzymes that have multiple steps in their reactions and in high throughput computational methods to accurately annotate uncharacterized proteins based on active site interaction analysis. 2008 Wiley-Liss, Inc.

Discovery of novel cold-induced CISP genes encoding small RNA-binding proteins related to cold adaptation in barley.

PubMed

Ying, Mengchao; Kidou, Shin-Ichiro

2017-07-01

To adapt to cold conditions, barley plants rely on specific mechanisms, which have not been fully understood. In this study, we characterized a novel barley cold-induced gene identified using a PCR-based high coverage gene expression profiling method. The identified gene encodes a small protein that we named CISP1 (Cold-induced Small Protein 1). Homology searches of sequence databases revealed that CISP1 homologs (CISP2 and CISP3) exist in barley genome. Further database analyses showed that the CISP1 homologs were widely distributed in cold-tolerant plants such as wheat and rye. Quantitative reverse transcription PCR analyses indicated that the expression of barley CISP genes was markedly increased in roots exposed to cold conditions. In situ hybridization analyses showed that the CISP1 transcripts were localized in the root tip and lateral root primordium. We also demonstrated that the CISP1 protein bound to RNA. Taken together, these findings indicate that CISP1 and its homologs encoding small RNA-binding proteins may serve as RNA chaperones playing a vital role in the cold adaptation of barley root. This is the first report describing the likely close relationship between root-specific genes and the cold adaptation process, as well as the potential function of the identified genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Using 3D printed models for planning and guidance during endovascular intervention: a technical advance.

PubMed

Itagaki, Michael W

2015-01-01

Three-dimensional (3D) printing applications in medicine have been limited due to high cost and technical difficulty of creating 3D printed objects. It is not known whether patient-specific, hollow, small-caliber vascular models can be manufactured with 3D printing, and used for small vessel endoluminal testing of devices. Manufacture of anatomically accurate, patient-specific, small-caliber arterial models was attempted using data from a patient's CT scan, free open-source software, and low-cost Internet 3D printing services. Prior to endovascular treatment of a patient with multiple splenic artery aneurysms, a 3D printed model was used preoperatively to test catheter equipment and practice the procedure. A second model was used intraoperatively as a reference. Full-scale plastic models were successfully produced. Testing determined the optimal puncture site for catheter positioning. A guide catheter, base catheter, and microcatheter combination selected during testing was used intraoperatively with success, and the need for repeat angiograms to optimize image orientation was minimized. A difficult and unconventional procedure was successful in treating the aneurysms while preserving splenic function. We conclude that creation of small-caliber vascular models with 3D printing is possible. Free software and low-cost printing services make creation of these models affordable and practical. Models are useful in preoperative planning and intraoperative guidance.

The sRNAome mining revealed existence of unique signature small RNAs derived from 5.8SrRNA from Piper nigrum and other plant lineages.

PubMed

Asha, Srinivasan; Soniya, E V

2017-02-01

Small RNAs derived from ribosomal RNAs (srRNAs) are rarely explored in the high-throughput data of plant systems. Here, we analyzed srRNAs from the deep-sequenced small RNA libraries of Piper nigrum, a unique magnoliid plant. The 5' end of the putative long form of 5.8S rRNA (5.8S L rRNA) was identified as the site for biogenesis of highly abundant srRNAs that are unique among the Piperaceae family of plants. A subsequent comparative analysis of the ninety-seven sRNAomes of diverse plants successfully uncovered the abundant existence and precise cleavage of unique rRF signature small RNAs upstream of a novel 5' consensus sequence of the 5.8S rRNA. The major cleavage process mapped identically among the different tissues of the same plant. The differential expression and cleavage of 5'5.8S srRNAs in Phytophthora capsici infected P. nigrum tissues indicated the critical biological functions of these srRNAs during stress response. The non-canonical short hairpin precursor structure, the association with Argonaute proteins, and the potential targets of 5'5.8S srRNAs reinforced their regulatory role in the RNAi pathway in plants. In addition, this novel lineage specific small RNAs may have tremendous biological potential in the taxonomic profiling of plants.

The sRNAome mining revealed existence of unique signature small RNAs derived from 5.8SrRNA from Piper nigrum and other plant lineages

PubMed Central

Asha, Srinivasan; Soniya, E. V.

2017-01-01

Small RNAs derived from ribosomal RNAs (srRNAs) are rarely explored in the high-throughput data of plant systems. Here, we analyzed srRNAs from the deep-sequenced small RNA libraries of Piper nigrum, a unique magnoliid plant. The 5′ end of the putative long form of 5.8S rRNA (5.8SLrRNA) was identified as the site for biogenesis of highly abundant srRNAs that are unique among the Piperaceae family of plants. A subsequent comparative analysis of the ninety-seven sRNAomes of diverse plants successfully uncovered the abundant existence and precise cleavage of unique rRF signature small RNAs upstream of a novel 5′ consensus sequence of the 5.8S rRNA. The major cleavage process mapped identically among the different tissues of the same plant. The differential expression and cleavage of 5′5.8S srRNAs in Phytophthora capsici infected P. nigrum tissues indicated the critical biological functions of these srRNAs during stress response. The non-canonical short hairpin precursor structure, the association with Argonaute proteins, and the potential targets of 5′5.8S srRNAs reinforced their regulatory role in the RNAi pathway in plants. In addition, this novel lineage specific small RNAs may have tremendous biological potential in the taxonomic profiling of plants. PMID:28145468

[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.

The diagnostic performance of expert dermoscopists vs a computer-vision system on small-diameter melanomas.

PubMed

Friedman, Robert J; Gutkowicz-Krusin, Dina; Farber, Michele J; Warycha, Melanie; Schneider-Kels, Lori; Papastathis, Nicole; Mihm, Martin C; Googe, Paul; King, Roy; Prieto, Victor G; Kopf, Alfred W; Polsky, David; Rabinovitz, Harold; Oliviero, Margaret; Cognetta, Armand; Rigel, Darrell S; Marghoob, Ashfaq; Rivers, Jason; Johr, Robert; Grant-Kels, Jane M; Tsao, Hensin

2008-04-01

To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter

Distinct management issues with Crohn's disease of the small intestine.

PubMed

Fong, Steven C M; Irving, Peter M

2015-03-01

Small bowel Crohn's disease can present with clinical challenges that are specific to its location. In this review, we address some of the areas that present particular problems in small bowel Crohn's disease. A key issue specific to small bowel Crohn's disease relates to its diagnosis given that access to the small bowel is limited. Radiological advances, particularly in small bowel ultrasonography and MRI, as well as the introduction of capsule endoscopy and balloon enteroscopy are helping to address this. In addition, our ability to differentiate small bowel Crohn's disease from other causes of inflammation, such as tuberculosis, is improving on the basis of better understanding of the features that differentiate these conditions. It is also becoming apparent that jejunal Crohn's disease represents a distinct disease phenotype with potentially worse clinical outcomes. Finally, because it is a rare complication, our understanding of small bowel cancer associated with Crohn's disease remains limited. Recent publications are, however, starting to improve our knowledge of this condition. Although small bowel Crohn's disease presents specific management issues not seen in patients with Crohn's disease elsewhere in the gastrointestinal tract, our knowledge of how to manage these is improving.

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.

Small-Scale Tropopause Dynamics and TOMS Total Ozone

NASA Technical Reports Server (NTRS)

Stanford, John L.

2002-01-01

This project used Earth Probe Total Ozone Mapping Spectrometer (EP TOMS) along-track ozone retrievals, in conjunction with ancillary meteorological fields and modeling studies, for high resolution investigations of upper troposphere and lower stratosphere dynamics. Specifically, high resolution along-track (Level 2) EP TOMS data were used to investigate the beautiful fine-scale structure in constituent and meteorological fields prominent in the evolution of highly non-linear baroclinic storm systems. Comparison was made with high resolution meteorological models. The analyses provide internal consistency checks and validation of the EP TOMS data which are vital for monitoring ozone depletion in both polar and midlatitude regions.

Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

NASA Astrophysics Data System (ADS)

Pal, Rahul; Yang, Jinping; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

2016-03-01

Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

New Airborne Sensors and Platforms for Solving Specific Tasks in Remote Sensing

NASA Astrophysics Data System (ADS)

Kemper, G.

2012-07-01

A huge number of small and medium sized sensors entered the market. Today's mid format sensors reach 80 MPix and allow to run projects of medium size, comparable with the first big format digital cameras about 6 years ago. New high quality lenses and new developments in the integration prepared the market for photogrammetric work. Companies as Phase One or Hasselblad and producers or integrators as Trimble, Optec, and others utilized these cameras for professional image production. In combination with small camera stabilizers they can be used also in small aircraft and make the equipment small and easy transportable e.g. for rapid assessment purposes. The combination of different camera sensors enables multi or hyper-spectral installations e.g. useful for agricultural or environmental projects. Arrays of oblique viewing cameras are in the market as well, in many cases these are small and medium format sensors combined as rotating or shifting devices or just as a fixed setup. Beside the proper camera installation and integration, also the software that controls the hardware and guides the pilot has to solve much more tasks than a normal FMS did in the past. Small and relatively cheap Laser Scanners (e.g. Riegl) are in the market and a proper combination with MS Cameras and an integrated planning and navigation is a challenge that has been solved by different softwares. Turnkey solutions are available e.g. for monitoring power line corridors where taking images is just a part of the job. Integration of thermal camera systems with laser scanner and video capturing must be combined with specific information of the objects stored in a database and linked when approaching the navigation point.

Applications of CRISPR/Cas9 technology for targeted mutagenesis, gene replacement and stacking of genes in higher plants.

PubMed

Luo, Ming; Gilbert, Brian; Ayliffe, Michael

2016-07-01

Mutagenesis continues to play an essential role for understanding plant gene function and, in some instances, provides an opportunity for plant improvement. The development of gene editing technologies such as TALENs and zinc fingers has revolutionised the targeted mutation specificity that can now be achieved. The CRISPR/Cas9 system is the most recent addition to gene editing technologies and arguably the simplest requiring only two components; a small guide RNA molecule (sgRNA) and Cas9 endonuclease protein which complex to recognise and cleave a specific 20 bp target site present in a genome. Target specificity is determined by complementary base pairing between the sgRNA and target site sequence enabling highly specific, targeted mutation to be readily engineered. Upon target site cleavage, error-prone endogenous repair mechanisms produce small insertion/deletions at the target site usually resulting in loss of gene function. CRISPR/Cas9 gene editing has been rapidly adopted in plants and successfully undertaken in numerous species including major crop species. Its applications are not restricted to mutagenesis and target site cleavage can be exploited to promote sequence insertion or replacement by recombination. The multiple applications of this technology in plants are described.

Detection of Non-Nucleic Acid Targets with an Unmodified Aptamer and a Fluorogenic Competitor

PubMed Central

Li, Na

2010-01-01

Aptamers are oligonucleotides that can bind to various non-nucleic acid targets, ranging from proteins to small molecules, with a specificity and affinity comparable to that of antibodies. Most aptamer-based detection strategies require modification on the aptamer, which could lead to a significant loss in its affinity and specificity to the target. Here we reported a generic strategy to design aptamer-based optical probes. An unmodified aptamer specific to the target and a fluorogenic competitor complementary to the aptamer are utilized for target recognition and signal generation, respectively. The competitor is a hairpin oligonucleotide with a fluorophore attached on one end and a quencher attached on the other. When no target is present, the competitor binds to the aptamer. However, when the target is introduced, the competitor will be displaced from the aptamer by the target, thus resulting in a target-specific decrease in fluorescence signal. Successful application of this strategy to different types of targets (small molecules and proteins) as well as different types of aptamers (DNA and RNA) has been demonstrated. Furthermore, a thermodynamics-based prediction model was established to further rationalize the optimization process. Due to its rapidness and simplicity, this aptamer-based detection strategy holds great promise in high throughput applications. PMID:20563298

MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer.

PubMed

Zhou, Qun; Huang, Shao-Xin; Zhang, Feng; Li, Shu-Jun; Liu, Cong; Xi, Yong-Yong; Wang, Liang; Wang, Xin; He, Qi-Qiang; Sun, Cheng-Cao; Li, De-Jia

2017-12-01

Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC. © 2017 John Wiley & Sons Ltd.

18 CFR 4.106 - Standard terms and conditions of case-specific exemption from licensing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.106 Standard terms and conditions of case-specific exemption from licensing. Any case-specific exemption from licensing granted for a small hydroelectric power project is...

18 CFR 4.103 - General provisions for case-specific exemption.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

18 CFR 4.103 - General provisions for case-specific exemption.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

18 CFR 4.106 - Standard terms and conditions of case-specific exemption from licensing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.106 Standard terms and conditions of case-specific exemption from licensing. Any case-specific exemption from licensing granted for a small hydroelectric power project is...

18 CFR 4.103 - General provisions for case-specific exemption.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

18 CFR 4.103 - General provisions for case-specific exemption.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

18 CFR 4.103 - General provisions for case-specific exemption.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.103 General provisions for case-specific exemption. (a) Exemptible projects. Subject to... exempt on a case-specific basis any small hydroelectric power project from all or part of Part I of the...

18 CFR 4.106 - Standard terms and conditions of case-specific exemption from licensing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION OF PROJECT COSTS Exemption of Small Hydroelectric Power Projects of 5 Megawatts or Less § 4.106 Standard terms and conditions of case-specific exemption from licensing. Any case-specific exemption from licensing granted for a small hydroelectric power project is...

Double-stranded RNA interferes in a sequence-specific manner with the infection of representative members of the two viroid families

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

Carbonell, Alberto; Martinez de Alba, Angel-Emilio; Flores, Ricardo

2008-02-05

Infection by viroids, non-protein-coding circular RNAs, occurs with the accumulation of 21-24 nt viroid-derived small RNAs (vd-sRNAs) with characteristic properties of small interfering RNAs (siRNAs) associated to RNA silencing. The vd-sRNAs most likely derive from dicer-like (DCL) enzymes acting on viroid-specific dsRNA, the key elicitor of RNA silencing, or on the highly structured genomic RNA. Previously, viral dsRNAs delivered mechanically or agroinoculated have been shown to interfere with virus infection in a sequence-specific manner. Here, we report similar results with members of the two families of nuclear- and chloroplast-replicating viroids. Moreover, homologous vd-sRNAs co-delivered mechanically also interfered with one ofmore » the viroids examined. The interference was sequence-specific, temperature-dependent and, in some cases, also dependent on the dose of the co-inoculated dsRNA or vd-sRNAs. The sequence-specific nature of these effects suggests the involvement of the RNA induced silencing complex (RISC), which provides sequence specificity to RNA silencing machinery. Therefore, viroid titer in natural infections might be regulated by the concerted action of DCL and RISC. Viroids could have evolved their secondary structure as a compromise between resistance to DCL and RISC, which act preferentially against RNAs with compact and relaxed secondary structures, respectively. In addition, compartmentation, association with proteins or active replication might also help viroids to elude their host RNA silencing machinery.« less

Metadata Standard and Data Exchange Specifications to Describe, Model, and Integrate Complex and Diverse High-Throughput Screening Data from the Library of Integrated Network-based Cellular Signatures (LINCS).

PubMed

Vempati, Uma D; Chung, Caty; Mader, Chris; Koleti, Amar; Datar, Nakul; Vidović, Dušica; Wrobel, David; Erickson, Sean; Muhlich, Jeremy L; Berriz, Gabriel; Benes, Cyril H; Subramanian, Aravind; Pillai, Ajay; Shamu, Caroline E; Schürer, Stephan C

2014-06-01

The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. Integration and analysis of diverse LINCS data sets depend on the availability of sufficient metadata to describe the assays and screening results and on their syntactic, structural, and semantic consistency. Here we report metadata specifications for the most important molecular and cellular components and recommend them for adoption beyond the LINCS project. We focus on the minimum required information to model LINCS assays and results based on a number of use cases, and we recommend controlled terminologies and ontologies to annotate assays with syntactic consistency and semantic integrity. We also report specifications for a simple annotation format (SAF) to describe assays and screening results based on our metadata specifications with explicit controlled vocabularies. SAF specifically serves to programmatically access and exchange LINCS data as a prerequisite for a distributed information management infrastructure. We applied the metadata specifications to annotate large numbers of LINCS cell lines, proteins, and small molecules. The resources generated and presented here are freely available. © 2014 Society for Laboratory Automation and Screening.

Comparison of Dengue Virus Type 2-Specific Small RNAs from RNA Interference-Competent and –Incompetent Mosquito Cells

PubMed Central

Scott, Jaclyn C.; Brackney, Doug E.; Campbell, Corey L.; Bondu-Hawkins, Virginie; Hjelle, Brian; Ebel, Greg D.; Olson, Ken E.; Blair, Carol D.

2010-01-01

The exogenous RNA interference (RNAi) pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (si)RNAs are key components of this pathway. Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to control arbovirus transmission. Using deep sequencing technology, we characterized dengue virus type 2 (DENV2)-specific small RNAs produced during infection of Aedes aegypti mosquitoes and A. aegypti Aag2 cell cultures and compared them to those produced in the C6/36 Aedes albopictus cell line. We show that the size and mixed polarity of virus-specific small RNAs from DENV-infected A. aegypti cells indicate that they are products of Dicer-2 (Dcr2) cleavage of long dsRNA, whereas C6/36 cells generate DENV2-specific small RNAs that are longer and predominantly positive polarity, suggesting that they originate from a different small RNA pathway. Examination of virus-specific small RNAs after infection of the two mosquito cell lines with the insect-only flavivirus cell fusing agent virus (CFAV) corroborated these findings. An in vitro assay also showed that Aag2 A. aegypti cells are capable of siRNA production, while C6/36 A. albopictus cells exhibit inefficient Dcr2 cleavage of long dsRNA. Defective expression or function of Dcr2, the key initiator of the RNAi pathway, might explain the comparatively robust growth of arthropod-borne viruses in the C6/36 cell line, which has been used frequently as a surrogate for studying molecular interactions between arboviruses and cells of their mosquito hosts. PMID:21049014

Small Microprocessor for ASIC or FPGA Implementation

NASA Technical Reports Server (NTRS)

Kleyner, Igor; Katz, Richard; Blair-Smith, Hugh

2011-01-01

A small microprocessor, suitable for use in applications in which high reliability is required, was designed to be implemented in either an application-specific integrated circuit (ASIC) or a field-programmable gate array (FPGA). The design is based on commercial microprocessor architecture, making it possible to use available software development tools and thereby to implement the microprocessor at relatively low cost. The design features enhancements, including trapping during execution of illegal instructions. The internal structure of the design yields relatively high performance, with a significant decrease, relative to other microprocessors that perform the same functions, in the number of microcycles needed to execute macroinstructions. The problem meant to be solved in designing this microprocessor was to provide a modest level of computational capability in a general-purpose processor while adding as little as possible to the power demand, size, and weight of a system into which the microprocessor would be incorporated. As designed, this microprocessor consumes very little power and occupies only a small portion of a typical modern ASIC or FPGA. The microprocessor operates at a rate of about 4 million instructions per second with clock frequency of 20 MHz.

Design of small confocal endo-microscopic probe working under multiwavelength environment

NASA Astrophysics Data System (ADS)

Kim, Young-Duk; Ahn, MyoungKi; Gweon, Dae-Gab

2010-02-01

Recently, optical imaging system is widely used in medical purpose. By using optical imaging system specific diseases can be easily diagnosed at early stage because optical imaging system has high resolution performance and various imaging method. These methods are used to get high resolution image of human body and can be used to verify whether the cell is infected by virus. Confocal microscope is one of the famous imaging systems which is used for in-vivo imaging. Because most of diseases are accompanied with cellular level changes, doctors can diagnosis at early stage by observing the cellular image of human organ. Current research is focused in the development of endo-microscope that has great advantage in accessibility to human body. In this research, I designed small probe that is connected to confocal microscope through optical fiber bundle and work as endo-microscope. And this small probe is mainly designed to correct chromatic aberration to use various laser sources for both fluorescence type and reflection type confocal images. By using two kinds of laser sources at the same time we demonstrated multi-modality confocal endo-microscope.

Circulating RNAs as new biomarkers for detecting pancreatic cancer

PubMed Central

Kishikawa, Takahiro; Otsuka, Motoyuki; Ohno, Motoko; Yoshikawa, Takeshi; Takata, Akemi; Koike, Kazuhiko

2015-01-01

Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes, and technical advances must also be achieved, such as creating a consensus normalization protocol for quantitative data analysis, circulating RNAs are largely unexplored and might represent novel clinical biomarkers. PMID:26229396

Recent radial turbine research at the NASA Lewis Research Center.

NASA Technical Reports Server (NTRS)

Rohlik, H. E.; Kofskey, M. G.

1972-01-01

The major results obtained in several recent experimental programs on small radial inflow turbines for space applications are presented and discussed. Specifically, experimental and analytical work associated with these systems that has included examination of blade-shroud clearance, blade loading, and exit diffuser design, is considered. Results indicate high efficiency over a wide range of specific speed, and also insensitivity to clearance and blade loading in the radial part of the rotor. The exit diffuser investigation indicated that a conventional conical outer wall may not provide the velocity variation consistent with minimum overall diffuser loss.

