Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT){sub n} {center_dot} (GA){sub n} microsatellite embedded within the U2 repeat unit

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

Liao, D.; Weiner, A.M.

1995-12-10

The RNU2 locus encoding human U2 small nuclear RNA (snRNA) is organized as a nearly perfect tandem array containing 5 to 22 copies of a 5.8-kb repeat unit. Just downstream of the U2 snRNA gene in each 5.8-kb repeat unit lies a large (CT){sub n}{center_dot}(GA){sub n} dinucleotide repeat (n {approx} 70). This form of genomic organization, in which one repeat is embedded within another, provides an unusual opportunity to study the balance of forces maintaining the homogeneity of both kinds of repeats. Using a combination of field inversion gel electrophoresis and polymerase chain reaction, we have been able to studymore » the CT microsatellites within individual U2 tandem arrays. We find that the CT microsatellites within an RNU2 allele exhibit significant length polymorphism, despite the remarkable homogeneity of the surrounding U2 repeat units. Length polymorphism is due primarily to loss or gain of CT dinucleotide repeats, but other types of deletions, insertions, and substitutions are also frequent. Polymorphism is greatly reduced in regions where pure (CT){sub n} tracts are interrupted by occasional G residues, suggesting that irregularities stabilize both the length and the sequence of the dinucleotide repeat. We further show that the RNU2 loci of other catarrhine primates (gorilla, chimpanzee, ogangutan, and baboon) contain orthologous CT microsatellites; these also exhibit length polymorphism, but are highly divergent from each other. Thus, although the CT microsatellite is evolving far more rapidly than the rest of the U2 repeat unit, it has persisted through multiple speciation events spanning >35 Myr. The persistence of the CT microsatellite, despite polymorphism and rapid evolution, suggests that it might play a functional role in concerted evolution of the RNU2 loci, perhaps as an initiation site for recombination and/or gene conversion. 70 refs., 5 figs.« less

A European mobile satellite system concept exploiting CDMA and OBP

NASA Technical Reports Server (NTRS)

Vernucci, A.; Craig, A. D.

1993-01-01

This paper describes a novel Land Mobile Satellite System (LMSS) concept applicable to networks allowing access to a large number of gateway stations ('Hubs'), utilizing low-cost Very Small Aperture Terminals (VSAT's). Efficient operation of the Forward-Link (FL) repeater can be achieved by adopting a synchronous Code Division Multiple Access (CDMA) technique, whereby inter-code interference (self-noise) is virtually eliminated by synchronizing orthogonal codes. However, with a transparent FL repeater, the requirements imposed by the highly decentralized ground segment can lead to significant efficiency losses. The adoption of a FL On-Board Processing (OBP) repeater is proposed as a means of largely recovering this efficiency impairment. The paper describes the network architecture, the system design and performance, the OBP functions and impact on implementation. The proposed concept, applicable to a future generation of the European LMSS, was developed in the context of a European Space Agency (ESA) study contract.

Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis: results from a German population-based case-control study.

PubMed

Rudolph, Anja; Shi, Hong; Försti, Asta; Hoffmeister, Michael; Sainz, Juan; Jansen, Lina; Hemminki, Kari; Brenner, Hermann; Chang-Claude, Jenny

2014-11-07

Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor β gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis. The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test. The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis. Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.

Feasibility of Multiple Repeat Gamma Knife Radiosurgeries for Trigeminal Neuralgia: A Case Report and Review of the Literature

PubMed Central

Jones, Guy C.; Elaimy, Ameer L.; Demakas, John J.; Jiang, Hansi; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Mackay, Alexander R.; Cooke, Barton S.; Lee, Christopher M.

2011-01-01

Treatment options for trigeminal neuralgia (TN) must be customized for the individual patient, and physicians must be aware of the medical, surgical, and radiation treatment modalities to prescribe optimal treatment courses for specific patients. The following case illustrates the potential for gamma knife radiosurgery (GKRS) to be repeated multiple times for the purpose of achieving facial pain control in cases of TN that have been refractory to other medical and surgical options, as well as prior GKRS. The patient described failed to achieve pain control with initial GKRS, as well as medical and surgical treatments, but experienced significant pain relief for a period of time with a second GKRS procedure and later underwent a third procedure. Only a small subset of patients have reportedly undergone more than two GKRS for TN; thus, further research and long-term clinical followup will be valuable in determining its usefulness in specific clinical situations. PMID:21904556

Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching.

PubMed

Parkesh, Raman; Childs-Disney, Jessica L; Nakamori, Masayuki; Kumar, Amit; Wang, Eric; Wang, Thomas; Hoskins, Jason; Tran, Tuan; Housman, David; Thornton, Charles A; Disney, Matthew D

2012-03-14

Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3'-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5'CUG/3'GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, sarco(endo)plasmic reticulum Ca(2+) ATPase 1, and cardiac troponin T. Based on these observations, the development of small-molecule ligands that target specifically expanded DM1 repeats could be of use as therapeutics. In the present study, chemical similarity searching was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of in vitro inhibitors of the RNA-protein complex were identified with low micromolar IC(50)'s, which are >20-fold more potent than the query compounds. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with chemical similarity searching.

Design of a Bioactive Small Molecule that Targets the Myotonic Dystrophy Type 1 RNA Via an RNA Motif-Ligand Database & Chemical Similarity Searching

PubMed Central

Parkesh, Raman; Childs-Disney, Jessica L.; Nakamori, Masayuki; Kumar, Amit; Wang, Eric; Wang, Thomas; Hoskins, Jason; Tran, Tuan; Housman, David; Thornton, Charles A.; Disney, Matthew D.

2012-01-01

Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5′CUG/3′GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, Sarco(endo)plasmic reticulum Ca2+ ATPase 1 (Serca1/Atp2a1), and cardiac troponin T (cTNT). Based on these observations, the development of small molecule ligands that target specifically expanded DM1 repeats could serve as therapeutics. In the present study, computational screening was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of inhibitors of the RNA-protein complex with low micromolar IC50’s, which are >20-fold more potent than the query compounds, were identified. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with virtual screening. PMID:22300544

Recent high-speed ballistics experiments at ORNL

NASA Astrophysics Data System (ADS)

Combs, S. K.; Gouge, M. J.; Baylor, L. R.; Fisher, P. W.; Foster, C. A.; Foust, C. R.; Milora, S. L.; Qualls, A. L.

Oak Ridge National Laboratory (ORNL) has been developing pellet injectors for plasma fueling experiments on magnetic confinement devices for almost 20 years. With these devices, pellets (1 to 8 mm in diameter) composed of hydrogen isotopes are formed (at temperatures less than 20 K) and typically accelerated to speeds of (approximately) 1.0 to 2.0 km/s for injection into plasmas of experimental fusion devices. A variety of pellet injector designs have been developed at ORNL, including repeating pneumatic injectors (single- and multiple-barrel light gas guns) that can inject up to hundreds of pellets for long-pulse plasma operation. The repeating pneumatic injectors are of particular importance because long-pulse fueling is required for present large experimental fusion devices, with steady-state operation the objective for future fusion reactors. In this paper, recent advancements in the development of repeating pneumatic injectors are described, including (1) a small-bore (1.8-mm), high-firing-rate (10-Hz) version of a single-stage light gas gun; (2) a repeating single-stage light gas gun for 8-mm-diam tritium pellets; (3) a repeating two-stage light gas gun for operation at higher pellet velocities; and (4) a steady-state hydrogen extruder feed system.

Recent high-speed ballistics experiments at ORNL

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

Combs, S.K.; Gouge, M.J.; Baylor, L.R.

1994-12-31

Oak Ridge National Laboratory (ORNL) has been developing pellet injectors for plasma fueling experiments on magnetic confinement devices for almost 20 years. With these devices, pellets (1 to 8 mm in diameter) composed of hydrogen isotopes are formed (at temperatures <20 K) and typically accelerated to speeds of {approximately} 1.0 to 2.0 km/s for injection into plasmas of experimental fusion devices. A variety of pellet injector designs have been developed at ORNL, including repeating pneumatic injectors (single- and multiple-barrel light gas guns) that can inject up to hundreds of pellets for long-pulse plasma operation. The repeating pneumatic injectors are ofmore » particular importance because long-pulse fueling is required for present large experimental fusion devices, with steady-state operation the objective for future fusion reactors. In this paper, recent advancements in the development of repeating pneumatic injectors are described, including (1) a small-bore (1.8-mm), high-firing-rate (10-Hz) version of a single-stage light gas gun; (2) a repeating single-stage light gas gun for 8-mm-diam tritium pellets; (3) a repeating two-stage light gas gun for operation at higher pellet velocities; and (4) a steady-state hydrogen extruder feed system.« less

Evaluation of normal findings using a detailed and focused technique for transcutaneous abdominal ultrasonography in the horse

PubMed Central

2014-01-01

Background Ultrasonography is an important diagnostic tool in the investigation of abdominal disease in the horse. Several factors may affect the ability to image different structures within the abdomen. The aim of the study was to describe the repeatability of identification of abdominal structures in normal horses using a detailed ultrasonographic examination technique and using a focused, limited preparation technique. Methods A detailed abdominal ultrasound examination was performed in five normal horses, repeated on five occasions (total of 25 examinations). The abdomen was divided into ten different imaging sites, and structures identified in each site were recorded. Five imaging sites were then selected for a single focused ultrasound examination in 20 normal horses. Limited patient preparation was performed. Structures were recorded as ‘identified’ if ultrasonographic features could be distinguished. The location of organs and their frequency of identification were recorded. Data from both phases were analysed to determine repeatability of identification of structures in each examination (irrespective of imaging site), and for each imaging site. Results Caecum, colon, spleen, liver and right kidney were repeatably identified using the detailed technique, and had defined locations. Large colon and right kidney were identified in 100% of examinations with both techniques. Liver, spleen, caecum, duodenum and other small intestine were identified more frequently with the detailed examination. Small intestine was most frequently identified in the ventral abdomen, its identification varied markedly within and between horses, and required repeated examinations in some horses. Left kidney could not be identified in every horse using either technique. Sacculated colon was identified in all ventral sites, and was infrequently identified in dorsal sites. Conclusions Caecum, sacculated large intestine, spleen, liver and right kidney were consistently identified with both techniques. There were some normal variations which should be considered when interpreting ultrasonographic findings in clinical cases: left kidney was not always identified, sacculated colon was occasionally identified in dorsal flank sites. Multiple imaging sites and repeated examinations may be required to identify small intestine. A focused examination identified most key structures, but has some limitations compared to a detailed examination. PMID:25238559

Polystyrene/Hyperbranched Polyester Blends and Reactive Polystyrene/Hyperbranched Polyester Blends

DTIC Science & Technology

1999-01-01

interfacial tension between the PE and polystyrene phases. This was brought about by the chemical interaction between the acidic anhydride groups in the...multiple 2,2 dimethylol propionic acid (C5H10O4) chain extenders or repeat units. 11 Core HO \\ HO’ /■ J OH V *OH Pentaerythritol Chain Extender...O 2,2 - Dimethylol propionic acid Figure 11. HBP Building Blocks. These materials were supplied in small quantities with little technical data. The

Clinical Development of Gamitrinib, a Novel Mitochondrial-Targeted Small Molecule Hsp90 Inhibitor

DTIC Science & Technology

2015-09-01

Group 2 and Group 3 animals examined at the end of the 7-repeated doses was comparable to those in control Group 1 animals (Figure 2). (7) Despite... posttest (for more than two- group comparisons) using a GraphPad software package (Prism 6.0) for Windows. Data are expressed as mean ± SD or mean ± SEM...Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Series B Stat

Molecular typing of Argentinian Mycobacterium avium subsp. paratuberculosis isolates by multiple-locus variable number-tandem repeat analysis

PubMed Central

Gioffré, Andrea; Correa Muñoz, Magnolia; Alvarado Pinedo, María F.; Vaca, Roberto; Morsella, Claudia; Fiorentino, María Andrea; Paolicchi, Fernando; Ruybal, Paula; Zumárraga, Martín; Travería, Gabriel E.; Romano, María Isabel

2015-01-01

Multiple-locus variable number-tandem repeat analysis (MLVA) of Mycobacterium avium subspecies paratuberculosis (MAP) isolates may contribute to the knowledge of strain diversity in Argentina. Although the diversity of MAP has been previously investigated in Argentina using IS900-RFLP, a small number of isolates were employed, and a low discriminative power was reached. The aim of the present study was to test the genetic diversity among MAP isolates using an MLVA approach based on 8 repetitive loci. We studied 97 isolates from cattle, goat and sheep and could describe 7 different patterns: INMV1, INMV2, INMV11, INMV13, INMV16, INMV33 and one incomplete pattern. INMV1 and INMV2 were the most frequent patterns, grouping 76.3% of the isolates. We were also able to demonstrate the coexistence of genotypes in herds and co-infection at the organism level. This study shows that all the patterns described are common to those described in Europe, suggesting an epidemiological link between the continents. PMID:26273274

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

PubMed

Dumitrescu, Laura; Popescu, Bogdan O

2015-01-01

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

Repeated Small Bowel Obstruction Caused by Chestnut Ingestion without the Formation of Phytobezoars.

PubMed

Satake, Ryu; Chinda, Daisuke; Shimoyama, Tadashi; Satake, Miwa; Oota, Rie; Sato, Satoshi; Yamai, Kiyonori; Hachimori, Hisashi; Okamoto, Yutaka; Yamada, Kyogo; Matsuura, Osamu; Hashizume, Tadashi; Soma, Yasushi; Fukuda, Shinsaku

2016-01-01

A small number of cases of small bowel obstruction caused by foods without the formation of phytobezoars have been reported. Repeated small bowel obstruction due to the ingestion of the same food is extremely rare. We present the case of 63-year-old woman who developed small bowel obstruction twice due to the ingestion of chestnuts without the formation of phytobezoars. This is the first reported case of repeated small bowel obstruction caused by chestnut ingestion. Careful interviews are necessary to determine the meal history of elderly patients and psychiatric patients.

Identification, variation and transcription of pneumococcal repeat sequences

PubMed Central

2011-01-01

Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

PubMed Central

Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus.

PubMed Central

Pavelitz, T; Rusché, L; Matera, A G; Scharf, J M; Weiner, A M

1995-01-01

In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous within each species but differs somewhat between species. Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages. The data suggest that the U2 tandem repeat, once established in the primate lineage, contained sequence elements favoring perpetuation and concerted evolution of the array in situ, despite a pericentric inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon and other Old World monkeys with the 6 kb U2 repeat unit in humans and other hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a 5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of the provirus by homologous recombination between the LTRs generated a 6 kb U2 repeat unit containing a solo LTR. Remarkably, both junctions between the human U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR sequence, suggesting a role for the LTR in the origin or maintenance of the primate U2 array. Images PMID:7828589

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

Fusion splicing small-core photonic crystal fibers and single-mode fibers by repeated arc discharges.

PubMed

Xiao, Limin; Jin, Wei; Demokan, M S

2007-01-15

We demonstrate a novel method for low-loss splicing small-core photonic crystal fibers (PCFs) and single-mode fibers (SMFs) by repeated arc discharges using a conventional fusion splicer. An optimum mode field match at the interface of PCF-SMF and an adiabatic mode field variation in the longitudinal direction of the small-core PCF can be achieved by repeated arc discharges applied over the splicing joint to gradually collapse the air holes of the small-core PCF. This method is simple and offers a practical solution for light coupling between small-core PCFs and SMFs.

Fusion splicing small-core photonic crystal fibers and single-mode fibers by repeated arc discharges

NASA Astrophysics Data System (ADS)

Xiao, Limin; Jin, Wei; Demokan, M. S.

2007-01-01

We demonstrate a novel method for low-loss splicing small-core photonic crystal fibers (PCFs) and single-mode fibers (SMFs) by repeated arc discharges using a conventional fusion splicer. An optimum mode field match at the interface of PCF-SMF and an adiabatic mode field variation in the longitudinal direction of the small-core PCF can be achieved by repeated arc discharges applied over the splicing joint to gradually collapse the air holes of the small-core PCF. This method is simple and offers a practical solution for light coupling between small-core PCFs and SMFs.

A ruler protein in a complex for antiviral defense determines the length of small interfering CRISPR RNAs.

PubMed

Hatoum-Aslan, Asma; Samai, Poulami; Maniv, Inbal; Jiang, Wenyan; Marraffini, Luciano A

2013-09-27

Small RNAs undergo maturation events that precisely determine the length and structure required for their function. CRISPRs (clustered regularly interspaced short palindromic repeats) encode small RNAs (crRNAs) that together with CRISPR-associated (cas) genes constitute a sequence-specific prokaryotic immune system for anti-viral and anti-plasmid defense. crRNAs are subject to multiple processing events during their biogenesis, and little is known about the mechanism of the final maturation step. We show that in the Staphylococcus epidermidis type III CRISPR-Cas system, mature crRNAs are measured in a Cas10·Csm ribonucleoprotein complex to yield discrete lengths that differ by 6-nucleotide increments. We looked for mutants that impact this crRNA size pattern and found that an alanine substitution of a conserved aspartate residue of Csm3 eliminates the 6-nucleotide increments in the length of crRNAs. In vitro, recombinant Csm3 binds RNA molecules at multiple sites, producing gel-shift patterns that suggest that each protein binds 6 nucleotides of substrate. In vivo, changes in the levels of Csm3 modulate the crRNA size distribution without disrupting the 6-nucleotide periodicity. Our data support a model in which multiple Csm3 molecules within the Cas10·Csm complex bind the crRNA with a 6-nucleotide periodicity to function as a ruler that measures the extent of crRNA maturation.

Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility.

PubMed

Cushman, R A; Miles, J R; Rempel, L A; McDaneld, T G; Kuehn, L A; Chitko-McKown, C G; Nonneman, D; Echternkamp, S E

2013-06-01

A proposed functional polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) has been reported to influence antral follicle numbers and fertility in cows. Repeat breeder cows that fail to produce a calf in multiple seasons have been reported to have reduced numbers of small (1 to 3 mm) antral follicles in their ovaries. Therefore, we tested the hypothesis that this GRIA1 polymorphism was affecting antral follicle numbers in repeat breeder cows. Repeat breeder cows (n = 64) and control cows (n = 72) that had always produced a calf were housed in a dry lot and observed twice daily for behavioral estrus. Blood samples were collected, and cows were genotyped for this GRIA1 polymorphism and for a polymorphism in the GnRH receptor (GnRHR) that was proposed to influence age at puberty. On d 3 to 8 after estrus cows were slaughtered, and reproductive organs were collected to determine antral follicle count, ovary size, and uterine horn diameter. Repeat breeder cows were older at first calving than control cows (P = 0.006). The length (P = 0.03) and height (P = 0.02) of the ovary contralateral to the corpus luteum (CL) were greater in control cows than repeat breeder cows. The endometrial diameter in the horn ipsilateral to the CL was greater in the control cows than the repeat breeder cows. Repeat breeder cows had fewer small (1 to 5 mm) antral follicles than control cows (P = 0.003); however, there was no association between GRIA1 genotype and antral follicle number. The GnRHR polymorphism was associated with age at first calving because cows that were homozygous for the C allele had a greater age at first calving than heterozygous cows or cows that were homozygous for the T allele (P = 0.01). In the granulosa cells from small (1 to 5 mm) antral follicles, mRNA abundances of 2 markers of oocyte quality, anti-Müllerian hormone and pentraxin 3, did not differ between fertility groups (P ≥ 0.12). We conclude that this GRIA1 polymorphism exists in beef cows but that it does not influence antral follicle numbers. The association between GnRHR genotype and age at first calving is likely not causal as this polymorphism is not functional. The utility of this polymorphism as a genetic marker for early conception in heifers will require further validation. Screening postpartum cows by ultrasonography to determine antral follicle numbers may aid in making culling decisions.

A fatal elephant attack.

PubMed

Hejna, Petr; Zátopková, Lenka; Safr, Miroslav

2012-01-01

A rare case of an elephant attack is presented. A 44-year-old man working as an elephant keeper was attacked by a cow elephant when he tripped over a foot chain while the animal was being medically treated. The man fell down and was consequently repeatedly attacked with elephant tusks. The man sustained multiple stab injuries to both groin regions, a penetrating injury to the abdominal wall with traumatic prolapse of the loops of the small bowel, multiple defects of the mesentery, and incomplete laceration of the abdominal aorta with massive bleeding into the abdominal cavity. In addition to the penetrating injuries, the man sustained multiple rib fractures with contusion of both lungs and laceration of the right lobe of the liver, and comminuted fractures of the pelvic arch and left femoral body. The man died shortly after he had been received at the hospital. The cause of death was attributed to traumatic shock. © 2011 American Academy of Forensic Sciences.

Whole-genome multiple displacement amplification from single cells.

PubMed

Spits, Claudia; Le Caignec, Cédric; De Rycke, Martine; Van Haute, Lindsey; Van Steirteghem, André; Liebaers, Inge; Sermon, Karen

2006-01-01

Multiple displacement amplification (MDA) is a recently described method of whole-genome amplification (WGA) that has proven efficient in the amplification of small amounts of DNA, including DNA from single cells. Compared with PCR-based WGA methods, MDA generates DNA with a higher molecular weight and shows better genome coverage. This protocol was developed for preimplantation genetic diagnosis, and details a method for performing single-cell MDA using the phi29 DNA polymerase. It can also be useful for the amplification of other minute quantities of DNA, such as from forensic material or microdissected tissue. The protocol includes the collection and lysis of single cells, and all materials and steps involved in the MDA reaction. The whole procedure takes 3 h and generates 1-2 microg of DNA from a single cell, which is suitable for multiple downstream applications, such as sequencing, short tandem repeat analysis or array comparative genomic hybridization.

Recent developments in the theory of protein folding: searching for the global energy minimum.

PubMed

Scheraga, H A

1996-04-16

Statistical mechanical theories and computer simulation are being used to gain an understanding of the fundamental features of protein folding. A major obstacle in the computation of protein structures is the multiple-minima problem arising from the existence of many local minima in the multidimensional energy landscape of the protein. This problem has been surmounted for small open-chain and cyclic peptides, and for regular-repeating sequences of models of fibrous proteins. Progress is being made in resolving this problem for globular proteins.

Frequency doubling of an InGaAs multiple quantum wells semiconductor disk laser

NASA Astrophysics Data System (ADS)

Lidan, Jiang; Renjiang, Zhu; Maohua, Jiang; Dingke, Zhang; Yuting, Cui; Peng, Zhang; Yanrong, Song

2018-01-01

We demonstrate a good beam quality 483 nm blue coherent radiation from a frequency doubled InGaAs multiple quantum wells semiconductor disk laser. The gain chip is consisted of 6 repeats of strain uncompensated InGaAs/GaAs quantum wells and 25 pairs of GaAs/AlAs distributed Bragg reflector. A 4 × 4 × 7 mm3 type I phase-matched BBO nonlinear crystal is used in a V-shaped laser cavity for the second harmonic generation, and 210 mW blue output power is obtained when the absorbed pump power is 3.5 W. The M2 factors of the laser beam in x and y directions are about 1.04 and 1.01, respectively. The output power of the blue laser is limited by the relatively small number of the multiple quantum wells, and higher power can be expected by increasing the number of the multiple quantum wells and improving the heat management of the laser.

A survey of small RNAs in human sperm

PubMed Central

Krawetz, Stephen A.; Kruger, Adele; Lalancette, Claudia; Tagett, Rebecca; Anton, Ester; Draghici, Sorin; Diamond, Michael P.

2011-01-01

BACKGROUND There has been substantial interest in assessing whether RNAs (mRNAs and sncRNAs, i.e. small non-coding) delivered from mammalian spermatozoa play a functional role in early embryo development. While the cadre of spermatozoal mRNAs has been characterized, comparatively little is known about the distribution or function of the estimated 24 000 sncRNAs within each normal human spermatozoon. METHODS RNAs of <200 bases in length were isolated from the ejaculates from three donors of proved fertility. RNAs of 18–30 nucleotides in length were then used to construct small RNA Digital Gene Expression libraries for Next Generation Sequencing. Known sncRNAs that uniquely mapped to a single location in the human genome were identified. RESULTS Bioinformatic analysis revealed the presence of multiple classes of small RNAs in human spermatozoa. The primary classes resolved included microRNA (miRNAs) (≈7%), Piwi-interacting piRNAs (≈17%), repeat-associated small RNAs (≈65%). A minor subset of short RNAs within the transcription start site/promoter fraction (≈11%) frames the histone promoter-associated regions enriched in genes of early embryonic development. These have been termed quiescent RNAs. CONCLUSIONS A complex population of male derived sncRNAs that are available for delivery upon fertilization was revealed. Sperm miRNA-targeted enrichment in the human oocyte is consistent with their role as modifiers of early post-fertilization. The relative abundance of piRNAs and repeat-associated RNAs suggests that they may assume a role in confrontation and consolidation. This may ensure the compatibility of the genomes at fertilization. PMID:21989093

Boosting sensitivity and suppressing artifacts via multi-acquisition in direct polarization NMR experiments with small flip-angle pulses.

PubMed

Fu, Riqiang; Hernández-Maldonado, Arturo J

2018-05-24

A small flip-angle pulse direct polarization is the simplest method commonly used to quantify various compositions in many materials applications. This method sacrifices the sensitivity per scan in exchange for rapid repeating of data acquisition for signal accumulation. In addition, the resulting spectrum often encounters artifacts from background signals from probe components and/or from acoustic rings leading to a distorted baseline, especially in low-γ nuclei and wideline NMR. In this work, a multi-acquisition scheme is proposed to boost the sensitivity per scan and at the same time effectively suppress these artifacts. Here, an adiabatic inversion pulse is first applied in order to bring the magnetization from the +z to -z axis and then a small flip-angle pulse excitation is used before the data acquisition. Right after the first acquisition, the adiabatic inversion pulse is applied again to flip the magnetization back to the +z axis. The second data acquisition takes place after another small flip-angle pulse excitation. The difference between the two consecutive acquisitions cancels out any artifacts, while the wanted signals are accumulated. This acquisition process can be repeated many times before going into next scan. Therefore, by acquiring the signals multiple times in a single scan the sensitivity is improved. A mixture sample of flufenamic acid and 3,5-difluorobenzoic acid and a titanium silicate sample have been used to demonstrate the advantages of this newly proposed method. Copyright © 2018 Elsevier Inc. All rights reserved.

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.

PubMed

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-09-10

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa.

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

DTIC Science & Technology

2015-10-01

characterization of the mouse model of repeated blast also found no cumula- tive effect of repeated blast on cortical levels of reactive oxygen species [39]. C...overpressure in rats to investigate the cumulative effects of multiple blast exposures on neurologic status, neurobehavioral function, and brain...preclinical model of blast overpressure in rats to investigate the cumulative effects of multiple blast exposures using neurological, neurochemical

Study of repeater technology for advanced multifunctional communications satellites

NASA Technical Reports Server (NTRS)

1972-01-01

Investigations are presented concerning design concepts and implementation approaches for the satellite communication repeater subsystems of advanced multifunctional satellites. In such systems the important concepts are the use of multiple antenna beams, repeater switching (routing), and efficient spectrum utilization through frequency reuse. An information base on these techniques was developed and tradeoff analyses were made of repeater design concepts, with the work design taken in a broad sense to include modulation beam coverage patterns. There were five major areas of study: requirements analysis and processing; study of interbeam interference in multibeam systems; characterization of multiple-beam switching repeaters; estimation of repeater weight and power for a number of alternatives; and tradeoff analyses based on these weight and power data.

A microfluidic platform for precision small-volume sample processing and its use to size separate biological particles with an acoustic microdevice [Precision size separation of biological particles in small-volume samples by an acoustic microfluidic system

DOE PAGES

Fong, Erika J.; Huang, Chao; Hamilton, Julie; ...

2015-11-23

Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

Autocorrelation peaks in congruential pseudorandom number generators

NASA Technical Reports Server (NTRS)

Neuman, F.; Merrick, R. B.

1976-01-01

The complete correlation structure of several congruential pseudorandom number generators (PRNG) of the same type and small cycle length was studied to deal with the problem of congruential PRNG almost repeating themselves at intervals smaller than their cycle lengths, during simulation of bandpass filtered normal random noise. Maximum period multiplicative and mixed congruential generators were studied, with inferences drawn from examination of several tractable members of a class of random number generators, and moduli from 2 to the 5th power to 2 to the 9th power. High correlation is shown to exist in mixed and multiplicative congruential random number generators and prime moduli Lehmer generators for shifts a fraction of their cycle length. The random noise sequences in question are required when simulating electrical noise, air turbulence, or time variation of wind parameters.

Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.

PubMed

Zhu, Luchang; Olsen, Randall J; Horstmann, Nicola; Shelburne, Samuel A; Fan, Jia; Hu, Ye; Musser, James M

2016-07-01

Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Ruler Protein in a Complex for Antiviral Defense Determines the Length of Small Interfering CRISPR RNAs

PubMed Central

Hatoum-Aslan, Asma; Samai, Poulami; Maniv, Inbal; Jiang, Wenyan; Marraffini, Luciano A.

2013-01-01

Small RNAs undergo maturation events that precisely determine the length and structure required for their function. CRISPRs (clustered regularly interspaced short palindromic repeats) encode small RNAs (crRNAs) that together with CRISPR-associated (cas) genes constitute a sequence-specific prokaryotic immune system for anti-viral and anti-plasmid defense. crRNAs are subject to multiple processing events during their biogenesis, and little is known about the mechanism of the final maturation step. We show that in the Staphylococcus epidermidis type III CRISPR-Cas system, mature crRNAs are measured in a Cas10·Csm ribonucleoprotein complex to yield discrete lengths that differ by 6-nucleotide increments. We looked for mutants that impact this crRNA size pattern and found that an alanine substitution of a conserved aspartate residue of Csm3 eliminates the 6-nucleotide increments in the length of crRNAs. In vitro, recombinant Csm3 binds RNA molecules at multiple sites, producing gel-shift patterns that suggest that each protein binds 6 nucleotides of substrate. In vivo, changes in the levels of Csm3 modulate the crRNA size distribution without disrupting the 6-nucleotide periodicity. Our data support a model in which multiple Csm3 molecules within the Cas10·Csm complex bind the crRNA with a 6-nucleotide periodicity to function as a ruler that measures the extent of crRNA maturation. PMID:23935102

SU-F-T-180: Evaluation of a Scintillating Screen Detector for Proton Beam QA and Acceptance Testing

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

Ghebremedhin, A; Taber, M; Koss, P

2016-06-15

Purpose: To test the performance of a commercial scintillating screen detector for acceptance testing and Quality Assurance of a proton pencil beam scanning system. Method: The detector (Lexitek DRD 400) has 40cm × 40cm field, uses a thin scintillator imaged onto a 16-bit scientific CCD with ∼0.5mm resolution. A grid target and LED illuminators are provided for spatial calibration and relative gain correction. The detector mounts to the nozzle with micron precision. Tools are provided for image processing and analysis of single or multiple Gaussian spots. Results: The bias and gain of the detector were studied to measure repeatability andmore » accuracy. Gain measurements were taken with the LED illuminators to measure repeatability and variation of the lens-CCD pair as a function with f-stop. Overall system gain was measured with a passive scattering (broad) beam whose shape is calibrated with EDR film placed in front of the scintillator. To create a large uniform field, overlapping small fields were recorded with the detector translated laterally and stitched together to cover the full field. Due to the long exposures required to obtain multiple spills of the synchrotron and very high detector sensitivity, borated polyethylene shielding was added to reduce direct radiation events hitting the CCD. Measurements with a micro ion chamber were compared to the detector’s spot profile. Software was developed to process arrays of Gaussian spots and to correct for radiation events. Conclusion: The detector background has a fixed bias, a small component linear in time, and is easily corrected. The gain correction method was validated with 2% accuracy. The detector spot profile matches the micro ion chamber data over 4 orders of magnitude. The multiple spot analyses can be easily used with plan data for measuring pencil beam uniformity and for regular QA comparison.« less

Investigation of vinegar production using a novel shaken repeated batch culture system.

PubMed

Schlepütz, Tino; Büchs, Jochen

2013-01-01

Nowadays, bioprocesses are developed or optimized on small scale. Also, vinegar industry is motivated to reinvestigate the established repeated batch fermentation process. As yet, there is no small-scale culture system for optimizing fermentation conditions for repeated batch bioprocesses. Thus, the aim of this study is to propose a new shaken culture system for parallel repeated batch vinegar fermentation. A new operation mode - the flushing repeated batch - was developed. Parallel repeated batch vinegar production could be established in shaken overflow vessels in a completely automated operation with only one pump per vessel. This flushing repeated batch was first theoretically investigated and then empirically tested. The ethanol concentration was online monitored during repeated batch fermentation by semiconductor gas sensors. It was shown that the switch from one ethanol substrate quality to different ethanol substrate qualities resulted in prolonged lag phases and durations of the first batches. In the subsequent batches the length of the fermentations decreased considerably. This decrease in the respective lag phases indicates an adaptation of the acetic acid bacteria mixed culture to the specific ethanol substrate quality. Consequently, flushing repeated batch fermentations on small scale are valuable for screening fermentation conditions and, thereby, improving industrial-scale bioprocesses such as vinegar production in terms of process robustness, stability, and productivity. Copyright © 2013 American Institute of Chemical Engineers.

[Crohn's disease surgery].

PubMed

Kala, Zdeněk; Marek, Filip; Válek, Vlastimil A; Bartušek, Daniel

2014-01-01

Surgery of Crohns disease is an important part of the general treatment algorithm. The role of surgery is changing with the development of conservative procedures. The recent years have seen the return to early treatment of patients with Crohns disease. Given the character of the disease and its intestinal symptoms, a specific approach to these patients is necessary, especially regarding the correct choice of surgery. The paper focuses on the luminal damage of the small and large intestine including complications of the disease. We describe the individual indications for a surgical solution, including the choice of anastomosis or multiple / repeated surgeries.

Testing Multiple Outcomes in Repeated Measures Designs

ERIC Educational Resources Information Center

Lix, Lisa M.; Sajobi, Tolulope

2010-01-01

This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

Effects of repeated transvaginal aspiration of immature follicles on mare health and ovarian status.

PubMed

Velez, I C; Arnold, C; Jacobson, C C; Norris, J D; Choi, Y H; Edwards, J F; Hayden, S S; Hinrichs, K

2012-12-01

Transvaginal ultrasound-guided follicle aspiration (TVA) is performed clinically but there is little information available on complications associated with this procedure. It is possible that TVA is associated with damage to the ovary and may induce peritonitis or peritoneal adhesions. This study was conducted to determine the effect of repeated TVA on mare health and ovarian status. Thirty-two mares were used for oocyte recovery via repeated TVA over a 3 year period; different mares were used each year. In Year 1, ovarian status was monitored in 11 mares by transrectal palpation and ultrasonography. In Year 2, 6 of 11 mares underwent abdominocentesis and were examined by laparoscopy after one TVA and again after multiple TVAs. In Year 3, 10 mares underwent multiple TVAs with either a 15 or a 12 gauge needle and the ovaries were removed for examination. Four hundred and twenty-seven aspiration sessions (390 via TVA and 37 via needle placement through the flank) and 3202 follicle punctures (3161 TVA and 41 flank) were performed. One mare developed an ovarian abscess. Transient rectal bleeding was evident after 16% of TVA sessions. No adhesions were found on laparoscopic or gross examination of ovaries and there were minimal changes on histological evaluation. Follicle aspiration carries a small possibility (< 0.5%) of ovarian abscess formation. There is a possibility of rectal abrasion or puncture but little gross or histological damage to the ovary. These results provide a basis for using prophylactic administration of antibiotics after TVA and for advising mare owners of the rare but potential complications associated with the procedure.

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

PubMed

Kobus, Thiele; Vykhodtseva, Natalia; Pilatou, Magdalini; Zhang, Yongzhi; McDannold, Nathan

2016-02-01

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Repeat Customer Success in Extension

ERIC Educational Resources Information Center

Bess, Melissa M.; Traub, Sarah M.

2013-01-01

Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.

PubMed

Disney, Matthew D

2013-12-01

RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi.

PubMed

Batty, Elizabeth M; Chaemchuen, Suwittra; Blacksell, Stuart; Richards, Allen L; Paris, Daniel; Bowden, Rory; Chan, Caroline; Lachumanan, Ramkumar; Day, Nicholas; Donnelly, Peter; Chen, Swaine; Salje, Jeanne

2018-06-01

Orientia tsutsugamushi is a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies of Orientia have revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species. We report new high-quality genomes of O. tsutsugamushi, generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene islands and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny of Orientia. Complete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have larger genomes compared with most other Rickettsiaceae, with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.

Meta-analysis of the technical performance of an imaging procedure: guidelines and statistical methodology.

PubMed

Huang, Erich P; Wang, Xiao-Feng; Choudhury, Kingshuk Roy; McShane, Lisa M; Gönen, Mithat; Ye, Jingjing; Buckler, Andrew J; Kinahan, Paul E; Reeves, Anthony P; Jackson, Edward F; Guimaraes, Alexander R; Zahlmann, Gudrun

2015-02-01

Medical imaging serves many roles in patient care and the drug approval process, including assessing treatment response and guiding treatment decisions. These roles often involve a quantitative imaging biomarker, an objectively measured characteristic of the underlying anatomic structure or biochemical process derived from medical images. Before a quantitative imaging biomarker is accepted for use in such roles, the imaging procedure to acquire it must undergo evaluation of its technical performance, which entails assessment of performance metrics such as repeatability and reproducibility of the quantitative imaging biomarker. Ideally, this evaluation will involve quantitative summaries of results from multiple studies to overcome limitations due to the typically small sample sizes of technical performance studies and/or to include a broader range of clinical settings and patient populations. This paper is a review of meta-analysis procedures for such an evaluation, including identification of suitable studies, statistical methodology to evaluate and summarize the performance metrics, and complete and transparent reporting of the results. This review addresses challenges typical of meta-analyses of technical performance, particularly small study sizes, which often causes violations of assumptions underlying standard meta-analysis techniques. Alternative approaches to address these difficulties are also presented; simulation studies indicate that they outperform standard techniques when some studies are small. The meta-analysis procedures presented are also applied to actual [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) test-retest repeatability data for illustrative purposes. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Meta-analysis of the technical performance of an imaging procedure: Guidelines and statistical methodology

PubMed Central

Huang, Erich P; Wang, Xiao-Feng; Choudhury, Kingshuk Roy; McShane, Lisa M; Gönen, Mithat; Ye, Jingjing; Buckler, Andrew J; Kinahan, Paul E; Reeves, Anthony P; Jackson, Edward F; Guimaraes, Alexander R; Zahlmann, Gudrun

2017-01-01

Medical imaging serves many roles in patient care and the drug approval process, including assessing treatment response and guiding treatment decisions. These roles often involve a quantitative imaging biomarker, an objectively measured characteristic of the underlying anatomic structure or biochemical process derived from medical images. Before a quantitative imaging biomarker is accepted for use in such roles, the imaging procedure to acquire it must undergo evaluation of its technical performance, which entails assessment of performance metrics such as repeatability and reproducibility of the quantitative imaging biomarker. Ideally, this evaluation will involve quantitative summaries of results from multiple studies to overcome limitations due to the typically small sample sizes of technical performance studies and/or to include a broader range of clinical settings and patient populations. This paper is a review of meta-analysis procedures for such an evaluation, including identification of suitable studies, statistical methodology to evaluate and summarize the performance metrics, and complete and transparent reporting of the results. This review addresses challenges typical of meta-analyses of technical performance, particularly small study sizes, which often causes violations of assumptions underlying standard meta-analysis techniques. Alternative approaches to address these difficulties are also presented; simulation studies indicate that they outperform standard techniques when some studies are small. The meta-analysis procedures presented are also applied to actual [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) test–retest repeatability data for illustrative purposes. PMID:24872353

Validation and Genotyping of Multiple Human Polymorphic Inversions Mediated by Inverted Repeats Reveals a High Degree of Recurrence

PubMed Central

Aguado, Cristina; Gayà-Vidal, Magdalena; Villatoro, Sergi; Oliva, Meritxell; Izquierdo, David; Giner-Delgado, Carla; Montalvo, Víctor; García-González, Judit; Martínez-Fundichely, Alexander; Capilla, Laia; Ruiz-Herrera, Aurora; Estivill, Xavier; Puig, Marta; Cáceres, Mario

2014-01-01

In recent years different types of structural variants (SVs) have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR) protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6–24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies. PMID:24651690

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa

PubMed Central

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-01-01

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa. DOI: http://dx.doi.org/10.7554/eLife.09560.001 PMID:26354291

Large tubular colonic duplication in an adult treated with a small midline incision

PubMed Central

Yong, Yuen Geng; Jung, Kyung Uk; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

2012-01-01

Tubular colonic duplication presenting in adults is rare and difficult to diagnose preoperatively. Only a few cases have been reported in the literature. We report a case of a 29-year-old lady presenting with a long history of chronic constipation, abdominal mass and repeated episodes of abdominal pain. The abdominal-pelvic computed tomography scan showed segmental bowel wall thickening thought to be small bowel, and dilatation with stasis of intraluminal content. The provisional diagnosis was small bowel duplication. She was scheduled for single port laparoscopic resection. However, a T-shaped tubular colonic duplication at sigmoid colon was found intraoperatively. Resection of the large T-shaped tubular colonic duplication containing multiple impacted large fecaloma and primary anastomosis was performed. There was no perioperative complication. We report, herein, the case of a T-shaped tubular colonic duplication at sigmoid colon in an adult who was successfully treated through mini-laparotomy assisted by single port laparoscopic surgery. PMID:22403754

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex.

PubMed

Onischenko, Evgeny; Tang, Jeffrey H; Andersen, Kasper R; Knockenhauer, Kevin E; Vallotton, Pascal; Derrer, Carina P; Kralt, Annemarie; Mugler, Christopher F; Chan, Leon Y; Schwartz, Thomas U; Weis, Karsten

2017-11-02

Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a new layer of connections to current models of the NPC architecture. Copyright © 2017 Elsevier Inc. All rights reserved.

Reconfigurable multiport EPON repeater

NASA Astrophysics Data System (ADS)

Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

2009-11-01

An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

A Dynamic Tandem Repeat in Monocotyledons Inferred from a Comparative Analysis of Chloroplast Genomes in Melanthiaceae.

PubMed

Do, Hoang Dang Khoa; Kim, Joo-Hwan

2017-01-01

Chloroplast genomes (cpDNA) are highly valuable resources for evolutionary studies of angiosperms, since they are highly conserved, are small in size, and play critical roles in plants. Slipped-strand mispairing (SSM) was assumed to be a mechanism for generating repeat units in cpDNA. However, research on the employment of different small repeated sequences through SSM events, which may induce the accumulation of distinct types of repeats within the same region in cpDNA, has not been documented. Here, we sequenced two chloroplast genomes from the endemic species Heloniopsis tubiflora (Korea) and Xerophyllum tenax (USA) to cover the gap between molecular data and explore "hot spots" for genomic events in Melanthiaceae. Comparative analysis of 23 complete cpDNA sequences revealed that there were different stages of deletion in the rps16 region across the Melanthiaceae. Based on the partial or complete loss of rps16 gene in cpDNA, we have firstly reported potential molecular markers for recognizing two sections ( Veratrum and Fuscoveratrum ) of Veratrum . Melathiaceae exhibits a significant change in the junction between large single copy and inverted repeat regions, ranging from trnH_GUG to a part of rps3 . Our results show an accumulation of tandem repeats in the rpl23-ycf2 regions of cpDNAs. Small conserved sequences exist and flank tandem repeats in further observation of this region across most of the examined taxa of Liliales. Therefore, we propose three scenarios in which different small repeated sequences were used during SSM events to generate newly distinct types of repeats. Occasionally, prior to the SSM process, point mutation event and double strand break repair occurred and induced the formation of initial repeat units which are indispensable in the SSM process. SSM may have likely occurred more frequently for short repeats than for long repeat sequences in tribe Parideae (Melanthiaceae, Liliales). Collectively, these findings add new evidence of dynamic results from SSM in chloroplast genomes which can be useful for further evolutionary studies in angiosperms. Additionally, genomics events in cpDNA are potential resources for mining molecular markers in Liliales.

Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS).

PubMed

Rajender, Singh; Carlus, Silas Justin; Bansal, Sandeep Kumar; Negi, Mahendra Pal Singh; Negi, Mahendra Pratap Singh; Sadasivam, Nirmala; Sadasivam, Muthusamy Narayanan; Thangaraj, Kumarasamy

2013-01-01

Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2) = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding without any true association with PCOS risk.

Pairwise Multiple Comparisons in Single Group Repeated Measures Analysis.

ERIC Educational Resources Information Center

Barcikowski, Robert S.; Elliott, Ronald S.

Research was conducted to provide educational researchers with a choice of pairwise multiple comparison procedures (P-MCPs) to use with single group repeated measures designs. The following were studied through two Monte Carlo (MC) simulations: (1) The T procedure of J. W. Tukey (1953); (2) a modification of Tukey's T (G. Keppel, 1973); (3) the…

Masonry fireplace emissions test method: Repeatability and sensitivity to fueling protocol.

PubMed

Stern, C H; Jaasma, D R; Champion, M R

1993-03-01

A test method for masonry fireplaces has been evaluated during testing on six masonry fireplace configurations. The method determines carbon monoxide and particulate matter emission rates (g/h) and factors (g/kg) and does not require weighing of the appliance to determine the timing of fuel loading.The intralaboratory repeatability of the test method has been determined from multiple tests on the six fireplaces. For the tested fireplaces, the ratio of the highest to lowest measured PM rate averaged 1.17 and in no case was greater than 1.32. The data suggest that some of the variation is due to differences in fuel properties.The influence of fueling protocol on emissions has also been studied. A modified fueling protocol, tested in large and small fireplaces, reduced CO and PM emission factors by roughly 40% and reduced CO and PM rates from 0 to 30%. For both of these fireplaces, emission rates were less sensitive to fueling protocol than emission factors.

Hemispherical breathing mode speaker using a dielectric elastomer actuator.

PubMed

Hosoya, Naoki; Baba, Shun; Maeda, Shingo

2015-10-01

Although indoor acoustic characteristics should ideally be assessed by measuring the reverberation time using a point sound source, a regular polyhedron loudspeaker, which has multiple loudspeakers on a chassis, is typically used. However, such a configuration is not a point sound source if the size of the loudspeaker is large relative to the target sound field. This study investigates a small lightweight loudspeaker using a dielectric elastomer actuator vibrating in the breathing mode (the pulsating mode such as the expansion and contraction of a balloon). Acoustic testing with regard to repeatability, sound pressure, vibration mode profiles, and acoustic radiation patterns indicate that dielectric elastomer loudspeakers may be feasible.

An automated device for appetitive conditioning in zebrafish (Danio rerio).