High yield neutron generators using the DD reaction

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

Vainionpaa, J. H.; Harris, J. L.; Piestrup, M. A.

2013-04-19

A product line of high yield neutron generators has been developed at Adelphi technology inc. The generators use the D-D fusion reaction and are driven by an ion beam supplied by a microwave ion source. Yields of up to 5 Multiplication-Sign 10{sup 9} n/s have been achieved, which are comparable to those obtained using the more efficient D-T reaction. The microwave-driven plasma uses the electron cyclotron resonance (ECR) to produce a high plasma density for high current and high atomic ion species. These generators have an actively pumped vacuum system that allows operation at reduced pressure in the target chamber,more » increasing the overall system reliability. Since no radioactive tritium is used, the generators can be easily serviced, and components can be easily replaced, providing essentially an unlimited lifetime. Fast neutron source size can be adjusted by selecting the aperture and target geometries according to customer specifications. Pulsed and continuous operation has been demonstrated. Minimum pulse lengths of 50 {mu}s have been achieved. Since the generators are easily serviceable, they offer a long lifetime neutron generator for laboratories and commercial systems requiring continuous operation. Several of the generators have been enclosed in radiation shielding/moderator structures designed for customer specifications. These generators have been proven to be useful for prompt gamma neutron activation analysis (PGNAA), neutron activation analysis (NAA) and fast neutron radiography. Thus these generators make excellent fast, epithermal and thermal neutron sources for laboratories and industrial applications that require neutrons with safe operation, small footprint, low cost and small regulatory burden.« less

High yield neutron generators using the DD reaction

NASA Astrophysics Data System (ADS)

Vainionpaa, J. H.; Harris, J. L.; Piestrup, M. A.; Gary, C. K.; Williams, D. L.; Apodaca, M. D.; Cremer, J. T.; Ji, Qing; Ludewigt, B. A.; Jones, G.

2013-04-01

A product line of high yield neutron generators has been developed at Adelphi technology inc. The generators use the D-D fusion reaction and are driven by an ion beam supplied by a microwave ion source. Yields of up to 5 × 109 n/s have been achieved, which are comparable to those obtained using the more efficient D-T reaction. The microwave-driven plasma uses the electron cyclotron resonance (ECR) to produce a high plasma density for high current and high atomic ion species. These generators have an actively pumped vacuum system that allows operation at reduced pressure in the target chamber, increasing the overall system reliability. Since no radioactive tritium is used, the generators can be easily serviced, and components can be easily replaced, providing essentially an unlimited lifetime. Fast neutron source size can be adjusted by selecting the aperture and target geometries according to customer specifications. Pulsed and continuous operation has been demonstrated. Minimum pulse lengths of 50 μs have been achieved. Since the generators are easily serviceable, they offer a long lifetime neutron generator for laboratories and commercial systems requiring continuous operation. Several of the generators have been enclosed in radiation shielding/moderator structures designed for customer specifications. These generators have been proven to be useful for prompt gamma neutron activation analysis (PGNAA), neutron activation analysis (NAA) and fast neutron radiography. Thus these generators make excellent fast, epithermal and thermal neutron sources for laboratories and industrial applications that require neutrons with safe operation, small footprint, low cost and small regulatory burden.

Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging

NASA Astrophysics Data System (ADS)

Donnelley, Martin; Parsons, David; Morgan, Kaye; Siu, Karen

2010-07-01

Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live-animal synchrotron X-ray imaging studies. Our group has extensive experience in high-resolution live-animal imaging at the Japanese SPring-8 synchrotron, primarily examining airways in two-dimensions. These experiments normally image an area of 1.8 mm×1.2 mm at a pixel resolution of 0.45 μm and are performed with live, intact, anaesthetized mice. There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small-animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, and deliver test substances while collecting images. The horizontal synchrotron X-ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions-of-interest slow and can result in a high radiation dose, and at this level of magnification small animal movements produce motion-artifacts that can render acquired images unusable. Here we describe our experimental techniques and how we have overcome several challenges involved in performing live mouse synchrotron imaging. Experiments have tested different mouse strains, with hairless strains minimizing overlying skin and hair artifacts. Different anesthetics have also be trialed due to the limited choices available at SPring-8. Tracheal-intubation methods have been refined and controlled-ventilation is now possible using a specialized small-animal ventilator. With appropriate animal restraint and respiratory-gating, motion-artifacts have been minimized. The animal orientation (supine vs. head-high) also appears to affect animal physiology, and can alter image quality. Our techniques and image quality at SPring-8 have dramatically improved and in the near future we plan to translate this experience to the Imaging and Medical Beamline at the Australian Synchrotron. Overcoming these challenges has permitted increasingly sophisticated imaging of animals with synchrotron X-rays, and we expect a bright future for these techniques.

Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging

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

Donnelley, Martin; Parsons, David; Women's and Children's Health Research Institute, Adelaide, South Australia

Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live-animal synchrotron X-ray imaging studies. Our group has extensive experience in high-resolution live-animal imaging at the Japanese SPring-8 synchrotron, primarily examining airways in two-dimensions. These experiments normally image an area of 1.8 mmx1.2 mm at a pixel resolution of 0.45 {mu}m and are performed with live, intact, anaesthetized mice.There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small-animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, andmore » deliver test substances while collecting images. The horizontal synchrotron X-ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions-of-interest slow and can result in a high radiation dose, and at this level of magnification small animal movements produce motion-artifacts that can render acquired images unusable. Here we describe our experimental techniques and how we have overcome several challenges involved in performing live mouse synchrotron imaging.Experiments have tested different mouse strains, with hairless strains minimizing overlying skin and hair artifacts. Different anesthetics have also be trialed due to the limited choices available at SPring-8. Tracheal-intubation methods have been refined and controlled-ventilation is now possible using a specialized small-animal ventilator. With appropriate animal restraint and respiratory-gating, motion-artifacts have been minimized. The animal orientation (supine vs. head-high) also appears to affect animal physiology, and can alter image quality. Our techniques and image quality at SPring-8 have dramatically improved and in the near future we plan to translate this experience to the Imaging and Medical Beamline at the Australian Synchrotron.Overcoming these challenges has permitted increasingly sophisticated imaging of animals with synchrotron X-rays, and we expect a bright future for these techniques.« less

Improving fitness of elite handball players: small-sided games vs. high-intensity intermittent training.

PubMed

Iacono, Antonio Dello; Eliakim, Alon; Meckel, Yoav

2015-03-01

The present study was designed to compare the effects of high-intensity intermittent training (HIIT) and small-sided games (SSGs) training on fitness variables of elite handball players. Eighteen highly trained players (mean age ± SD: 25.6 ± 0.5 years) were assigned to either HIIT or SSGs group training protocols twice per week for 8 weeks. The HIIT consisted of 12-24 × 15 seconds of high-intensity runs interspersed by 15 seconds of recovery. The SSGs training consisted of 3 against 3 small-sided handball games. Both training methods were matched for exercise duration and recovery at each training session. Before and after 8-week training, the following fitness variables were assessed-speed: 10- and 20-m sprint time, agility: handball agility specific test (HAST), upper arm strength: 1 repetition maximum (1RM) bench press test, lower limb power: counter-movement jump tests with (CMJarm) and without (CMJ) arm movement, and aerobic fitness (yo-yo intermittent recovery test level 1 [YYIRTL1]). Significant improvement was found in the YYIRTL1 (23.3 and 26.3%, respectively), 10-m sprint (2.3 and 4.1%, respectively) and 20-m sprint (2.1 and 4%, respectively), HAST (1.1 and 2.2%, respectively), 1RM bench press (6.8 and 12.3%, respectively), CMJ (7.4 and 10.8%, respectively), and CMJarm (6.4 and 8.9%, respectively) following training in both groups (p ≤ 0.05 for all). There was a significantly greater improvement in 10- and 20-m sprint, HAST, 1RM, CMJ, and CMJarm following the SSGs training compared with the HIIT (p ≤ 0.05 for all). These results indicated that both HIIT and SSGs are effective training methods for fitness development among elite adult handball players. However, SSGs training may be considered as the preferred training regimen for improving handball-specific fitness variables during the in-season period.

Hantaan virus surveillance targeting small mammals at nightmare range, a high elevation military training area, Gyeonggi Province, Republic of Korea.

PubMed

Klein, Terry A; Kim, Heung-Chul; Chong, Sung-Tae; Kim, Jeong-Ah; Lee, Sook-Young; Kim, Won-Keun; Nunn, Peter V; Song, Jin-Won

2015-01-01

Rodent-borne disease surveillance was conducted at Nightmare Range (NM-R), near the demilitarized zone in northeast Gyeonggi Province, Republic of Korea, to identify hemorrhagic fever with renal syndrome (HFRS) risks for a mountainous high-elevation (500 m) military training site. Monthly surveys were conducted from January 2008-December 2009. A total of 1,720 small mammals were captured belonging to the Orders Rodentia [Families, Sciuridae (1 species) and Muridae (7 species)] and Soricomorpha [Family, Soricidae (1species)]. Apodemus agrarius, the primary reservoir for Hantaan virus (HTNV), accounted for 89.9% (1,546) of all small mammals captured, followed by Myodes regulus (4.0%), Crocidura lasiura (3.9%), Micromys minutus (1.4%), Mus musculus (0.3%), Microtus fortis (0.2%), Apodemus peninsulae (0.2%), Tamias sibiricus (0.1%), and Rattus norvegicus (<0.1%). Three species were antibody-positive (Ab+) for hantaviruses: A. agrarius (8.2%), M. minutus (4.2%), and C. lasiura (1.5%). HTNV specific RNA was detected in 93/127 Ab+ A. agrarius, while Imjin virus specific RNA was detected in 1/1 Ab+ C. lasiura. Overall, hantavirus Ab+ rates for A. agrarius increased with weight (age) and were significantly higher among males (10.9%) than females (5.1%) (P<0.0001). High A. agrarius gravid rates during the fall (August-September) were associated with peak numbers of HFRS cases in Korea that followed high gravid rates. From 79 RT-PCR positive A. agrarius, 12 HTNV RNA samples were sequenced and compared phylogenetically based on a 320 nt sequence from the GC glycoprotein-encoding M segment. These results demonstrate that the HTNV isolates from NM-R are distinctly separated from HTNV isolated from the People's Republic of China. These studies provide for improved disease risk assessments that identify military activities, rodent HTNV rates, and other factors associated with the transmission of hantaviruses during field training exercises.

A small-diameter NMR logging tool for groundwater investigations

USGS Publications Warehouse

Walsh, David; Turner, Peter; Grunewald, Elliot; Zhang, Hong; Butler, James J.; Reboulet, Ed; Knobbe, Steve; Christy, Tom; Lane, John W.; Johnson, Carole D.; Munday, Tim; Fitzpatrick, Andrew

2013-01-01

A small-diameter nuclear magnetic resonance (NMR) logging tool has been developed and field tested at various sites in the United States and Australia. A novel design approach has produced relatively inexpensive, small-diameter probes that can be run in open or PVC-cased boreholes as small as 2 inches in diameter. The complete system, including surface electronics and various downhole probes, has been successfully tested in small-diameter monitoring wells in a range of hydrogeological settings. A variant of the probe that can be deployed by a direct-push machine has also been developed and tested in the field. The new NMR logging tool provides reliable, direct, and high-resolution information that is of importance for groundwater studies. Specifically, the technology provides direct measurement of total water content (total porosity in the saturated zone or moisture content in the unsaturated zone), and estimates of relative pore-size distribution (bound vs. mobile water content) and hydraulic conductivity. The NMR measurements show good agreement with ancillary data from lithologic logs, geophysical logs, and hydrogeologic measurements, and provide valuable information for groundwater investigations.

Discovery of Small Molecules that Inhibit the Disordered Protein, p27Kip1

PubMed Central

Iconaru, Luigi I.; Ban, David; Bharatham, Kavitha; Ramanathan, Arvind; Zhang, Weixing; Shelat, Anang A.; Zuo, Jian; Kriwacki, Richard W.

2015-01-01

Disordered proteins are highly prevalent in biological systems, they control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27Kip1 (p27). Two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groups of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule:disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of-principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A). PMID:26507530

Discovery of Small Molecules that Inhibit the Disordered Protein, p27 Kip1

DOE PAGES

Iconaru, Luigi I.; Ban, David; Bharatham, Kavitha; ...

2015-10-28

In disordered proteins we see that they are highly prevalent in biological systems. They control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27 Kip1 (p27). Moreover, two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groupsmore » of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule: disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of- principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A).« less

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

The Association between Childhood and Adolescent Sexual Abuse and Proxies for Sexual Risk Behavior: A Random Sample of the General Population of Sweden

ERIC Educational Resources Information Center

Steel, Jennifer L.; Herlitz, Claes A.

2005-01-01

Objective: Several studies with small and ''high risk'' samples have demonstrated that a history of childhood or adolescent sexual abuse (CASA) is associated with sexual risk behaviors (SRBs). However, few studies with large random samples from the general population have specifically examined the relationship between CASA and SRBs with a…

Army TLS

DTIC Science & Technology

2014-12-10

depends on: 1- the properties of the ambient fluid (density, viscosity, thermal conductivity , specific heat) and, 2- the parameters of the flow (U...of the sensor element. Typical of such applications is the use of bead thermistors in gas chromatog- raphy and thermal conductivity gas analysis...length between the bead and the test terminals. All bead thermistors, by reason of their small size and the relatively high thermal conductivity of

Cable yarding residue after thinning young stands: a break-even simulation

Treesearch

Chris B. LeDoux

1984-01-01

The use of cable logging to extract small pieces of residue wood may result in low rates of production and a high cost per unit of wood produced. However, the logging manager can improve yarding productivity and break even in cable residue removal operations by using the proper planning techniques. In this study, breakeven zones for specific young-growth stands were...

Sensitivity and Specificity of CT and Its signs for Diagnosis of Strangulation in Patients with Acute Small Bowel Obstruction.

PubMed

Jha, Ashwini Kumar; Tang, Wen Hao; Bai, Zhi Bin; Xiao, Jia Quan

2014-01-01

To perform a meta-analysis to review the sensitivity and specificity of computed tomography and different known computed yomography signs for the diagnosis of strangulation in patients with acute small bowel obstruction. A comprehensive Pubmed search was performed for all reports that evaluated the use of CT and discussed different CT criteria for the diagnosis of acute SBO. Articles published in English language from January 1978 to June 2008 were included. Review articles, case reports, pictorial essays and articles without original data were excluded. The bivariate random effect model was used to obtain pooled sensitivity and pooled specificity. Summary receiver operating curve was calculated using Meta-Disc. Software Openbugs 3.0.3 was used to summarize the data. A total of 12 studies fulfilled the inclusion criteria. The pooled sensitivity and specificity of CT in the diagnosis of strangulation was 0.720 (95% CI 0.674 to 0.763) and 0.866 (95% CI 0.837 to 0.892) respectively. Among different CT signs, mesenteric edema had highest Pooled sensitivity of 0. 741 and lack of bowel wall enhancement had highest pooled specificity of 0.991. This review demonstrates that CT is highly sensitive as well as specific in the preoperative diagnosis of strangulation SBO which are in accordance with the published studies. Our analysis also shows that "presence of mesenteric fluid" is most sensitive, and "lack of bowel wall enhancement" is most specific CT sign of strangulation, and also justifies need of large scale prospective studies to validate the results obtained as well as to determine a clinical protocol.

In situ fabrication of nickel based oxide on nitrogen-doped graphene for high electrochemical performance supercapacitors

NASA Astrophysics Data System (ADS)

Pan, Denghui; Zhang, Mingmei; Wang, Ying; Yan, Zaoxue; Jing, Junjie; Xie, Jimin

2017-10-01

In this article, we synthesize Ni(OH)2 homogeneous grown on nitrogen-doped graphene (Ni(OH)2/NG), subsequently, small and uniform nickel oxide nanoparticle (NiO/NG) is also successfully obtained through tube furnace calcination method. The high specific capacitance of the NiO/NG electrode can reach to 1314.1 F/g at a charge and discharge current density of 2 A/g, meanwhile the specific capacitance of Ni(OH)2/NG electrode is also 1350 F/g. The capacitance of NiO/NG can remain 93.7% of the maximum value after 1000 cycles, while the Ni(OH)2/NG electrode losses 16.9% of the initial capacitance after 1000 cycles. It can be attributed to nickel hydroxide instability during charge-discharge cycles.

Identifying genes that extend life span using a high-throughput screening system.

PubMed

Chen, Cuiying; Contreras, Roland

2007-01-01

We developed a high-throughput functional genomic screening system that allows identification of genes prolonging lifespan in the baker's yeast Saccharomyces cerevisiae. The method is based on isolating yeast mother cells with a higher than average number of cell divisions as indicated by the number of bud scars on their surface. Fluorescently labeled wheat germ agglutinin (WGA) was used for specific staining of chitin, a major component of bud scars. The critical new steps in our bud-scar-sorting system are the use of small microbeads, which allows successive rounds of purification and regrowth of the mother cells (M-cell), and utilization of flow cytometry to sort and isolate cells with a longer lifespan based on the number of bud scars specifically labeled with WGA.

Nonpeptide-Based Small-Molecule Probe for Fluorogenic and Chromogenic Detection of Chymotrypsin.

PubMed

Wu, Lei; Yang, Shu-Hou; Xiong, Hao; Yang, Jia-Qian; Guo, Jun; Yang, Wen-Chao; Yang, Guang-Fu

2017-03-21

We report herein a nonpeptide-based small-molecule probe for fluorogenic and chromogenic detection of chymotrypsin, as well as the primary application for this probe. This probe was rationally designed by mimicking the peptide substrate and optimized by adjusting the recognition group. The refined probe 2 exhibits good specificity toward chymotrypsin, producing about 25-fold higher enhancement in both the fluorescence intensity and absorbance upon the catalysis by chymotrypsin. Compared with the most widely used peptide substrate (AMC-FPAA-Suc) of chymotrypsin, probe 2 shows about 5-fold higher binding affinity and comparable catalytical efficiency against chymotrypsin. Furthermore, it was successfully applied for the inhibitor characterization. To the best of our knowledge, probe 2 is the first nonpeptide-based small-molecule probe for chymotrypsin, with the advantages of simple structure and high sensitivity compared to the widely used peptide-based substrates. This small-molecule probe is expected to be a useful molecular tool for drug discovery and chymotrypsin-related disease diagnosis.

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

Flyby Characterization of Lower-Degree Spherical Harmonics Around Small Bodies

NASA Technical Reports Server (NTRS)

Takahashi, Yu; Broschart, Stephen; Lantoine, Gregory

2014-01-01

Interest in studying small bodies has grown significantly in the last two decades, and there are a number of past, present, and future missions. These small body missions challenge navigators with significantly different kinds of problems than the planets and moons do. The small bodies' shape is often irregular and their gravitational field significantly weak, which make the designing of a stable orbit a complex dynamical problem. In the initial phase of spacecraft rendezvous with a small body, the determination of the gravitational parameter and lower-degree spherical harmonics are of crucial importance for safe navigation purposes. This motivates studying how well one can determine the total mass and lower-degree spherical harmonics in a relatively short time in the initial phase of the spacecraft rendezvous via flybys. A quick turnaround for the gravity data is of high value since it will facilitate the subsequent mission design of the main scientific observation campaign. We will present how one can approach the problem to determine a desirable flyby geometry for a general small body. We will work in the non-dimensional formulation since it will generalize our results across different size/mass bodies and the rotation rate for a specific combination of gravitational coefficients.

Identification of Salmonella Typhimurium-specific DNA aptamers developed using whole-cell SELEX and FACS analysis.

PubMed

Moon, Jihea; Kim, Giyoung; Lee, Sangdae; Park, Saetbyeol

2013-11-01

Conventional methods for detection of infective organisms, such as Salmonella, are complicated and require multiple steps, and the need for rapid detection has increased. Biosensors show great potential for rapid detection of pathogens. In turn, aptamers have great potential for biosensor assay development, given their small size, ease of synthesis and labeling, lack of immunogenicity, a lower cost of production than antibodies, and high target specificity. In this study, ssDNA aptamers specific to Salmonella Typhimurium were obtained by a whole bacterium-based systematic evolution of ligands by exponential enrichment (SELEX) procedure and applied to probing S. Typhimurium. After 10 rounds of selection with S. Typhimurium as the target and Salmonella Enteritidis, Escherichia coli and Staphylococcus aureus as counter targets, the highly enriched oligonucleic acid pool was sorted using flow cytometry. In total, 12 aptamer candidates from different families were sequenced and grouped. Fluorescent analysis demonstrated that aptamer C4 had particularly high binding affinity and selectivity; this aptamer was then further characterized. © 2013 Elsevier B.V. All rights reserved.

Guide Specification For Small, Dual Agent Aircraft Rescue and Firefighting Vehicles

DOT National Transportation Integrated Search

1993-12-07

This advisory circular (AC) contains performance standards, specifications, and : recommendations for the design, construction, and testing of a family of small, : dual agent aircraft rescue and fire fighting (ARFF) vehicles. The National : Fire Prot...

High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

PubMed

Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

2017-09-01

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p < 0.001) and, similarly, at centers performing 70 per year (HR 1.35; 95% CI 1.26, 1.43; p < 0.001). The interaction between high donor risk index and center volume was not statistically significant (p = 0.747), confirming that the risk associated with using marginal donor livers was comparable between smaller and larger centers. Results were consistent when examining graft loss. At both small and large centers, high-risk donor allografts were associated with reduced patient and graft survival after liver transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

An isolation-enhanced quad-element antenna using suspended solid wires for LTE small-cell base stations

NASA Astrophysics Data System (ADS)

Chen, Yen-Sheng; Zhou, Huang-Cheng

2017-05-01

This paper presents a multiple-input-multiple-output (MIMO) antenna that has four-unit elements enabled by an isolation technique for long-term evolution (LTE) small-cell base stations. While earlier studies on MIMO base-station antennas cope with either a lower LTE band (698-960 MHz) or an upper LTE band (1710-2690 MHz), the proposed antenna meets the full LTE specification, yet it uses the maximum number of unit elements to increase channel capacity. The antenna configuration is optimized for good impedance matching and high radiation efficiency. In particular, as the spacing between unit elements is so small that severe mutual coupling occurs, we propose a simple structure with extremely low costs to enhance the isolation. By using suspended solid wires interconnecting the position having strong coupled current of two adjacent elements, an isolation enhancement of 37 dB is achieved. Although solid wires inherently aim at direct-current applications, this work successfully employs such a low-cost technique to microwave antenna development. Experimental results have validated the design guidelines and the proposed configuration, showing that antenna performances including impedance matching, isolation, radiation features, signal correlation, and channel capacity gain are highly desired for LTE small-cell base stations.

Compact survey and inspection day/night image sensor suite for small unmanned aircraft systems (EyePod)

NASA Astrophysics Data System (ADS)

Bird, Alan; Anderson, Scott A.; Linne von Berg, Dale; Davidson, Morgan; Holt, Niel; Kruer, Melvin; Wilson, Michael L.

2010-04-01

EyePod is a compact survey and inspection day/night imaging sensor suite for small unmanned aircraft systems (UAS). EyePod generates georeferenced image products in real-time from visible near infrared (VNIR) and long wave infrared (LWIR) imaging sensors and was developed under the ONR funded FEATHAR (Fusion, Exploitation, Algorithms, and Targeting for High-Altitude Reconnaissance) program. FEATHAR is being directed and executed by the Naval Research Laboratory (NRL) in conjunction with the Space Dynamics Laboratory (SDL) and FEATHAR's goal is to develop and test new tactical sensor systems specifically designed for small manned and unmanned platforms (payload weight < 50 lbs). The EyePod suite consists of two VNIR/LWIR (day/night) gimbaled sensors that, combined, provide broad area survey and focused inspection capabilities. Each EyePod sensor pairs an HD visible EO sensor with a LWIR bolometric imager providing precision geo-referenced and fully digital EO/IR NITFS output imagery. The LWIR sensor is mounted to a patent-pending jitter-reduction stage to correct for the high-frequency motion typically found on small aircraft and unmanned systems. Details will be presented on both the wide-area and inspection EyePod sensor systems, their modes of operation, and results from recent flight demonstrations.

Signal-enhancer molecules encapsulated liposome as a valuable sensing and amplification platform combining the aptasensor for ultrasensitive ECL immunoassay.

PubMed

Mao, Li; Yuan, Ruo; Chai, Yaqin; Zhuo, Ying; Xiang, Yun

2011-06-15

An innovatory ECL immunoassay strategy was proposed to detect the newly developing heart failure biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). Firstly, this strategy used small molecules encapsulated liposome as immune label to construct a sandwich immune sensing platform for NT-proBNP. Then the ECL aptasensor was prepared to collect and detect the small molecules released from the liposome. Finally, based on the ECL signal changes caused by the small molecules, the ECL signal indirectly reflected the level of NT-proBNP antigen. In this experiment, the cocaine was chosen as the proper small molecule that can act as signal-enhancer to enhance the ECL of Ru(bpy)(3)(2+). The cocaine-encapsulated liposomes were successfully characterized by TEM. The quantificational calculation proved the ∼5.3×10(3) cocaine molecules per liposome enough to perform the assignment of signal amplification. The cocaine-binding ECL aptasensor further promoted the work aimed at amplifying signal. The performance of NT-proBNP assay by the proposed strategy exhibited high sensitivity and high specificities with a linear relationship over 0.01-500 ng mL(-1) range, and a detection limit down to 0.77 pg mL(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic and epigenetic variation in the lineage specification of regulatory T cells

PubMed Central

Arvey, Aaron; van der Veeken, Joris; Plitas, George; Rich, Stephen S; Concannon, Patrick; Rudensky, Alexander Y

2015-01-01

Regulatory T (Treg) cells, which suppress autoimmunity and other inflammatory states, are characterized by a distinct set of genetic elements controlling their gene expression. However, the extent of genetic and associated epigenetic variation in the Treg cell lineage and its possible relation to disease states in humans remain unknown. We explored evolutionary conservation of regulatory elements and natural human inter-individual epigenetic variation in Treg cells to identify the core transcriptional control program of lineage specification. Analysis of single nucleotide polymorphisms in core lineage-specific enhancers revealed disease associations, which were further corroborated by high-resolution genotyping to fine map causal polymorphisms in lineage-specific enhancers. Our findings suggest that a small set of regulatory elements specify the Treg lineage and that genetic variation in Treg cell-specific enhancers may alter Treg cell function contributing to polygenic disease. DOI: http://dx.doi.org/10.7554/eLife.07571.001 PMID:26510014

Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

PubMed Central

2010-01-01

Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients. PMID:21167064

Assessing Specific Oligonucleotides and Small Molecule Antibiotics for the Ability to Inhibit the CRD-BP-CD44 RNA Interaction

PubMed Central

Thomsen, Dana; Lee, Chow H.

2014-01-01

Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3′UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862–3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862–3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions. PMID:24622399

Assessing specific oligonucleotides and small molecule antibiotics for the ability to inhibit the CRD-BP-CD44 RNA interaction.

PubMed

King, Dustin T; Barnes, Mark; Thomsen, Dana; Lee, Chow H

2014-01-01

Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3'UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862-3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862-3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions.

Specific surface area of a crushed welded tuff before and after aqueous dissolution

USGS Publications Warehouse

Reddy, M.M.; Claassen, H.C.

1994-01-01

Specific surface areas were measured for several reference minerals (anorthoclase, labradorite and augite), welded tuff and stream sediments from Snowshoe Mountain, near Creede, Colorado. Crushed and sieved tuff had an unexpectedly small variation in specific surface area over a range of size fractions. Replicate surface area measurements of the largest and smallest tuff particle size fractions examined (1-0.3 mm and <0.212 mm) were 2.3 ?? 0.2 m2/g for each size fraction. Reference minerals prepared in the same way as the tuff had smaller specific surface areas than that of the tuff of the same size fraction. Higher than expected tuff specific surface areas appear to be due to porous matrix. Tuff, reacted in solutions with pH values from 2 to 6, had little change in specific surface area in comparison with unreacted tuff. Tuff, reacted with solutions having high acid concentrations (0.1 M hydrochloric acid or sulfuric-hydrofluoric acid), exhibited a marked increase in specific surface area compared to unreacted tuff. ?? 1994.

Alternative reproductive tactics and inverse size-assortment in a high-density fish spawning aggregation.

PubMed

Karkarey, Rucha; Zambre, Amod; Isvaran, Kavita; Arthur, Rohan

2017-02-28

At high densities, terrestrial and marine species often employ alternate reproductive tactics (ARTs) to maximize reproductive benefits. We describe ARTs in a high-density and unfished spawning aggregation of the squaretail grouper (Plectropomus areolatus) in Lakshadweep, India. As previously reported for this species, territorial males engage in pair-courtship, which is associated with a pair-spawning tactic. Here, we document a previously unreported school-courtship tactic; where territorial males court multiple females in mid-water schools, which appears to culminate in a unique 'school-spawning' tactic. Courtship tactics were conditional on body size, local mate density and habitat, likely associated with changing trade-offs between potential mating opportunities and intra-sexual competition. Counter-intuitively, the aggregation showed a habitat-specific inverse size-assortment: large males courted small females on the reef slope while small males courted equal-sized or larger females on the shelf. These patterns remained stable across two years of observation at high, unfished densities. These unique density-dependent behaviours may disappear from this aggregation as overall densities decline due to increasing commercial fishing pressure, with potentially large consequences for demographics and fitness.

Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors.

PubMed

Pop, Laura A; Pileczki, Valentina; Cojocneanu-Petric, Roxana M; Petrut, Bogdan; Braicu, Cornelia; Jurj, Ancuta M; Buiga, Rares; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2016-01-01

Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors). Nanotechnologies help improve the quality and quantity control for gene expression studies. The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three housekeeping genes and one small nuclear RNA gene using the ViiA 7 platform, with specific primers. Every step of the sample handling protocol, which begins with sample harvest and ends with the data analysis, is of utmost importance due to the fact that it is time consuming, labor intensive, and highly expensive. High temperature of the surgical procedure does not affect the small nucleic acid sequences in comparison with the mRNA. Gene expression is clearly affected by the RNA quality, but less affected in the case of small nuclear RNAs. We proved that the high-temperature, highly invasive transurethral resection of bladder tumor procedure damages the tissue and affects the integrity of the RNA from biological specimens.

Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors

PubMed Central

Pop, Laura A; Pileczki, Valentina; Cojocneanu-Petric, Roxana M; Petrut, Bogdan; Braicu, Cornelia; Jurj, Ancuta M; Buiga, Rares; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2016-01-01

Background Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors). Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three housekeeping genes and one small nuclear RNA gene using the ViiA 7 platform, with specific primers. Results Every step of the sample handling protocol, which begins with sample harvest and ends with the data analysis, is of utmost importance due to the fact that it is time consuming, labor intensive, and highly expensive. High temperature of the surgical procedure does not affect the small nucleic acid sequences in comparison with the mRNA. Conclusion Gene expression is clearly affected by the RNA quality, but less affected in the case of small nuclear RNAs. We proved that the high-temperature, highly invasive transurethral resection of bladder tumor procedure damages the tissue and affects the integrity of the RNA from biological specimens. PMID:27330317

Strategic Environmental Assessment practices in European small islands: Insights from Azores and Orkney islands

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

Polido, Alexandra, E-mail: a.polido@campus.fct.unl.pt; João, Elsa, E-mail: elsa.joao@strath.ac.uk; Ramos, Tomás B., E-mail: tabr@fct.unl.pt

The literature concerning Strategic Environmental Assessment (SEA) often refers to the importance of context-specific approaches. However, there is a lack of systematised and consistent studies that enhance tailor-made SEA practices and procedures. Small islands are bounded units of study which may help explore SEA theory and practice in special territories. Small islands present particular features and unique values, such as, small size and population, geographic isolation, limited resources and vulnerable ecosystems. Hence, the main goal of this research was to profile SEA practices and procedures in European small islands and provide a background for future research aiming to improve context-specificmore » SEA applications. To achieve this goal, an exploratory case study was developed using Azores (Portugal) and Orkney (Scotland) archipelagos. An analysis of the corresponding mainland was also carried out to contextualise both case studies. The data collection was achieved through a qualitative content analysis of 43 Environmental Reports. The research found that there is not an SEA context-specific approach used within these European small islands, including guidelines, assessment topics, assessment techniques, follow-up and stakeholders engagement. The debate concerning specific approaches to small islands must be re-focused on the enhancement of SEA capacity-building amongst different stakeholders (including decision-makers), on the development and implementation of collaborative approaches, and on the exchange of knowledge and experiences between small islands networks. - Highlights: • Reviewed the differences between the Portuguese and Scottish SEA system • Showed a low integration of SEA specific features in reports of European small islands • Provides background for future SEA research for small islands approaches.« less

Rare high-impact disease variants: properties and identifications.

PubMed

Park, Leeyoung; Kim, Ju Han

2016-03-21

Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene-gene or gene-environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation.

A small-scale dynamo in feedback-dominated galaxies - III. Cosmological simulations

NASA Astrophysics Data System (ADS)

Rieder, Michael; Teyssier, Romain

2017-12-01

Magnetic fields are widely observed in the Universe in virtually all astrophysical objects, from individual stars to entire galaxies, even in the intergalactic medium, but their specific genesis has long been debated. Due to the development of more realistic models of galaxy formation, viable scenarios are emerging to explain cosmic magnetism, thanks to both deeper observations and more efficient and accurate computer simulations. We present here a new cosmological high-resolution zoom-in magnetohydrodynamic (MHD) simulation, using the adaptive mesh refinement technique, of a dwarf galaxy with an initially weak and uniform magnetic seed field that is amplified by a small-scale dynamo (SSD) driven by supernova-induced turbulence. As first structures form from the gravitational collapse of small density fluctuations, the frozen-in magnetic field separates from the cosmic expansion and grows through compression. In a second step, star formation sets in and establishes a strong galactic fountain, self-regulated by supernova explosions. Inside the galaxy, the interstellar medium becomes highly turbulent, dominated by strong supersonic shocks, as demonstrated by the spectral analysis of the gas kinetic energy. In this turbulent environment, the magnetic field is quickly amplified via a SSD process and is finally carried out into the circumgalactic medium by a galactic wind. This realistic cosmological simulation explains how initially weak magnetic seed fields can be amplified quickly in early, feedback-dominated galaxies, and predicts, as a consequence of the SSD process, that high-redshift magnetic fields are likely to be dominated by their small-scale components.

Development of novel cardiovascular therapeutics from small regulatory RNA molecules--an outline of key requirements.

PubMed

Poller, W; Fechner, H

2010-01-01

Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are based on non-coding regulatory RNAs inducing RNA interference (RNAi) to silence single genes, and on modulation of cellular microRNAs (miRNAs) to alter complex gene expression patterns in diseased organs. Only recently it became possible to target therapeutic RNAi to specific organs via organotropic viral vector systems and we discuss the most recent strategies in this field, e.g. heart failure treatment by cardiac-targeted RNAi. Due to the peculiar biochemical properties of small RNA molecules, true therapeutic translation of results in vitro is more demanding than with small molecule drugs or proteins. Specifically, there is a critical requirement for extensive studies in animal models of human disease after pre-testing of the RNAi tools in vitro. This requirement likewise applies for miRNA modulations which have complex consequences in the recipient dependent on biochemical stability and distribution of the therapeutic RNA. Problems not yet fully solved are the prediction of targets and specificity of the RNA tools. However, major progress has been made to achieve their tissue-specific and regulatable expression, and breakthroughs in vector technologies from the gene therapy field have fundamentally improved safety and efficacy of RNA-based therapeutic approaches, too. In summary, insight into the molecular mechanisms of action of regulatory RNAs in combination with new delivery tools for RNA therapeutics will significantly expand our cardiovascular therapeutic repertoire beyond classical pharmacology.

Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

PubMed

Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Iida, Hiroya; Okumura, Tadayoshi; Sakaguchi, Tatsuma; Inoue, Kentaro; Ikeura, Tsukasa; Asano, Hiroaki; Kon, Masanori

2016-04-01

Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing.

PubMed

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing.

Recent radial turbine research at the NASA Lewis Research Center

NASA Technical Reports Server (NTRS)

Rohlik, H. E.; Kofskey, M. G.

1971-01-01

The high efficiencies of small radial turbines led to their application in space power systems and numerous APU and shaft power engines. Experimental and analytical work associated with these systems included examination of blade-shroud clearance, blade loading, and exit diffuser design. Results indicate high efficiency over a wide range of specific speed and also insensitivity to clearance and blade loading in the radial part of the rotor. The exit diffuser investigation indicated that a conventional conical outer wall may not provide the velocity variation consistent with minimum overall diffuser loss.

Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing

PubMed Central

Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

2003-01-01

Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing. PMID:14519201

Highly flexible and all-solid-state paperlike polymer supercapacitors.

PubMed

Meng, Chuizhou; Liu, Changhong; Chen, Luzhuo; Hu, Chunhua; Fan, Shoushan

2010-10-13

In recent years, much effort have been dedicated to achieve thin, lightweight and even flexible energy-storage devices for wearable electronics. Here we demonstrate a novel kind of ultrathin all-solid-state supercapacitor configuration with an extremely simple process using two slightly separated polyaniline-based electrodes well solidified in the H(2)SO(4)-polyvinyl alcohol gel electrolyte. The thickness of the entire device is much comparable to that of a piece of commercial standard A4 print paper. Under its highly flexible (twisting) state, the integrate device shows a high specific capacitance of 350 F/g for the electrode materials, well cycle stability after 1000 cycles and a leakage current of as small as 17.2 μA. Furthermore, due to its polymer-based component structure, it has a specific capacitance of as high as 31.4 F/g for the entire device, which is more than 6 times that of current high-level commercial supercapacitor products. These highly flexible and all-solid-state paperlike polymer supercapacitors may bring new design opportunities of device configuration for energy-storage devices in the future wearable electronic area.

A technical assessment of the porcine ejaculated spermatozoa for a sperm-specific RNA-seq analysis.

PubMed

Gòdia, Marta; Mayer, Fabiana Quoos; Nafissi, Julieta; Castelló, Anna; Rodríguez-Gil, Joan Enric; Sánchez, Armand; Clop, Alex

2018-04-26

The study of the boar sperm transcriptome by RNA-seq can provide relevant information on sperm quality and fertility and might contribute to animal breeding strategies. However, the analysis of the spermatozoa RNA is challenging as these cells harbor very low amounts of highly fragmented RNA, and the ejaculates also contain other cell types with larger amounts of non-fragmented RNA. Here, we describe a strategy for a successful boar sperm purification, RNA extraction and RNA-seq library preparation. Using these approaches our objectives were: (i) to evaluate the sperm recovery rate (SRR) after boar spermatozoa purification by density centrifugation using the non-porcine-specific commercial reagent BoviPure TM ; (ii) to assess the correlation between SRR and sperm quality characteristics; (iii) to evaluate the relationship between sperm cell RNA load and sperm quality traits and (iv) to compare different library preparation kits for both total RNA-seq (SMARTer Universal Low Input RNA and TruSeq RNA Library Prep kit) and small RNA-seq (NEBNext Small RNA and TailorMix miRNA Sample Prep v2) for high-throughput sequencing. Our results show that pig SRR (~22%) is lower than in other mammalian species and that it is not significantly dependent of the sperm quality parameters analyzed in our study. Moreover, no relationship between the RNA yield per sperm cell and sperm phenotypes was found. We compared a RNA-seq library preparation kit optimized for low amounts of fragmented RNA with a standard kit designed for high amount and quality of input RNA and found that for sperm, a protocol designed to work on low-quality RNA is essential. We also compared two small RNA-seq kits and did not find substantial differences in their performance. We propose the methodological workflow described for the RNA-seq screening of the boar spermatozoa transcriptome. FPKM: fragments per kilobase of transcript per million mapped reads; KRT1: keratin 1; miRNA: micro-RNA; miscRNA: miscellaneous RNA; Mt rRNA: mitochondrial ribosomal RNA; Mt tRNA: mitochondrial transference RNA; OAZ3: ornithine decarboxylase antizyme 3; ORT: osmotic resistance test; piRNA: Piwi-interacting RNA; PRM1: protamine 1; PTPRC: protein tyrosine phosphatase receptor type C; rRNA: ribosomal RNA; snoRNA: small nucleolar RNA; snRNA: small nuclear RNA; SRR: sperm recovery rate; tRNA: transfer RNA.

Light chain typing of immunoglobulins in small samples of biological material

PubMed Central

Rádl, J.

1970-01-01

A method is described for the typing of the light chains of immunoglobulins in small samples of sera or external secretions and without their previous isolation. It consists of immunoelectrophoresis in agar plates which contain specific antisera against one of the light chain types. All immunoglobulins of this type are thus selected by precipitation in the central area during the electrophoretic phase. Immunoglobulins of the opposite light chain type diffuse through the agar and react with the class specific antisera from the troughs. This results in the precipitin lines as in conventional immunoelectrophoresis. This technique has proved most useful for typing heterogenous or homogeneous immunoglobulins in normal and low concentration. The antisera used for incorporation in the agar should fulfil special requirements. They should contain a high level of antibodies against common surface determinants of the immunoglobulin light chains. The further possibilities of this immunoselection technique for typing different protein mixtures is discussed. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4098592

A Software Development Platform for Wearable Medical Applications.