PubMed

Manabe, Kazuchika; Dooling, R J; Takaku, Shinichi

2013-12-01

An automated device and a procedure for the operant conditioning individual zebrafish were developed. The key feature of this procedure was the construction of a simple, inexpensive feeder that can deliver extremely small amounts of food, thus preventing rapid satiation. This allows the experimenter to run multiple trails in a single test session and multiple sessions in one day. In addition, small response keys made from acryl rods and fiber sensors were developed that were sufficiently sensitive to detect fish contact. To illustrate the efficiency and utility of the device for traditional learning paradigms, we trained zebrafish in a fixed ratio schedule where subjects were reinforced with food after 10 responses. Zebrafish reliably responded on the response key for sessions that lasted as long 80-reinforcements. They also showed the traditional "break and run" response pattern that has been found in many species. These results show that this system will be valuable for behavioral studies with zebrafish, especially for experiments that need many repeated trials using food reinforcer in a session. The present system can be used for sensory and learning investigations, as well applications in behavioral pharmacology, behavioral genetics, and toxicology where the zebrafish is becoming the vertebrate model of choice.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

PubMed

Klement, R J; Hoerner-Rieber, J; Adebahr, S; Andratschke, N; Blanck, O; Boda-Heggemann, J; Duma, M; Eble, M J; Eich, H C; Flentje, M; Gerum, S; Hass, P; Henkenberens, C; Hildebrandt, G; Imhoff, D; Kahl, K H; Klass, N D; Krempien, R; Lohaus, F; Petersen, C; Schrade, E; Wendt, T G; Wittig, A; Guckenberger, M

2018-03-03

Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Small tandemly repeated DNA sequences of higher plants likely originate from a tRNA gene ancestor.

PubMed Central

Benslimane, A A; Dron, M; Hartmann, C; Rode, A

1986-01-01

Several monomers (177 bp) of a tandemly arranged repetitive nuclear DNA sequence of Brassica oleracea have been cloned and sequenced. They share up to 95% homology between one another and up to 80% with other satellite DNA sequences of Cruciferae, suggesting a common ancestor. Both strands of these monomers show more than 50% homology with many tRNA genes; the best homologies have been obtained with Lys and His yeast mitochondrial tRNA genes (respectively 64% and 60%). These results suggest that small tandemly repeated DNA sequences of plants may have evolved from a tRNA gene ancestor. These tandem repeats have probably arisen via a process involving reverse transcription of polymerase III RNA intermediates, as is the case for interspersed DNA sequences of mammalians. A model is proposed to explain the formation of such small tandemly repeated DNA sequences. Images PMID:3774553

Statistical technique for analysing functional connectivity of multiple spike trains.

PubMed

Masud, Mohammad Shahed; Borisyuk, Roman

2011-03-15

A new statistical technique, the Cox method, used for analysing functional connectivity of simultaneously recorded multiple spike trains is presented. This method is based on the theory of modulated renewal processes and it estimates a vector of influence strengths from multiple spike trains (called reference trains) to the selected (target) spike train. Selecting another target spike train and repeating the calculation of the influence strengths from the reference spike trains enables researchers to find all functional connections among multiple spike trains. In order to study functional connectivity an "influence function" is identified. This function recognises the specificity of neuronal interactions and reflects the dynamics of postsynaptic potential. In comparison to existing techniques, the Cox method has the following advantages: it does not use bins (binless method); it is applicable to cases where the sample size is small; it is sufficiently sensitive such that it estimates weak influences; it supports the simultaneous analysis of multiple influences; it is able to identify a correct connectivity scheme in difficult cases of "common source" or "indirect" connectivity. The Cox method has been thoroughly tested using multiple sets of data generated by the neural network model of the leaky integrate and fire neurons with a prescribed architecture of connections. The results suggest that this method is highly successful for analysing functional connectivity of simultaneously recorded multiple spike trains. Copyright © 2011 Elsevier B.V. All rights reserved.

The heptad repeats region is essential for AcMNPV P10 filament formation and not the proline-rich or the C-terminus basic regions.

PubMed

Dong, Chunsheng; Deng, Fei; Li, Dan; Wang, Hualin; Hu, Zhihong

2007-09-01

Baculovirus P10 protein is a small conserved protein and is expressed as bundles of filaments in the host cell during the late phase of virus infection. So far the published results on the domain responsible for filament structural formation have been contradictory. Electron microscopy revealed that the C-terminus basic region was involved in filament structural formation in the Autographa californica multiple nucleocapsid nucleopolyhedrovirus (AcMNPV) [van Oers, M.M., Flipsen, J.T., Reusken, C.B., Sliwinsky, E.L., Vlak, J.M., 1993. Functional domains of the p10 protein of Autographa californica nuclear polyhedorsis virus. J. Gen. Virol. 74, 563-574.]. While in the Helicoverpa armigera nucleopolyhedrovirus (HearNPV), the heptad repeats region but not the C-terminus domain was proven to be responsible for filament formation [Dong, C., Li, D., Long, G., Deng, F., Wang, H., Hu, Z., 2005. Identification of functional domains required for HearNPV P10 filament formation. Virology 338, 112-120.]. In this manuscript, fluorescence confocal microscopy was applied to study AcMNPV P10 filament formation. A set of plasmids containing different P10 structural domains fused with a fluorescent protein were constructed and transfected into Sf-9 cells. The data indicated that the heptad repeats region, but not the proline-rich region or the C-terminus basic region, is essential for AcMNPV P10 filament formation. Co-transfection of P10s tagged with different fluorescent revealed that P10s with defective heptad repeats region could not interact with intact heptad repeats region or even full-length P10s to form filament structure. Within the heptad repeats region, deletion of the three amino acids spacing of AcMNPV P10 appeared to have no significant impact on the formation of filament structures, but the content of the heptad repeats region appeared to play a role in the morphology of the filaments.

Comparison of Two Procedures for Analyzing Small Sets of Repeated Measures Data

ERIC Educational Resources Information Center

Vallejo, Guillermo; Livacic-Rojas, Pablo

2005-01-01

This article compares two methods for analyzing small sets of repeated measures data under normal and non-normal heteroscedastic conditions: a mixed model approach with the Kenward-Roger correction and a multivariate extension of the modified Brown-Forsythe (BF) test. These procedures differ in their assumptions about the covariance structure of…

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

PubMed

Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

2017-07-01

Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.

PubMed

Childs-Disney, Jessica L; Hoskins, Jason; Rzuczek, Suzanne G; Thornton, Charles A; Disney, Matthew D

2012-05-18

RNA is an important drug target, but it is difficult to design or discover small molecules that modulate RNA function. In the present study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models. DM1 is caused when an expansion of r(CUG) repeats, or r(CUG)(exp), is present in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) mRNA. r(CUG)(exp) folds into a hairpin with regularly repeating 5'CUG/3'GUC motifs and sequesters muscleblind-like 1 protein (MBNL1). A variety of defects are associated with DM1, including (i) formation of nuclear foci, (ii) decreased translation of DMPK mRNA due to its nuclear retention, and (iii) pre-mRNA splicing defects due to inactivation of MBNL1, which controls the alternative splicing of various pre-mRNAs. Previously, modularly assembled ligands targeting r(CUG)(exp) were designed using information in an RNA motif-ligand database. These studies showed that a bis-benzimidazole (H) binds the 5'CUG/3'GUC motif in r(CUG)(exp.) Therefore, we designed multivalent ligands to bind simultaneously multiple copies of this motif in r(CUG)(exp). Herein, we report that the designed compounds improve DM1-associated defects including improvement of translational and pre-mRNA splicing defects and the disruption of nuclear foci. These studies may establish a foundation to exploit other RNA targets in genomic sequence.

Inhibition of Hepatitis C Virus Replication by Intracellular Delivery of Multiple siRNAs by Nanosomes

PubMed Central

Chandra, Partha K; Kundu, Anup K; Hazari, Sidhartha; Chandra, Sruti; Bao, Lili; Ooms, Tara; Morris, Gilbert F; Wu, Tong; Mandal, Tarun K; Dash, Srikanta

2012-01-01

Sustained antiviral responses of chronic hepatitis C virus (HCV) infection have improved recently by the use of direct-acting antiviral agents along with interferon (IFN)-α and ribavirin. However, the emergence of drug-resistant variants is expected to be a major problem. We describe here a novel combinatorial small interfering RNA (siRNA) nanosome-based antiviral approach to clear HCV infection. Multiple siRNAs targeted to the highly conserved 5′-untranslated region (UTR) of the HCV genome were synthesized and encapsulated into lipid nanoparticles called nanosomes. We show that siRNA can be repeatedly delivered to 100% of cells in culture using nanosomes without toxicity. Six siRNAs dramatically reduced HCV replication in both the replicon and infectious cell culture model. Repeated treatments with two siRNAs were better than a single siRNA treatment in minimizing the development of an escape mutant, resulting in rapid inhibition of viral replication. Systemic administration of combinatorial siRNA-nanosomes is well tolerated in BALB/c mice without liver injury or histological toxicity. As a proof-of-principle, we showed that systemic injections of siRNA nanosomes significantly reduced HCV replication in a liver tumor-xenotransplant mouse model of HCV. Our results indicate that systemic delivery of combinatorial siRNA nanosomes can be used to minimize the development of escape mutants and inhibition of HCV infection. PMID:22617108

Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

ERIC Educational Resources Information Center

Fenton, Kathleen S.

Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

Genetic parameters for first lactation test-day milk flow in Holstein cows.

PubMed

Laureano, M M M; Bignardi, A B; El Faro, L; Cardoso, V L; Albuquerque, L G

2012-01-01

Genetic parameters for test-day milk flow (TDMF) of 2175 first lactations of Holstein cows were estimated using multiple-trait and repeatability models. The models included the direct additive genetic effect as a random effect and contemporary group (defined as the year and month of test) and age of cow at calving (linear and quadratic effect) as fixed effects. For the repeatability model, in addition to the effects cited, the permanent environmental effect of the animal was also included as a random effect. Variance components were estimated using the restricted maximum likelihood method in single- and multiple-trait and repeatability analyses. The heritability estimates for TDMF ranged from 0.23 (TDMF 6) to 0.32 (TDMF 2 and TDMF 4) in single-trait analysis and from 0.28 (TDMF 7 and TDMF 10) to 0.37 (TDMF 4) in multiple-trait analysis. In general, higher heritabilities were observed at the beginning of lactation until the fourth month. Heritability estimated with the repeatability model was 0.27 and the coefficient of repeatability for first lactation TDMF was 0.66. The genetic correlations were positive and ranged from 0.72 (TDMF 1 and 10) to 0.97 (TDMF 4 and 5). The results indicate that milk flow should respond satisfactorily to selection, promoting rapid genetic gains because the estimated heritabilities were moderate to high. Higher genetic gains might be obtained if selection was performed in the TDMF 4. Both the repeatability model and the multiple-trait model are adequate for the genetic evaluation of animals in terms of milk flow, but the latter provides more accurate estimates of breeding values.

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes

PubMed Central

Crowther, Caroline A; McKinlay, Christopher JD; Middleton, Philippa; Harding, Jane E

2014-01-01

Background It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial. Objectives To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data. Selection criteria Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth. Data collection and analysis We assessed trial quality and extracted data independently. Main results We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79). Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) −75.79 g, 95% CI −117.63 to −33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups. At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments. Authors’ conclusions The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit. Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm. PMID:21678343

The Violent and Sexual Victimization of College Women: Is Repeat Victimization a Problem?

ERIC Educational Resources Information Center

Daigle, Leah E.; Fisher, Bonnie S.; Cullen, Francis T.

2008-01-01

Little attention has been given to repeat violent and sexual victimization among college women. Using two national-level data sets, the authors find that a small proportion of college women experience a large proportion of violent and sexual victimizations. Women are more likely to experience repeat sexual victimization than repeat violence…

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

PubMed Central

Singh, Deepak K.; Rath, Pramod C.

2012-01-01

We report strong somatic and germ line expression of LINE RNAs in eight different tissues of rat by using a novel ~2.8 kb genomic PstI-LINE DNA (P1-LINE) isolated from the rat brain. P1-LINE is present in a 93 kb LINE-SINE-cluster in sub-telomeric region of chromosome 12 (12p12) and as multiple truncated copies interspersed in all rat chromosomes. P1-LINEs occur as inverted repeats at multiple genomic loci in tissue-specific and mosaic patterns. P1-LINE RNAs are strongly expressed in brain, liver, lungs, heart, kidney, testes, spleen and thymus into large to small heterogeneous RNAs (~5.0 to 0.2 kb) in tissue-specific and dynamic patterns in individual rats. P1-LINE DNA is strongly methylated at CpG-dinucleotides in most genomic copies in all the tissues and weakly hypomethylated in few copies in some tissues. Small (700–75 nt) P1-LINE RNAs expressed in all tissues may be possible precursors for small regulatory RNAs (PIWI-interacting/piRNAs) bioinformatically derived from P1-LINE. The strong and dynamic expression of LINE RNAs from multiple chromosomal loci and the putative piRNAs in somatic tissues of rat under normal physiological conditions may define functional chromosomal domains marked by LINE RNAs as long noncoding RNAs (lncRNAs) unrestricted by DNA methylation. The tissue-specific, dynamic RNA expression and mosaic genomic distribution of LINEs representing a steady-state genomic flux of retrotransposon RNAs suggest for biological role of LINE RNAs as long ncRNAs and small piRNAs in mammalian tissues independent of their cellular fate for translation, reverse-transcription and retrotransposition. This may provide evolutionary advantages to LINEs and mammalian genomes. PMID:23064113

Repeatability of standard metabolic rate (SMR) in a small fish, the spined loach (Cobitis taenia).

PubMed

Maciak, Sebastian; Konarzewski, Marek

2010-10-01

Significant repeatability of a trait of interest is an essential assumption for undertaking studies of phenotypic variability. It is especially important in studies on highly variable traits, such as metabolic rates. Recent publications suggest that resting/basal metabolic rate of homeotherms is repeatable across wide range of species. In contrast, studies on the consistency of standard metabolic rate (SMR) in ectotherms, particularly fish, are scarce. Here we present a comprehensive analysis of several important technical aspects of body mass-corrected SMR measurements and its repeatability in a small (average weight approximately 3g) fish, the spined loach (Cobitis taenia). First we demonstrated that release of oxygen from the walls of metabolic chambers exposed to hypoxic conditions did not confound SMR measurements. Next, using principle of propagation of measurement uncertainties we demonstrated that in aquatic systems, measurement error is significantly higher in open than closed respirometry setups. The measurement error for SMR of a small fish determined in a closed aquatic system is comparable to that obtainable using top-notch open-flow systems used for air-breathing terrestrial animals. Using a closed respirometer we demonstrated that body mass-corrected SMR in spined loaches was repeatable under both normoxia and hypoxia over a 5-month period (Pearson correlation r=0.68 and r=0.73, respectively) as well as across both conditions (intraclass correlation coefficient tau=0.30). In these analyses we accounted for possible effect of oxygen consumption of the oxygen electrode on repeatability of SMR. Significant SMR consistency was accompanied by significant repeatability of body mass (intraclass correlation coefficient tau=0.86). To our knowledge, this is the first study showing long-term repeatability of body mass and SMR in a small fish, and is consistent with the existence of heritable variation of these two traits. 2010 Elsevier Inc. All rights reserved.

Protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1995-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

Protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1994-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

Short bowel mucosal morphology, proliferation and inflammation at first and repeat STEP procedures.

PubMed

Mutanen, Annika; Barrett, Meredith; Feng, Yongjia; Lohi, Jouko; Rabah, Raja; Teitelbaum, Daniel H; Pakarinen, Mikko P

2018-04-17

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7-3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p=0.05), while enteral caloric intake increased from 6% to 36% (p=0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p=0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p>0.05 for all). Patients, who required repeat STEP tended to be younger (p=0.057) with less apoptotic crypt cells (p=0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (p<0.05 for both). No adaptive mucosal hyperplasia or muscular alterations occurred between first and repeat STEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level IV, retrospective study. Copyright © 2018 Elsevier Inc. All rights reserved.

ACMES: fast multiple-genome searches for short repeat sequences with concurrent cross-species information retrieval

PubMed Central

Reneker, Jeff; Shyu, Chi-Ren; Zeng, Peiyu; Polacco, Joseph C.; Gassmann, Walter

2004-01-01

We have developed a web server for the life sciences community to use to search for short repeats of DNA sequence of length between 3 and 10 000 bases within multiple species. This search employs a unique and fast hash function approach. Our system also applies information retrieval algorithms to discover knowledge of cross-species conservation of repeat sequences. Furthermore, we have incorporated a part of the Gene Ontology database into our information retrieval algorithms to broaden the coverage of the search. Our web server and tutorial can be found at http://acmes.rnet.missouri.edu. PMID:15215469

Repeated Reading, Turn Taking, and Augmentative and Alternative Communication (AAC)

ERIC Educational Resources Information Center

Edmister, Evette; Wegner, Jane

2015-01-01

This single participant multiple baseline research design measured the effects of repeatedly reading narrative books to children who used voice output augmentative communication devices to communicate. The study sought to determine if there was a difference observed in the number of turns taken when reading stories repeatedly. Three girls ranging…

Perfect quantum multiple-unicast network coding protocol

NASA Astrophysics Data System (ADS)

Li, Dan-Dan; Gao, Fei; Qin, Su-Juan; Wen, Qiao-Yan

2018-01-01

In order to realize long-distance and large-scale quantum communication, it is natural to utilize quantum repeater. For a general quantum multiple-unicast network, it is still puzzling how to complete communication tasks perfectly with less resources such as registers. In this paper, we solve this problem. By applying quantum repeaters to multiple-unicast communication problem, we give encoding-decoding schemes for source nodes, internal ones and target ones, respectively. Source-target nodes share EPR pairs by using our encoding-decoding schemes over quantum multiple-unicast network. Furthermore, quantum communication can be accomplished perfectly via teleportation. Compared with existed schemes, our schemes can reduce resource consumption and realize long-distance transmission of quantum information.

Object strength--an accurate measure for small objects that is insensitive to partial volume effects.

PubMed

Tofts, P S; Silver, N C; Barker, G J; Gass, A

2005-07-01

There are currently four problems in characterising small nonuniform lesions or other objects in Magnetic Resonance images where partial volume effects are significant. Object size is over- or under-estimated; boundaries are often not reproducible; mean object value cannot be measured; and fuzzy borders cannot be accommodated. A new measure, Object Strength, is proposed. This is the sum of all abnormal intensities, above a uniform background value. For a uniform object, this is simply the product of the increase in intensity and the size of the object. Biologically, this could be at least as relevant as existing measures of size or mean intensity. We hypothesise that Object Strength will perform better than traditional area measurements in characterising small objects. In a pilot study, the reproducibility of object strength measurements was investigated using MR images of small multiple sclerosis (MS) lesions. In addition, accuracy was investigated using artificial lesions of known volume (0.3-6.2 ml) and realistic appearance. Reproducibility approached that of area measurements (in 33/90 lesion reports the difference between repeats was less than for area measurements). Total lesion volume was accurate to 0.2%. In conclusion, Object Strength has potential for improved characterisation of small lesions and objects in imaging and possibly spectroscopy.

Repeated irradiations with gamma-rays at a Dose of 0.5 Gy may exacerbate asthma.

PubMed

Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Muto, Yasuko; Goto, Resuke; Kojima, Shuji

2005-06-01

We previously showed that 0.5 Gy whole-body gamma-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFN-gamma/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy gamma-rays irradiation can improve asthma in an OVA-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of gamma-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the gamma-ray-irradiated group, while that of IFN-gamma was significantly lower, resulting in a further decrease of the IFN-gamma/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with gamma-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures.

Assessment and quantification of sources of variability in breast apparent diffusion coefficient (ADC) measurements at diffusion weighted imaging.

PubMed

Giannotti, E; Waugh, S; Priba, L; Davis, Z; Crowe, E; Vinnicombe, S

2015-09-01

Apparent Diffusion Coefficient (ADC) measurements are increasingly used for assessing breast cancer response to neoadjuvant chemotherapy although little data exists on ADC measurement reproducibility. The purpose of this work was to investigate and characterise the magnitude of errors in ADC measures that may be encountered in such follow-up studies- namely scanner stability, scan-scan reproducibility, inter- and intra- observer measures and the most reproducible measurement of ADC. Institutional Review Board approval was obtained for the prospective study of healthy volunteers and written consent acquired for the retrospective study of patient images. All scanning was performed on a 3.0-T MRI scanner. Scanner stability was assessed using an ice-water phantom weekly for 12 weeks. Inter-scan repeatability was assessed across two scans of 10 healthy volunteers (26-61 years; mean: 44.7 years). Inter- and intra-reader analysis repeatability was measured in 52 carcinomas from clinical patients (29-70 years; mean: 50.0 years) by measuring the whole tumor ADC value on a single slice with maximum tumor diameter (ADCS) and the ADC value of a small region of interest (ROI) on the same slice (ADCmin). Repeatability was assessed using intraclass correlation coefficients (ICC) and coefficients of repeatability (CoR). Scanner stability contributed 6% error to phantom ADC measurements (0.071×10(-3)mm(2)/s; mean ADC=1.089×10(-3)mm(2)/s). The measured scan-scan CoR in the volunteers was 0.122×10(-3)mm(2)/s, contributing an error of 8% to the mean measured values (ADCscan1=1.529×10(-3)mm(2)/s; ADCscan2=1.507×10(-3)mm(2)/s). Technical and clinical observers demonstrated excellent intra-observer repeatability (ICC>0.9). Clinical observer CoR values were marginally better than technical observer measures (ADCS=0.035×10(-3)mm(2)/s vs. 0.097×10(-3)mm(2)/s; ADCmin=0.09×10(-3)mm(2)/s vs. 0.114×10(-3)mm(2)/s). Inter-reader ICC values were good 0.864 (ADCS) and fair 0.677 (ADCmin). Corresponding CoR values were 0.202×10(-3)mm(2)/s and 0.264×10(-3)mm(2)/s, respectively. Both scanner stability and scan-scan variation have minimal influence on breast ADC measurements, contributing less than 10% error of average measured ADC values. Measurement of ADC values from a small ROI contributes a greater variability in measurements compared with measurement of ADC across the whole visible tumor on one slice. The greatest source of error in follow-up studies is likely to be associated with measures made by multiple observers, and this should be considered where multiple measures are required to assess response to treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.

PubMed

Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F; Bauer, Peter O; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K; Berry, James D; Cudkowicz, Merit E; Boeve, Bradley F; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H; Rothstein, Jeffrey D; Boylan, Kevin B; Petrucelli, Leonard; Disney, Matthew D

2014-09-03

A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. Copyright © 2014 Elsevier Inc. All rights reserved.

Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS

PubMed Central

Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F.; Bauer, Peter O.; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V.; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K.; Berry, James D.; Cudkowicz, Merit E.; Boeve, Bradley F.; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J.; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H.; Rothstein, Jeffrey D.; Boylan, Kevin B.; Petrucelli, Leonard; Disney, Matthew D.

2014-01-01

Summary A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation producing “c9RAN proteins”. Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons trans-differentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic, and suggest c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. PMID:25132468

Determination of Sources of Escherichia coli on Beef by Multiple-Locus Variable-Number Tandem Repeat Analysis.