PubMed

Zhang, Ruikai; Lin, Wei

2015-10-01

Wearable medical devices have become a leading trend in healthcare industry. Microcontrollers are computers on a chip with sufficient processing power and preferred embedded computing units in those devices. We have developed a software platform specifically for the design of the wearable medical applications with a small code footprint on the microcontrollers. It is supported by the open source real time operating system FreeRTOS and supplemented with a set of standard APIs for the architectural specific hardware interfaces on the microcontrollers for data acquisition and wireless communication. We modified the tick counter routine in FreeRTOS to include a real time soft clock. When combined with the multitasking features in the FreeRTOS, the platform offers the quick development of wearable applications and easy porting of the application code to different microprocessors. Test results have demonstrated that the application software developed using this platform are highly efficient in CPU usage while maintaining a small code foot print to accommodate the limited memory space in microcontrollers.

Exploring miRNA based approaches in cancer diagnostics and therapeutics.

PubMed

Mishra, Shivangi; Yadav, Tanuja; Rani, Vibha

2016-02-01

MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cyclin-dependent Kinase 9 Links RNA Polymerase II Transcription to Processing of Ribosomal RNA*

PubMed Central

Burger, Kaspar; Mühl, Bastian; Rohrmoser, Michaela; Coordes, Britta; Heidemann, Martin; Kellner, Markus; Gruber-Eber, Anita; Heissmeyer, Vigo; Strässer, Katja; Eick, Dirk

2013-01-01

Ribosome biogenesis is a process required for cellular growth and proliferation. Processing of ribosomal RNA (rRNA) is highly sensitive to flavopiridol, a specific inhibitor of cyclin-dependent kinase 9 (Cdk9). Cdk9 has been characterized as the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Here we studied the connection between RNAPII transcription and rRNA processing. We show that inhibition of RNAPII activity by α-amanitin specifically blocks processing of rRNA. The block is characterized by accumulation of 3′ extended unprocessed 47 S rRNAs and the entire inhibition of other 47 S rRNA-specific processing steps. The transcription rate of rRNA is moderately reduced after inhibition of Cdk9, suggesting that defective 3′ processing of rRNA negatively feeds back on RNAPI transcription. Knockdown of Cdk9 caused a strong reduction of the levels of RNAPII-transcribed U8 small nucleolar RNA, which is essential for 3′ rRNA processing in mammalian cells. Our data demonstrate a pivotal role of Cdk9 activity for coupling of RNAPII transcription with small nucleolar RNA production and rRNA processing. PMID:23744076

Biological response modifiers: their possibilities for cancer treatment.

PubMed

Franz, G

1989-01-01

Immunotherapy with the so-called 'Biological Response Modifiers' is based on the concept that the immune system can be activated to control neoplastic growth. Immunotherapy gained popularity as a treatment in the 1960's because of data from experimental tumor models. This indicated that mainly nonspecific stimulation with products of bacterial or fungal origine could prevent recurrence of, or delay growth of experimentally transplanted tumors. Since immunotherapy was most effective against relatively small tumors, clinical investigators began to view it mainly as a post-surgical treatment for a inhibition of micrometastasis. Mainly the activation of the non specific killer cells, macrophages and lymphocytes seems very promising to target an immune stimulant in the tumor site with a relatively high specificity. In the present study a whole series of biological polymers were tested in view of their capacity to enhance the immune system. However, the relatively small number of such compounds which can be applied therapeutically demonstrates that the ability of a compound to stimulate the immune systems is dependent on several conditions, such as the molecular dimension, the structure type and the solubility criteria. It will be shown that specific fungal glucans are very promising candidates for a successful cancer treatment.

Habitat-specific foraging strategies in Australasian gannets

PubMed Central

Wells, Melanie R.; Arnould, John P. Y.

2016-01-01

ABSTRACT Knowledge of top predator foraging adaptability is imperative for predicting their biological response to environmental variability. While seabirds have developed highly specialised techniques to locate prey, little is known about intraspecific variation in foraging strategies with many studies deriving information from uniform oceanic environments. Australasian gannets (Morus serrator) typically forage in continental shelf regions on small schooling prey. The present study used GPS and video data loggers to compare habitat-specific foraging strategies at two sites of contrasting oceanographic regimes (deep water near the continental shelf edge, n=23; shallow inshore embayment, n=26), in south-eastern Australia. Individuals from the continental shelf site exhibited pelagic foraging behaviours typical of gannet species, using local enhancement to locate and feed on small schooling fish; in contrast only 50% of the individuals from the inshore site foraged offshore, displaying the typical pelagic foraging strategy. The remainder adopted a strategy of searching sand banks in shallow inshore waters in the absence of conspecifics and other predators for large, single prey items. Furthermore, of the individuals foraging inshore, 93% were male, indicating that the inshore strategy may be sex-specific. Large inter-colony differences in Australasian gannets suggest strong plasticity in foraging behaviours, essential for adapting to environmental change. PMID:27305927

Steps toward quantitative infrasound propagation modeling

NASA Astrophysics Data System (ADS)

Waxler, Roger; Assink, Jelle; Lalande, Jean-Marie; Velea, Doru

2016-04-01

Realistic propagation modeling requires propagation models capable of incorporating the relevant physical phenomena as well as sufficiently accurate atmospheric specifications. The wind speed and temperature gradients in the atmosphere provide multiple ducts in which low frequency sound, infrasound, can propagate efficiently. The winds in the atmosphere are quite variable, both temporally and spatially, causing the sound ducts to fluctuate. For ground to ground propagation the ducts can be borderline in that small perturbations can create or destroy a duct. In such cases the signal propagation is very sensitive to fluctuations in the wind, often producing highly dispersed signals. The accuracy of atmospheric specifications is constantly improving as sounding technology develops. There is, however, a disconnect between sound propagation and atmospheric specification in that atmospheric specifications are necessarily statistical in nature while sound propagates through a particular atmospheric state. In addition infrasonic signals can travel to great altitudes, on the order of 120 km, before refracting back to earth. At such altitudes the atmosphere becomes quite rare causing sound propagation to become highly non-linear and attenuating. Approaches to these problems will be presented.

Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

PubMed

Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

2014-09-26

Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

PubMed

Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

2013-08-13

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

PubMed Central

Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

2013-01-01

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis. PMID:23904484

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.

Biogas utilization

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

Moser, M.A.

1996-01-01

Options for successfully using biogas depend on project scale. Almost all biogas from anaerobic digesters must first go through a gas handling system that pressurizes, meters, and filters the biogas. Additional treatment, including hydrogen sulfide-mercaptan scrubbing, gas drying, and carbon dioxide removal may be necessary for specialized uses, but these are complex and expensive processes. Thus, they can be justified only for large-scale projects that require high-quality biogas. Small-scale projects (less than 65 cfm) generally use biogas (as produced) as a boiler fuel or for fueling internal combustion engine-generators to produce electricity. If engines or boilers are selected properly, theremore » should be no need to remove hydrogen sulfide. Small-scale combustion turbines, steam turbines, and fuel cells are not used because of their technical complexity and high capital cost. Biogas cleanup to pipeline or transportation fuel specifications is very costly, and energy economics preclude this level of treatment.« less

Mango core inner shell membrane template-directed synthesis of porous ZnO films and their application for enzymatic glucose biosensor

NASA Astrophysics Data System (ADS)

Zhou, Yu; Wang, Lei; Ye, Zhizhen; Zhao, Minggang; Cai, Hui; Huang, Jingyun

2013-11-01

Micro/nano-porous ZnO films were synthesized through a simple biotemplate-directed method using mango core inner shell membranes as templates. The achieved ZnO films with wrinkles on the surface are combined of large holes and small pores in the bulk. High specific surface area, numerous microspaces, and small channels for fluid circulation provided by this unique structure along with the good biocompatibility and electron communication features of ZnO material make the product an ideal platform for the immobilization of enzymes The fabricated glucose biosensor based on the porous ZnO films exhibits good selective detection ability of analyte with good stability, high sensitivity of 50.58 μA cm-2 mM-1 and a wide linear range of 0.2-5.6 mM along with a low detection limit of 10 μM.

The suite of small-angle neutron scattering instruments at Oak Ridge National Laboratory

DOE PAGES

Heller, William T.; Cuneo, Matthew J.; Debeer-Schmitt, Lisa M.; ...

2018-02-21

Oak Ridge National Laboratory is home to the High Flux Isotope Reactor (HFIR), a high-flux research reactor, and the Spallation Neutron Source (SNS), the world's most intense source of pulsed neutron beams. The unique co-localization of these two sources provided an opportunity to develop a suite of complementary small-angle neutron scattering instruments for studies of large-scale structures: the GP-SANS and Bio-SANS instruments at the HFIR and the EQ-SANS and TOF-USANS instruments at the SNS. This article provides an overview of the capabilities of the suite of instruments, with specific emphasis on how they complement each other. As a result, amore » description of the plans for future developments including greater integration of the suite into a single point of entry for neutron scattering studies of large-scale structures is also provided.« less

The suite of small-angle neutron scattering instruments at Oak Ridge National Laboratory

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

Heller, William T.; Cuneo, Matthew J.; Debeer-Schmitt, Lisa M.

Oak Ridge National Laboratory is home to the High Flux Isotope Reactor (HFIR), a high-flux research reactor, and the Spallation Neutron Source (SNS), the world's most intense source of pulsed neutron beams. The unique co-localization of these two sources provided an opportunity to develop a suite of complementary small-angle neutron scattering instruments for studies of large-scale structures: the GP-SANS and Bio-SANS instruments at the HFIR and the EQ-SANS and TOF-USANS instruments at the SNS. This article provides an overview of the capabilities of the suite of instruments, with specific emphasis on how they complement each other. As a result, amore » description of the plans for future developments including greater integration of the suite into a single point of entry for neutron scattering studies of large-scale structures is also provided.« less

Innovation in Deep Space Habitat Interior Design: Lessons Learned From Small Space Design in Terrestrial Architecture

NASA Technical Reports Server (NTRS)

Simon, Matthew A.; Toups, Larry

2014-01-01

Increased public awareness of carbon footprints, crowding in urban areas, and rising housing costs have spawned a 'small house movement' in the housing industry. Members of this movement desire small, yet highly functional residences which are both affordable and sensitive to consumer comfort standards. In order to create comfortable, minimum-volume interiors, recent advances have been made in furniture design and approaches to interior layout that improve both space utilization and encourage multi-functional design for small homes, apartments, naval, and recreational vehicles. Design efforts in this evolving niche of terrestrial architecture can provide useful insights leading to innovation and efficiency in the design of space habitats for future human space exploration missions. This paper highlights many of the cross-cutting architectural solutions used in small space design which are applicable to the spacecraft interior design problem. Specific solutions discussed include reconfigurable, multi-purpose spaces; collapsible or transformable furniture; multi-purpose accommodations; efficient, space saving appliances; stowable and mobile workstations; and the miniaturization of electronics and computing hardware. For each of these design features, descriptions of how they save interior volume or mitigate other small space issues such as confinement stress or crowding are discussed. Finally, recommendations are provided to provide guidance for future designs and identify potential collaborations with the small spaces design community.

Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

PubMed

Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

2016-09-01

The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Are Alcohol Taxation and Pricing Policies Regressive? Product-Level Effects of a Specific Tax and a Minimum Unit Price for Alcohol.

PubMed

Vandenberg, Brian; Sharma, Anurag

2016-07-01

To compare estimated effects of two policy alternatives, (i) a minimum unit price (MUP) for alcohol and (ii) specific (per-unit) taxation, upon current product prices, per capita spending (A$), and per capita consumption by income quintile, consumption quintile and product type. Estimation of baseline spending and consumption, and modelling policy-to-price and price-to-consumption effects of policy changes using scanner data from a panel of demographically representative Australian households that includes product-level details of their off-trade alcohol spending (n = 885; total observations = 12,505). Robustness checks include alternative price elasticities, tax rates, minimum price thresholds and tax pass-through rates. Current alcohol taxes and alternative taxation and pricing policies are not highly regressive. Any regressive effects are small and concentrated among heavy consumers. The lowest-income consumers currently spend a larger proportion of income (2.3%) on alcohol taxes than the highest-income consumers (0.3%), but the mean amount is small in magnitude [A$5.50 per week (95%CI: 5.18-5.88)]. Both a MUP and specific taxation will have some regressive effects, but the effects are limited, as they are greatest for the heaviest consumers, irrespective of income. Among the policy alternatives, a MUP is more effective in reducing consumption than specific taxation, especially for consumers in the lowest-income quintile: an estimated mean per capita reduction of 11.9 standard drinks per week (95%CI: 11.3-12.6). Policies that increase the cost of the cheapest alcohol can be effective in reducing alcohol consumption, without having highly regressive effects. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Small heat shock protein 27: An effective adjuvant for enhancement of HIV-1 Nef antigen-specific immunity.

PubMed

Milani, Alireza; Bolhassani, Azam; Shahbazi, Sepideh; Motevalli, Fatemeh; Sadat, Seyed Mehdi; Soleymani, Sepehr

2017-11-01

Novel vaccine modalities have been designed to improve the efficiency of vaccines against HIV infections. In this way, the HIV-1 Nef protein has been known as an attractive antigenic candidate in therapeutic vaccine development. Moreover, the endogenous adjuvants such as heat shock proteins (HSPs) and high mobility group box 1 protein (HMGB1) have been suggested effectively to induce antigen-specific humoral and cellular immune responses. In this study, different Nef DNA and protein constructs were produced in eukaryotic and prokaryotic expression systems, and their immunostimulatory properties were evaluated using small heat shock protein 27 (Hsp27) and the HMGB1-derived peptide (Hp91) in a mouse model. Generally, our results indicated that the Hsp27-Nef fusion DNA or protein could significantly elicit higher humoral and cellular immune responses than Nef DNA or protein, respectively. Analysis of the immune responses demonstrated that the Hsp27-Nef fusion protein, and also the mixture of Nef and Hp91 significantly enhanced the Nef-specific T cell responses. Indeed, these regimens induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also Granzyme B secretion as compared to other immunization strategies. The immunostimulatory properties of Freund's adjuvant were significantly less than Hsp27 and Hp91 peptide in various immunization strategies. These findings showed that the use of Hsp27 and Hp91 in protein strategy could improve HIV-1 Nef-specific B- and T-cell immune responses, and also represent a promising HIV-1 vaccine candidate in future. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Comparison of small-area deprivation measures as predictors of chronic disease burden in a low-income population.

PubMed

Lòpez-De Fede, Ana; Stewart, John E; Hardin, James W; Mayfield-Smith, Kathy

2016-06-10

Measures of small-area deprivation may be valuable in geographically targeting limited resources to prevent, diagnose, and effectively manage chronic conditions in vulnerable populations. We developed a census-based small-area socioeconomic deprivation index specifically to predict chronic disease burden among publically insured Medicaid recipients in South Carolina, a relatively poor state in the southern United States. We compared the predictive ability of the new index with that of four other small-area deprivation indicators. To derive the ZIP Code Tabulation Area-Level Palmetto Small-Area Deprivation Index (Palmetto SADI), we evaluated ten census variables across five socioeconomic deprivation domains, identifying the combination of census indicators most highly correlated with a set of five chronic disease conditions among South Carolina Medicaid enrollees. In separate validation studies, we used both logistic and spatial regression methods to assess the ability of Palmetto SADI to predict chronic disease burden among state Medicaid recipients relative to four alternative small-area socioeconomic deprivation measures: the Townsend index of material deprivation; a single-variable poverty indicator; and two small-area designations of health care resource deprivation, Primary Care Health Professional Shortage Area and Medically Underserved Area/Medically Underserved Population. Palmetto SADI was the best predictor of chronic disease burden (presence of at least one condition and presence of two or more conditions) among state Medicaid recipients compared to all alternative deprivation measures tested. A low-cost, regionally optimized socioeconomic deprivation index, Palmetto SADI can be used to identify areas in South Carolina at high risk for chronic disease burden among Medicaid recipients and other low-income Medicaid-eligible populations for targeted prevention, screening, diagnosis, disease self-management, and care coordination activities.

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

PubMed

Zhang, Chao; Lu, Jing; Zhang, Quan-Wu; Zhao, Wei; Guo, Jia-Hui; Liu, Shan-Ling; Wu, Ying-Li; Jiang, Bin; Gao, Feng-Hou

2016-10-01

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

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

Zhang Jian; Yang Fujun; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan

2011-11-15

Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data weremore » combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.« less

Specificity of cell–cell adhesion by classical cadherins: Critical role for low-affinity dimerization through β-strand swapping

PubMed Central

Chen, Chien Peter; Posy, Shoshana; Ben-Shaul, Avinoam; Shapiro, Lawrence; Honig, Barry H.

2005-01-01

Cadherins constitute a family of cell-surface proteins that mediate intercellular adhesion through the association of protomers presented from juxtaposed cells. Differential cadherin expression leads to highly specific intercellular interactions in vivo. This cell–cell specificity is difficult to understand at the molecular level because individual cadherins within a given subfamily are highly similar to each other both in sequence and structure, and they dimerize with remarkably low binding affinities. Here, we provide a molecular model that accounts for these apparently contradictory observations. The model is based in part on the fact that cadherins bind to one another by “swapping” the N-terminal β-strands of their adhesive domains. An inherent feature of strand swapping (or, more generally, the domain swapping phenomenon) is that “closed” monomeric conformations act as competitive inhibitors of dimer formation, thus lowering affinities even when the dimer interface has the characteristics of high-affinity complexes. The model describes quantitatively how small affinity differences between low-affinity cadherin dimers are amplified by multiple cadherin interactions to establish large specificity effects at the cellular level. It is shown that cellular specificity would not be observed if cadherins bound with high affinities, thus emphasizing the crucial role of strand swapping in cell–cell adhesion. Numerical estimates demonstrate that the strength of cellular adhesion is extremely sensitive to the concentration of cadherins expressed at the cell surface. We suggest that the domain swapping mechanism is used by a variety of cell-adhesion proteins and that related mechanisms to control affinity and specificity are exploited in other systems. PMID:15937105

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

PubMed

Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

2010-12-30

Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization

PubMed Central

Sun, Yuxin; Best, Katharine; Cinelli, Mattia; Heather, James M.; Reich-Zeliger, Shlomit; Shifrut, Eric; Friedman, Nir; Shawe-Taylor, John; Chain, Benny

2017-01-01

T cells recognize antigen using a large and diverse set of antigen-specific receptors created by a complex process of imprecise somatic cell gene rearrangements. In response to antigen-/receptor-binding-specific T cells then divide to form memory and effector populations. We apply high-throughput sequencing to investigate the global changes in T cell receptor sequences following immunization with ovalbumin (OVA) and adjuvant, to understand how adaptive immunity achieves specificity. Each immunized mouse contained a predominantly private but related set of expanded CDR3β sequences. We used machine learning to identify common patterns which distinguished repertoires from mice immunized with adjuvant with and without OVA. The CDR3β sequences were deconstructed into sets of overlapping contiguous amino acid triplets. The frequencies of these motifs were used to train the linear programming boosting (LPBoost) algorithm LPBoost to classify between TCR repertoires. LPBoost could distinguish between the two classes of repertoire with accuracies above 80%, using a small subset of triplet sequences present at defined positions along the CDR3. The results suggest a model in which such motifs confer degenerate antigen specificity in the context of a highly diverse and largely private set of T cell receptors. PMID:28450864

Discharge formation in a XеCl laser pumped by high specific power

NASA Astrophysics Data System (ADS)

Panchenko, Yu. N.; Losev, V. F.

2013-02-01

Stable glow of the discharge of various types in the gas mixture of a XeCl laser is investigated for specific pumping power in the range 1.2-4.6 MW/cm3 and pulse duration of 40 ns. It is demonstrated that formation of partially homogeneous plasma with many intensive cathode spots on the electrode allows the maximum energy and duration of the lasing pulse to be obtained with laser efficiency of 2.4%. It is revealed that for the specific pumping powers up to 1.5 MW/cm3, a very homogeneous volume discharge with a small number of lowintensive cathode spots is formed in the discharge gap. With further increase in the specific pumping power exceeding 4.5 MW/cm3, current microinhomogeneities are formed in the volume discharge of this type leading to lasing breakdown.

The Oxford scanning proton microprobe: A medical diagnostic application

NASA Astrophysics Data System (ADS)

Watt, F.; Grime, G. W.; Takacs, J.; Vaux, D. J. T.

1984-04-01

Primary biliary cirrhosis (PBC) is a disease characterised by progressive destruction of small intrahepatic bile ducts, cholestasis, and high levels of copper within the liver. The Oxford 1 μm scanning proton microprobe (SPM) has been used to construct elemental maps of a 7 μm section of diseased liver at several different magnifications. The results of these investigations have shown that the copper is distributed in small deposits ( < 5 μm) at specific locations in the liver. Further there appears to be a 1:1 atomic correlation between copper and sulphur, indicating the presence of an inorganic salt or a protein with approximately equal numbers of copper and sulphur atoms.

Generation and evaluation of antibody agents for molecular imaging of CD44v6-expressing cancers

PubMed Central

Haylock, Anna-Karin; Nilvebrant, Johan; Mortensen, Anja; Velikyan, Irina; Nestor, Marika; Falk, Ronny

2017-01-01

Aim The aim of this study was to generate and characterize scFv antibodies directed to human CD44v6, as well as to radiolabel and evaluate top candidates in vitro and in vivo for their potential use in CD44v6-targeted molecular imaging in cancer patients. Materials and methods Phage display selections were used to isolate CD44v6-specific scFvs. A chain shuffling strategy was employed for affinity maturation based on a set of CD44v6-specific first-generation clones. Two second-generation scFv clones were then chosen for labeling with 111In or 125I and assessed for CD44v6-specific binding on cultured tumor cells. In vivo uptake and distribution was evaluated in tumor-bearing mice using a dual tumor model. Finally, a proof-of-concept small animal PET-CT study was performed on one of the candidates labeled with 124I. Results Two affinity-matured clones, CD44v6-scFv-A11 and CD44v6-scFv-H12, displayed promising binding kinetics. Seven out of eight radiolabeled conjugates demonstrated CD44v6-specific binding. In vivo studies on selected candidates demonstrated very advantageous tumor-to-organ ratios, in particular for iodinated conjugates, where 125I-labeled scFvs exhibited favorable kinetics and tumor-to-blood ratios above five already at 24 hours p.i.. The small animal PET-CT study using 124I-labeled CD44v6-scFv-H12 was in line with the biodistribution data, clearly visualizing the high CD44v6-expressing tumor. Conclusion The single chain fragments, CD44v6-scFv-A11 and CD44v6-scFv-H12 specifically bind to CD44v6, and the radiolabeled counterparts provide high tumor-to-blood ratios and fast clearance from organs and blood. We conclude that radioiodinated CD44v6-scFv-A11 and CD44v6-scFv-H12 possess features highly suitable for stringent molecular imaging. PMID:29029420

Designing Polyamide Inhibitors of TWIST 1 for Prosenescence Therapy

DTIC Science & Technology

2014-09-01

Pyrrole -Imidazole Polyamides; TWIST1; KRAS; non-small cell lung cancer (NSCLC); senescence 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF... Pyrrole -Imidazole Polyamides (PIP) are a class of cell permeable programmable small-molecule heterocyclic amino acid oligomers that can be designed...The original specific aims are below: Specific Aim#1. Design and synthesize a TWIST1-inhibitory specific Pyrrole -Imidazole Polyamides (PIP

Unusual case of small cell gastric carcinoma: case report and literature review.

PubMed

Richards, David; Davis, Daniel; Yan, Peisha; Guha, Sushovan

2011-04-01

Small cell carcinomas are among the most aggressive, poorly differentiated, and highly malignant of the neuroendocrine tumors (NETs). Of which, small cell gastric carcinoma is a rare small cell neuroendocrine tumor. The purpose of our study was to present this case and perform a comprehensive literature review. We review a case of small cell gastric carcinoma that is particularly unusual in that it occurred in a woman from the US when the majority of cases of small cell gastric carcinoma have been reported in men from East Asia, and more specifically, from Japan. The diagnosis was made after endoscopy revealed a large ulcerated mass in the gastric cardia of Borrmann type 3. Biopsies revealed multiple small basophilic cells underlying the squamous epithelium of the esophagus and cardiac mucosa, indicating the presence of a tumor at the gastroesophageal junction. Immunostaining established the diagnosis with positive stains for chromogranin, synaptophysin, and CD56. Our patient is being treated with chemotherapy, but many different treatment regimens have been tried for small cell gastric carcinoma with variable success. Overall prognosis for small cell gastric carcinoma is dismal. Neuroendocrine tumors in general have variable clinical behaviors and prognosis is dependent on the neuroendocrine tumor type. The adoption of a standardized classification system for neuroendocrine tumors could improve the recognition of infrequently encountered neuroendocrine tumors like small cell gastric carcinoma and will enhance strategies for treatment and thus improve prognosis for patients with these rare and aggressive tumors.

Inhibitors of Proton Pumping

PubMed Central

Bisson, Mary A.

1986-01-01

Reported inhibitors of the Characean plasmalemma proton pump were tested for their ability to inhibit the passive H+ conductance which develops in Chara corallina Klein ex Willd. at high pH. Diethylstilbestrol inhibits the proton pump and the passive H+ conductance with about the same time course, at concentrations that have no effect on cytoplasmic streaming. N-Ethylmaleimide, a sulfhydryl reagent which is small and relatively nonpolar, also inhibits both pumping and passive conductance of H+. However, it also inhibits cytoplasmic streaming with about the same time course, and therefore could not be considered a specific ATPase inhibitor. p-Chloromercuribenzene sulfonate (PCMBS), a sulfhydryl reagent which is large and charged and hence less able to penetrate the membrane, does not inhibit pumping or conductance at low concentration. At high concentration, PCMBS sometimes inhibits pumping without affecting H+ conductance, but since streaming is also inhibited, the effect on the pump cannot be said to be specific. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, a water soluble carbodiimide, weakly inhibits both pump and conductance, apparently specifically. PMID:16664807

Structure of a designed protein cage that self-assembles into a highly porous cube

DOE PAGES

Lai, Yen-Ting; Reading, Eamonn; Hura, Greg L.; ...

2014-11-10

Natural proteins can be versatile building blocks for multimeric, self-assembling structures. Yet, creating protein-based assemblies with specific geometries and chemical properties remains challenging. Highly porous materials represent particularly interesting targets for designed assembly. Here we utilize a strategy of fusing two natural protein oligomers using a continuous alpha-helical linker to design a novel protein that self assembles into a 750 kDa, 225 Å diameter, cube-shaped cage with large openings into a 130 Å diameter inner cavity. A crystal structure of the cage showed atomic level agreement with the designed model, while electron microscopy, native mass spectrometry, and small angle x-raymore » scattering revealed alternate assembly forms in solution. These studies show that accurate design of large porous assemblies with specific shapes is feasible, while further specificity improvements will likely require limiting flexibility to select against alternative forms. Finally, these results provide a foundation for the design of advanced materials with applications in bionanotechnology, nanomedicine and material sciences.« less

A combinatorial optogenetic approach to medial habenula function

NASA Astrophysics Data System (ADS)

Turner, Eric E.; Hsu, Yun-Wei; Wang, Si; Morton, Glenn; Zeng, Hongkui

2013-03-01

The habenula is a brain region found in all vertebrate species. It consists of medial and lateral subnuclei which make complex descending connections to the brainstem. Although the medial habenula (MHb) and its projection, the fasciculus retroflexus (FR), have been recognized for decades, their function remains obscure. The small size of the MHb in rodents, and the cellular and molecular complexity of this region, have made it difficult to study the function of this region with high specificity. Here we describe a Cre-mediated genetic system for expressing the microbial opsin channelrhodopsin (ChR2) specifically in the dorsal (dMHb) and ventral (vMHb) medial habenula. Genetically targeted expression of ChR2 allows MHb neurons to be selectively activated with light in acute brain slices with electrophysiological readouts, and in vivo by means of custom-built fiber optic cannulas. These tools will allow highly specific studies of MHb circuitry and the role of the MHb in behaviors related to addiction and mood regulation.

Examining the Feasibility, Tolerability, and Preliminary Efficacy of Repetitive Task-Specific Practice for People With Unilateral Spatial Neglect

PubMed Central

Lang, Catherine E.; Birkenmeier, Rebecca; Holm, Margo; Rubinstein, Elaine; Van Swearingen, Jessie; Skidmore, Elizabeth R.

2016-01-01

OBJECTIVE. We examined the feasibility, tolerability, and preliminary efficacy of repetitive task-specific practice for people with unilateral spatial neglect (USN). METHOD. People with USN ≥6 mo poststroke participated in a single-group, repeated-measures study. Attendance, total repetitions, and satisfaction indicated feasibility and pain indicated tolerability. Paired t tests and effect sizes were used to estimate changes in upper-extremity use (Motor Activity Log), function (Action Research Arm Test), and attention (Catherine Bergego Scale). RESULTS. Twenty participants attended 99.4% of sessions and completed a high number of repetitions. Participants reported high satisfaction and low pain, and they demonstrated small, significant improvements in upper-extremity use (before Bonferroni corrections; t = –2.1, p = .04, d = .30), function (t = –3.0, p < .01, d = .20), and attention (t = –3.4, p < .01, d = –.44). CONCLUSION. Repetitive task-specific practice is feasible and tolerable for people with USN. Improvements in upper-extremity use, function, and attention may be attainable. PMID:27294994

Self-calibration performance in stereoscopic PIV acquired in a transonic wind tunnel

DOE PAGES

Beresh, Steven J.; Wagner, Justin L.; Smith, Barton L.

2016-03-16

Three stereoscopic PIV experiments have been examined to test the effectiveness of self-calibration under varied circumstances. Furthermore, we our measurements taken in a streamwise plane yielded a robust self-calibration that returned common results regardless of the specific calibration procedure, but measurements in the crossplane exhibited substantial velocity bias errors whose nature was sensitive to the particulars of the self-calibration approach. Self-calibration is complicated by thick laser sheets and large stereoscopic camera angles and further exacerbated by small particle image diameters and high particle seeding density. In spite of the different answers obtained by varied self-calibrations, each implementation locked onto anmore » apparently valid solution with small residual disparity and converged adjustment of the calibration plane. Thus, the convergence of self-calibration on a solution with small disparity is not sufficient to indicate negligible velocity error due to the stereo calibration.« less

Pulsed Plasma Thruster Technology for Small Satellite Missions

NASA Technical Reports Server (NTRS)

Myers, Roger M.; Oleson, Steven R.; Mcguire, Melissa; Meckel, Nicole J.; Cassady, R. Joseph

1995-01-01

Pulsed plasma thrusters (PPT's) offer the combined benefits of extremely low average electric power requirements (1 to 150 W), high specific impulse (approximately 1000 s), and system simplicity derived from the use of an inert solid propellant. Potential applications range from orbit insertion and maintenance of small satellites to attitude control for large geostationary communications satellites. While PPT's have been used operationally on several spacecraft, there has been no new PPT technology development since the early 1970's. As result of the rapid growth in the small satellite community and the broad range of PPT applications, NASA has initiated a development program with the objective of dramatically reducing the PPT dry mass, increasing PPT performance, and demonstrating a flight ready system by October 1997. This paper presents the results of a series of near-Earth mission studies including both primary and auxiliary propulsion and attitude control functions and reviews the status of NASA's on-going development program.

Large-Eddy Simulations of Noise Generation in Supersonic Jets at Realistic Engine Temperatures

NASA Astrophysics Data System (ADS)

Liu, Junhui; Corrigan, Andrew; Kailasanath, K.; Taylor, Brian

2015-11-01

Large-eddy simulations (LES) have been carried out to investigate the noise generation in highly heated supersonic jets at temperatures similar to those observed in high-performance jet engine exhausts. It is found that the exhaust temperature of high-performance jet engines can range from 1000K at an intermediate power to above 2000K at a maximum afterburning power. In low-temperature jets, the effects of the variation of the specific heat ratio as well as the radial temperature profile near the nozzle exit are small and are ignored, but it is not clear whether those effects can be also ignored in highly heated jets. The impact of the variation of the specific heat ratio is assessed by comparing LES results using a variable specific heat ratio with those using a constant specific heat ratio. The impact on both the flow field and the noise distributions are investigated. Because the total temperature near the nozzle wall can be substantially lower than the nozzle total temperature either due to the heating loss through the nozzle wall or due to the cooling applied near the wall, this lower wall temperature may impact the temperature in the shear layer, and thus impact the noise generation. The impact of the radial temperature profile on the jet noise generation is investigated by comparing results of lower nozzle wall temperatures with those of the adiabatic wall condition.

Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

ClinicalTrials.gov

2012-12-13

Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Multiple cis-acting sequence elements are required for efficient splicing of simian virus 40 small-t antigen pre-mRNA.

PubMed Central

Fu, X Y; Colgan, J D; Manley, J L

1988-01-01

We have determined the effects of a number of mutations in the small-t antigen mRNA intron on the alternative splicing pattern of the simian virus 40 early transcript. Expansion of the distance separating the small-t pre-mRNA lariat branch point and the shared large T-small t 3' splice site from 18 to 29 nucleotides (nt) resulted in a relative enhancement of small-t splicing in vivo. This finding, coupled with the observation that large-T pre-RNA splicing in vitro was not affected by this expansion, suggests that small-t splicing is specifically constrained by a short branch point-3' splice site distance. Similarly, the distance separating the 5' splice site and branch point (48 nt) was found to be at or near a minimum for small-t splicing, because deletions in this region as small as 2 nt dramatically reduced the ratio of small-t to large-T mRNA that accumulated in transfected cells. Finally, a specific sequence within the small-t intron, encompassing the upstream branch sites used in large-T splicing, was found to be an important element in the cell-specific pattern of early alternative splicing. Substitutions within this region reduced the ratio of small-t to large-T mRNA produced in HeLa cells but had only minor effects in human 293 cells. Images PMID:2851720

Update on Healthy Aging: Reading Material on Health Topics for the New Reader and Tutor. Literacy Education for the Elderly Project.

ERIC Educational Resources Information Center

Jacobs, Bella; Ventura-Merkel, Catherine

Fifteen lessons contain low-vocabulary, high interest reading materials on health issues to enhance the learning of the new older reader. Each lesson is preceded by tutor guidelines with specific goals and objectives and review exercises. The materials are useful in either one-to-one or small-group tutoring. Reading selections in the lessons,…

Adaptive Probabilistic Protocols for Advanced Networks/Assuring the Integrity of Highly Decentralized Communications Systems

DTIC Science & Technology

2005-03-01

to obtain a protocol customized to the needs of a specific setting, under control of an automated theorem proving system that can guarantee...new “compositional” method for protocol design and implementation, in which small microprotocols are combined to obtain a protocol customized to the...and Network Centric Enterprise (NCES) visions. This final report documents a wide range of contributions and technology transitions, including: A

The Golden Age of Greece: Imperial Democracy 500-400 B.C. A Unit of Study for Grades 6-12.

ERIC Educational Resources Information Center

Cheoros, Peter; And Others

This unit is one of a series that represents specific moments in history from which students focus on the meanings of landmark events. This unit explores Greece's most glorious century, the high point of Athenian culture. Rarely has so much genius been concentrated in one small region over such a short period of time. Students discover in studying…

Microtubule-Targeting Therapy for Prostate Cancer

DTIC Science & Technology

2007-02-01

that were done to achieve the above specific goals. 1. Biological effects of ribozyme -carrying adenoviruses that target stathmin mRNA in human...prostate cancer cells: A ribozyme is a small RNA molecule that acts stoichiometrically to cleave multiple target RNA molecules [1]. This unique ability...of a ribozyme to degrade multiple target RNA molecules is a more efficient approach for down regulating genes that are expressed at very high levels

Universities, SMEs and Social Capital: Can You Get Too Much of a Good Thing? An Illustrative Analysis of One University's Knowledge Exchange Programme

ERIC Educational Resources Information Center

Gordon, Ian

2016-01-01

This article explores a university knowledge exchange programme for small and medium-sized enterprise (SME) owner-managers. Specifically, it considers why a programme designed to achieve growth in a group of SMEs through the creation of a network high in social capital may have become a constraint on the programme's effectiveness over a period of…

Rapid Covalent Fluorescence Labeling of Membrane Proteins on Live Cells via Coiled-Coil Templated Acyl Transfer.

PubMed

Reinhardt, Ulrike; Lotze, Jonathan; Mörl, Karin; Beck-Sickinger, Annette G; Seitz, Oliver

2015-10-21

Fluorescently labeled proteins enable the microscopic imaging of protein localization and function in live cells. In labeling reactions targeted against specific tag sequences, the size of the fluorophore-tag is of major concern. The tag should be small to prevent interference with protein function. Furthermore, rapid and covalent labeling methods are desired to enable the analysis of fast biological processes. Herein, we describe the development of a method in which the formation of a parallel coiled coil triggers the transfer of a fluorescence dye from a thioester-linked coil peptide conjugate onto a cysteine-modified coil peptide. This labeling method requires only small tag sequences (max 23 aa) and occurs with high tag specificity. We show that size matching of the coil peptides and a suitable thioester reactivity allow the acyl transfer reaction to proceed within minutes (rather than hours). We demonstrate the versatility of this method by applying it to the labeling of different G-protein coupled membrane receptors including the human neuropeptide Y receptors 1, 2, 4, 5, the neuropeptide FF receptors 1 and 2, and the dopamine receptor 1. The labeled receptors are fully functional and able to bind the respective ligand with high affinity. Activity is not impaired as demonstrated by activation, internalization, and recycling experiments.

Modified T-history method for measuring thermophysical properties of phase change materials at high temperature

NASA Astrophysics Data System (ADS)

Omaraa, Ehsan; Saman, Wasim; Bruno, Frank; Liu, Ming

2017-06-01

Latent heat storage using phase change materials (PCMs) can be used to store large amounts of energy in a narrow temperature difference during phase transition. The thermophysical properties of PCMs such as latent heat, specific heat and melting and solidification temperature need to be defined at high precision for the design and estimating the cost of latent heat storage systems. The existing laboratory standard methods, such as differential thermal analysis (DTA) and differential scanning calorimetry (DSC), use a small sample size (1-10 mg) to measure thermophysical properties, which makes these methods suitable for homogeneous elements. In addition, this small amount of sample has different thermophysical properties when compared with the bulk sample and may have limitations for evaluating the properties of mixtures. To avoid the drawbacks in existing methods, the temperature - history (T-history) method can be used with bulk quantities of PCM salt mixtures to characterize PCMs. This paper presents a modified T-history setup, which was designed and built at the University of South Australia to measure the melting point, heat of fusion, specific heat, degree of supercooling and phase separation of salt mixtures for a temperature range between 200 °C and 400 °C. Sodium Nitrate (NaNO3) was used to verify the accuracy of the new setup.

Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical Applications.

PubMed

Ellis, Matthew A; Grandinetti, Giovanna; Fichter, Katye M; Fichter, Kathryn M

2016-02-06

Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, quantum dots should be highly fluorescent and small/monodisperse in size. While commonly used cadmium-based quantum dots possess these qualities, they are potentially toxic due to the possible release of Cd(2+) ions through nanoparticle degradation. Indium-based quantum dots, specifically InP/ZnS, have recently been explored as a viable alternative to cadmium-based quantum dots due to their relatively similar fluorescence characteristics and size. The synthesis presented here uses standard hot-injection techniques for effective nanoparticle growth; however, nanoparticle properties such as size, emission wavelength, and emission intensity can drastically change due to small changes in the reaction conditions. Therefore, reaction conditions such temperature, reaction duration, and precursor concentration should be maintained precisely to yield reproducible products. Because quantum dots are not inherently soluble in aqueous solutions, they must also undergo surface modification to impart solubility in water. In this protocol, an amphiphilic polymer is used to interact with both hydrophobic ligands on the quantum dot surface and bulk solvent water molecules. Here, a detailed protocol is provided for the synthesis of highly fluorescent InP/ZnS quantum dots that are suitable for use in biomedical applications.

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer.

PubMed

Chang, Hae Ryung; Nam, Seungyoon; Lee, Jinhyuk; Kim, Jin-Hee; Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-12-06

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of "hit" compounds.

Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical Applications

PubMed Central

Ellis, Matthew A.; Grandinetti, Giovanna; Fichter, Katye M.

2016-01-01

Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, quantum dots should be highly fluorescent and small/monodisperse in size. While commonly used cadmium-based quantum dots possess these qualities, they are potentially toxic due to the possible release of Cd2+ ions through nanoparticle degradation. Indium-based quantum dots, specifically InP/ZnS, have recently been explored as a viable alternative to cadmium-based quantum dots due to their relatively similar fluorescence characteristics and size. The synthesis presented here uses standard hot-injection techniques for effective nanoparticle growth; however, nanoparticle properties such as size, emission wavelength, and emission intensity can drastically change due to small changes in the reaction conditions. Therefore, reaction conditions such temperature, reaction duration, and precursor concentration should be maintained precisely to yield reproducible products. Because quantum dots are not inherently soluble in aqueous solutions, they must also undergo surface modification to impart solubility in water. In this protocol, an amphiphilic polymer is used to interact with both hydrophobic ligands on the quantum dot surface and bulk solvent water molecules. Here, a detailed protocol is provided for the synthesis of highly fluorescent InP/ZnS quantum dots that are suitable for use in biomedical applications. PMID:26891282

Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

PubMed

Koniari, Katerina; Mahera, Helen; Nikolaou, Marinos; Chatzis, Odysseas; Glezakou, Ourania; Magiasis, Vasilios; Kiratzis, Georgios

2011-01-01

Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

Melting and vibrational properties of planetary materials under deep Earth conditions

NASA Astrophysics Data System (ADS)

Jackson, Jennifer

2013-06-01

The large chemical, density, and dynamical contrasts associated with the juxtaposition of a liquid iron-dominant alloy and silicates at Earth's core-mantle boundary (CMB) are associated with a rich range of complex seismological features. For example, seismic heterogeneity at this boundary includes small patches of anomalously low sound velocities, called ultralow-velocity zones. Their small size (5 to 40 km thick) and depth (about 2800 km) present unique challenges for seismic characterization and geochemical interpretation. In this contribution, we will present recent nuclear resonant inelastic x-ray scattering measurements on iron-bearing silicates, oxides, and metals, and their application towards our understanding of Earth's interior. Specifically, we will present measurements on silicates and oxide minerals that are important in Earth's upper and lower mantles, as well as iron to over 1 megabar in pressure. The nuclear resonant inelastic x-ray scattering method provides specific vibrational information, e.g., the phonon density of states, and in combination with compression data permits the determination of sound velocities and other vibrational information under high pressure and high temperature. For example, accurate determination of the sound velocities and density of chemically complex Earth materials is essential for understanding the distribution and behavior of minerals and iron-alloys with depth. The high statistical quality of the data in combination with high energy resolution and a small x-ray focus size permit accurate evaluation of the vibrational-related quantities of iron-bearing Earth materials as a function of pressure, such as the Grüneisen parameter, thermal pressure, sound velocities, and iron isotope fractionation quantities. Finally, we will present a novel method detecting the solid-liquid phase boundary of compressed iron at high temperatures using synchrotron Mössbauer spectroscopy. Our approach is unique because the dynamics of the iron atoms are monitored. This process is described by the Lamb-Mössbauer factor, which is related to the mean-square displacement of the iron atoms. We will discuss the implications of our results as they relate to Earth's core and core-mantle boundary regions.