PubMed

Yang, Xianqin; Tran, Frances; Youssef, Mohamed K; Gill, Colin O

2015-07-01

The possible origin of Escherichia coli found on cuts and trimmings in the breaking facility of a beef packing plant was examined using multiple-locus variable-number tandem repeat analysis. Coliforms and E. coli were enumerated in samples obtained from 160 carcasses that would enter the breaking facility when work commenced and after each of the three production breaks throughout the day, from the conveyor belt before work and after each break, and from cuts and trimmings when work commenced and after each break. Most samples yielded no E. coli, irrespective of the surface types. E. coli was recovered from 7 (<5%) carcasses, at numbers mostly ≤1.0 log CFU/160,000 cm(2). The log total numbers of E. coli recovered from the conveyor belt, cuts, and trimmings were mostly between 1 and 2 log CFU/80,000 cm(2). A total of 554 E. coli isolates were recovered. Multiple-locus variable-number tandem repeat analysis of 327 selected isolates identified 80 distinct genotypes, with 37 (46%) each containing one isolate. However, 28% of the isolates were of genotypes that were recovered from more than one sampling day. Of the 80 genotypes, 65 and 2% were found in one or all four sampling periods throughout the day. However, they represented 23 and 14% of the isolates, respectively. Of the genotypes identified for each surface type, at least one contained ≥9 isolates. No unique genotypes were associated with carcasses, but 10, 17, and 19 were uniquely associated with cuts, trimmings, and the belt, respectively. Of the isolates recovered from cuts, 49, 3, and 19% were of genotypes that were found among isolates recovered from the belt, carcasses, or both the belt and carcasses, respectively. A similar composition was found for isolates recovered from trimmings. These findings show that the E. coli found on cuts and trimmings at this beef packing plant mainly originated from the conveyor belt and that small number of E. coli strains survived the daily cleaning and sanitation process, thus persisting in the plant.

Optical Survey of the Tumble Rates of Retired GEO Satellites

DTIC Science & Technology

2014-09-01

objects while the sun- satellite -observer geometry was most favorable; typically over a one- to two-hour period, repeated multiple times over the course of...modeling and simulation of the optical characteristics of the satellite can help to resolve ambigu- ities. This process was validated on spacecraft for... satellite -observer geometry was most favorable; typically over a one- to two-hour period, repeated multiple times over the course of weeks. By

A small graphene oxide sheet/polyvinylidene fluoride bilayer actuator with large and rapid responses to multiple stimuli.

PubMed

Xu, Guochuang; Zhang, Miao; Zhou, Qinqin; Chen, Hongwu; Gao, Tiantian; Li, Chun; Shi, Gaoquan

2017-11-16

A high-performance actuator should be able to deliver large-shape deformations, fast actuations and sensitive responses to multiple stimuli. Here, we report such an actuator constructed from one layer of polyvinylidene fluoride (PVDF) with a high coefficient of thermal expansion (CTE), and another layer of small sheets of graphene oxide (SGO) with a negative CTE. The opposite deformations of both actuation layers make the SGO/PVDF bilayer actuator highly sensitive to the temperature stimulus with a large bending sensitivity of 1.5 cm -1 °C -1 . Upon irradiation with 60 mW cm -2 infrared light, this SGO/PVDF bilayer actuator displayed an extremely rapid tip displacement rate of 140 mm s -1 . Furthermore, this actuator can also sensitively respond to moisture because of its SGO layer, showing a curvature change from -22 to 13 cm -1 upon changing the relative humidity (RH) from 11% to 86%. This actuator can generate a contractile or relaxed stress 18 times that of mammalian skeletal muscle, under light irradiation or moisture with a response time as short as 1 s, being capable of lifting an object with a weight 80 times that of itself. Furthermore, it also showed excellent stability and repeatability.

Somatic mosaicism of androgen receptor CAG repeats in colorectal carcinoma epithelial cells from men.

PubMed

Di Fabio, Francesco; Alvarado, Carlos; Gologan, Adrian; Youssef, Emad; Voda, Linda; Mitmaker, Elliot; Beitel, Lenore K; Gordon, Philip H; Trifiro, Mark

2009-06-01

The X-linked human androgen receptor gene (AR) contains an exonic polymorphic trinucleotide CAG. The length of this encoded CAG tract inversely affects AR transcriptional activity. Colorectal carcinoma is known to express the androgen receptor, but data on somatic CAG repeat lengths variations in malignant and normal epithelial cells are still sporadic. Using laser capture microdissection (LCM), epithelial cells from colorectal carcinoma and normal-appearing mucosa were collected from the fresh tissue of eight consecutive male patients undergoing surgery (mean age, 70 y; range, 54-82). DNA isolated from each LCM sample underwent subsequent PCR and DNA sequencing to precisely determine AR CAG repeat lengths and the presence of microsatellite instability (MSI). Different AR CAG repeat lengths were observed in colorectal carcinoma (ranging from 0 to 36 CAG repeats), mainly in the form of multiple shorter repeat lengths. This genetic heterogeneity (somatic mosaicism) was also found in normal-appearing colorectal mucosa. Half of the carcinoma cases examined tended to have a higher number of AR CAG repeat lengths with a wider range of repeat size variation compared to normal mucosa. MSI carcinomas tended to have longer median AR CAG repeat lengths (n = 17) compared to microsatellite stable carcinomas (n = 14), although the difference was not significant (P = 0.31, Mann-Whitney test). Multiple unique somatic mutations of the AR CAG repeats occur in colorectal mucosa and in carcinoma, predominantly resulting in shorter alleles. Colorectal epithelial cells carrying AR alleles with shorter CAG repeat lengths may be more androgen-sensitive and therefore have a growth advantage.

Improved variance estimation of classification performance via reduction of bias caused by small sample size.

PubMed

Wickenberg-Bolin, Ulrika; Göransson, Hanna; Fryknäs, Mårten; Gustafsson, Mats G; Isaksson, Anders

2006-03-13

Supervised learning for classification of cancer employs a set of design examples to learn how to discriminate between tumors. In practice it is crucial to confirm that the classifier is robust with good generalization performance to new examples, or at least that it performs better than random guessing. A suggested alternative is to obtain a confidence interval of the error rate using repeated design and test sets selected from available examples. However, it is known that even in the ideal situation of repeated designs and tests with completely novel samples in each cycle, a small test set size leads to a large bias in the estimate of the true variance between design sets. Therefore different methods for small sample performance estimation such as a recently proposed procedure called Repeated Random Sampling (RSS) is also expected to result in heavily biased estimates, which in turn translates into biased confidence intervals. Here we explore such biases and develop a refined algorithm called Repeated Independent Design and Test (RIDT). Our simulations reveal that repeated designs and tests based on resampling in a fixed bag of samples yield a biased variance estimate. We also demonstrate that it is possible to obtain an improved variance estimate by means of a procedure that explicitly models how this bias depends on the number of samples used for testing. For the special case of repeated designs and tests using new samples for each design and test, we present an exact analytical expression for how the expected value of the bias decreases with the size of the test set. We show that via modeling and subsequent reduction of the small sample bias, it is possible to obtain an improved estimate of the variance of classifier performance between design sets. However, the uncertainty of the variance estimate is large in the simulations performed indicating that the method in its present form cannot be directly applied to small data sets.

A model for incomplete longitudinal multivariate ordinal data.

PubMed

Liu, Li C

2008-12-30

In studies where multiple outcome items are repeatedly measured over time, missing data often occur. A longitudinal item response theory model is proposed for analysis of multivariate ordinal outcomes that are repeatedly measured. Under the MAR assumption, this model accommodates missing data at any level (missing item at any time point and/or missing time point). It allows for multiple random subject effects and the estimation of item discrimination parameters for the multiple outcome items. The covariates in the model can be at any level. Assuming either a probit or logistic response function, maximum marginal likelihood estimation is described utilizing multidimensional Gauss-Hermite quadrature for integration of the random effects. An iterative Fisher-scoring solution, which provides standard errors for all model parameters, is used. A data set from a longitudinal prevention study is used to motivate the application of the proposed model. In this study, multiple ordinal items of health behavior are repeatedly measured over time. Because of a planned missing design, subjects answered only two-third of all items at a given point. Copyright 2008 John Wiley & Sons, Ltd.

Mechanism of Small Current Generation under Impulse Voltage Applications in Vacuum

NASA Astrophysics Data System (ADS)

Aoki, Keita; Yasukawa, Hideaki; Kojima, Hiroki; Homma, Mitsutaka; Shioiri, Tetsu; Okubo, Hitoshi

Small discharge not to accompany breakdown can occur under high electric field in vacuum, however the mechanism is not well clarified. We have found that the current of small discharge decreases with repeated voltage applications, and leads to electrode conditioning effect of raising withstand voltage. The inception of the current is delayed with the decrease of current, and the inception time and waveform change by gap length. On the other hand, under low vacuum condition, the current increases and reaches saturation with repeated voltage applications. From these discussions, we concluded that the generating process of small current depended on the adsorption and absorption gas of electrodes.

Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012.

PubMed

Blake, Mary Kay; Carr, Brittany J; Mauldin, Glenna E

2016-02-01

Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing.

Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007–2012

PubMed Central

Blake, Mary Kay; Carr, Brittany J.; Mauldin, Glenna E.

2016-01-01

Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing. PMID:26834270

Reliability of segmental accelerations measured using a new wireless gait analysis system.

PubMed

Kavanagh, Justin J; Morrison, Steven; James, Daniel A; Barrett, Rod

2006-01-01

The purpose of this study was to determine the inter- and intra-examiner reliability, and stride-to-stride reliability, of an accelerometer-based gait analysis system which measured 3D accelerations of the upper and lower body during self-selected slow, preferred and fast walking speeds. Eight subjects attended two testing sessions in which accelerometers were attached to the head, neck, lower trunk, and right shank. In the initial testing session, two different examiners attached the accelerometers and performed the same testing procedures. A single examiner repeated the procedure in a subsequent testing session. All data were collected using a new wireless gait analysis system, which features near real-time data transmission via a Bluetooth network. Reliability for each testing condition (4 locations, 3 directions, 3 speeds) was quantified using a waveform similarity statistic known as the coefficient of multiple determination (CMD). CMD's ranged from 0.60 to 0.98 across all test conditions and were not significantly different for inter-examiner (0.86), intra-examiner (0.87), and stride-to-stride reliability (0.86). The highest repeatability for the effect of location, direction and walking speed were for the shank segment (0.94), the vertical direction (0.91) and the fast walking speed (0.91), respectively. Overall, these results indicate that a high degree of waveform repeatability was obtained using a new gait system under test-retest conditions involving single and dual examiners. Furthermore, differences in acceleration waveform repeatability associated with the reapplication of accelerometers were small in relation to normal motor variability.

De novo identification of highly diverged protein repeats by probabilistic consistency.

PubMed

Biegert, A; Söding, J

2008-03-15

An estimated 25% of all eukaryotic proteins contain repeats, which underlines the importance of duplication for evolving new protein functions. Internal repeats often correspond to structural or functional units in proteins. Methods capable of identifying diverged repeated segments or domains at the sequence level can therefore assist in predicting domain structures, inferring hypotheses about function and mechanism, and investigating the evolution of proteins from smaller fragments. We present HHrepID, a method for the de novo identification of repeats in protein sequences. It is able to detect the sequence signature of structural repeats in many proteins that have not yet been known to possess internal sequence symmetry, such as outer membrane beta-barrels. HHrepID uses HMM-HMM comparison to exploit evolutionary information in the form of multiple sequence alignments of homologs. In contrast to a previous method, the new method (1) generates a multiple alignment of repeats; (2) utilizes the transitive nature of homology through a novel merging procedure with fully probabilistic treatment of alignments; (3) improves alignment quality through an algorithm that maximizes the expected accuracy; (4) is able to identify different kinds of repeats within complex architectures by a probabilistic domain boundary detection method and (5) improves sensitivity through a new approach to assess statistical significance. Server: http://toolkit.tuebingen.mpg.de/hhrepid; Executables: ftp://ftp.tuebingen.mpg.de/pub/protevo/HHrepID

Impact of Repeated Questioning on Interviewers: Learning From a Forensic Interview Training Project.

PubMed

Duron, Jacquelynn F; Cheung, Monit

2016-01-01

Forensic interviewers have a difficult job with high risk for career burnout and secondary trauma. Few studies have addressed how new forensic interviewers or trainees experience repeated questioning and multiple interviews. This study simulated the process of training new forensic interviewers through the creation of two interview videos in which social work graduate students participated as actors portraying the roles of interviewer and child. These films served as instructional aids preparing graduate social work students for professional child welfare roles while promoting research-based approaches to interviewing children about sexual abuse allegations. Qualitative data from two cohorts of student actors were collected to analyze interviewers' perspectives on repeated questioning and interviews in child sexual abuse cases. Two themes were extracted from the subjects' experiences: "It is emotionally taxing" and "Navigating the interviewer role is unexpectedly complex." Exposure to repeated questions and multiple interviews affected the performance and confidence of the interviewers.

The effect of omalizumab on small airway inflammation as measured by exhaled nitric oxide in moderate-to-severe asthmatic patients.

PubMed

Pasha, M Asghar; Jourd'heuil, David; Jourd'heuil, Francis; Mahon, Lori; Romero, Francisco; Feustel, Paul J; Evans, Mary; Smith, Thomas; Mitchell, Jesse; Gendapodi, Pradeep; Demeyere-Coursey, Kelly C; Townley, Robert G

2014-01-01

Measurement of fractional nitric oxide concentration in exhaled breath (FENO) is a simple, noninvasive method to evaluate eosinophilic airway inflammation. Nitric oxide (NO) arising from peripheral small airways/alveoli (alveolar NO concentration [CalvNO]) can be estimated using multiple flow rates and a two-compartment model of the airways and alveoli. Omalizumab, a monoclonal anti-IgE antibody, is approved for the treatment of allergic asthma and also has been shown to decrease FENO levels. This study investigates the effects of omalizumab, when added to an inhaled corticosteroid (ICS) ± long-acting beta-adrenergic agonist (LABA) treatment, on peripheral small airway/alveolar inflammation reflected by FENO measurements at higher flow rates. We hypothesized that compared with placebo, omalizumab would decrease CalvNO levels in asthmatic patients on ICS ± LABA. Forty-two patients with moderate-to-severe asthma were randomly assigned 2:1 to either omalizumab (n = 29) or placebo treatment (n = 13) for 16 weeks. Selection criteria included moderate-to-severe asthmatic patients on an ICS ± LABA, positive skin test to one or more perennial allergen, screening FENO of >13 ppb, and a baseline IgE of 30-700 IU/mL. FENO measured at multiple flow rates was used to calculate CalvNO over the course of 16 weeks. FENO levels decrease with increasing flow rates (p < 0.05 repeated measures ANOVA) but no differences between the placebo and treatment groups in overall CalvNO levels or in the changes of CalvNO with time were found. Omalizumab did not lower the CalvNO, which could have been caused by the initial low CalvNO in this asthmatic population. The model used may not be completely sufficient and/or sensitive enough to detect small changes in CalvNO.

A methodological pilot: parenting among women in substance abuse treatment.

PubMed

Lewin, Linda; Farkas, Kathleen; Niazi, Maryam

2014-01-01

Mothers who abuse substances are likely to have insecure emotional attachment with their children, placing their children at risk for social-emotional and psychiatric conditions. Sobriety does not inevitably improve parenting. We tested recruitment methods, audiovisual (AV) recording procedures, the protocol for identifying child abuse risk, the coding of mother-child interactions, and retention of the sample for repeated measures as the first phase in examining mother-child relational quality of women in substance abuse treatment. This innovative study involved AV recordings to capture the in-vivo mother-child interactional behaviors that were later coded and analyzed for mean scores on the 64-item Parent-Child Relational Quality Assessment. Repeated measurement was planned during treatment and two months after discharge from treatment. The pilot involved a small sample (n = 11) of mother-child (<6 years) dyads. Highest and lowest ratings of interaction behaviors were identified. Mothers showed less enthusiasm and creativity but matched their child's emotional state. The children showed appropriate motor skill items and attachment behaviors. The dyad coding showed less mutual enjoyment between the mother and child. Eight of the participants could not be located for the second measurement despite multiple contact methods. AV recordings capture rich, descriptive information that can be coded for interactional quality analysis. Repeated measurement with this cohort was not feasible, thus needing to assess for additional/more frequent contacts to maintain the sample.

Identification and characterization of cryptic SHOX intragenic deletions in three Japanese patients with Léri-Weill dyschondrosteosis.

PubMed

Fukami, Maki; Dateki, Sumito; Kato, Fumiko; Hasegawa, Yukihiro; Mochizuki, Hiroshi; Horikawa, Reiko; Ogata, Tsutomu

2008-01-01

Although short-stature homeobox-containing gene (SHOX ) haploinsufficiency is responsible for Léri-Weill dyschondrosteosis (LWD), the molecular defect has not been identified in approximately 20% of Japanese LWD patients. Furthermore, although high prevalence of microdeletions affecting SHOX is primarily ascribed to the presence of repeat sequences such as Alu elements around SHOX, it remains to be determined whether microdeletions are actually mediated by repeat sequences. We performed multiple ligation probe amplification (MLPA) assay in six Japanese LWD patients with apparently normal SHOX, followed by fluorescent in situ hybridization (FISH) analysis and sequencing for polymerase chain reaction (PCR) products encompassing the deletion junctions in patients with abnormal MLPA patterns. Consequently, heterozygous intragenic deletions were identified in three cases, i.e., a 5,906-bp deletion involving exons 4-5 in case 1, a 5,594-bp deletion involving exons 4-6a in case 2, and a 50,199-bp deletion involving exons 4-6b in case 3. The deletion breakpoints of cases 1 and 2 were present in nonrepeat sequences, whereas those of case 3 resided within Alu elements. The results suggest that cryptic SHOX intragenic deletions account for a small fraction of LWD and that microdeletions affecting SHOX can be generated by repeat-sequence-mediated aberrant recombinations and by nonhomologous end joining.

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

Evolutionary conservation of sequence and secondary structures inCRISPR repeats

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

Kunin, Victor; Sorek, Rotem; Hugenholtz, Philip

Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in {approx}40% of bacterial and all archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CAS), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been proposed that the CRISPR/CAS system samples, maintains a record of, and inactivates invasive DNA that the cell has encountered, and therefore constitutes a prokaryotic analog of an immune system. Here we analyze CRISPR repeatsmore » identified in 195 microbial genomes and show that they can be organized into multiple clusters based on sequence similarity. All individual repeats in any given cluster were inferred to form characteristic RNA secondary structure, ranging from non-existent to pronounced. Stable secondary structures included G:U base pairs and exhibited multiple compensatory base changes in the stem region, indicating evolutionary conservation and functional importance. We also show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification including specific relationships between CRISPR and CAS subtypes.« less

A new human (psycho)pharmacology tool: the multiple organs coincidences counter (MOCC).

PubMed

Malizia, A; Forse, G; Haida, A; Gunn, R; Melichar, J; Poole, K; Bateman, D; Fahy, D; Schnorr, L; Brown, D; Rhodes, C; Nutt, D J; Jones, T

1995-01-01

We describe a novel instrument which is capable of measuring the uptake of radioligand in human organs in vivo with the administration of very small doses of positron-emitting radioligands. This technique readily detects the displacement or reduced uptake of radioligand when a competitive agonist or antagonist is administered. This system provides no tomographic information, but the small radioactive doses involved mean that investigations can be repeated at regular intervals and that female volunteers can also participate. We administered [(11) C]flumazenil, [(11)C]diprenorphine, [(11)C]meta -hydroxyephedrine (MHED) and [(11)C]RTI 55 to healthy male volunteers and performed control, pre-loading and displacement experiments. These demonstrate the feasibility of using this technique to investigate benzodiazepine and opiate receptor occupancy, as well as occupancy at dopamine, noradrenaline and serotonin (5-HT) re-uptake sites. This method is likely to be useful in pharmacokinetic/pharmacodynamic experiments, in drug development and discovery and in the development of novel imaging radioligands.

Repression of small toxic protein synthesis by the Sib and OhsC small RNAs.

PubMed

Fozo, Elizabeth M; Kawano, Mitsuoki; Fontaine, Fanette; Kaya, Yusuf; Mendieta, Kathy S; Jones, Kristi L; Ocampo, Alejandro; Rudd, Kenneth E; Storz, Gisela

2008-12-01

The sequences encoding the QUAD1 RNAs were initially identified as four repeats in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely related bacteria, although the number of repeats varies. All five Sib RNAs in E. coli MG1655 are expressed, and no phenotype was observed for a five-sib deletion strain. However, a phenotype reminiscent of plasmid addiction was observed for overexpression of the Sib RNAs, and further examination of the SIB repeat sequences revealed conserved open reading frames encoding highly hydrophobic 18- to 19-amino-acid proteins (Ibs) opposite each sib gene. The Ibs proteins were found to be toxic when overexpressed and this toxicity could be prevented by coexpression of the corresponding Sib RNA. Two other RNAs encoded divergently in the yfhL-acpS intergenic region were similarly found to encode a small hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression of both IbsC and ShoB led to immediate changes in membrane potential suggesting both proteins affect the cell envelope. Whole genome expression analysis showed that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and TisB proteins, has both overlapping and unique consequences for the cell.

Repression of small toxic protein synthesis by the Sib and OhsC small RNAs

PubMed Central

Fozo, Elizabeth M.; Kawano, Mitsuoki; Fontaine, Fanette; Kaya, Yusuf; Mendieta, Kathy S.; Jones, Kristi L.; Ocampo, Alejandro; Rudd, Kenneth E.; Storz, Gisela

2008-01-01

Summary The sequences encoding the QUAD1 RNAs were initially identified as four repeats in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely related bacteria, though the number of repeats varies. All five Sib RNAs in E. coli MG1655 are expressed, and no phenotype was observed for a five sib deletion strain. However, a phenotype reminiscent of plasmid addiction was observed for overexpression of the Sib RNAs, and further examination of the SIB repeat sequences revealed conserved open reading frames encoding highly hydrophobic 18–19 amino acid proteins (Ibs) opposite each sib gene. The Ibs proteins were found to be toxic when overexpressed and this toxicity could be prevented by co-expression of the corresponding Sib RNA. Two other RNAs encoded divergently in the yfhL-acpS intergenic region were similarly found to encode a small hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression of both IbsC and ShoB led to immediate changes in membrane potential suggesting both proteins affect the cell envelope. Whole genome expression analysis showed that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and TisB proteins, has both overlapping and unique consequences for the cell. PMID:18710431

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.

Reinforcement Learning with Orthonormal Basis Adaptation Based on Activity-Oriented Index Allocation

NASA Astrophysics Data System (ADS)

Satoh, Hideki

An orthonormal basis adaptation method for function approximation was developed and applied to reinforcement learning with multi-dimensional continuous state space. First, a basis used for linear function approximation of a control function is set to an orthonormal basis. Next, basis elements with small activities are replaced with other candidate elements as learning progresses. As this replacement is repeated, the number of basis elements with large activities increases. Example chaos control problems for multiple logistic maps were solved, demonstrating that the method for adapting an orthonormal basis can modify a basis while holding the orthonormality in accordance with changes in the environment to improve the performance of reinforcement learning and to eliminate the adverse effects of redundant noisy states.

Broadening participation in Natural Sciences and Mathematics at the University of Maryland Baltimore County

NASA Astrophysics Data System (ADS)

Rous, Philip

2013-03-01

Over the past two decades, UMBC has undertaken a series of efforts to broaden participation in the natural sciences and mathematics, beginning with the establishment of the Meyerhoff program. Using as examples the multiple initiatives that followed, and with a focus on the challenge of increasing access and success of all students who enter as both freshmen and transfer students, I will describe a model of culture change that we have employed repeatedly to understand and guide our efforts in broadening participation. Particular attention will be paid to the concept of cultural capital, the role of innovators and the challenge of scaling small-scale innovations towards institutional change. Supported by the National Science Foundation and the Bill and Melinda Gates Foundation.