The direct detection of boosted dark matter at high energies and PeV events at IceCube

DOE PAGES

Bhattacharya, A.; Gandhi, R.; Gupta, A.

2015-03-13

We study the possibility of detecting dark matter directly via a small but energetic component that is allowed within present-day constraints. Drawing closely upon the fact that neutral current neutrino nucleon interactions are indistinguishable from DM-nucleon interactions at low energies, we extend this feature to high energies for a small, non-thermal but highly energetic population of DM particle χ, created via the decay of a significantly more massive and long-lived non-thermal relic Φ, which forms the bulk of DM. If χ interacts with nucleons, its cross-section, like the neutrino-nucleus coherent cross-section, can rise sharply with energy leading to deep inelasticmore » scattering, similar to neutral current neutrino-nucleon interactions at high energies. Thus, its direct detection may be possible via cascades in very large neutrino detectors. As a specific example, we apply this notion to the recently reported three ultra-high energy PeV cascade events clustered around 1 – 2 PeV at IceCube (IC). We discuss the features which may help discriminate this scenario from one in which only astrophysical neutrinos constitute the event sample in detectors like IC.« less

Hierarchically Structured Co3O4@Pt@MnO2 Nanowire Arrays for High-Performance Supercapacitors

PubMed Central

Xia, Hui; Zhu, Dongdong; Luo, Zhentao; Yu, Yue; Shi, Xiaoqin; Yuan, Guoliang; Xie, Jianping

2013-01-01

Here we proposed a novel architectural design of a ternary MnO2-based electrode – a hierarchical Co3O4@Pt@MnO2 core-shell-shell structure, where the complemental features of the three key components (a well-defined Co3O4 nanowire array on the conductive Ti substrate, an ultrathin layer of small Pt nanoparticles, and a thin layer of MnO2 nanoflakes) are strategically combined into a single entity to synergize and construct a high-performance electrode for supercapacitors. Owing to the high conductivity of the well-defined Co3O4 nanowire arrays, in which the conductivity was further enhanced by a thin metal (Pt) coating layer, in combination with the large surface area provided by the small MnO2 nanoflakes, the as-fabricated Co3O4@Pt@MnO2 nanowire arrays have exhibited high specific capacitances, good rate capability, and excellent cycling stability. The architectural design demonstrated in this study provides a new approach to fabricate high-performance MnO2–based nanowire arrays for constructing next-generation supercapacitors. PMID:24132040

Specific receptors for epidermal growth factor in rat intestinal microvillus membranes

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

Thompson, J.F.

Epidermal growth factor (EGF) is present in high concentrations in milk, salivary, and pancreaticobiliary secretions. EGF, delivered to the intestinal lumen by these fluids, appears to influence intestinal proliferation. Because EGF exerts its mitogenic effect through binding to specific membrane-bound receptors, binding studies of {sup 125}I-labeled EGF to purified microvillus membrane (MVM) preparations fetal, newborn, and adult rat small intestine were performed. Using the membrane filter technique, binding of {sup 125}I-EGF to adult MVM was specific, saturable, and reversible. Adult and fetal MVM binding was rapid and reached a plateau after 30 min at both 20 and 37{degree}C. No bindingmore » was detected at 4{degree}C. Specific binding increased linearly from 0 to 75 {mu}g MVM protein. Scatchard analysis revealed a single class of receptors in fetal and adult MVM with an association constant of 1.0 {+-} 0.35 {times} 10{sup 9} and 2.3 {+-} 1.6 {times} 10{sup 9} M{sup {minus}1}, respectively. Binding capacity was 435.0 {+-} 89 and 97.7 {+-} 41.3 fmol {sup 125}I-EGF bound/mg MVM protein for fetal and adult MVM, respectively. Newborn MVM binding was negligible. After binding, cross-linking utilizing disuccinimidyl suberate, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography revealed a 170-kDa receptor. These data demonstrate specific receptors for EGF on MVM of rat small intestine and, thus, suggest a mechanism for the intraluminal regulation of enterocyte proliferation by EGF.« less

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

PubMed

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Atom probe study of grain boundary segregation in technically pure molybdenum

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

Babinsky, K., E-mail: katharina.babinsky@stud.unileoben.ac.at; Weidow, J., E-mail: jonathan.weidow@chalmers.se; Knabl, W., E-mail: wolfram.knabl@plansee.com

2014-01-15

Molybdenum, a metal with excellent physical, chemical and high-temperature properties, is an interesting material for applications in lighting-technology, high performance electronics, high temperature furnace construction and coating technology. However, its applicability as a structural material is limited because of the poor oxidation resistance at high temperatures and a brittle-to-ductile transition around room temperature, which is influenced by the grain size and the content of interstitial impurities at the grain boundaries. Due to the progress of the powder metallurgical production during the last decades, the amount of impurities in the current quality of molybdenum has become so small that surface sensitivemore » techniques are not applicable anymore. Therefore, the atom probe, which allows the detection of small amounts of impurities as well as their location, seems to be a more suitable technique. However, a site-specific specimen preparation procedure for grain boundaries in refractory metals with a dual focused ion beam/scanning electron microscope is still required. The present investigation describes the development and successful application of such a site-specific preparation technique for grain boundaries in molybdenum, which is significantly improved by a combination with transmission electron microscopy. This complimentary technique helps to improve the visibility of grain boundaries during the last preparation steps and to evidence the presence of grain and subgrain boundaries without segregants in atom probe specimens. Furthermore, in industrially processed and recrystallized molybdenum sheets grain boundary segregation of oxygen, nitrogen and potassium is successfully detected close to segregated regions which are believed to be former sinter pores. - Highlights: • First study of grain boundary segregation in molybdenum by atom probe • Site-specific preparation technique by FIB and TEM successfully developed • Grain boundary segregation of oxygen, nitrogen and potassium found • Segregation in former sinter-pores detected • Presence of grain boundaries without segregation evidenced.« less

76 FR 2076 - Endangered and Threatened Wildlife and Plants; Designation of Critical Habitat for Tumbling Creek...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-12

... interested in any impacts on small entities (i.e., small businesses, small organizations, and small... impacts to specific areas or small businesses, including small businesses in the land development sector... designation, and whether that increase in threat outweighs the benefit of designation such that the...

Small RNA Profiling of Two Important Cultivars of Banana and Overexpression of miRNA156 in Transgenic Banana Plants

PubMed Central

Ganapathi, Thumballi R.

2015-01-01

Micro RNAs (miRNAs) are a class of non-coding, short RNAs having important roles in regulation of gene expression. Although plant miRNAs have been studied in detail in some model plants, less is known about these miRNAs in important fruit plants like banana. miRNAs have pivotal roles in plant growth and development, and in responses to diverse biotic and abiotic stress stimuli. Here, we have analyzed the small RNA expression profiles of two different economically significant banana cultivars by using high-throughput sequencing technology. We identified a total of 170 and 244 miRNAs in the two libraries respectively derived from cv. Grand Naine and cv. Rasthali leaves. In addition, several cultivar specific microRNAs along with their putative target transcripts were also detected in our studies. To validate our findings regarding the small RNA profiles, we also undertook overexpression of a common microRNA, MusamiRNA156 in transgenic banana plants. The transgenic plants overexpressing the stem-loop sequence derived from MusamiRNA156 gene were stunted in their growth together with peculiar changes in leaf anatomy. These results provide a foundation for further investigations into important physiological and metabolic pathways operational in banana in general and cultivar specific traits in particular. PMID:25962076

A semi-nested real-time PCR method to detect low chimerism percentage in small quantity of hematopoietic stem cell transplant DNA samples.

PubMed

Aloisio, Michelangelo; Bortot, Barbara; Gandin, Ilaria; Severini, Giovanni Maria; Athanasakis, Emmanouil

2017-02-01

Chimerism status evaluation of post-allogeneic hematopoietic stem cell transplantation samples is essential to predict post-transplant relapse. The most commonly used technique capable of detecting small increments of chimerism is quantitative real-time PCR. Although this method is already used in several laboratories, previously described protocols often lack sensitivity and the amount of the DNA required for each chimerism analysis is too high. In the present study, we compared a novel semi-nested allele-specific real-time PCR (sNAS-qPCR) protocol with our in-house standard allele-specific real-time PCR (gAS-qPCR) protocol. We selected two genetic markers and analyzed technical parameters (slope, y-intercept, R2, and standard deviation) useful to determine the performances of the two protocols. The sNAS-qPCR protocol showed better sensitivity and precision. Moreover, the sNAS-qPCR protocol requires, as input, only 10 ng of DNA, which is at least 10-fold less than the gAS-qPCR protocols described in the literature. Finally, the proposed sNAS-qPCR protocol could prove very useful for performing chimerism analysis with a small amount of DNA, as in the case of blood cell subsets.

Small Launch Vehicle Trade Space Definition: Development of a Zero Level Mass Estimation Tool with Trajectory Validation

NASA Technical Reports Server (NTRS)

Waters, Eric D.

2013-01-01

Recent high level interest in the capability of small launch vehicles has placed significant demand on determining the trade space these vehicles occupy. This has led to the development of a zero level analysis tool that can quickly determine the minimum expected vehicle gross liftoff weight (GLOW) in terms of vehicle stage specific impulse (Isp) and propellant mass fraction (pmf) for any given payload value. Utilizing an extensive background in Earth to orbit trajectory experience a total necessary delta v the vehicle must achieve can be estimated including relevant loss terms. This foresight into expected losses allows for more specific assumptions relating to the initial estimates of thrust to weight values for each stage. This tool was further validated against a trajectory model, in this case the Program to Optimize Simulated Trajectories (POST), to determine if the initial sizing delta v was adequate to meet payload expectations. Presented here is a description of how the tool is setup and the approach the analyst must take when using the tool. Also, expected outputs which are dependent on the type of small launch vehicle being sized will be displayed. The method of validation will be discussed as well as where the sizing tool fits into the vehicle design process.

Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Achilefu, Samuel I.; Dorshow, Richard B.; Rajagopalan, Raghavan

2001-04-01

We have designed, synthesized, and evaluated the efficacy of novel dye-peptide conjugates that are receptor specific. Contrary to the traditional approach of conjugating dyes to large proteins and antibodies, we used small peptide-dye conjugates that target over-expressed receptors on tumors. Despite the fact that the peptide and the dye probe have similar molecular mass, our results demonstrate that the affinity of the peptide for its receptor and the dye fluorescence properties are both retained. The use of small peptides has several advantages over large biomolecules, including ease of synthesis of a variety of compounds for potential combinatorial screening of new targets, reproducibility of high purity compounds, diffusiveness to solid tumors, and the ability to incorporate a variety of functional groups that modify the pharmacokinetics of the peptide-dye conjugates. The efficacy of these new fluorescent optical contrast agents was evaluated in vivo in well-characterized rat tumor lines expressing somatostatin (sst2) and bombesin receptors. A simple continuous wave optical imaging system was employed. The resulting optical images clearly show that successful specific tumor targeting was achieved. Thus, we have demonstrated that small peptide- dye conjugates are effective as contrast agents for optical imaging of tumors.

Community-specific hydraulic conductance potential of soil water decomposed for two Alpine grasslands by small-scale lysimetry

NASA Astrophysics Data System (ADS)

Frenck, Georg; Leitinger, Georg; Obojes, Nikolaus; Hofmann, Magdalena; Newesely, Christian; Deutschmann, Mario; Tappeiner, Ulrike; Tasser, Erich

2018-02-01

For central Europe in addition to rising temperatures an increasing variability in precipitation is predicted. This will increase the probability of drought periods in the Alps, where water supply has been sufficient in most areas so far. For Alpine grasslands, community-specific imprints on drought responses are poorly analyzed so far due to the sufficient natural water supply. In a replicated mesocosm experiment we compared evapotranspiration (ET) and biomass productivity of two differently drought-adapted Alpine grassland communities during two artificial drought periods divided by extreme precipitation events using high-precision small lysimeters. The drought-adapted vegetation type showed a high potential to utilize even scarce water resources. This is combined with a low potential to translate atmospheric deficits into higher water conductance and a lower biomass production as those measured for the non-drought-adapted type. The non-drought-adapted type, in contrast, showed high water conductance potential and a strong increase in ET rates when environmental conditions became less constraining. With high rates even at dry conditions, this community appears not to be optimized to save water and might experience drought effects earlier and probably more strongly. As a result, the water use efficiency of the drought-adapted plant community is with 2.6 gDW kg-1 of water much higher than that of the non-drought-adapted plant community (0.16 gDW kg-1). In summary, the vegetation's reaction to two covarying gradients of potential evapotranspiration and soil water content revealed a clear difference in vegetation development and between water-saving and water-spending strategies regarding evapotranspiration.

Psychological distress, related work attendance, and productivity loss in small-to-medium enterprise owner/managers.

PubMed

Cocker, Fiona; Martin, Angela; Scott, Jenn; Venn, Alison; Sanderson, Kristy

2013-10-15

Owner/managers of small-to-medium enterprises (SMEs) are an under-researched population in terms of psychological distress and the associated health and economic consequences. Using baseline data from the evaluation of the Business in Mind program, a mental health promotion intervention amongst SME owner/managers, this study investigated: (i) prevalence of high/very high psychological distress, past-month sickness absenteeism and presenteeism days in SME owner/managers; (ii) associated, self-reported lost productivity; and (iii) associations between work, non-work and business-specific factors and work attendance behaviours. In our sample of 217 SME owner/managers 36.8% reported high/very high psychological distress. Of this group 38.7% reported past-month absenteeism, 82.5% reported past-month presenteeism, and those reporting presenteeism were 50% less productive as than usual. Negative binomial regression was used to demonstrate the independent effects of socio-demographic, work-related wellbeing and health-related factors, as well as various individual and business characteristics on continuous measures of absenteeism and presenteeism days. Health-related factors (self-rated health and treatment) were the strongest correlates of higher presenteeism days (p < 0.05). Work-related wellbeing factors (job tension and job satisfaction) were the strongest correlates of higher absenteeism days (p < 0.05). Higher educational attainment, treatment and neuroticism were also correlated with more absenteeism days. SME-specific information about the occurrence of psychological distress, work attendance behaviour, and the variables that influence these decisions, are needed for the development of guidelines for managing psychological distress within this sector.

Psychological Distress, Related Work Attendance, and Productivity Loss in Small-to-Medium Enterprise Owner/Managers

PubMed Central

Cocker, Fiona; Martin, Angela; Scott, Jenn; Venn, Alison; Sanderson, Kristy

2013-01-01

Owner/managers of small-to-medium enterprises (SMEs) are an under-researched population in terms of psychological distress and the associated health and economic consequences. Using baseline data from the evaluation of the Business in Mind program, a mental health promotion intervention amongst SME owner/managers, this study investigated: (i) prevalence of high/very high psychological distress, past-month sickness absenteeism and presenteeism days in SME owner/managers; (ii) associated, self-reported lost productivity; and (iii) associations between work, non-work and business-specific factors and work attendance behaviours. In our sample of 217 SME owner/managers 36.8% reported high/very high psychological distress. Of this group 38.7% reported past-month absenteeism, 82.5% reported past-month presenteeism, and those reporting presenteeism were 50% less productive as than usual. Negative binomial regression was used to demonstrate the independent effects of socio-demographic, work-related wellbeing and health-related factors, as well as various individual and business characteristics on continuous measures of absenteeism and presenteeism days. Health-related factors (self-rated health and treatment) were the strongest correlates of higher presenteeism days (p < 0.05). Work-related wellbeing factors (job tension and job satisfaction) were the strongest correlates of higher absenteeism days (p < 0.05). Higher educational attainment, treatment and neuroticism were also correlated with more absenteeism days. SME-specific information about the occurrence of psychological distress, work attendance behaviour, and the variables that influence these decisions, are needed for the development of guidelines for managing psychological distress within this sector. PMID:24132134

Surface-Engineered Multifunctional Eu:Gd2O3 Nanoplates for Targeted and pH-Responsive Drug Delivery and Imaging Applications.

PubMed

Saha, Arindam; Mohanta, Subas Chandra; Deka, Kashmiri; Deb, Pritam; Devi, Parukuttyamma Sujatha

2017-02-01

In this paper, we report the synthesis of surface-engineered multifunctional Eu:Gd 2 O 3 triangular nanoplates with small size and uniform shape via a high-temperature solvothermal technique. Surface engineering has been performed by a one-step polyacrylate coating, followed by controlled conjugation chemistry. This creates the desired number of surface functional groups that can be used to attach folic acid as a targeting ligand on the nanoparticle surface. To specifically deliver the drug molecules in the nucleus, the folate density on the nanoparticle surface has been kept low. We have also modified the drug molecules with terminal double bond and ester linkage for the easy conjugation of nanoparticles. The nanoparticle surface was further modified with free thiols to specifically attach the modified drug molecules with a pH-responsive feature. High drug loading has been encountered for both hydrophilic drug daunorubicin (∼69% loading) and hydrophobic drug curcumin (∼75% loading) with excellent pH-responsive drug release. These nanoparticles have also been used as imaging probes in fluorescence imaging. Some preliminary experiments to evaluate their application in magnetic resonance imaging have also been explored. A detailed fluorescence imaging study has confirmed the efficient delivery of drugs to the nuclei of cancer cells with a high cytotoxic effect. Synthesized surface-engineered nanomaterials having small hydrodynamic size, excellent colloidal stability, and high drug-loading capacity, along with targeted and pH-responsive delivery of dual drugs to the cancer cells, will be potential nanobiomaterials for various biomedical applications.

Transcription factors, coregulators, and epigenetic marks are linearly correlated and highly redundant

PubMed Central

Ahsendorf, Tobias; Müller, Franz-Josef; Topkar, Ved; Gunawardena, Jeremy; Eils, Roland

2017-01-01

The DNA microstates that regulate transcription include sequence-specific transcription factors (TFs), coregulatory complexes, nucleosomes, histone modifications, DNA methylation, and parts of the three-dimensional architecture of genomes, which could create an enormous combinatorial complexity across the genome. However, many proteins and epigenetic marks are known to colocalize, suggesting that the information content encoded in these marks can be compressed. It has so far proved difficult to understand this compression in a systematic and quantitative manner. Here, we show that simple linear models can reliably predict the data generated by the ENCODE and Roadmap Epigenomics consortia. Further, we demonstrate that a small number of marks can predict all other marks with high average correlation across the genome, systematically revealing the substantial information compression that is present in different cell lines. We find that the linear models for activating marks are typically cell line-independent, while those for silencing marks are predominantly cell line-specific. Of particular note, a nuclear receptor corepressor, transducin beta-like 1 X-linked receptor 1 (TBLR1), was highly predictive of other marks in two hematopoietic cell lines. The methodology presented here shows how the potentially vast complexity of TFs, coregulators, and epigenetic marks at eukaryotic genes is highly redundant and that the information present can be compressed onto a much smaller subset of marks. These findings could be used to efficiently characterize cell lines and tissues based on a small number of diagnostic marks and suggest how the DNA microstates, which regulate the expression of individual genes, can be specified. PMID:29216191

Changing resonator geometry to boost sound power decouples size and song frequency in a small insect.