Strain accumulation in bituminous binders under repeated creep-recovery loading predicted from small-amplitude oscillatory shear (SAOS) experiments

NASA Astrophysics Data System (ADS)

Laukkanen, Olli-Ville; Winter, H. Henning

2017-11-01

The creep-recovery (CR) test starts out with a period of shearing at constant stress (creep) and is followed by a period of zero-shear stress where some of the accumulated shear strain gets reversed. Linear viscoelasticity (LVE) allows one to predict the strain response to repeated creep-recovery (RCR) loading from measured small-amplitude oscillatory shear (SAOS) data. Only the relaxation and retardation time spectra of a material need to be known and these can be determined from SAOS data. In an application of the Boltzmann superposition principle (BSP), the strain response to RCR loading can be obtained as a linear superposition of the strain response to many single creep-recovery tests. SAOS and RCR data were collected for several unmodified and modified bituminous binders, and the measured and predicted RCR responses were compared. Generally good agreement was found between the measured and predicted strain accumulation under RCR loading. However, in the case of modified binders, the strain accumulation was slightly overestimated (≤20% relative error) due to the insufficient SAOS information at long relaxation times. Our analysis also demonstrates that the evolution in the strain response under RCR loading, caused by incomplete recovery, can be reasonably well predicted by the presented methodology. It was also shown that the outlined modeling framework can be used, as a first approximation, to estimate the rutting resistance of bituminous binders by predicting the values of the Multiple Stress Creep Recovery (MSCR) test parameters.

A Novel Sensor System for Measuring Wheel Loads of Vehicles on Highways

PubMed Central

Zhang, Wenbin; Suo, Chunguang; Wang, Qi

2008-01-01

With the development of the highway transportation and business trade, vehicle Weigh-In-Motion (WIM) technology has become a key technology for measuring traffic loads. In this paper a novel WIM system based on monitoring of pavement strain responses in rigid pavement was investigated. In this WIM system multiple low cost, light weight, small volume and high accuracy embedded concrete strain sensors were used as WIM sensors to measure rigid pavement strain responses. In order to verify the feasibility of the method, a system prototype based on multiple sensors was designed and deployed on a relatively busy freeway. Field calibration and tests were performed with known two-axle truck wheel loads and the measurement errors were calculated based on the static weights measured with a static weighbridge. This enables the weights of other vehicles to be calculated from the calibration constant. Calibration and test results for individual sensors or three-sensor fusions are both provided. Repeatability, sources of error, and weight accuracy are discussed. Successful results showed that the proposed method was feasible and proven to have a high accuracy. Furthermore, a sample mean approach using multiple fused individual sensors could provide better performance compared to individual sensors. PMID:27873952

Multiple Hypothesis Testing for Experimental Gingivitis Based on Wilcoxon Signed Rank Statistics

PubMed Central

Preisser, John S.; Sen, Pranab K.; Offenbacher, Steven

2011-01-01

Dental research often involves repeated multivariate outcomes on a small number of subjects for which there is interest in identifying outcomes that exhibit change in their levels over time as well as to characterize the nature of that change. In particular, periodontal research often involves the analysis of molecular mediators of inflammation for which multivariate parametric methods are highly sensitive to outliers and deviations from Gaussian assumptions. In such settings, nonparametric methods may be favored over parametric ones. Additionally, there is a need for statistical methods that control an overall error rate for multiple hypothesis testing. We review univariate and multivariate nonparametric hypothesis tests and apply them to longitudinal data to assess changes over time in 31 biomarkers measured from the gingival crevicular fluid in 22 subjects whereby gingivitis was induced by temporarily withholding tooth brushing. To identify biomarkers that can be induced to change, multivariate Wilcoxon signed rank tests for a set of four summary measures based upon area under the curve are applied for each biomarker and compared to their univariate counterparts. Multiple hypothesis testing methods with choice of control of the false discovery rate or strong control of the family-wise error rate are examined. PMID:21984957

Polyandry promotes enhanced offspring survival in decorated crickets.

PubMed

Ivy, Tracie M; Sakaluk, Scott K

2005-01-01

Although female multiple mating is ubiquitous in insects, its adaptive significance remains poorly understood. Benefits to multiple mating can accrue via direct material benefits, indirect genetic benefits, or both. We investigated the effects of multiple mating in the decorated cricket, Gryllodes sigillatus, by simultaneously varying the number of times that females mated and the number of different males with which they mated, measuring aspects of female fecundity and elements of offspring performance and viability. Multiple matings resulted in enhanced female fitness relative to single matings when females mated with different partners, but not when females mated repeatedly with the same male. Specifically, polyandrous females produced significantly more offspring surviving to reproductive maturity than did monogamous females mating once or mating repeatedly with the same male. These results suggest that the benefit females gain from multiple mating is influenced primarily by genetic and not material benefits.

LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

PubMed

Røsby, O; Berg, K

2000-01-01

In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

On the analysis of very small samples of Gaussian repeated measurements: an alternative approach.

PubMed

Westgate, Philip M; Burchett, Woodrow W

2017-03-15

The analysis of very small samples of Gaussian repeated measurements can be challenging. First, due to a very small number of independent subjects contributing outcomes over time, statistical power can be quite small. Second, nuisance covariance parameters must be appropriately accounted for in the analysis in order to maintain the nominal test size. However, available statistical strategies that ensure valid statistical inference may lack power, whereas more powerful methods may have the potential for inflated test sizes. Therefore, we explore an alternative approach to the analysis of very small samples of Gaussian repeated measurements, with the goal of maintaining valid inference while also improving statistical power relative to other valid methods. This approach uses generalized estimating equations with a bias-corrected empirical covariance matrix that accounts for all small-sample aspects of nuisance correlation parameter estimation in order to maintain valid inference. Furthermore, the approach utilizes correlation selection strategies with the goal of choosing the working structure that will result in the greatest power. In our study, we show that when accurate modeling of the nuisance correlation structure impacts the efficiency of regression parameter estimation, this method can improve power relative to existing methods that yield valid inference. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Robust Statistical Fusion of Image Labels

PubMed Central

Landman, Bennett A.; Asman, Andrew J.; Scoggins, Andrew G.; Bogovic, John A.; Xing, Fangxu; Prince, Jerry L.

2011-01-01

Image labeling and parcellation (i.e. assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability. PMID:22010145

Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia

PubMed Central

Kojima, Kenji K.

2015-01-01

Most non-long terminal repeat (non-LTR) retrotransposons encoding a restriction-like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an “archaeal” RNase H domain upstream of reverse transcriptase (RT), which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes. PMID:26556480

The reliability and validity of fatigue measures during multiple-sprint work: an issue revisited.

PubMed

Glaister, Mark; Howatson, Glyn; Pattison, John R; McInnes, Gill

2008-09-01

The ability to repeatedly produce a high-power output or sprint speed is a key fitness component of most field and court sports. The aim of this study was to evaluate the validity and reliability of eight different approaches to quantify this parameter in tests of multiple-sprint performance. Ten physically active men completed two trials of each of two multiple-sprint running protocols with contrasting recovery periods. Protocol 1 consisted of 12 x 30-m sprints repeated every 35 seconds; protocol 2 consisted of 12 x 30-m sprints repeated every 65 seconds. All testing was performed in an indoor sports facility, and sprint times were recorded using twin-beam photocells. All but one of the formulae showed good construct validity, as evidenced by similar within-protocol fatigue scores. However, the assumptions on which many of the formulae were based, combined with poor or inconsistent test-retest reliability (coefficient of variation range: 0.8-145.7%; intraclass correlation coefficient range: 0.09-0.75), suggested many problems regarding logical validity. In line with previous research, the results support the percentage decrement calculation as the most valid and reliable method of quantifying fatigue in tests of multiple-sprint performance.

Alterations in the small intestinal wall and motor function after repeated cisplatin in rat.

PubMed

Uranga, J A; García-Martínez, J M; García-Jiménez, C; Vera, G; Martín-Fontelles, M I; Abalo, R

2017-07-01

Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin. Male Wistar rats received saline or cisplatin (2 mg kg -1  week -1 , for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR. Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent). Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated. © 2017 John Wiley & Sons Ltd.

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.

PubMed

Fratta, Pietro; Polke, James M; Newcombe, Jia; Mizielinska, Sarah; Lashley, Tammaryn; Poulter, Mark; Beck, Jon; Preza, Elisavet; Devoy, Anny; Sidle, Katie; Howard, Robin; Malaspina, Andrea; Orrell, Richard W; Clarke, Jan; Lu, Ching-Hua; Mok, Kin; Collins, Toby; Shoaii, Maryam; Nanji, Tina; Wray, Selina; Adamson, Gary; Pittman, Alan; Renton, Alan E; Traynor, Bryan J; Sweeney, Mary G; Revesz, Tamas; Houlden, Henry; Mead, Simon; Isaacs, Adrian M; Fisher, Elizabeth M C

2015-01-01

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

New paradigm in ankyrin repeats: Beyond protein-protein interaction module.

PubMed

Islam, Zeyaul; Nagampalli, Raghavendra Sashi Krishna; Fatima, Munazza Tamkeen; Ashraf, Ghulam Md

2018-04-01

Classically, ankyrin repeat (ANK) proteins are built from tandems of two or more repeats and form curved solenoid structures that are associated with protein-protein interactions. These are short, widespread structural motif of around 33 amino acids repeats in tandem, having a canonical helix-loop-helix fold, found individually or in combination with other domains. The multiplicity of structural pattern enables it to form assemblies of diverse sizes, required for their abilities to confer multiple binding and structural roles of proteins. Three-dimensional structures of these repeats determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. Recent work on the ANK has proposed novel structural information, especially protein-lipid, protein-sugar and protein-protein interaction. Self-assembly of these repeats was also shown to prevent the associated protein in forming filaments. In this review, we summarize the latest findings and how the new structural information has increased our understanding of the structural determinants of ANK proteins. We discussed latest findings on how these proteins participate in various interactions to diversify the ANK roles in numerous biological processes, and explored the emerging and evolving field of designer ankyrins and its framework for protein engineering emphasizing on biotechnological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Laparoscopic Myomectomy for a Plethora of Submucous Myomas.

PubMed

Paul, P G; Paul, George; Radhika, K T; Bulusu, Saumya; Shintre, Hemant

To demonstrate a laparoscopic myomectomy technique for the removal of multiple submucous myomas. A step-by-step demonstration of the surgical procedure (Canadian Task Force classification III-C). In cases of multiple submucous myomas, hysteroscopic resection of myomas might not be a viable option, especially in cases requiring fertility preservation. It may cause significant damage to the endometrial surface, leading to the formation of endometrial synechiae [1]. The procedure is technically challenging and requires prolonged operating time owing to impaired visibility and the need for repeated specimen removal. This can lead to complications, such as fluid overload and, rarely, air embolism [2]. Thus, laparoscopic myomectomy may be a better option in such cases [1]. A 30-year-old nulligravida presented with a 3-year history of heavy menstrual bleeding and dysmenorrhea. She had received no symptom relief with hormonal medications and magnetic resonance-guided focused ultrasound. On examination, she was anemic, and her uterus was enlarged to 16-weeks gravid size. Ultrasonography revealed an intramural fundal myoma of 6 × 4.2 cm and numerous submucous myomas of 1 to 3.2 cm. During hysteroscopy, multiple submucous myomas of varying sizes ranging from type 0 to type 1 were seen. On laparoscopy, an incision was made on the uterine fundus with an ultrasonic device after injecting vasopressin (20 U in 200 mL dilution), and the fundal myoma was enucleated. The incision was then extended to open the endometrial cavity for the removal of the submucous myomas. Most of the myomas were removed with mechanical force, along with the minimal use of ultrasonic energy. A total of 46 myomas were removed, and the myometrium was closed in 2 layers. The duration of the surgery was 210 minutes, and estimated blood loss was 850 mL. The patient did not require blood transfusion, but was advised to take hematinics. At a 6-month follow-up, the patient reported significant improvement in her symptoms. A repeat hysteroscopy revealed moderate synechiae in the midline and 2 small submucous myomas near the internal os. The synechiae were incised with hysteroscopic scissors, and the submucous myomas were resected with a bipolar resectoscope. The patient was advised to attempt conception after 2 months. Laparoscopic myomectomy is an alternative to hysteroscopic resection for multiple submucous myomas. A repeat hysteroscopy is useful for identifying any residual myomas and synechiae. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Recombination-dependent replication and gene conversion homogenize repeat sequences and diversify plastid genome structure.

PubMed

Ruhlman, Tracey A; Zhang, Jin; Blazier, John C; Sabir, Jamal S M; Jansen, Robert K

2017-04-01

There is a misinterpretation in the literature regarding the variable orientation of the small single copy region of plastid genomes (plastomes). The common phenomenon of small and large single copy inversion, hypothesized to occur through intramolecular recombination between inverted repeats (IR) in a circular, single unit-genome, in fact, more likely occurs through recombination-dependent replication (RDR) of linear plastome templates. If RDR can be primed through both intra- and intermolecular recombination, then this mechanism could not only create inversion isomers of so-called single copy regions, but also an array of alternative sequence arrangements. We used Illumina paired-end and PacBio single-molecule real-time (SMRT) sequences to characterize repeat structure in the plastome of Monsonia emarginata (Geraniaceae). We used OrgConv and inspected nucleotide alignments to infer ancestral nucleotides and identify gene conversion among repeats and mapped long (>1 kb) SMRT reads against the unit-genome assembly to identify alternative sequence arrangements. Although M. emarginata lacks the canonical IR, we found that large repeats (>1 kilobase; kb) represent ∼22% of the plastome nucleotide content. Among the largest repeats (>2 kb), we identified GC-biased gene conversion and mapping filtered, long SMRT reads to the M. emarginata unit-genome assembly revealed alternative, substoichiometric sequence arrangements. We offer a model based on RDR and gene conversion between long repeated sequences in the M. emarginata plastome and provide support that both intra-and intermolecular recombination between large repeats, particularly in repeat-rich plastomes, varies unit-genome structure while homogenizing the nucleotide sequence of repeats. © 2017 Botanical Society of America.

Comparative analysis of the small RNA transcriptomes of Pinus contorta and Oryza sativa

PubMed Central

Morin, Ryan D.; Aksay, Gozde; Dolgosheina, Elena; Ebhardt, H. Alexander; Magrini, Vincent; Mardis, Elaine R.; Sahinalp, S. Cenk; Unrau, Peter J.

2008-01-01

The diversity of microRNAs and small-interfering RNAs has been extensively explored within angiosperms by focusing on a few key organisms such as Oryza sativa and Arabidopsis thaliana. A deeper division of the plants is defined by the radiation of the angiosperms and gymnosperms, with the latter comprising the commercially important conifers. The conifers are expected to provide important information regarding the evolution of highly conserved small regulatory RNAs. Deep sequencing provides the means to characterize and quantitatively profile small RNAs in understudied organisms such as these. Pyrosequencing of small RNAs from O. sativa revealed, as expected, ∼21- and ∼24-nt RNAs. The former contained known microRNAs, and the latter largely comprised intergenic-derived sequences likely representing heterochromatin siRNAs. In contrast, sequences from Pinus contorta were dominated by 21-nt small RNAs. Using a novel sequence-based clustering algorithm, we identified sequences belonging to 18 highly conserved microRNA families in P. contorta as well as numerous clusters of conserved small RNAs of unknown function. Using multiple methods, including expressed sequence folding and machine learning algorithms, we found a further 53 candidate novel microRNA families, 51 appearing specific to the P. contorta library. In addition, alignment of small RNA sequences to the O. sativa genome revealed six perfectly conserved classes of small RNA that included chloroplast transcripts and specific types of genomic repeats. The conservation of microRNAs and other small RNAs between the conifers and the angiosperms indicates that important RNA silencing processes were highly developed in the earliest spermatophytes. Genomic mapping of all sequences to the O. sativa genome can be viewed at http://microrna.bcgsc.ca/cgi-bin/gbrowse/rice_build_3/. PMID:18323537

Multivariate and repeated measures (MRM): A new toolbox for dependent and multimodal group-level neuroimaging data

PubMed Central

McFarquhar, Martyn; McKie, Shane; Emsley, Richard; Suckling, John; Elliott, Rebecca; Williams, Stephen

2016-01-01

Repeated measurements and multimodal data are common in neuroimaging research. Despite this, conventional approaches to group level analysis ignore these repeated measurements in favour of multiple between-subject models using contrasts of interest. This approach has a number of drawbacks as certain designs and comparisons of interest are either not possible or complex to implement. Unfortunately, even when attempting to analyse group level data within a repeated-measures framework, the methods implemented in popular software packages make potentially unrealistic assumptions about the covariance structure across the brain. In this paper, we describe how this issue can be addressed in a simple and efficient manner using the multivariate form of the familiar general linear model (GLM), as implemented in a new MATLAB toolbox. This multivariate framework is discussed, paying particular attention to methods of inference by permutation. Comparisons with existing approaches and software packages for dependent group-level neuroimaging data are made. We also demonstrate how this method is easily adapted for dependency at the group level when multiple modalities of imaging are collected from the same individuals. Follow-up of these multimodal models using linear discriminant functions (LDA) is also discussed, with applications to future studies wishing to integrate multiple scanning techniques into investigating populations of interest. PMID:26921716

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

PubMed

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains.

Highly Sensitive Detection of Individual HEAT and ARM Repeats with HHpred and COACH

PubMed Central

Kippert, Fred; Gerloff, Dietlind L.

2009-01-01

Background HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Methodology and Principal Findings Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. Significance A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains. PMID:19777061

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

Does Repeated Reading Improve Reading Fluency and Comprehension for Struggling Adolescent Readers?

ERIC Educational Resources Information Center

Still, Kristine Lynn; Flynt, Christine A.

2012-01-01

This was a 12-week study that explored the effects of repeated peer readings on struggling adolescent readers. It was a quasi-experimental design with one treatment group and one control group. There were two small group English classes that were consistently using the repeated reading strategy (the treatment group) and students in the co-teach…

Vertebral sarcoidosis: demonstration of bone involvement by computerized axial tomography

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

Dinerstein, S.L.; Kovarsky, J.

1984-08-01

A report is given of a rare case of vertebral sarcoidosis with negative conventional spinal x-ray films, yet with typical cystic lesions of the spine found incidentally during abdominal computerized axial tomography (CAT). The patient was a 28-year-old black man, who was admitted for evaluation of a 1 1/2-year history of diffuse myalgias, intermittent fever to 102 F orally, bilateral hilar adenopathy, and leukopenia. A technetium polyphosphate bone scan revealed diffuse areas of increased uptake over the sternum, entire vertebral column, and pelvis. Conventional x-ray films of the cervical, thoracic, and lumbar spine, and an AP view of the pelvismore » were all normal. Chest x-ray film revealed only bilateral hilar adenopathy. During the course of an extensive negative evaluation for infection, an abdominal CAT scan was done, showing multiple, small, sclerotic-rimmed cysts at multiple levels of the lower thoracic and lumbar spine. Bone marrow biopsy revealed only changes consistent with anemia of chronic disease. Mediastinal lymph node biopsy revealed noncaseating granulomas. A tentative diagnosis of sarcoidosis was made, and treatment with prednisone, isoniazid and rifampin was begun. Within two weeks of initiation of prednisone therapy, the patient was symptom-free. A repeat technetium polyphosphate bone scan revealed only a small residual area of mildly increased uptake over the upper thoracic vertebrae.« less

The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats

DOE PAGES

Pasquali, Camila Cristina; Islam, Zeyaul; Adamoski, Douglas; ...

2017-05-19

On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. But, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform,more » glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. In order to obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We also found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC. Collectively, these results provide information about glutaminases that may aid in the design of isoform-specific glutaminase inhibitors.« less

The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats

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

Pasquali, Camila Cristina; Islam, Zeyaul; Adamoski, Douglas

On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. But, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform,more » glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. In order to obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We also found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC. Collectively, these results provide information about glutaminases that may aid in the design of isoform-specific glutaminase inhibitors.« less

Fragile X syndrome

MedlinePlus

Martin-Bell syndrome; Marker X syndrome ... Fragile X syndrome is caused by a change in a gene called FMR1 . A small part of the gene ... repeated several times in one area of the X chromosome. The more repeats, the more likely the ...

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

Fong, Erika J.; Huang, Chao; Hamilton, Julie

Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds.

PubMed

Lee, JiYong; Park, Seung Hyun; Seo, Il Ho; Lee, Kang Ju; Ryu, WonHyoung

2015-08-01

Thermal drawing is a versatile rapid prototyping method that can freely form microneedle (MN) structures with ultra-high aspect ratio without relying on any complex and expensive process. However, it is still challenging to repeatedly produce MNs with identical shapes using this thermal drawing due to small fluctuations in processing conditions such as temperatures, drawing speeds, drawing heights, or parallelism in the drawing setup. In addition, thermal drawing is only applicable to thermoplastic materials and most natural biomaterials are incompatible with this method. Thus, we propose use of thermal drawing to fabricate master molds with high aspect ratios and replicate the shape by micromolding. In this work, high A/R MNs with various body profiles were fabricated by thermal drawing and replicated to silk fibroin (SF) MNs multiple times using micromolding. The original MN shape was precisely copied to the SF MNs. Methanol treatment enhanced the mechanical strength of SF MNs up to about 113% more depending on the treatment duration. We also demonstrated that methanol exposure time could effectively control drug release rates from SF MNs. Copyright © 2015 Elsevier B.V. All rights reserved.

Smart repeater system for communications interoperability during multiagency law enforcement operations

NASA Astrophysics Data System (ADS)

Crutcher, Richard I.; Jones, R. W.; Moore, Michael R.; Smith, S. F.; Tolley, Alan L.; Rochelle, Robert W.

1997-02-01

A prototype 'smart' repeater that provides interoperability capabilities for radio communication systems in multi-agency and multi-user scenarios is being developed by the Oak Ridge National Laboratory. The smart repeater functions as a deployable communications platform that can be dynamically reconfigured to cross-link the radios of participating federal, state, and local government agencies. This interconnection capability improves the coordination and execution of multi-agency operations, including coordinated law enforcement activities and general emergency or disaster response scenarios. The repeater provides multiple channels of operation in the 30-50, 118-136, 138-174, and 403-512 MHz land mobile communications and aircraft bands while providing the ability to cross-connect among multiple frequencies, bands, modulation types, and encryption formats. Additionally, two telephone interconnects provide links to the fixed and cellular telephone networks. The 800- and 900-MHz bands are not supported by the prototype, but the modular design of the system accommodates future retrofits to extend frequency capabilities with minimal impact to the system. Configuration of the repeater is through a portable personal computer with a Windows-based graphical interface control screen that provides dynamic reconfiguration of network interconnections and formats.

Parametrically excited multidegree-of-freedom systems with repeated frequencies

NASA Astrophysics Data System (ADS)

Nayfeh, A. H.

1983-05-01

An analysis is presented of the linear response of multidegree-of-freedom systems with a repeated frequency of order three to a harmonic parametric excitation. The method of multiple scales is used to determine the modulation of the amplitudes and phases for two cases: fundamental resonance of the modes with the repeated frequency and combination resonance involving these modes and another mode. Conditions are then derived for determining the stability of the motion.

Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.

PubMed

Mabuchi, Akihiko; Manabe, Noriyo; Haga, Nobuhiko; Kitoh, Hiroshi; Ikeda, Toshiyuki; Kawaji, Hiroyuki; Tamai, Kazuya; Hamada, Junichiro; Nakamura, Shigeru; Brunetti-Pierri, Nicola; Kimizuka, Mamori; Takatori, Yoshio; Nakamura, Kozo; Nishimura, Gen; Ohashi, Hirofumi; Ikegawa, Shiro

2003-01-01

Mutations in the gene encoding cartilage oligomeric matrix protein ( COMP) cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). More than 40 mutations have been identified; however, genotype-phenotype relationships are not well delineated. Further, mutations other than in-frame insertion/deletions and substitutions have not been found, and currently known mutations are clustered within relatively small regions. Here we report the identification of nine novel and three recurrent COMP mutations in PSACH and MED patients. These include two novel types of mutations; the first, a gross deletion spanning an exon-intron junction, causes an exon deletion. The second, a frameshift mutation that results in a truncation of the C-terminal domain, is the first known truncating mutation in the COMP gene. The remaining mutations, other than a novel exon 18 mutation, affected highly conserved aspartate or cysteine residues in the calmodulin-like repeat (CLR) region. Genotype-phenotype analysis revealed a correlation between the position and type of mutations and the severity of short stature. Mutations in the seventh CLR produced more severe short stature compared with mutations elsewhere in the CLRs ( P=0.0003) and elsewhere in the COMP gene ( P=0.0007). Patients carrying mutations within the five-aspartates repeat (aa 469-473) in the seventh CLR were extremely short (below -6 SD). Patients with deletion mutations were significantly shorter than those with substitution mutations ( P=0.0024). These findings expand the mutation spectrum of the COMP gene and highlight genotype-phenotype relationships, facilitating improved genetic diagnosis and analysis of COMP function in humans.

Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.

PubMed

Keohane, Denis; Schwartz, Jeffrey; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

2017-03-01

Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. NCT00409175.

Cross-talk between abscisic acid-dependent and abscisic acid-independent pathways during abiotic stress.

PubMed

Roychoudhury, Aryadeep; Paul, Saikat; Basu, Supratim

2013-07-01

Salinity, drought and low temperature are the common forms of abiotic stress encountered by land plants. To cope with these adverse environmental factors, plants execute several physiological and metabolic responses. Both osmotic stress (elicited by water deficit or high salt) and cold stress increase the endogenous level of the phytohormone abscisic acid (ABA). ABA-dependent stomatal closure to reduce water loss is associated with small signaling molecules like nitric oxide, reactive oxygen species and cytosolic free calcium, and mediated by rapidly altering ion fluxes in guard cells. ABA also triggers the expression of osmotic stress-responsive (OR) genes, which usually contain single/multiple copies of cis-acting sequence called abscisic acid-responsive element (ABRE) in their upstream regions, mostly recognized by the basic leucine zipper-transcription factors (TFs), namely, ABA-responsive element-binding protein/ABA-binding factor. Another conserved sequence called the dehydration-responsive element (DRE)/C-repeat, responding to cold or osmotic stress, but not to ABA, occurs in some OR promoters, to which the DRE-binding protein/C-repeat-binding factor binds. In contrast, there are genes or TFs containing both DRE/CRT and ABRE, which can integrate input stimuli from salinity, drought, cold and ABA signaling pathways, thereby enabling cross-tolerance to multiple stresses. A strong candidate that mediates such cross-talk is calcium, which serves as a common second messenger for abiotic stress conditions and ABA. The present review highlights the involvement of both ABA-dependent and ABA-independent signaling components and their interaction or convergence in activating the stress genes. We restrict our discussion to salinity, drought and cold stress.

Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1

PubMed Central

Schuster-Gossler, Karin; Cordes, Ralf; Müller, Julia; Geffers, Insa; Delany-Heiken, Patricia; Taft, Manuel; Preller, Matthias; Gossler, Achim

2016-01-01

The highly conserved Notch-signaling pathway mediates cell-to-cell communication and is pivotal for multiple developmental processes and tissue homeostasis in adult organisms. Notch receptors and their ligands are transmembrane proteins with multiple epidermal-growth-factor-like (EGF) repeats in their extracellular domains. In vitro the EGF repeats of mammalian ligands that are essential for Notch activation have been defined. However, in vivo the significance of the structural integrity of each EGF repeat in the ligand ectodomain for ligand function is still unclear. Here, we analyzed the mouse Notch ligand DLL1. We expressed DLL1 proteins with mutations disrupting disulfide bridges in each individual EGF repeat from single-copy transgenes in the HPRT locus of embryonic stem cells. In Notch transactivation assays all mutations impinged on DLL1 function and affected both NOTCH1 and NOTCH2 receptors similarly. An allelic series in mice that carried the same point mutations in endogenous Dll1, generated using a mini-gene strategy, showed that early developmental processes depending on DLL1-mediated NOTCH activation were differently sensitive to mutation of individual EGF repeats in DLL1. Notably, some mutations affected only somite patterning and resulted in vertebral column defects resembling spondylocostal dysostosis. In conclusion, the structural integrity of each individual EGF repeat in the extracellular domain of DLL1 is necessary for full DLL1 activity, and certain mutations in Dll1 might contribute to spondylocostal dysostosis in humans. PMID:26801181

The Impact of Repeated Freeze-Thaw Cycles on the Quality of Biomolecules in Four Different Tissues.

PubMed

Ji, Xiaoli; Wang, Min; Li, Lingling; Chen, Fang; Zhang, Yanyang; Li, Qian; Zhou, Junmei

2017-10-01

High-quality biosamples are valuable resources for biomedical research. However, some tissues are stored without being sectioned into small aliquots and have to undergo repeated freeze-thaw cycles throughout prolonged experimentation. Little is known regarding the effects of repeated freeze-thaw cycles on the quality of biomolecules in tissues. The aim of this study was to evaluate the impact of repeated freeze-thaw (at room temperature or on ice) cycles on biomolecules and gene expression in four different types of tissues. Each fresh tissue was sectioned into seven aliquots and snap-frozen before undergoing repeated freeze-thaw cycles at room temperature or on ice. Biomolecules were extracted and analyzed. Both relative and absolute quantification were used to detect the changes in gene expression. The results indicated that the impact of repeated freeze-thaw cycles on RNA integrity varied by tissue type. Gene expression, including the housekeeping gene, was affected in RNA-degraded samples according to absolute quantification rather than relative quantification. Furthermore, our results suggest that thawing on ice could protect RNA integrity compared with thawing at room temperature. No obvious degradation of protein or DNA was observed with repeated freeze-thaw cycles either at room temperature or on ice. This research provides ample evidence for the necessity of sectioning fresh tissues into small aliquots before snap-freezing, thus avoiding degradation of RNA and alteration of gene expression resulting from repeated freeze-thaw cycles. For frozen tissue samples that were already in storage and had to be used repeatedly during their lifecycle, thawing on ice or sectioned at ultralow temperature is recommended.

Multiple collagenase injections are safe for treatment of Dupuytren's contractures.

PubMed

Gajendran, Varun K; Hentz, Vincent; Kenney, Deborah; Curtin, Catherine M

2014-07-01

The authors report the case of a 65-year-old, right-hand-dominant man who had severe Dupuytren's disease with multiple cords and flexion contractures of the metacarpophalangeal and proximal interphalangeal joints of both hands and underwent repeated collagenase injections for treatment. Collagenase has been shown to be safe and effective in the treatment of Dupuytren's contractures when administered as a single dose, but the results of multiple injections over a prolonged period are unknown. Antibodies to collagenase develop in all patients after several treatments, raising concerns about safety and efficacy as a result of sensitization from repeated exposures. The antibodies generated as a result of repeated exposure to collagenase could theoretically render it less effective with time and could also lead to immune reactions as severe as anaphylaxis. The authors present the case of a single patient who experienced continued correction of his contractures with only minor and self-limited adverse reactions after administration of 12 collagenase doses through 15 injections during a 4-year period. Over time, the injections continued to be effective at correcting metacarpophalangeal joint contractures, but less effective at correcting proximal interphalangeal joint contractures. The patient did eventually require a fasciectomy, but the safety and modest success of the repeated collagenase injections shows promise for a less invasive treatment with a better risk profile than open fasciectomy. Although further studies are needed, repeated administration of collagenase appears to be safe and modestly effective for severe Dupuytren's contractures, although a fasciectomy may ultimately be required in the most severe cases. Copyright 2014, SLACK Incorporated.

Storage of multiple single-photon pulses emitted from a quantum dot in a solid-state quantum memory.

PubMed

Tang, Jian-Shun; Zhou, Zong-Quan; Wang, Yi-Tao; Li, Yu-Long; Liu, Xiao; Hua, Yi-Lin; Zou, Yang; Wang, Shuang; He, De-Yong; Chen, Geng; Sun, Yong-Nan; Yu, Ying; Li, Mi-Feng; Zha, Guo-Wei; Ni, Hai-Qiao; Niu, Zhi-Chuan; Li, Chuan-Feng; Guo, Guang-Can

2015-10-15

Quantum repeaters are critical components for distributing entanglement over long distances in presence of unavoidable optical losses during transmission. Stimulated by the Duan-Lukin-Cirac-Zoller protocol, many improved quantum repeater protocols based on quantum memories have been proposed, which commonly focus on the entanglement-distribution rate. Among these protocols, the elimination of multiple photons (or multiple photon-pairs) and the use of multimode quantum memory are demonstrated to have the ability to greatly improve the entanglement-distribution rate. Here, we demonstrate the storage of deterministic single photons emitted from a quantum dot in a polarization-maintaining solid-state quantum memory; in addition, multi-temporal-mode memory with 1, 20 and 100 narrow single-photon pulses is also demonstrated. Multi-photons are eliminated, and only one photon at most is contained in each pulse. Moreover, the solid-state properties of both sub-systems make this configuration more stable and easier to be scalable. Our work will be helpful in the construction of efficient quantum repeaters based on all-solid-state devices.

Storage of multiple single-photon pulses emitted from a quantum dot in a solid-state quantum memory

PubMed Central

Tang, Jian-Shun; Zhou, Zong-Quan; Wang, Yi-Tao; Li, Yu-Long; Liu, Xiao; Hua, Yi-Lin; Zou, Yang; Wang, Shuang; He, De-Yong; Chen, Geng; Sun, Yong-Nan; Yu, Ying; Li, Mi-Feng; Zha, Guo-Wei; Ni, Hai-Qiao; Niu, Zhi-Chuan; Li, Chuan-Feng; Guo, Guang-Can

2015-01-01

Quantum repeaters are critical components for distributing entanglement over long distances in presence of unavoidable optical losses during transmission. Stimulated by the Duan–Lukin–Cirac–Zoller protocol, many improved quantum repeater protocols based on quantum memories have been proposed, which commonly focus on the entanglement-distribution rate. Among these protocols, the elimination of multiple photons (or multiple photon-pairs) and the use of multimode quantum memory are demonstrated to have the ability to greatly improve the entanglement-distribution rate. Here, we demonstrate the storage of deterministic single photons emitted from a quantum dot in a polarization-maintaining solid-state quantum memory; in addition, multi-temporal-mode memory with 1, 20 and 100 narrow single-photon pulses is also demonstrated. Multi-photons are eliminated, and only one photon at most is contained in each pulse. Moreover, the solid-state properties of both sub-systems make this configuration more stable and easier to be scalable. Our work will be helpful in the construction of efficient quantum repeaters based on all-solid-state devices. PMID:26468996

The Value of Interrupted Time-Series Experiments for Community Intervention Research

PubMed Central

Biglan, Anthony; Ary, Dennis; Wagenaar, Alexander C.

2015-01-01

Greater use of interrupted time-series experiments is advocated for community intervention research. Time-series designs enable the development of knowledge about the effects of community interventions and policies in circumstances in which randomized controlled trials are too expensive, premature, or simply impractical. The multiple baseline time-series design typically involves two or more communities that are repeatedly assessed, with the intervention introduced into one community at a time. It is particularly well suited to initial evaluations of community interventions and the refinement of those interventions. This paper describes the main features of multiple baseline designs and related repeated-measures time-series experiments, discusses the threats to internal validity in multiple baseline designs, and outlines techniques for statistical analyses of time-series data. Examples are given of the use of multiple baseline designs in evaluating community interventions and policy changes. PMID:11507793

Small leucine-rich repeat proteoglycans associated with mature insoluble elastin serve as binding sites for galectins.

PubMed

Itoh, Aiko; Nonaka, Yasuhiro; Ogawa, Takashi; Nakamura, Takanori; Nishi, Nozomu

2017-11-01

We previously reported that galectin-9 (Gal-9), an immunomodulatory animal lectin, could bind to insoluble collagen preparations and exerted direct cytocidal effects on immune cells. In the present study, we found that mature insoluble elastin is capable of binding Gal-9 and other members of the human galectin family. Lectin blot analysis of a series of commercial water-soluble elastin preparations, PES-(A) ~ PES-(E), revealed that only PES-(E) contained substances recognized by Gal-9. Gal-9-interacting substances in PES-(E) were affinity-purified, digested with trypsin and then analyzed by reversed-phase HPLC. Peptide fragments derived from five members of the small leucine-rich repeat proteoglycan family, versican, lumican, osteoglycin/mimecan, prolargin, and fibromodulin, were identified by N-terminal amino acid sequence analysis. The results indicate that Gal-9 and possibly other galectins recognize glycans attached to small leucine-rich repeat proteoglycans associated with insoluble elastin and also indicate the possibility that mature insoluble elastin serves as an extracellular reservoir for galectins.

A fault-tolerant small world topology control model in ad hoc networks for search and rescue

NASA Astrophysics Data System (ADS)

Tan, Mian; Fang, Ling; Wu, Yue; Zhang, Bo; Chang, Bowen; Holme, Petter; Zhao, Jing

2018-02-01

Due to their self-organized, multi-hop and distributed characteristics, ad hoc networks are useful in search and rescue. Topology control models need to be designed for energy-efficient, robust and fast communication in ad hoc networks. This paper proposes a topology control model which specializes for search and rescue-Compensation Small World-Repeated Game (CSWRG)-which integrates mobility models, constructing small world networks and a game-theoretic approach to the allocation of resources. Simulation results show that our mobility models can enhance the communication performance of the constructed small-world networks. Our strategy, based on repeated game, can suppress selfish behavior and compensate agents that encounter selfish or faulty neighbors. This model could be useful for the design of ad hoc communication networks.

Slide Set: Reproducible image analysis and batch processing with ImageJ.

PubMed

Nanes, Benjamin A

2015-11-01

Most imaging studies in the biological sciences rely on analyses that are relatively simple. However, manual repetition of analysis tasks across multiple regions in many images can complicate even the simplest analysis, making record keeping difficult, increasing the potential for error, and limiting reproducibility. While fully automated solutions are necessary for very large data sets, they are sometimes impractical for the small- and medium-sized data sets common in biology. Here we present the Slide Set plugin for ImageJ, which provides a framework for reproducible image analysis and batch processing. Slide Set organizes data into tables, associating image files with regions of interest and other relevant information. Analysis commands are automatically repeated over each image in the data set, and multiple commands can be chained together for more complex analysis tasks. All analysis parameters are saved, ensuring transparency and reproducibility. Slide Set includes a variety of built-in analysis commands and can be easily extended to automate other ImageJ plugins, reducing the manual repetition of image analysis without the set-up effort or programming expertise required for a fully automated solution.

[The Huber needle as a special cannula for the puncture of implanted ports and pumps--a mistake in multiple variations].

PubMed

Müller, H; Zierski, J

1988-10-03

Huber-point needles, which are thought to be noncoring, are usually recommended for puncture of implanted drug-delivery devices, such as ports and pumps. Nevertheless, we found occlusion by silicone chips deriving from the silicone inlet septum to be a major technical complication. Electron microscopic investigations demonstrated substantial loss of material from the port membrane after repeated puncture with this type of needle. During an in vitro test, multiple puncture with Huber-type cannulas led to a pressure-dependent leakage of a port after only 150 to 750 insertions of a needle. In addition, the forces necessary for puncture or for withdrawal of the needle were increased with Huber-point needles, possibly due to a coring effect. Another disadvantage of the available port needles is the formation of a hook at the tip, which may lead to additional lesion of the port or pump membrane. In our opinion, resterilization of Huber needles, recommended by the manufactures, is not advisable, because it is well known that safe sterilization of small lumina, e.g., the lumen of the needle, is impossible.

Design-Comparable Effect Sizes in Multiple Baseline Designs: A General Modeling Framework

ERIC Educational Resources Information Center

Pustejovsky, James E.; Hedges, Larry V.; Shadish, William R.

2014-01-01

In single-case research, the multiple baseline design is a widely used approach for evaluating the effects of interventions on individuals. Multiple baseline designs involve repeated measurement of outcomes over time and the controlled introduction of a treatment at different times for different individuals. This article outlines a general…

Multiple independent insertions of 5S rRNA genes in the spliced-leader gene family of trypanosome species.

PubMed

Beauparlant, Marc A; Drouin, Guy

2014-02-01

Analyses of the 5S rRNA genes found in the spliced-leader (SL) gene repeat units of numerous trypanosome species suggest that such linkages were not inherited from a common ancestor, but were the result of independent 5S rRNA gene insertions. In trypanosomes, 5S rRNA genes are found either in the tandemly repeated units coding for SL genes or in independent tandemly repeated units. Given that trypanosome species where 5S rRNA genes are within the tandemly repeated units coding for SL genes are phylogenetically related, one might hypothesize that this arrangement is the result of an ancestral insertion of 5S rRNA genes into the tandemly repeated SL gene family of trypanosomes. Here, we use the types of 5S rRNA genes found associated with SL genes, the flanking regions of the inserted 5S rRNA genes and the position of these insertions to show that most of the 5S rRNA genes found within SL gene repeat units of trypanosome species were not acquired from a common ancestor but are the results of independent insertions. These multiple 5S rRNA genes insertion events in trypanosomes are likely the result of frequent founder events in different hosts and/or geographical locations in species having short generation times.

Repeatability study of replicate crash tests: A signal analysis approach.

PubMed

Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

2017-10-03

To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test protocols.

Persistent rupture terminations at a restraining bend from slip rates on the eastern Altyn Tagh fault

NASA Astrophysics Data System (ADS)

Elliott, A. J.; Oskin, M. E.; Liu-zeng, J.; Shao, Y.-X.

2018-05-01

Restraining double-bends along strike-slip faults inhibit or permit throughgoing ruptures depending on bend angle, length, and prior rupture history. Modeling predicts that for mature strike-slip faults in a regional stress regime characterized by simple shear, a restraining bend of >18° and >4 km length impedes propagating rupture. Indeed, natural evidence shows that the most recent rupture(s) of the Xorkoli section (90°-93°E) of the eastern Altyn Tagh fault (ATF) ended at large restraining bends. However, when multiple seismic cycles are considered in numerical dynamic rupture modeling, heterogeneous residual stresses enable some ruptures to propagate further, modulating whether the bends persistently serve as barriers. These models remain to be tested using observations of the cumulative effects of multiple earthquake ruptures. Here we investigate whether a large restraining double-bend on the ATF serves consistently as a barrier to rupture by measuring long-term slip rates around the terminus of its most recent surface rupture at the Aksay bend. Our results show a W-E decline in slip as the SATF enters the bend, as would be predicted from repeated rupture terminations there. Prior work demonstrated no Holocene slip on the central, most misoriented portion of the bend, while 19-79 m offsets suggest that multiple ruptures have occurred on the west side of the bend during the Holocene. Thus we conclude the gradient in the SATF's slip rate results from the repeated termination of earthquake ruptures there. However, a finite slip rate east of the bend represents the transmission of some slip, suggesting that a small fraction of ruptures may fully traverse or jump the double-bend. This agreement between natural observations of slip accumulation and multi-cycle models of fault rupture enables us to translate observed slip rates into insight about the dynamic rupture process of individual earthquakes as they encounter geometric complexities along faults.

In Vitro Expansion of CAG, CAA, and Mixed CAG/CAA Repeats.

PubMed

Figura, Grzegorz; Koscianska, Edyta; Krzyzosiak, Wlodzimierz J

2015-08-11

Polyglutamine diseases, including Huntington's disease and a number of spinocerebellar ataxias, are caused by expanded CAG repeats that are located in translated sequences of individual, functionally-unrelated genes. Only mutant proteins containing polyglutamine expansions have long been thought to be pathogenic, but recent evidence has implicated mutant transcripts containing long CAG repeats in pathogenic processes. The presence of two pathogenic factors prompted us to attempt to distinguish the effects triggered by mutant protein from those caused by mutant RNA in cellular models of polyglutamine diseases. We used the SLIP (Synthesis of Long Iterative Polynucleotide) method to generate plasmids expressing long CAG repeats (forming a hairpin structure), CAA-interrupted CAG repeats (forming multiple unstable hairpins) or pure CAA repeats (not forming any secondary structure). We successfully modified the original SLIP protocol to generate repeats of desired length starting from constructs containing short repeat tracts. We demonstrated that the SLIP method is a time- and cost-effective approach to manipulate the lengths of expanded repeat sequences.

Thermodynamic stability of RNA structures formed by CNG trinucleotide repeats. Implication for prediction of RNA structure.

PubMed

Broda, Magdalena; Kierzek, Elzbieta; Gdaniec, Zofia; Kulinski, Tadeusz; Kierzek, Ryszard

2005-08-16

Trinucleotide repeat expansion diseases (TREDs) are correlated with elongation of CNG DNA and RNA repeats to pathological level. This paper shows, for the first time, complete data concerning thermodynamic stabilities of RNA with CNG trinucleotide repeats. Our studies include the stability of oligoribonucleotides composed of two to seven of CAG, CCG, CGG, and CUG repeats. The thermodynamic parameters of helix propagation correlated with the presence of multiple N-N mismatches within CNG RNA duplexes were also determined. Moreover, the total stability of CNG RNA hairpins, as well as the contribution of trinucleotide repeats placed only in the stem or loop regions, was evaluated. The improved thermodynamic parameters allow to predict much more accurately the thermodynamic stabilities and structures of CNG RNAs.

Multivariate and repeated measures (MRM): A new toolbox for dependent and multimodal group-level neuroimaging data.

PubMed

McFarquhar, Martyn; McKie, Shane; Emsley, Richard; Suckling, John; Elliott, Rebecca; Williams, Stephen

2016-05-15

Repeated measurements and multimodal data are common in neuroimaging research. Despite this, conventional approaches to group level analysis ignore these repeated measurements in favour of multiple between-subject models using contrasts of interest. This approach has a number of drawbacks as certain designs and comparisons of interest are either not possible or complex to implement. Unfortunately, even when attempting to analyse group level data within a repeated-measures framework, the methods implemented in popular software packages make potentially unrealistic assumptions about the covariance structure across the brain. In this paper, we describe how this issue can be addressed in a simple and efficient manner using the multivariate form of the familiar general linear model (GLM), as implemented in a new MATLAB toolbox. This multivariate framework is discussed, paying particular attention to methods of inference by permutation. Comparisons with existing approaches and software packages for dependent group-level neuroimaging data are made. We also demonstrate how this method is easily adapted for dependency at the group level when multiple modalities of imaging are collected from the same individuals. Follow-up of these multimodal models using linear discriminant functions (LDA) is also discussed, with applications to future studies wishing to integrate multiple scanning techniques into investigating populations of interest. Copyright © 2016 The Authors. Published by Elsevier Inc. 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.