PubMed

Mhatre, Natasha; Montealegre-Z, Fernando; Balakrishnan, Rohini; Robert, Daniel

2012-05-29

Despite their small size, some insects, such as crickets, can produce high amplitude mating songs by rubbing their wings together. By exploiting structural resonance for sound radiation, crickets broadcast species-specific songs at a sharply tuned frequency. Such songs enhance the range of signal transmission, contain information about the signaler's quality, and allow mate choice. The production of pure tones requires elaborate structural mechanisms that control and sustain resonance at the species-specific frequency. Tree crickets differ sharply from this scheme. Although they use a resonant system to produce sound, tree crickets can produce high amplitude songs at different frequencies, varying by as much as an octave. Based on an investigation of the driving mechanism and the resonant system, using laser Doppler vibrometry and finite element modeling, we show that it is the distinctive geometry of the crickets' forewings (the resonant system) that is responsible for their capacity to vary frequency. The long, enlarged wings enable the production of high amplitude songs; however, as a mechanical consequence of the high aspect ratio, the resonant structures have multiple resonant modes that are similar in frequency. The drive produced by the singing apparatus cannot, therefore, be locked to a single frequency, and different resonant modes can easily be engaged, allowing individual males to vary the carrier frequency of their songs. Such flexibility in sound production, decoupling body size and song frequency, has important implications for conventional views of mate choice, and offers inspiration for the design of miniature, multifrequency, resonant acoustic radiators.

Highly ordered mesoporous cobalt oxide nanostructures: synthesis, characterisation, magnetic properties, and applications for electrochemical energy devices.

PubMed

Wang, Guoxiu; Liu, Hao; Horvat, Josip; Wang, Bei; Qiao, Shizhang; Park, Jinsoo; Ahn, Hyojun

2010-09-24

Highly ordered mesoporous Co(3)O(4) nanostructures were prepared using KIT-6 and SBA-15 silica as hard templates. The structures were confirmed by small angle X-ray diffraction, high resolution transmission electron microscopy, and N(2) adsorption-desorption isotherm analysis. Both KIT-6 cubic and SBA-15 hexagonal mesoporous Co(3)O(4) samples exhibited a low Néel temperature and bulk antiferromagnetic coupling due to geometric confinement of antiferromagnetic order within the nanoparticles. Mesoporous Co(3)O(4) electrode materials have demonstrated the high lithium storage capacity of more than 1200 mAh g(-1) with an excellent cycle life. They also exhibited a high specific capacitance of 370 F g(-1) as electrodes in supercapacitors.

48 CFR 19.705-4 - Reviewing the subcontracting plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... disadvantaged business, and women-owned small business subcontractors to the maximum practicable extent. The..., service-disabled veteran-owned small business, HUBZone small business, or women-owned small business... women-owned small business concerns. If information is not available on a specific type of product or...

48 CFR 19.705-4 - Reviewing the subcontracting plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... disadvantaged business, and women-owned small business subcontractors to the maximum practicable extent. The..., service-disabled veteran-owned small business, HUBZone small business, or women-owned small business... women-owned small business concerns. If information is not available on a specific type of product or...

Material Density Distribution of Small Debris in Earth Orbit

NASA Technical Reports Server (NTRS)

Krisko, P. H.; Xu, Y.-l.; Opiela, J. N.; Hill, N. M.; Matney, M. J.

2008-01-01

Over 200 spacecraft and rocket body breakups in Earth orbit have populated that regime with debris fragments in the sub-micron through meter size range. Though the largest debris fragments can cause significant collisional damage to active (operational) spacecraft, these are few and trackable by radar. Fragments on the order of a millimeter to a centimeter in size are as yet untrackable. But this smaller debris can result in damage to critical spacecraft systems and, under the worst conditions, fragmenting collision events. Ongoing research at the NASA Orbital Debris Program Office on the sources of these small fragments has focused on the material components of spacecraft and rocket bodies and on breakup event morphology. This has led to fragment material density estimates, and also the beginnings of shape categorizations. To date the NASA Standard Breakup Model has not considered specific material density distinctions of small debris. The basis of small debris in that model is the fourth hypervelocity impact event of the Satellite Orbital Debris Characterization Impact Test (SOCIT) series. This test targeted a flight-ready, U.S. Transit navigation satellite with a solid aluminum sphere impactor. Results in this event yield characteristic length (size) and area-to-mass distributions of fragments smaller than 10 cm in the NASA model. Recent re-analysis of the SOCIT4 small fragment dataset highlighted the material-specific characteristics of metals and non-metals. Concurrent analysis of Space Shuttle in-situ impact data showed a high percentage of aluminum debris in shuttle orbit regions. Both analyses led to the definition of three main on-orbit debris material density categories -low density (< 2 g/cc), medium density (2 to 6 g/cc), and high density (> 6 g/cc). This report considers the above studies in an explicit extension of the NASA Standard Breakup Model where separate material densities for debris are generated and these debris fragments are propagated in Earth orbit. The near Earth environment is thus parameterized by debris density percentages within subsections of that environment. This model version is used in the upgraded NASA Orbital Debris Engineering Model (ORDEM).

Community- Weighted Mean Plant Traits Predict Small Scale Distribution of Insect Root Herbivore Abundance

PubMed Central

Jeltsch, Florian; Wurst, Susanne

2015-01-01

Small scale distribution of insect root herbivores may promote plant species diversity by creating patches of different herbivore pressure. However, determinants of small scale distribution of insect root herbivores, and impact of land use intensity on their small scale distribution are largely unknown. We sampled insect root herbivores and measured vegetation parameters and soil water content along transects in grasslands of different management intensity in three regions in Germany. We calculated community-weighted mean plant traits to test whether the functional plant community composition determines the small scale distribution of insect root herbivores. To analyze spatial patterns in plant species and trait composition and insect root herbivore abundance we computed Mantel correlograms. Insect root herbivores mainly comprised click beetle (Coleoptera, Elateridae) larvae (43%) in the investigated grasslands. Total insect root herbivore numbers were positively related to community-weighted mean traits indicating high plant growth rates and biomass (specific leaf area, reproductive- and vegetative plant height), and negatively related to plant traits indicating poor tissue quality (leaf C/N ratio). Generalist Elaterid larvae, when analyzed independently, were also positively related to high plant growth rates and furthermore to root dry mass, but were not related to tissue quality. Insect root herbivore numbers were not related to plant cover, plant species richness and soil water content. Plant species composition and to a lesser extent plant trait composition displayed spatial autocorrelation, which was not influenced by land use intensity. Insect root herbivore abundance was not spatially autocorrelated. We conclude that in semi-natural grasslands with a high share of generalist insect root herbivores, insect root herbivores affiliate with large, fast growing plants, presumably because of availability of high quantities of food. Affiliation of insect root herbivores with large, fast growing plants may counteract dominance of those species, thus promoting plant diversity. PMID:26517119

Developmental Environment Effects on Sexual Selection in Male and Female Drosophila melanogaster

PubMed Central

Morimoto, Juliano; Pizzari, Tommaso; Wigby, Stuart

2016-01-01

The developmental environment can potentially alter the adult social environment and influence traits targeted by sexual selection such as body size. In this study, we manipulated larval density in male and female Drosophila melanogaster, which results in distinct adult size phenotypes–high (low) densities for small (large) adults–and measured sexual selection in experimental groups consisting of adult males and females from high, low, or a mixture of low and high larval densities. Overall, large adult females (those reared at low larval density) had more matings, more mates and produced more offspring than small females (those reared at high larval density). The number of offspring produced by females was positively associated with their number of mates (i.e. there was a positive female Bateman gradient) in social groups where female size was experimentally varied, likely due to the covariance between female productivity and mating rate. For males, we found evidence that the larval environment affected the relative importance of sexual selection via mate number (Bateman gradients), mate productivity, paternity share, and their covariances. Mate number and mate productivity were significantly reduced for small males in social environments where males were of mixed sizes, versus social environments where all males were small, suggesting that social heterogeneity altered selection on this subset of males. Males are commonly assumed to benefit from mating with large females, but in contrast to expectations we found that in groups where both the male and female size varied, males did not gain more offspring per mating with large females. Collectively, our results indicate sex-specific effects of the developmental environment on the operation of sexual selection, via both the phenotype of individuals, and the phenotype of their competitors and mates. PMID:27167120

TaqMan based real time PCR assay targeting EML4-ALK fusion transcripts in NSCLC.

PubMed

Robesova, Blanka; Bajerova, Monika; Liskova, Kvetoslava; Skrickova, Jana; Tomiskova, Marcela; Pospisilova, Sarka; Mayer, Jiri; Dvorakova, Dana

2014-07-01

Lung cancer with the ALK rearrangement constitutes only a small fraction of patients with non-small cell lung cancer (NSCLC). However, in the era of molecular-targeted therapy, efficient patient selection is crucial for successful treatment. In this context, an effective method for EML4-ALK detection is necessary. We developed a new highly sensitive variant specific TaqMan based real time PCR assay applicable to RNA from formalin-fixed paraffin-embedded tissue (FFPE). This assay was used to analyze the EML4-ALK gene in 96 non-selected NSCLC specimens and compared with two other methods (end-point PCR and break-apart FISH). EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR. All real time PCR positive samples were confirmed with direct sequencing. A total of 46 specimens were subsequently analyzed by all three detection methods. Using variant specific real time PCR we identified EML4-ALK transcript in 17/46 (37%) specimens, using end-point PCR in 13/46 (28%) specimens and positive ALK rearrangement by FISH was detected in 8/46 (17.4%) specimens. Moreover, using variant specific real time PCR, 5 specimens showed more than one EML4-ALK variant simultaneously (in 2 cases the variants 1+3a+3b, in 2 specimens the variants 1+3a and in 1 specimen the variant 1+3b). In one case of 96 EML4-ALK fusion gene and EGFR mutation were detected. All simultaneous genetic variants were confirmed using end-point PCR and direct sequencing. Our variant specific real time PCR assay is highly sensitive, fast, financially acceptable, applicable to FFPE and seems to be a valuable tool for the rapid prescreening of NSCLC patients in clinical practice, so, that most patients able to benefit from targeted therapy could be identified. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Generating Safety-Critical PLC Code From a High-Level Application Software Specification

NASA Technical Reports Server (NTRS)

2008-01-01

The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is shown.

A SIMPLE AND EFFECTIVE MULTIPLEX PCR TECHNIQUE FOR DETECTING HUMAN PATHOGENIC TAENIA EGGS IN HOUSEFLIES.

PubMed

Pornruseetriratn, Siritavee; Maipanich, Wanna; Sa-nguankiat, Surapol; Pubampen, Somchit; Poodeepiyasawat, Akkarin; Thaenkham, Urusa

2017-01-01

Taenia solium, T. saginata, and T. asiatica are cestode pathogens causing taeniasis in humans. Houseflies can transfer Taenia eggs to food. However, houseflies are thought to carry only small numbers of Taenia eggs, sometimes fewer than 10. Although several PCR-based methods have been developed to detect Taenia DNA, these require more than 10 eggs for adequate detection. We developed a multiplex PCR method with high specificity for the discrimination among the eggs of the three Taenia species, T. solium, T. saginata, and T. asiatica, using 18S ribosomal DNA (rDNA) as a genetic marker. This technique was found to be highly sensitive, capable of identifying the Taenia species from only one egg. This multiplex PCR technique using 18S rDNA specific primers should be suitable to diagnose Taenia eggs.

Carbon nanotube-mediated siRNA delivery for gene silencing in cancer cells

NASA Astrophysics Data System (ADS)

Hong, Tu; Guo, Honglian; Xu, Yaqiong

2011-10-01

Small interfering RNA (siRNA) is potentially a promising tool in influencing gene expression with a high degree of target specificity. However, its poor intracellular uptake, instability in vivo, and non-specific immune stimulations impeded its effect in clinical applications. In this study, carbon nanotubes (CNTs) functionalized with two types of phospholipid-polyethylene glycol (PEG) have shown capabilities to stabilize siRNA in cell culture medium during the transfection and efficiently deliver siRNA into neuroblastoma and breast cancer cells. Moreover, the intrinsic optical properties of CNTs have been investigated through absorption and fluorescence measurements. We have found that the directly-functionalized groups play an important role on the fluorescence imaging of functionalized CNTs. The unique fluorescence imaging and high delivery efficiency make CNTs a promising material to deliver drugs and evaluate the treatment effect simultaneously.

A small field for fertile science: the low visibility of reproductive science in high impact journals.

PubMed

Duncan, Francesca E; Derman, Benjamin; Woodruff, Teresa K

2014-05-01

Our success as a field and as individuals in reproductive science and medicine relies on our ability to produce high quality work that has broad visibility and impact. A common metric for assessing such success is the quantity of publications that are published in journals with high impact factors. It is unclear, however, how frequently work related to reproductive science and medicine actually appears in what are considered the highest impact journals. To address this gap in knowledge, we first determined how the field of reproductive biology in general compared to other research areas in terms of composite journal impact factor. Second, using a targeted search approach in the PubMed database, we examined the relationship between a journal's impact factor and the number of reproductive research articles published per journal issue. We found that compared to other major scientific disciplines, our field lacks journals with impact factors above 4. In addition, primary original research articles on reproduction-irrespective of male or female search terms-do not appear often in high impact journals. Instead, there is an increased percentage of secondary reproductive literature in high impact journals compared to topic-specific journals of lower impact. There are likely several explanations for why reproductive science and medicine has low visibility, including the field's small relative size, its lack of a specific disease and associated strong advocacy, and its surrounding social, ethical, and political unease. Nevertheless, there are concrete actions we can take to minimize the role of impact factor in our evaluation while simultaneously increasing influence through global awareness of the importance and need for reproductive research.

High-accuracy measurements of N2O concentration and site-specific nitrogen isotopes in small or high concentration samples

NASA Astrophysics Data System (ADS)

Palmer, M. R.; Arata, C.; Huang, K.

2014-12-01

Nitrous oxide (N2O) gas is among the major contributors to global warming and ozone depletion in stratosphere. Quantitative estimate of N­2O production in various pathways and N­2O fluxes across different reservoirs is the key to understanding the role of N­2O in the global change. To achieve this goal, accurate and concurrent measurement of both N2O concentration ([N2O]) and its site-specific isotopic composition (SP-δ15N), namely δ15Nα and δ15Nβ, is desired. Recent developments in Cavity Ring-Down Spectroscopy (CRDS) have enabled high precision measurements of [N2O] and SP-δ15N of a continuous gas flow. However, many N­­2O samples are discrete with limited volume (< 500 ml), and/or high [N2O] (> 2 ppm), and are not suitable for direct measurements by CRDS. Here we present results of a Small Sample Isotope Module 2 (SSIM2) which is coupled to and automatically coordinated with a Picarro isotopic N2O CRDS analyzer to handle and measure high concentration and/or small volume samples. The SSIM2 requires 20 ml of sample per analysis, and transfers the sample to the CRDS for high precision measurement. When the sample injection is < 20 ml, a zero gas is optionally filled to make up the volume. We used the SSIM2 to dilute high [N2O] samples and < 20 ml samples, and tested the effect of dilution on the measured SP-δ15N. In addition, we employed and tested a newly developed double injection method for samples adequate for two 20 ml injections. After the SSIM2 and the CRDS cavity was primed with the first injection, the second injection, which has negligible dilution of the sample, can be accurately measured for both [N2O] and SP-δ15N. Results of these experiments indicate that the precision of SSIM2-CRDS is similar to that of the continuous measurements using the CRDS alone, and that dilution has minimal effect on SP-δ15N, as along as the [N2O] is > 300 ppb after dilution. Overall, the precision of SP-δ15N measured using the SSIM2 is < 0.5 ‰.

Tidal reversal and flow velocities using temperature and specific conductance in a small wetland creek

NASA Astrophysics Data System (ADS)

Eaton, Timothy T.

2016-11-01

Characterizing flow dynamics in very small tidal creeks is complicated and not well suited to methods developed for upland streams or coastal estuaries, due to low flows, bidirectionality and shallow waters. Simple instrumentation enables thermal and salinity signals to be used to observe flow directions and estimate velocities in these settings. Using multiple inexpensive sensors over 500 m along a tidally influenced wetland creek, I demonstrate how advection of temperature and specific conductance pulses reveal flood and ebb tides and the temporary reversal of flow by warmer, estuarine water from the receiving embayment. The sequential rise of temperature upstream was most evident under hot and dry conditions, after daily peak air temperatures of 25 °C or above, and was subdued or disrupted under cooler or rainy conditions in summertime. Changes in specific conductance at successive sites upstream were less susceptible to environmental influences and confirm tidal flood velocity of between 0.07 and 0.37 m/s. The tidally-induced flow reversal suggests that periodic high tide conditions can interfere with rapid dispersal of pollution discharges, such as from the combined sewer overflow (CSO) located upstream of the studied creek reach. This low-cost approach of temperature and specific conductance sensing in vegetated coastal wetlands where access, precise elevation control and creek discharge measurements are difficult, provides a simple way of tracking water masses when sufficient contrast exists between water sources.

Identification of 2-phenylethanol with a rose-like odor from anal sac secretions of the small Indian mongoose (Herpestes auropunctatus).

PubMed

Miyazaki, Tamako; Nakata, Katsushi; Nishimura, Takashi; Abe, Shintaro; Yamashita, Tetsuro; Miyazaki, Masao

2018-02-01

The small Indian mongoose (Herpestes auropunctatus) is an invasive species in Okinawa and Amami-Oshima, Japan. Major strategies for their eradication have been the use of baited traps, which suffer from decreasing efficiency with declining populations and the bycatch of native animals. To address these concerns, mongoose-specific lures are required. In this study, we aimed to identify species- and/or sex-specific compounds from anal sac secretions of small Indian mongooses. Volatile compounds emitted from male and female mongoose anal sac secretions were analyzed by thermal desorption-gas chromatography-mass spectrometry. In addition to several fatty acids, 2-phenylethanol was identified as a minor compound, which is uncommon in mammalian secretions but a dominant odorant in roses. Female samples emitted higher levels of 2-phenylethanol than male samples did. These findings indicate that 2-phenylethanol is a female-specific volatile compound of anal sac secretions in small Indian mongooses, and it may be useful as an ingredient of mongoose-specific scent lures.

Prediction of bacterial small RNAs in the RsmA (CsrA) and ToxT pathways: a machine learning approach.

PubMed

Fakhry, Carl Tony; Kulkarni, Prajna; Chen, Ping; Kulkarni, Rahul; Zarringhalam, Kourosh

2017-08-22

Small RNAs (sRNAs) constitute an important class of post-transcriptional regulators that control critical cellular processes in bacteria. Recent research using high-throughput transcriptomic approaches has led to a dramatic increase in the discovery of bacterial sRNAs. However, it is generally believed that the currently identified sRNAs constitute a limited subset of the bacterial sRNA repertoire. In several cases, sRNAs belonging to a specific class are already known and the challenge is to identify additional sRNAs belonging to the same class. In such cases, machine-learning approaches can be used to predict novel sRNAs in a given class. In this work, we develop novel bioinformatics approaches that integrate sequence and structure-based features to train machine-learning models for the discovery of bacterial sRNAs. We show that features derived from recurrent structural motifs in the ensemble of low energy secondary structures can distinguish the RNA classes with high accuracy. We apply this approach to predict new members in two broad classes of bacterial small RNAs: 1) sRNAs that bind to the RNA-binding protein RsmA/CsrA in diverse bacterial species and 2) sRNAs regulated by the master regulator of virulence, ToxT, in Vibrio cholerae. The involvement of sRNAs in bacterial adaptation to changing environments is an increasingly recurring theme in current research in microbiology. It is likely that future research, combining experimental and computational approaches, will discover many more examples of sRNAs as components of critical regulatory pathways in bacteria. We have developed a novel approach for prediction of small RNA regulators in important bacterial pathways. This approach can be applied to specific classes of sRNAs for which several members have been identified and the challenge is to identify additional sRNAs.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

PubMed

She, Xiaodong; Chen, Lijue; Velleman, Leonora; Li, Chengpeng; Zhu, Haijin; He, Canzhong; Wang, Tao; Shigdar, Sarah; Duan, Wei; Kong, Lingxue

2015-05-01

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670 m(2)/g), small diameter (120 nm) and uniform pore size (2.5 nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5 mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

A gene-specific non-enhancer sequence is critical for expression from the promoter of the small heat shock protein gene αB-crystallin

PubMed Central

2014-01-01

Background Deciphering of the information content of eukaryotic promoters has remained confined to universal landmarks and conserved sequence elements such as enhancers and transcription factor binding motifs, which are considered sufficient for gene activation and regulation. Gene-specific sequences, interspersed between the canonical transacting factor binding sites or adjoining them within a promoter, are generally taken to be devoid of any regulatory information and have therefore been largely ignored. An unanswered question therefore is, do gene-specific sequences within a eukaryotic promoter have a role in gene activation? Here, we present an exhaustive experimental analysis of a gene-specific sequence adjoining the heat shock element (HSE) in the proximal promoter of the small heat shock protein gene, αB-crystallin (cryab). These sequences are highly conserved between the rodents and the humans. Results Using human retinal pigment epithelial cells in culture as the host, we have identified a 10-bp gene-specific promoter sequence (GPS), which, unlike an enhancer, controls expression from the promoter of this gene, only when in appropriate position and orientation. Notably, the data suggests that GPS in comparison with the HSE works in a context-independent fashion. Additionally, when moved upstream, about a nucleosome length of DNA (−154 bp) from the transcription start site (TSS), the activity of the promoter is markedly inhibited, suggesting its involvement in local promoter access. Importantly, we demonstrate that deletion of the GPS results in complete loss of cryab promoter activity in transgenic mice. Conclusions These data suggest that gene-specific sequences such as the GPS, identified here, may have critical roles in regulating gene-specific activity from eukaryotic promoters. PMID:24589182