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

PubMed Central

McMurchy, Alicia N; Stempor, Przemyslaw; Gaarenstroom, Tessa; Wysolmerski, Brian; Dong, Yan; Aussianikava, Darya; Appert, Alex; Huang, Ni; Kolasinska-Zwierz, Paulina; Sapetschnig, Alexandra; Miska, Eric A; Ahringer, Julie

2017-01-01

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means. DOI: http://dx.doi.org/10.7554/eLife.21666.001 PMID:28294943

Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

PubMed

Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

2012-04-01

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Reproducibility and Repeatability of Site-noise and Instrument Self-noise from Multiple Installations of Broadband Seismometers

NASA Astrophysics Data System (ADS)

Holland, A. A.; Ringler, A. T.; Wilson, D.

2016-12-01

We attempt to estimate lower bounds on the repeatability for a number of common instrumentation parameters and provide estimates on the errors associated with the instrument installation itself. These parameters include the self-noise, the orientation, and the sensitivity. We installed three Trillium Compact instruments within 30 cm of each other in the same seismic vault at the Albuquerque Seismological Laboratory. We then repeatedly uninstall and reinstall one of the Trillium Compact instruments multiple times, while leaving the other two in place as reference installations. Using these trials we are then able to examine how repeatable several parameters are between the two reference instruments and the other instrument. We also completely uninstalled and reinstalled the three seismometers once during the testing, in order to examine the reproducibility of the entire experiment. Results indicate that relative sensitivity is highly repeatable, which is partly why we chose this particular sensor for this evaluation. We find that self-noise in the band of 0.1 to 30 s period of an instrument is repeatable to within about 2 dB. Increasing the period of interest from 30 to 100 s period we observe that the self-noise of an instrument can only be repeated to within about 3 dB and that the relative self-noise is not repeatable amongst the sensors. We also find that even though the seismometers are centimeters apart on a single marked line, that the relative orientation between installations is only repeatable to within 1-2 degrees. However, the relative orientations are reproducible, that is, with each installation the relative orientations are within the same amount of uncertainty. Some other broadband or very broadband instruments may not show as much repeatability between installations for some of the metrics we examined. From these tests we can say that instrument self-noise tests are reproducible to within a few dB.

Does Bootstrap Procedure Provide Biased Estimates? An Empirical Examination for a Case of Multiple Regression.

ERIC Educational Resources Information Center

Fan, Xitao

This paper empirically and systematically assessed the performance of bootstrap resampling procedure as it was applied to a regression model. Parameter estimates from Monte Carlo experiments (repeated sampling from population) and bootstrap experiments (repeated resampling from one original bootstrap sample) were generated and compared. Sample…

Evaluating the Performance of Repeated Measures Approaches in Replicating Experimental Benchmark Results

ERIC Educational Resources Information Center

McConeghy, Kevin; Wing, Coady; Wong, Vivian C.

2015-01-01

Randomized experiments have long been established as the gold standard for addressing causal questions. However, experiments are not always feasible or desired, so observational methods are also needed. When multiple observations on the same variable are available, a repeated measures design may be used to assess whether a treatment administered…

An approach for evaluating the repeatability of rapid wetland assessment methods: The effects of training and experience

EPA Science Inventory

We sampled 92 wetlands from four different basins in the United States to quantify observer repeatability in rapid wetland condition assessment using the Delaware Rapid Assessment Protocol (DERAP). In the Inland Bays basin of Delaware, 58 wetland sites were sampled by multiple ob...

Metacognitive Control and Strategy Selection: Deciding to Practice Retrieval during Learning

ERIC Educational Resources Information Center

Karpicke, Jeffrey D.

2009-01-01

Retrieval practice is a potent technique for enhancing learning, but how often do students practice retrieval when they regulate their own learning? In 4 experiments the subjects learned foreign-language items across multiple study and test periods. When items were assigned to be repeatedly tested, repeatedly studied, or removed after they were…

A Complete and Accurate Ab Initio Repeat Finding Algorithm.

PubMed

Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

2016-03-01

It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy.

Expanded complexity of unstable repeat diseases

PubMed Central

Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek

2015-01-01

Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequences of the repeat expansions is critical to developing successful therapies for these diseases. Recent technological breakthroughs in whole genome, transcriptome and proteome analyses will almost certainly lead to new discoveries regarding the mechanisms of repeat instability, the pathogenesis of URDs, and will facilitate development of novel therapeutic approaches. The aim of this review is to give a general overview of unstable repeats diseases, highlight the complexities of these diseases, and feature the emerging discoveries in the field. PMID:23233240

Multiple bidirectional initiations and terminations of transcription in the Marek's disease virus long repeat regions.

PubMed Central

Chen, X B; Velicer, L F

1991-01-01

Marek's disease is an oncogenic disease of chickens caused by a herpesvirus, Marek's disease virus (MDV). Serial in vitro passage of pathogenic MDV results in amplification of a 132-bp direct repeat in the MDV genome's TRL and IRL repeat regions and loss of tumorigenicity. This led to the hypothesis that upon such expansion, one or more tumor-inducing genes fail to be expressed. In this report a group of cDNAs mapping in the expanded regions were isolated from a pathogenic MDV strain in which the 132-bp direct repeat number was found to range between one and seven. Partial cDNA sequencing and S1 nuclease protection analysis revealed that the corresponding transcripts are either initiated or terminated within or near the expanded regions at multiple sites in both rightward and leftward directions. Furthermore, each 132-bp repeat contains one TATA box and two polyadenylation consensus sequences in each direction. These RNAs contain a partial copy or one or more full copies of the 132-bp direct repeat at either their 5' or 3' end. Northern (RNA) blot analysis showed that the majority of transcripts are 1.8 kb in size, while the minor species range in size from 0.67 to 3.1 kb. Together, these data raise the possibility that the 132-bp direct repeat, and indirectly its copy number, may be involved in the regulation of transcriptional initiation and termination and therefore in the generation of four groups of transcripts from the TRL and IRL, although this remains to be demonstrated. Images PMID:1850022

Robotically assisted small animal MRI-guided mouse biopsy

NASA Astrophysics Data System (ADS)

Wilson, Emmanuel; Chiodo, Chris; Wong, Kenneth H.; Fricke, Stanley; Jung, Mira; Cleary, Kevin

2010-02-01

Small mammals, namely mice and rats, play an important role in biomedical research. Imaging, in conjunction with accurate therapeutic agent delivery, has tremendous value in small animal research since it enables serial, non-destructive testing of animals and facilitates the study of biomarkers of disease progression. The small size of organs in mice lends some difficulty to accurate biopsies and therapeutic agent delivery. Image guidance with the use of robotic devices should enable more accurate and repeatable targeting for biopsies and delivery of therapeutic agents, as well as the ability to acquire tissue from a pre-specified location based on image anatomy. This paper presents our work in integrating a robotic needle guide device, specialized stereotaxic mouse holder, and magnetic resonance imaging, with a long-term goal of performing accurate and repeatable targeting in anesthetized mice studies.

MSDB: A Comprehensive Database of Simple Sequence Repeats

PubMed Central

Avvaru, Akshay Kumar; Saxena, Saketh; Mishra, Rakesh Kumar

2017-01-01

Abstract Microsatellites, also known as Simple Sequence Repeats (SSRs), are short tandem repeats of 1–6 nt motifs present in all genomes, particularly eukaryotes. Besides their usefulness as genome markers, SSRs have been shown to perform important regulatory functions, and variations in their length at coding regions are linked to several disorders in humans. Microsatellites show a taxon-specific enrichment in eukaryotic genomes, and some may be functional. MSDB (Microsatellite Database) is a collection of >650 million SSRs from 6,893 species including Bacteria, Archaea, Fungi, Plants, and Animals. This database is by far the most exhaustive resource to access and analyze SSR data of multiple species. In addition to exploring data in a customizable tabular format, users can view and compare the data of multiple species simultaneously using our interactive plotting system. MSDB is developed using the Django framework and MySQL. It is freely available at http://tdb.ccmb.res.in/msdb. PMID:28854643

Assessment of the effects of CT dose in averaged x-ray CT images of a dose-sensitive polymer gel

NASA Astrophysics Data System (ADS)

Kairn, T.; Kakakhel, M. B.; Johnston, H.; Jirasek, A.; Trapp, J. V.

2015-01-01

The signal-to-noise ratio achievable in x-ray computed tomography (CT) images of polymer gels can be increased by averaging over multiple scans of each sample. However, repeated scanning delivers a small additional dose to the gel which may compromise the accuracy of the dose measurement. In this study, a NIPAM-based polymer gel was irradiated and then CT scanned 25 times, with the resulting data used to derive an averaged image and a "zero-scan" image of the gel. Comparison between these two results and the first scan of the gel showed that the averaged and zero-scan images provided better contrast, higher contrast-to- noise and higher signal-to-noise than the initial scan. The pixel values (Hounsfield units, HU) in the averaged image were not noticeably elevated, compared to the zero-scan result and the gradients used in the linear extrapolation of the zero-scan images were small and symmetrically distributed around zero. These results indicate that the averaged image was not artificially lightened by the small, additional dose delivered during CT scanning. This work demonstrates the broader usefulness of the zero-scan method as a means to verify the dosimetric accuracy of gel images derived from averaged x-ray CT data.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

PubMed

Washington, Patricia M; Villapol, Sonia; Burns, Mark P

2016-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Demonstration of repeatability in a high-energy-density planar shear mixing layer experiment

DOE PAGES

Merritt, Elizabeth Catherine; Doss, Forrest William; Di Stefano, Carlos A.; ...

2017-03-11

On laser-driven platforms the assumption of experiment repeatability is particularly important due to a typically low data acquisition rate that doesn’t often allow for data redundancy. If the platform is repeatable, then measurements of the repeatable dynamics from multiple experiments can be treated as measurements of the same system. In high-energy-density hydrodynamic instability experiments the interface growth is assumed to be one of the repeatable aspects of the system. In this paper we demonstrate the repeatability of the instability growth in the counter-propagating shear experiment at the OMEGA laser facility, where the instability growth is characterized by the tracer layermore » thickness or mix-width evolution. Furthermore, in our previous experiment campaigns we have assumed the instability growth was repeatable enough to identify trends, but in this work we explicitly show that the mix-width measurements for nominally identical experiments are repeatable within the measurement error bars.« less

The reproducibility of adenosine monophosphate bronchial challenges in mild, steroid-naive asthmatics

PubMed Central

Singh, Dave; Fairwood, Jennifer; Murdoch, Robert; Weeks, Amanda; Russell, Paul; Roy, Kay; Langley, Steve; Woodcock, Ashley

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Repeated adenosine monophosphate (AMP) challenges are used to assess drug effects in asthma clinical trials, but may be prone to tachyphylaxis when repeated at short intervals. Possible tachyphylaxis at 12- and 24-h intervals has not been studied. WHAT THIS STUDY ADDS Clinically relevant tachyphylaxis after repeated AMP challenges does not occur when repeated at 12- and 24-h intervals. AMP challenges at these intervals can be used to assess drug effects in clinical trials. AIMS Repeated adenosine monophosphate (AMP) challenges are used to assess drug efficacy in clinical trials of mild, steroid-naive asthmatics. Refractoriness has been reported after repeated challenges over short intervals. This study evaluated possible tachyphylaxis after repeated AMP challenges at 12 and 24 h in mild, steroid-naive asthmatics. METHODS This was an open, three-way crossover study. Twenty-six steroid-naive asthmatic subjects were randomized to the following AMP challenge regimens separated by 7–14 days: (A) challenge at 08.00 h, repeated 24 h later; (B) challenge at 08.00 h, repeated 12 and 24 h later; (C) challenge at 20.00 h, repeated 12 h later. Comparisons within day were assessed using 90% confidence intervals (CIs). Non-inferiority approach taken with 1 doubling concentration (DC) as a clinically relevant difference. RESULTS Regimen A: Significant increase in AMP reactivity at 24 h. Mean DC difference was 0.6 (90% CI 0.24, 0.96). Regimen B: No evidence of difference between AMP reactivity at 08.00 h and a repeated challenge 12 h later. Repeated challenge at 24 h caused a significant increase in provocation concentration (PC)20 compared with 12 h (mean DC difference 0.48, 90% CI 0.02, 0.95) and 0 h (mean DC difference 0.82, 90% CI 0.49, 1.14 – the upper CI exceeds the criteria of 1 DC). Challenge regimen C: No difference between challenges; mean DC difference of 0.28 (90% CI −0.2, 0.76). CONCLUSION The small decline in AMP reactivity during repeated challenges was not consistently observed, and was small compared with the known effects of inhaled drugs. PMID:18507658

Reduction of speckle noise from optical coherence tomography images using multi-frame weighted nuclear norm minimization method

NASA Astrophysics Data System (ADS)

Thapa, Damber; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

2015-12-01

In this paper, we propose a speckle noise reduction method for spectral-domain optical coherence tomography (SD-OCT) images called multi-frame weighted nuclear norm minimization (MWNNM). This method is a direct extension of weighted nuclear norm minimization (WNNM) in the multi-frame framework since an adequately denoised image could not be achieved with single-frame denoising methods. The MWNNM method exploits multiple B-scans collected from a small area of a SD-OCT volumetric image, and then denoises and averages them together to obtain a high signal-to-noise ratio B-scan. The results show that the image quality metrics obtained by denoising and averaging only five nearby B-scans with MWNNM method is considerably better than those of the average image obtained by registering and averaging 40 azimuthally repeated B-scans.

Swarms of repeating stick-slip glacierquakes triggered by snow loading at Mount Rainier volcano

NASA Astrophysics Data System (ADS)

Allstadt, K.; Malone, S. D.; Shean, D. E.; Fahnestock, M. A.; Vidale, J. E.

2013-12-01

We have detected over 150,000 low-frequency (~1-5 Hz) repeating earthquakes over the past decade at Mount Rainier volcano by scanning continuous seismic data from the permanent seismic network. Most of these were previously undetected due to their small size (M<1), shallow locations, and emergent waveforms. The earthquakes are located high (>3000 m) on the glacier-covered part of the edifice. They occur primarily in week- to month-long swarms of activity that strongly correlate with precipitation, namely snowfall, with a lag of about 1-2 days. Furthermore, there is a linear relationship between inter-event repeat time and the size of the subsequent event - consistent with slip-predictable stick-slip behavior. This pattern suggests that the additional load imparted by the sudden added weight of snow during winter storms triggers a temporary change from smooth aseismic sliding to seismic stick-slip basal sliding in locations where basal conditions are close to frictional instability. This sensitivity is analogous to the triggering of repeating earthquakes due to tiny overall stress changes in more traditional tectonic environments (e.g., tremor modulated by tides, dynamic triggering of repeating earthquakes). Using codawave interferometry on stacks of the repeating waveforms of the families with the most events, we found that the sources move at speeds of ~1 m/day. Using a GAMMA ground based radar interferometer, we collected spatially continuous line-of-sight velocities of several glaciers at Mount Rainier in both summer and late fall. We found that the faster parts of the glaciers also move at ~1 m/day or faster, even in late fall. Movement of the sources of these repeating earthquakes at glacial speeds indicates that the asperities are dirty patches that move with the ice rather than stationary bedrock bumps. The reappearance of some event families up to several years apart suggests that certain areas at the base of certain glaciers are prodigious producers of conditions favorable to this behavior. Stick-slip basal sliding of glaciers is supported over other potential moving shallow source mechanisms such as crevassing, unsteady fluid flow, and calving because the source must be non-destructive, highly repeatable at regular intervals, large enough to be detected on multiple stations, lack strong spectral peaks, and have a potential physical tie to the effects of winter precipitation. Identification of the source of these frequent signals offers a view of basal glacier processes, discriminates against alarming volcanic noises, and documents effects of weather on the cryosphere.

Obscure recurrent gastrointestinal bleeding: a revealed mystery?

PubMed

Riccioni, Maria Elena; Urgesi, Riccardo; Cianci, Rossella; Marmo, Clelia; Galasso, Domenico; Costamagna, Guido

2014-08-01

Nowadays, capsule endoscopy (CE) is the first-line procedure after negative upper and lower gastrointestinal (GI) endoscopy for obscure gastrointestinal bleeding (OGIB). Approximately, two-thirds of patients undergoing CE for OGIB will have a small-bowel abnormality. However, several patients who underwent CE for OGIB had the source of their blood loss in the stomach or in the colon. The aim of the present study is to determine the incidence of bleeding lesions missed by the previous gastroscopy/colonoscopy with CE and to evaluate the indication to repeat a new complete endoscopic workup in subjects related to a tertiary center for obscure bleeding before CE. We prospectively reviewed data from 637/1008 patients underwent to CE for obscure bleeding in our tertiary center after performing negative gastroscopy and colonoscopy. CE revealed a definite or likely cause of bleeding in stomach in 138/637 patients (yield 21.7%) and in the colon in 41 patients (yield 6.4%) with a previous negative gastroscopy and colonoscopy, respectively. The lesions found were outside the small bowel in only 54/637 (8.5%) patients. In 111/138 patients, CE found lesions both in stomach and small bowel (small-bowel erosions in 54, AVMs in 45, active small-bowel bleeding in 4, neoplastic lesions in 3 and distal ileum AVMs in 5 patients). In 24/41 (58.5%) patients, CE found lesions both in small bowel and colon (multiple small-bowel erosions in 15; AVMs in 8 and neoplastic lesion in 1 patients. All patients underwent endoscopic therapy or surgery for their nonsmall-bowel lesions. Lesions in upper or lower GI tract have been missed in about 28% of patients submitted to CE for obscure bleeding. CE may play an important role in identifying lesions missed at conventional endoscopy.

Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex.

PubMed

Raveh, Barak; Karp, Jerome M; Sparks, Samuel; Dutta, Kaushik; Rout, Michael P; Sali, Andrej; Cowburn, David

2016-05-03

Nucleocytoplasmic transport is mediated by the interaction of transport factors (TFs) with disordered phenylalanine-glycine (FG) repeats that fill the central channel of the nuclear pore complex (NPC). However, the mechanism by which TFs rapidly diffuse through multiple FG repeats without compromising NPC selectivity is not yet fully understood. In this study, we build on our recent NMR investigations showing that FG repeats are highly dynamic, flexible, and rapidly exchanging among TF interaction sites. We use unbiased long timescale all-atom simulations on the Anton supercomputer, combined with extensive enhanced sampling simulations and NMR experiments, to characterize the thermodynamic and kinetic properties of FG repeats and their interaction with a model transport factor. Both the simulations and experimental data indicate that FG repeats are highly dynamic random coils, lack intrachain interactions, and exhibit significant entropically driven resistance to spatial confinement. We show that the FG motifs reversibly slide in and out of multiple TF interaction sites, transitioning rapidly between a strongly interacting state and a weakly interacting state, rather than undergoing a much slower transition between strongly interacting and completely noninteracting (unbound) states. In the weakly interacting state, FG motifs can be more easily displaced by other competing FG motifs, providing a simple mechanism for rapid exchange of TF/FG motif contacts during transport. This slide-and-exchange mechanism highlights the direct role of the disorder within FG repeats in nucleocytoplasmic transport, and resolves the apparent conflict between the selectivity and speed of transport.

Classification of proteins with shared motifs and internal repeats in the ECOD database

PubMed Central

Kinch, Lisa N.; Liao, Yuxing

2016-01-01

Abstract Proteins and their domains evolve by a set of events commonly including the duplication and divergence of small motifs. The presence of short repetitive regions in domains has generally constituted a difficult case for structural domain classifications and their hierarchies. We developed the Evolutionary Classification Of protein Domains (ECOD) in part to implement a new schema for the classification of these types of proteins. Here we document the ways in which ECOD classifies proteins with small internal repeats, widespread functional motifs, and assemblies of small domain‐like fragments in its evolutionary schema. We illustrate the ways in which the structural genomics project impacted the classification and characterization of new structural domains and sequence families over the decade. PMID:26833690

Repeated isolation of virulent Newcastle disease viruses in poultry and captive non-poultry avian species in Pakistan from 2011 to 2016

USDA-ARS?s Scientific Manuscript database

Virulent viruses of the panzootic Avian avulavirus 1 (AAvV-1) of sub-genotype VIIi were repeatedly isolated (2011–2016) from commercial chickens and from multiple non-poultry avian species in Pakistan. These findings provide evidence for the existence of epidemiological links between Newcastle disea...

Microevolution of the Direct Repeat Locus of Mycobacterium tuberculosis in a Strain Prevalent in San Francisco

PubMed Central

Aga, Roxanne S.; Fair, Elizabeth; Abernethy, Neil F.; DeRiemer, Kathryn; Paz, E. Antonio; Kawamura, L. Masae; Small, Peter M.; Kato-Maeda, Midori

2006-01-01

We describe a microevolutionary event of a prevalent strain of Mycobacterium tuberculosis that caused two outbreaks in San Francisco. During the second outbreak, a direct variable repeat was lost. We discuss the mechanisms of this change and the implications of analyzing multiple genetic loci in this context. PMID:16597893

The Effects of Repeated Readings on the Reading Performances of Hispanic English Language Learners with Specific Learning Disabilities

ERIC Educational Resources Information Center

Landa, Katrina G.; Barbetta, Patricia M.

2017-01-01

A multiple probe across participants design was used to explore the effects of repeated readings on the reading fluency, errors, and comprehension of 4, third-to-fifth grade English language learners (ELLs) with specific learning disabilities (SLD). Also, generalization measures to untaught passages and maintenance data were collected. In…

Leptospira interrogans serovars Bratislava and Muenchen animal infections: Implications for epidemiology and control.

PubMed

Arent, Z; Frizzell, C; Gilmore, C; Allen, A; Ellis, W A

2016-07-15

Strains of Leptospira interrogans belonging to two very closely related serovars - Bratislava and Muenchen - have been associated with disease in domestic animals, in particular pigs, but also in horses and dogs. Similar strains have also been recovered from various wildlife species. Their epidemiology is poorly understood. Two hundred and forty seven such isolates, from UK domestic animal and wildlife species, were examined by restriction endonuclease analysis in an attempt to elucidate their epidemiology. A representative sub-sample of 65 of these isolates was further examined by multiple-locus variable-number tandem repeat analysis and 22 by secY sequencing. Ten restriction pattern types were identified. The majority of isolates fell into one of three restriction endonuclease analysis pattern types designated B2a, B2b and M2a. B2a was ubiquitous and was isolated from 10 species and represented the majority of the horse and all dog isolates. B2b was very different, being isolated only from pigs, indicating that this type was maintained by pigs. The pattern M2a was reported for the majority of isolates from pigs but also was common in small rodents isolates. Five restriction pattern types were found only in wildlife suggesting that they are unlikely to pose a disease threat to domestic animals. Multiple-locus variable-number tandem repeat analysis identified six clusters. The REA types B2a and B2b were all found in one MLVA cluster while the majority of the M2a strains examined occurred in another cluster. The secY sequencing detected only one sequence type, clustered with other serovars of Leptospira interrogans. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential recognition of the multiple banded antigen isoforms across Ureaplasma parvum and Ureaplasma urealyticum species by monoclonal antibodies.