A Novel Real-Time PCR Assay of microRNAs Using S-Poly(T), a Specific Oligo(dT) Reverse Transcription Primer with Excellent Sensitivity and Specificity

PubMed Central

Kang, Kang; Zhang, Xiaoying; Liu, Hongtao; Wang, Zhiwei; Zhong, Jiasheng; Huang, Zhenting; Peng, Xiao; Zeng, Yan; Wang, Yuna; Yang, Yi; Luo, Jun; Gou, Deming

2012-01-01

Background MicroRNAs (miRNAs) are small, non-coding RNAs capable of postranscriptionally regulating gene expression. Accurate expression profiling is crucial for understanding the biological roles of miRNAs, and exploring them as biomarkers of diseases. Methodology/Principal Findings A novel, highly sensitive, and reliable miRNA quantification approach,termed S-Poly(T) miRNA assay, is designed. In this assay, miRNAs are subjected to polyadenylation and reverse transcription with a S-Poly(T) primer that contains a universal reverse primer, a universal Taqman probe, an oligo(dT)11 sequence and six miRNA-specific bases. Individual miRNAs are then amplified by a specific forward primer and a universal reverse primer, and the PCR products are detected by a universal Taqman probe. The S-Poly(T) assay showed a minimum of 4-fold increase in sensitivity as compared with the stem-loop or poly(A)-based methods. A remarkable specificity in discriminating among miRNAs with high sequence similarity was also obtained with this approach. Using this method, we profiled miRNAs in human pulmonary arterial smooth muscle cells (HPASMC) and identified 9 differentially expressed miRNAs associated with hypoxia treatment. Due to its outstanding sensitivity, the number of circulating miRNAs from normal human serum was significantly expanded from 368 to 518. Conclusions/Significance With excellent sensitivity, specificity, and high-throughput, the S-Poly(T) method provides a powerful tool for miRNAs quantification and identification of tissue- or disease-specific miRNA biomarkers. PMID:23152780

A universal small molecule, inorganic phosphate, restricts the substrate specificity of Dicer-2 in small RNA biogenesis

PubMed Central

Fukunaga, Ryuya; Zamore, Phillip D

2014-01-01

The enzyme Dicer is central to the production of small silencing RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). Like other insects, Drosophila melanogaster uses different Dicers to make siRNAs and miRNAs: Dicer-1 produces miRNAs from pre-miRNAs, whereas Dicer-2 generates siRNAs from long double-stranded RNA (dsRNA). How do the 2 Dicers achieve their substrate specificity? Here, we review recent findings that inorganic phosphate restricts the substrate specificity of Dicer-2 to long dsRNA. Inorganic phosphate inhibits Dicer-2 from binding and cleaving pre-miRNAs, without affecting the processing of long dsRNA. Crystal structures of a fragment of human Dicer in complex with an RNA duplex identify a phosphate-binding pocket that recognizes both the 5′-monophosphate of a substrate RNA and inorganic phosphate. We propose that inorganic phosphate occupies the phosphate-binding pocket in the fly Dicer-2, blocking binding of pre-miRNA and restricting pre-miRNA processing to Dicer-1. Thus, a small molecule can alter the substrate specificity of a nucleic acid-processing enzyme. PMID:24787225

Improved scintimammography using a high-resolution camera mounted on an upright mammography gantry

NASA Astrophysics Data System (ADS)

Itti, Emmanuel; Patt, Bradley E.; Diggles, Linda E.; MacDonald, Lawrence; Iwanczyk, Jan S.; Mishkin, Fred S.; Khalkhali, Iraj

2003-01-01

99mTc-sestamibi scintimammography (SMM) is a useful adjunct to conventional X-ray mammography (XMM) for the assessment of breast cancer. An increasing number of studies has emphasized fair sensitivity values for the detection of tumors >1 cm, compared to XMM, particularly in situations where high glandular breast densities make mammographic interpretation difficult. In addition, SMM has demonstrated high specificity for cancer, compared to various functional and anatomic imaging modalities. However, large field-of-view (FOV) gamma cameras are difficult to position close to the breasts, which decreases spatial resolution and subsequently, the sensitivity of detection for tumors <1 cm. New dedicated detectors featuring small FOV and increased spatial resolution have recently been developed. In this setting, improvement in tumor detection sensitivity, particularly with regard to small cancers is expected. At Division of Nuclear Medicine, Harbor-UCLA Medical Center, we have performed over 2000 SMM within the last 9 years. We have recently used a dedicated breast camera (LumaGEM™) featuring a 12.8×12.8 cm 2 FOV and an array of 2×2×6 mm 3 discrete crystals coupled to a photon-sensitive photomultiplier tube readout. This camera is mounted on a mammography gantry allowing upright imaging, medial positioning and use of breast compression. Preliminary data indicates significant enhancement of spatial resolution by comparison with standard imaging in the first 10 patients. Larger series will be needed to conclude on sensitivity/specificity issues.

Advanced solar panel designs

NASA Technical Reports Server (NTRS)

Ralph, E. L.; Linder, E.

1995-01-01

This paper describes solar cell panel designs that utilize new hgih efficiency solar cells along with lightweight rigid panel technology. The resulting designs push the W/kg and W/sq m parameters to new high levels. These new designs are well suited to meet the demand for higher performance small satellites. This paper reports on progress made on two SBIR Phase 1 contracts. One panel design involved the use of large area (5.5 cm x 6.5 cm) GaAs/Ge solar cells of 19% efficiency combined with a lightweight rigid graphite fiber epoxy isogrid substrate configuration. A coupon (38 cm x 38 cm) was fabricated and tested which demonstrated an array specific power level of 60 W/kg with a potential of reaching 80 W/kg. The second panel design involved the use of newly developed high efficiency (22%) dual junction GaInP2/GaAs/Ge solar cells combined with an advanced lightweight rigid substrate using aluminum honeycomb core with high strength graphite fiber mesh facesheets. A coupon (38 cm x 38 cm) was fabricated and tested which demonstrated an array specific power of 105 W/kg and 230 W/sq m. This paper will address the construction details of the panels and an a analysis of the component weights. A strawman array design suitable for a typical small-sat mission is described for each of the two panel design technologies being studied. Benefits in respect to weight reduction, area reduction, and system cost reduction are analyzed and compared to conventional arrays.

The relationship of temperature rise to specific absorption rate and current in the human leg for exposure to electromagnetic radiation in the high frequency band.

PubMed

Wainwright, P R

2003-10-07

Of the biological effects of human exposure to radiofrequency and microwave radiation, the best-established are those due to elevation of tissue temperature. To prevent harmful levels of heating, restrictions have been proposed on the specific absorption rate (SAR). However, the relationship between SAR and temperature rise is not an invariant, since not only the heat capacity but also the efficiency of heat dissipation varies between different tissues and exposure scenarios. For small enough SAR, the relationship is linear and may be characterized by a 'heating factor' deltaT/SAR. Under whole-body irradiation the SAR may be particularly high in the ankles due to the concentration of current flowing through a relatively small cross-sectional area. In a previous paper, the author has presented calculations of the SAR distribution in a human leg in the high frequency (HF) band. In this paper, the heating factor for this situation is derived using a finite element approximation of the Pennes bioheat equation. The sensitivity of the results to different blood perfusion rates is investigated, and a simple local thermoregulatory model is applied. Both time-dependent and steady-state solutions are considered. Results confirm the appropriateness of the ICNIRP reference level of 100 mA on current through the leg, but suggest that at higher currents significant thermoregulatory adjustments to muscle blood flow will occur.

Identification and Classification of New Transcripts in Dorper and Small-Tailed Han Sheep Skeletal Muscle Transcriptomes.

PubMed

Chao, Tianle; Wang, Guizhi; Wang, Jianmin; Liu, Zhaohua; Ji, Zhibin; Hou, Lei; Zhang, Chunlan

2016-01-01

High-throughput mRNA sequencing enables the discovery of new transcripts and additional parts of incompletely annotated transcripts. Compared with the human and cow genomes, the reference annotation level of the sheep genome is still low. An investigation of new transcripts in sheep skeletal muscle will improve our understanding of muscle development. Therefore, applying high-throughput sequencing, two cDNA libraries from the biceps brachii of small-tailed Han sheep and Dorper sheep were constructed, and whole-transcriptome analysis was performed to determine the unknown transcript catalogue of this tissue. In this study, 40,129 transcripts were finally mapped to the sheep genome. Among them, 3,467 transcripts were determined to be unannotated in the current reference sheep genome and were defined as new transcripts. Based on protein-coding capacity prediction and comparative analysis of sequence similarity, 246 transcripts were classified as portions of unannotated genes or incompletely annotated genes. Another 1,520 transcripts were predicted with high confidence to be long non-coding RNAs. Our analysis also revealed 334 new transcripts that displayed specific expression in ruminants and uncovered a number of new transcripts without intergenus homology but with specific expression in sheep skeletal muscle. The results confirmed a complex transcript pattern of coding and non-coding RNA in sheep skeletal muscle. This study provided important information concerning the sheep genome and transcriptome annotation, which could provide a basis for further study.

Densely-packed graphene/conducting polymer nanoparticle papers for high-volumetric-performance flexible all-solid-state supercapacitors

NASA Astrophysics Data System (ADS)

Yang, Chao; Zhang, Liling; Hu, Nantao; Yang, Zhi; Wei, Hao; Xu, Zhichuan J.; Wang, Yanyan; Zhang, Yafei

2016-08-01

Graphene-based all-solid-state supercapacitors (ASSSCs) are one of the most ideal candidates for high-performance flexible power sources. The achievement of high volumetric energy density is highly desired for practical application of this type of ASSSCs. Here, we present a facile method to boost volumetric performances of graphene-based flexible ASSSCs through incorporation of ultrafine polyaniline-poly(4-styrenesulfonate) (PANI-PSS) nanoparticles in reduced graphene oxide (rGO) papers. A compact structure is obtained via intimate contact and π-π interaction between PANI-PSS nanoparticles and rGO sheets. The hybrid paper electrode with the film thickness of 13.5 μm, shows an extremely high volumetric specific capacitance of 272 F/cm3 (0.37 A/cm3 in a three-electrode cell). The assembled ASSSCs show a large volumetric specific capacitance of 217 F/cm3 (0.37 A/cm3 in a two-electrode cell), high volumetric energy and power density, excellent capacitance stability, small leakage current as well as low self-discharge characteristics, revealing the usefulness of this robust hybrid paper for high-performance flexible energy storage devices.

25 CFR 39.144 - What is the small high school adjustment?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false What is the small high school adjustment? 39.144 Section... EQUALIZATION PROGRAM Indian School Equalization Formula Small School Adjustment § 39.144 What is the small high school adjustment? (a) The small high school adjustment is a WSU adjustment given to a small high school...

25 CFR 39.144 - What is the small high school adjustment?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true What is the small high school adjustment? 39.144 Section... EQUALIZATION PROGRAM Indian School Equalization Formula Small School Adjustment § 39.144 What is the small high school adjustment? (a) The small high school adjustment is a WSU adjustment given to a small high school...

25 CFR 39.144 - What is the small high school adjustment?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false What is the small high school adjustment? 39.144 Section... EQUALIZATION PROGRAM Indian School Equalization Formula Small School Adjustment § 39.144 What is the small high school adjustment? (a) The small high school adjustment is a WSU adjustment given to a small high school...

25 CFR 39.144 - What is the small high school adjustment?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false What is the small high school adjustment? 39.144 Section... EQUALIZATION PROGRAM Indian School Equalization Formula Small School Adjustment § 39.144 What is the small high school adjustment? (a) The small high school adjustment is a WSU adjustment given to a small high school...

25 CFR 39.144 - What is the small high school adjustment?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What is the small high school adjustment? 39.144 Section... EQUALIZATION PROGRAM Indian School Equalization Formula Small School Adjustment § 39.144 What is the small high school adjustment? (a) The small high school adjustment is a WSU adjustment given to a small high school...

Adaptive evolution and functional innovation of Populus-specific recently evolved microRNAs.

PubMed

Xie, Jianbo; Yang, Xiaohui; Song, Yuepeng; Du, Qingzhang; Li, Ying; Chen, Jinhui; Zhang, Deqiang

2017-01-01

Lineage-specific microRNAs (miRNAs) undergo rapid turnover during evolution; however, their origin and functional importance have remained controversial. Here, we examine the origin, evolution, and potential roles in local adaptation of Populus-specific miRNAs, which originated after the recent salicoid-specific, whole-genome duplication. RNA sequencing was used to generate extensive, comparable miRNA and gene expression data for six tissues. A natural population of Populus trichocarpa and closely related species were used to study the divergence rates, evolution, and adaptive variation of miRNAs. MiRNAs that originated in 5' untranslated regions had higher expression levels and their expression showed high correlation with their host genes. Compared with conserved miRNAs, a significantly higher proportion of Populus-specific miRNAs appear to target genes that were duplicated in salicoids. Examination of single nucleotide polymorphisms in Populus-specific miRNA precursors showed high amounts of population differentiation. We also characterized the newly emerged MIR6445 family, which could trigger the production of phased small interfering RNAs from NAC mRNAs, which encode a transcription factor with primary roles in a variety of plant developmental processes. Together, these observations provide evolutionary insights into the birth and potential roles of Populus-specific miRNAs in genome maintenance, local adaptation, and functional innovation. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Mitochondria-specific photoactivation to monitor local sphingosine metabolism and function

PubMed Central

Feng, Suihan; Harayama, Takeshi; Montessuit, Sylvie; David, Fabrice PA; Winssinger, Nicolas; Martinou, Jean-Claude

2018-01-01

Photoactivation ('uncaging’) is a powerful approach for releasing bioactive small-molecules in living cells. Current uncaging methods are limited by the random distribution of caged molecules within cells. We have developed a mitochondria-specific photoactivation method, which permitted us to release free sphingosine inside mitochondria and thereafter monitor local sphingosine metabolism by lipidomics. Our results indicate that sphingosine was quickly phosphorylated into sphingosine 1-phosphate (S1P) driven by sphingosine kinases. In time-course studies, the mitochondria-specific uncaged sphingosine demonstrated distinct metabolic patterns compared to globally-released sphingosine, and did not induce calcium spikes. Our data provide direct evidence that sphingolipid metabolism and signaling are highly dependent on the subcellular location and opens up new possibilities to study the effects of lipid localization on signaling and metabolic fate. PMID:29376826

Recent Methods for Purification and Structure Determination of Oligonucleotides.

PubMed

Zhang, Qiulong; Lv, Huanhuan; Wang, Lili; Chen, Man; Li, Fangfei; Liang, Chao; Yu, Yuanyuan; Jiang, Feng; Lu, Aiping; Zhang, Ge

2016-12-18

Aptamers are single-stranded DNA or RNA oligonucleotides that can interact with target molecules through specific three-dimensional structures. The excellent features, such as high specificity and affinity for target proteins, small size, chemical stability, low immunogenicity, facile chemical synthesis, versatility in structural design and engineering, and accessible for site-specific modifications with functional moieties, make aptamers attractive molecules in the fields of clinical diagnostics and biopharmaceutical therapeutics. However, difficulties in purification and structural identification of aptamers remain a major impediment to their broad clinical application. In this mini-review, we present the recently attractive developments regarding the purification and identification of aptamers. We also discuss the advantages, limitations, and prospects for the major methods applied in purifying and identifying aptamers, which could facilitate the application of aptamers.

Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors.

PubMed

Anantpadma, Manu; Kouznetsova, Jennifer; Wang, Hang; Huang, Ruili; Kolokoltsov, Andrey; Guha, Rajarshi; Lindstrom, Aaron R; Shtanko, Olena; Simeonov, Anton; Maloney, David J; Maury, Wendy; LaCount, Douglas J; Jadhav, Ajit; Davey, Robert A

2016-08-01

Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis.

PubMed

Chen, Wei; Zhang, Shan; Jiang, Peixia; Yao, Jun; He, Yongzhi; Chen, Lincai; Gui, Xiwu; Dong, Zhiyang; Tang, Shuang-Yan

2015-07-01

Advanced high-throughput screening methods for small molecules may have important applications in the metabolic engineering of the biosynthetic pathways of these molecules. Ectoine is an excellent osmoprotectant that has been widely used in cosmetics. In this study, the Escherichia coli regulatory protein AraC was engineered to recognize ectoine as its non-natural effector and to activate transcription upon ectoine binding. As an endogenous reporter of ectoine, the mutated AraC protein was successfully incorporated into high-throughput screening of ectoine hyper-producing strains. The ectoine biosynthetic cluster from Halomonas elongata was cloned into E. coli. By engineering the rate-limiting enzyme L-2,4-diaminobutyric acid (DABA) aminotransferase (EctB), ectoine production and the specific activity of the EctB mutant were increased. Thus, these results demonstrated the effectiveness of engineering regulatory proteins into sensitive and rapid screening tools for small molecules and highlighted the importance and efficacy of directed evolution strategies applied to the engineering of genetic components for yield improvement in the biosynthesis of small molecules. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Soil Microbial Community Contribution to Small Headwater Stream Metabolism.

NASA Astrophysics Data System (ADS)

Clapcott, J. E.; Gooderham, J. P.; Barmuta, L. A.; Davies, P. E.

2005-05-01

The temporal dynamics of sediment respiration were examined in seven small headwater streams in forested catchments in 2004. A strong seasonal response was observed with higher respiration rates in depositional zones than in gravel runs. The data were also examined in the context of proportional habitat distributions that highlighted the importance of high flow events in shaping whole stream metabolic budgets. This study specifically examines the question of terrestrial soil respiration contribution to whole stream metabolism by the controlled inundation of terrestrial soils. The experiment included six experimentally inundated terrestrial zones, six terrestrial controls, and six in-stream depositional zones. Sediment bacterial respiration was measured using 14C leucine incorporation and cotton strip bioassays were also employed to provide an indicative measure of sediment microbial activity. Despite high variability and exhibiting significantly lower bacterial activity than in-stream sediments, modelling using flow data and habitat mapping illustrated the important contribution of terrestrial soil respiration to the whole stream metabolic budgets of small headwater streams. In addition, microbial community composition examined using phospholipid fatty acid analysis clearly differentiated between terrestrial and aquatic communities. Freshly inundated terrestrial communities remained similar to un-inundated controls after 28 days.

Small Scale Turbopump Manufacturing Technology and Material Processes

NASA Technical Reports Server (NTRS)

Alvarez, Erika; Morgan, Kristin; Wells, Doug; Zimmerman, Frank

2011-01-01

As part of an internal research and development project, NASA Marshall Space Flight Center (MSFC) has been developing a high specific impulse 9,000-lbf LOX/LH2 pump-fed engine testbed with the capability to throttle 10:1. A Fuel Turbopump (FTP) with the ability to operate across a speed range of 30,000-rpm to 100,000-rpm was developed and analyzed. This small size and flight-like Fuel Turbopump has completed the design and analysis phase and is currently in the manufacturing phase. This paper highlights the manufacturing and processes efforts to fabricate an approximately 20-lb turbopump with small flow passages, intricately bladed components and approximately 3-in diameter impellers. As a result of the small scale and tight tolerances of the hardware on this turbopump, several unique manufacturing and material challenges were encountered. Some of the technologies highlighted in this paper include the use of powder metallurgy technology to manufacture small impellers, electron beam welding of a turbine blisk shroud, and casting challenges. The use of risk reduction efforts such as non-destructive testing (NDT) and evaluation (NDE), fractography, material testing, and component spin testing are also discussed in this paper.

Small GTPases and Stress Responses of vvran1 in the Straw Mushroom Volvariella volvacea

PubMed Central

Yan, Jun-Jie; Xie, Bin; Zhang, Lei; Li, Shao-Jie; van Peer, Arend F.; Wu, Ta-Ju; Chen, Bing-Zhi; Xie, Bao-Gui

2016-01-01

Small GTPases play important roles in the growth, development and environmental responses of eukaryotes. Based on the genomic sequence of the straw mushroom Volvariella volvacea, 44 small GTPases were identified. A clustering analysis using human small GTPases as the references revealed that V. volvacea small GTPases can be grouped into five families: nine are in the Ras family, 10 are in the Rho family, 15 are in the Rab family, one is in the Ran family and nine are in the Arf family. The transcription of vvran1 was up-regulated upon hydrogen peroxide (H2O2) stress, and could be repressed by diphenyleneiodonium chloride (DPI), a NADPH oxidase-specific inhibitor. The number of vvran1 transcripts also increased upon cold stress. Diphenyleneiodonium chloride, but not the superoxide dismutase (SOD) inhibitor diethy dithiocarbamate (DDC), could suppress the up-regulation of vvran1 gene expression to cold stress. These results combined with the high correlations between gene expression and superoxide anion (O2−) generation indicated that vvran1 could be one of the candidate genes in the downstream of O2− mediated pathways that are generated by NADPH oxidase under low temperature and oxidative stresses. PMID:27626406