PubMed

Aboklaish, Ali F; Ahmed, Shatha; McAllister, Douglas; Cassell, Gail; Zheng, Xiaotian T; Spiller, Owen B

2016-08-01

Two separate species of Ureaplasma have been identified that infect humans: Ureaplasma parvum and Ureaplasma urealyticum. Most notably, these bacteria lack a cell wall and are the leading infectious organism associated with infection-related induction of preterm birth. Fourteen separate representative prototype bacterial strains, called serovars, are largely differentiated by the sequence of repeating units in the C-terminus of the major surface protein: multiple-banded antigen (MBA). Monoclonal antibodies that recognise single or small groups of serovars have been previously reported, but these reagents remain sequestered in individual research laboratories. Here we characterise a panel of commercially available monoclonal antibodies raised against the MBA and describe the first monoclonal antibody that cross-reacts by immunoblot with all serovars of U. parvum and U. urealyticum species. We also describe a recombinant MBA expressed by Escherichia coli which facilitated further characterisation by immunoblot and demonstrate immunohistochemistry of paraffin-embedded antigens. Immunoblot reactivity was validated against well characterised previously published monoclonal antibodies and individual commercial antibodies were found to recognise all U. parvum strains, only serovars 3 and 14 or only serovars 1 and 6, or all strains belonging to U. parvum and U. urealyticum. MBA mass was highly variable between strains, consistent with variation in the number of C-terminal repeats between strains. Antibody characterisation will enable future investigations to correlate severity of pathogenicity to MBA isoform number or mass, in addition to development of antibody-based diagnostics that will detect infection by all Ureaplasma species or alternately be able to differentiate between U. parvum, U. urealyticum or mixed infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Genotyping of Brucella melitensis strains from dromedary camels (Camelus dromedarius) from the United Arab Emirates with multiple-locus variable-number tandem repeat analysis.

PubMed

Gyuranecz, Miklós; Wernery, Ulli; Kreizinger, Zsuzsa; Juhász, Judit; Felde, Orsolya; Nagy, Péter

2016-04-15

Camel brucellosis is a widespread zoonotic disease in camel-rearing countries caused by Brucella melitensis and Brucella abortus. The aim of this study was the first genetic analysis of B. melitensis strains isolated from dromedary camels (Camelus dromedarius) using multiple-locus variable-number tandem repeat analysis (MLVA). MLVA 16 and its MLVA 8 and MLVA11 subsets were used to determine the genotypes of 15 B. melitensis isolates from dromedary camels (11 strains) and other host species (4 strains) from the United Arab Emirates and the results were then compared to B. melitensis MLVA genotypes from other parts of the world. Five, including two novel genotypes were identified with MLVA 8. MLVA 16 further discriminated these five genotypes to ten variants. The eleven camel isolates clustered into four main genetic groups within the East-Mediterranean and African clades and this clustering correlated with the geographic origin of the hosts (United Arab Emirates, Kingdom of Saudi Arabia and Sudan) and the date of their isolation. The camel strains were also genetically related to strains isolated from wild and domestic ruminants from their close habitat or from other parts of the world. Although limited number of strains were analysed, based on our data imported animals from foreign countries, local small ruminants and wildlife species are hypothesized to be the main sources of camel brucellosis in the United Arab Emirates. MLVA was successfully applied to determine the epidemiological links between the different camel B. melitensis infections in the United Arab Emirates and it can be a beneficial tool in future disease control programs. Copyright © 2016 Elsevier B.V. All rights reserved.

A synergetic combination of small and large neighborhood schemes in developing an effective procedure for solving the job shop scheduling problem.

PubMed

Amirghasemi, Mehrdad; Zamani, Reza

2014-01-01

This paper presents an effective procedure for solving the job shop problem. Synergistically combining small and large neighborhood schemes, the procedure consists of four components, namely (i) a construction method for generating semi-active schedules by a forward-backward mechanism, (ii) a local search for manipulating a small neighborhood structure guided by a tabu list, (iii) a feedback-based mechanism for perturbing the solutions generated, and (iv) a very large-neighborhood local search guided by a forward-backward shifting bottleneck method. The combination of shifting bottleneck mechanism and tabu list is used as a means of the manipulation of neighborhood structures, and the perturbation mechanism employed diversifies the search. A feedback mechanism, called repeat-check, detects consequent repeats and ignites a perturbation when the total number of consecutive repeats for two identical makespan values reaches a given threshold. The results of extensive computational experiments on the benchmark instances indicate that the combination of these four components is synergetic, in the sense that they collectively make the procedure fast and robust.

Hearing loss associated with repeated MRI acquisition procedure-related acoustic noise exposure: an occupational cohort study.

PubMed

Bongers, Suzan; Slottje, Pauline; Kromhout, Hans

2017-11-01

To study the effects of repeated exposure to MRI-related acoustic noise during image acquisition procedures (scans) on hearing. A retrospective occupational cohort study was performed among workers of an MRI manufacturing facility (n=474). Longitudinal audiometry data from the facility's medical surveillance scheme collected from 1973 to 2010 were analysed by studying the association of cumulative exposure to MRI-related acoustic noise from voluntary (multiple) MRI scans and the hearing threshold of the volunteer. Repeated acoustic noise exposure during volunteer MRI scans was found to be associated with a small exposure-dependent increased rate change of hearing threshold level (dB/year), but the association was only found related to the number of voluntary MRI scans and not to modelled cumulative noise exposure (dB*hour) based on MRI-system type. The increased rate change of hearing threshold level was found to be statistically significant for the frequencies 500, 1000, 2000, 3000 and 4000 Hz in the right ear. From our longitudinal cohort study, it appeared that exposure to noise from voluntarily MRI scans may have resulted in a slight amount of hearing loss. Mandatory use of hearing protection might have prevented more severe hearing loss. Lack of consistency in findings between the left and right ears and between the two exposure measures prohibits definitive conclusions. Further research that addresses the study's methodological limitations is warranted to corroborate our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

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

Voort van Zyp, Noelle C. van der, E-mail: n.vandervoortvanzyp@erasmusmc.nl; Hoogeman, Mischa S.; Water, Steven van de

2011-11-01

Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and {>=}2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliabilitymore » of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of {>=}2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of {>=}2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization was not compromised.« less

Elucidating Microbial Adaptation Dynamics via Autonomous Exposure and Sampling

NASA Technical Reports Server (NTRS)

Grace, Joseph M.; Verseux, Cyprien; Gentry, Diana; Moffet, Amy; Thayabaran, Ramanen; Wong, Nathan; Rothschild, Lynn

2013-01-01

The adaptation of micro-organisms to their environments is a complex process of interaction between the pressures of the environment and of competition. Reducing this multifactorial process to environmental exposure in the laboratory is a common tool for elucidating individual mechanisms of evolution, such as mutation rates. Although such studies inform fundamental questions about the way adaptation and even speciation occur, they are often limited by labor-intensive manual techniques. Current methods for controlled study of microbial adaptation limit the length of time, the depth of collected data, and the breadth of applied environmental conditions. Small idiosyncrasies in manual techniques can have large effects on outcomes; for example, there are significant variations in induced radiation resistances following similar repeated exposure protocols. We describe here a project under development to allow rapid cycling of multiple types of microbial environmental exposure. The system allows continuous autonomous monitoring and data collection of both single species and sampled communities, independently and concurrently providing multiple types of controlled environmental pressure (temperature, radiation, chemical presence or absence, and so on) to a microbial community in dynamic response to the ecosystem's current status. When combined with DNA sequencing and extraction, such a controlled environment can cast light on microbial functional development, population dynamics, inter- and intra-species competition, and microbe-environment interaction. The project's goal is to allow rapid, repeatable iteration of studies of both natural and artificial microbial adaptation. As an example, the same system can be used both to increase the pH of a wet soil aliquot over time while periodically sampling it for genetic activity analysis, or to repeatedly expose a culture of bacteria to the presence of a toxic metal, automatically adjusting the level of toxicity based on the number or growth rate of surviving cells. We are on our second prototype iteration, with demonstrated functions of microbial growth monitoring and dynamic exposure to UV-C radiation and temperature. We plan to add functionality for general chemical presence or absence by Nov. 2013. By making the project low-cost and open-source, we hope to encourage others to use it as a basis for future development of a common microbial environmental adaptation testbed.

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

PubMed

Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

2016-06-01

RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

E-Cigarette Vapor Induces an Apoptotic Response in Human Gingival Epithelial Cells Through the Caspase-3 Pathway.

PubMed

Rouabhia, Mahmoud; Park, Hyun Jin; Semlali, Abdelhabib; Zakrzewski, Andrew; Chmielewski, Witold; Chakir, Jamila

2017-06-01

Electronic cigarettes represent an increasingly significant proportion of today's consumable tobacco products. E-cigarettes contain several chemicals which may promote oral diseases. The aim of this study was to investigate the effect of e-cigarette vapor on human gingival epithelial cells. Results show that e-cigarette vapor altered the morphology of cells from small cuboidal form to large undefined shapes. Both single and multiple exposures to e-cigarette vapor led to a bulky morphology with large faint nuclei and an enlarged cytoplasm. E-cigarette vapor also increased L-lactate dehydrogenase (LDH) activity in the targeted cells. This activity was greater with repeated exposures. Furthermore, e-cigarette vapor increased apoptotic/necrotic epithelial cell percentages compared to that observed in the control. Epithelial cell apoptosis was confirmed by TUNEL assay showing that exposure to e-cigarette vapor increased apoptotic cell numbers, particularly after two and three exposures. This negative effect involved the caspase-3 pathway, the activity of which was greater with repeated exposure and which decreased following the use of caspase-3 inhibitor. The adverse effects of e-cigarette vapor on gingival epithelial cells may lead to dysregulated gingival cell function and result in oral disease. J. Cell. Physiol. 232: 1539-1547, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

Structure of the myotonic dystrophy type 2 RNA and designed small molecules that reduce toxicity.

PubMed

Childs-Disney, Jessica L; Yildirim, Ilyas; Park, HaJeung; Lohman, Jeremy R; Guan, Lirui; Tran, Tuan; Sarkar, Partha; Schatz, George C; Disney, Matthew D

2014-02-21

Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disorder caused by a r(CCUG) expansion (r(CCUG)(exp)) that folds into an extended hairpin with periodically repeating 2×2 nucleotide internal loops (5'CCUG/3'GUCC). We designed multivalent compounds that improve DM2-associated defects using information about RNA-small molecule interactions. We also report the first crystal structure of r(CCUG) repeats refined to 2.35 Å. Structural analysis of the three 5'CCUG/3'GUCC repeat internal loops (L) reveals that the CU pairs in L1 are each stabilized by one hydrogen bond and a water-mediated hydrogen bond, while CU pairs in L2 and L3 are stabilized by two hydrogen bonds. Molecular dynamics (MD) simulations reveal that the CU pairs are dynamic and stabilized by Na(+) and water molecules. MD simulations of the binding of the small molecule to r(CCUG) repeats reveal that the lowest free energy binding mode occurs via the major groove, in which one C residue is unstacked and the cross-strand nucleotides are displaced. Moreover, we modeled the binding of our dimeric compound to two 5'CCUG/3'GUCC motifs, which shows that the scaffold on which the RNA-binding modules are displayed provides an optimal distance to span two adjacent loops.

History, rare, and multiple events of mechanical unfolding of repeat proteins

NASA Astrophysics Data System (ADS)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Newborn human brain identifies repeated auditory feature conjunctions of low sequential probability.

PubMed

Ruusuvirta, Timo; Huotilainen, Minna; Fellman, Vineta; Näätänen, Risto

2004-11-01

Natural environments are usually composed of multiple sources for sounds. The sounds might physically differ from one another only as feature conjunctions, and several of them might occur repeatedly in the short term. Nevertheless, the detection of rare sounds requires the identification of the repeated ones. Adults have some limited ability to effortlessly identify repeated sounds in such acoustically complex environments, but the developmental onset of this finite ability is unknown. Sleeping newborn infants were presented with a repeated tone carrying six frequent (P = 0.15 each) and six rare (P approximately 0.017 each) conjunctions of its frequency, intensity and duration. Event-related potentials recorded from the infants' scalp were found to shift in amplitude towards positive polarity selectively in response to rare conjunctions. This finding suggests that humans are relatively hard-wired to preattentively identify repeated auditory feature conjunctions even when such conjunctions occur rarely among other similar ones.

Mission design for NISAR repeat-pass Interferometric SAR

NASA Astrophysics Data System (ADS)

Alvarez-Salazar, Oscar; Hatch, Sara; Rocca, Jennifer; Rosen, Paul; Shaffer, Scott; Shen, Yuhsyen; Sweetser, Theodore; Xaypraseuth, Peter

2014-10-01

The proposed spaceborne NASA-ISRO SAR (NISAR) mission would use the repeat-pass interferometric Synthetic Aperture Radar (InSAR) technique to measure the changing shape of Earth's surface at the centimeter scale in support of investigations in solid Earth and cryospheric sciences. Repeat-pass InSAR relies on multiple SAR observations acquired from nearly identical positions of the spacecraft as seen from the ground. Consequently, there are tight constraints on the repeatability of the orbit, and given the narrow field of view of the radar antenna beam, on the repeatability of the beam pointing. The quality and accuracy of the InSAR data depend on highly precise control of both orbital position and observatory pointing throughout the science observation life of the mission. This paper describes preliminary NISAR requirements and rationale for orbit repeatability and attitude control in order to meet science requirements. A preliminary error budget allocation and an implementation approach to meet these allocations are also discussed.

Multiple sleep bruxism data collected using a self-contained EMG detector/analyzer system in asymptomatic healthy subjects.

PubMed

Minakuchi, Hajime; Sakaguchi, Chiyomi; Hara, Emilio S; Maekawa, Kenji; Matsuka, Yoshizo; Clark, Glenn T; Kuboki, Takuo

2012-12-01

Small, self-contained electromyographic (EMG) detector/analyzer (D/A) devices have become available for the detection of jaw muscle activity events above threshold. These devices claim to be less intrusive to the subjects sleep so it is less prone to induce disturbed sleep. The objective of this study was to evaluate for night-to-night variability and examine for a systematic alteration on the first night in EMG levels. Ten asymptomatic healthy volunteers (mean age, 26.8 ± 3.78) were recorded for six sequential nights in their home environment using EMG D/A system. The device yields a nightly EMG level above threshold score on a 0-4 level. Because the data are categorical and nonparametric, the data of the ten subjects across six nights were submitted to a Friedman repeated measures ANOVA. The significant level was set as alpha equal to 0.05. The median and mode values of the subjects were tabulated and analyzed and we did not find a significant difference in EMG D/A level across the six nights (p = 0.287, Kendall's coefficient of concordance = 0.124, Friedman two-way repeated measures ANOVA). The data did show clear and substantial night-to-night variability. Substantial night-to-night variability in masseter EMG activity levels was clearly observed in our subjects. There was no evidence of a suppressed or elevated first-night effect-like variability on masseter muscle EMG level seen in these subjects using a small portable self-contained EMG detector/analyzer. These data suggest that recordings should be at least 5-6-nights duration to establish a reasonable measure of an individual's average nightly masseter EMG level.

Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro.

PubMed

Gallenberger, Martin; Meinel, Dominik M; Kroeber, Markus; Wegner, Michael; Milkereit, Philipp; Bösl, Michael R; Tamm, Ernst R

2011-02-01

Mutations in WD repeat domain 36 gene (WDR36) play a causative role in some forms of primary open-angle glaucoma, a leading cause of blindness worldwide. WDR36 is characterized by the presence of multiple WD40 repeats and shows homology to Utp21, an essential protein component of the yeast small subunit (SSU) processome required for maturation of 18S rRNA. To clarify the functional role of WDR36 in the mammalian organism, we generated and investigated mutant mice with a targeted deletion of Wdr36. In parallel experiments, we used RNA interference to deplete WDR36 mRNA in mouse embryos and cultured human trabecular meshwork (HTM-N) cells. Deletion of Wdr36 in the mouse caused preimplantation embryonic lethality, and essentially similar effects were observed when WDR36 mRNA was depleted in mouse embryos by RNA interference. Depletion of WDR36 mRNA in HTM-N cells caused apoptotic cell death and upregulation of mRNA for BAX, TP53 and CDKN1A. By immunocytochemistry, staining for WDR36 was observed in the nucleolus of cells, which co-localized with that of nucleolar proteins such as nucleophosmin and PWP2. In addition, recombinant and epitope-tagged WDR36 localized to the nucleolus of HTM-N cells. By northern blot analysis, a substantial decrease in 21S rRNA, the precursor of 18S rRNA, was observed following knockdown of WDR36. In addition, metabolic-labeling experiments consistently showed a delay of 18S rRNA maturation in WDR36-depleted cells. Our results provide evidence that WDR36 is an essential protein in mammalian cells which is involved in the nucleolar processing of SSU 18S rRNA.

The Latest in Surgical Management of Stage IIIA Non-Small Cell Lung Cancer: Video-Assisted Thoracic Surgery and Tumor Molecular Profiling.

PubMed

Woodard, Gavitt A; Jablons, David M

2015-01-01

Stage IIIA non-small cell lung cancer (NSCLC) remains a treatment challenge and requires a multidisciplinary care team to optimize survival outcomes. Thoracic surgeons play an important role in selecting operative candidates and assisting with pathologic mediastinal staging via cervical mediastinoscopy, endobronchial ultrasound, or esophageal ultrasound with fine needle aspiration. The majority of patients with stage IIIA disease will receive induction therapy followed by repeat staging before undergoing lobectomy or pneumonectomy; occasionally, a patient with an incidentally found, single-station microscopic IIIA tumor will undergo resection as the primary initial therapy. Multiple large clinical trials, including SWOG-8805, EORTC-8941, INT-0139, and ANITA, have shown 5-year overall survival rates of up to 30% to 40% using triple-modality treatments, and the best outcomes repeatedly are seen among patients who respond to induction treatment or who have tumors amenable to lobectomy instead of pneumonectomy. The need for a pneumonectomy is not a reason to deny patients an operation, because current operative mortality and morbidity rates are acceptably low at 5% and 30%, respectively. In select patients with stage IIIA disease, video-assisted thoracic surgery and open resections have been shown to have comparable rates of local recurrence and long-term survival. New developments in genetic profiling and personalized medicine are exciting areas of research, and early data suggest that molecular profiling of stage IIIA NSCLC tumors can accurately stratify patients by risk within this stage and predict survival outcomes. Future advances in treating stage IIIA disease will involve developing better systemic therapies and customizing treatment plans on the basis of an individual tumor's genetic profile.

Repeat retail clinic visits: impact of insurance coverage and age of patient.

PubMed

Angstman, Kurt B; Bernard, Matthew E; Rohrer, James E; Garrison, Gregory M; Maclaughlin, Kathy L

2012-12-01

As retail clinics provide a less costly alternative for health care, it would be reasonable to expect an increase in multiple (repeat) retail visits by those patients who may have expenses for receiving primary care. If costs were not a significant factor, then repeat visits should not be significantly different between these patients and those with coverage for primary care visits. The hypothesis for this study was that patients with the potential for out-of-pocket expenses would have a higher frequency of repeat retail clinic visits within 180 days compared to those with primary care coverage. A retrospective chart review was conducted of 5703 patients utilizing a retail clinic in Rochester, Minnesota from January 1, 2009 through June 30, 2009. The first visit to the retail clinic was considered the index visit and the chart was reviewed for repeat retail clinic visits within the next 180 days. Using a multiple logistic regression model, the odds of a pediatric patient (N=2344) having a repeat retail visit within 180 days of the index visit were not significantly impacted by insurance coverage (P=0.4209). Of the 3359 adult patients, those with unknown coverage had a 25.6% higher odds ratio of repeat retail clinic visits than those with insurance coverage (odds ratio 1.2557, confidence interval 1.0421-1.5131). This study suggested that when cost is an issue, the adult patient may favor retail clinics for episodic, low-acuity health care. In contrast, the pediatric population did not, suggesting that other factors, such as convenience, may play more of a role in the choice of episodic health care for this age group.

Repeat workers' compensation claims: risk factors, costs and work disability

PubMed Central

2011-01-01

Background The objective of our study was to describe factors associated with repeat workers' compensation claims and to compare the work disability arising in workers with single and multiple compensation claims. Methods All initial injury claims lodged by persons of working age during a five year period (1996 to 2000) and any repeat claims were extracted from workers' compensation administrative data in the state of Victoria, Australia. Groups of workers with single and multiple claims were identified. Descriptive analysis of claims by affliction, bodily location, industry segment, occupation, employer and workplace was undertaken. Survival analysis determined the impact of these variables on the time between the claims. The economic impact and duration of work incapacity associated with initial and repeat claims was compared between groups. Results 37% of persons with an initial claim lodged a second claim. This group contained a significantly greater proportion of males, were younger and more likely to be employed in manual occupations and high-risk industries than those with single claims. 78% of repeat claims were for a second injury. Duration between the claims was shortest when the working conditions had not changed. The initial claims of repeat claimants resulted in significantly (p < 0.001) lower costs and work disability than the repeat claims. Conclusions A substantial proportion of injured workers experience a second occupational injury or disease. These workers pose a greater economic burden than those with single claims, and also experience a substantially greater cumulative period of work disability. There is potential to reduce the social, health and economic burden of workplace injury by enacting prevention programs targeted at these workers. PMID:21696637

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of Ascaris reveals a novel fold and two discrete lipid-binding sites.

PubMed

Meenan, Nicola A G; Ball, Graeme; Bromek, Krystyna; Uhrín, Dušan; Cooper, Alan; Kennedy, Malcolm W; Smith, Brian O

2011-04-19

Nematode polyprotein allergens (NPAs) are an unusual class of lipid-binding proteins found only in nematodes. They are synthesized as large, tandemly repetitive polyproteins that are post-translationally cleaved into multiple copies of small lipid binding proteins with virtually identical fatty acid and retinol (Vitamin A)-binding characteristics. They are probably central to transport and distribution of small hydrophobic compounds between the tissues of nematodes, and may play key roles in nutrient scavenging, immunomodulation, and IgE antibody-based responses in infection. In some species the repeating units are diverse in amino acid sequence, but, in ascarid and filarial nematodes, many of the units are identical or near-identical. ABA-1A is the most common repeating unit of the NPA of Ascaris suum, and is closely similar to that of Ascaris lumbricoides, the large intestinal roundworm of humans. Immune responses to NPAs have been associated with naturally-acquired resistance to infection in humans, and the immune repertoire to them is under strict genetic control. The solution structure of ABA-1A was determined by protein nuclear magnetic resonance spectroscopy. The protein adopts a novel seven-helical fold comprising a long central helix that participates in two hollow four-helical bundles on either side. Discrete hydrophobic ligand-binding pockets are found in the N-terminal and C-terminal bundles, and the amino acid sidechains affected by ligand (fatty acid) binding were identified. Recombinant ABA-1A contains tightly-bound ligand(s) of bacterial culture origin in one of its binding sites. This is the first mature, post-translationally processed, unit of a naturally-occurring tandemly-repetitive polyprotein to be structurally characterized from any source, and it belongs to a new structural class. NPAs have no counterparts in vertebrates, so represent potential targets for drug or immunological intervention. The nature of the (as yet) unidentified bacterial ligand(s) may be pertinent to this, as will our characterization of the unusual binding sites.

Repeatability of Cryogenic Multilayer Insulation

NASA Technical Reports Server (NTRS)

Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

2017-01-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

Repeatability of Cryogenic Multilayer Insulation

NASA Technical Reports Server (NTRS)

Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

2017-01-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

Immediate Small Number Perception : Evidence from a New Numerical Carry-Over Procedure

ERIC Educational Resources Information Center

Demeyere, Nele; Humphreys, Glyn W.

2012-01-01

Evidence is presented for the immediate apprehension of exact small quantities. Participants performed a quantification task (are the number of items greater or smaller than?), and carry-over effects were examined between numbers requiring the same response. Carry-over effects between small numbers were strongly affected by repeats of pattern and…

Identification of miniature inverted-repeat transposable elements (MITEs) and biogenesis of their siRNAs in the Solanaceae: New functional implications for MITEs

USDA-ARS?s Scientific Manuscript database

Small RNAs regulate the genome by guiding transcriptional and post-transcriptional silencing machinery to specific target sequences, including genes and transposable elements (TEs). Although miniature inverted-repeat transposable elements (MITEs) are closely associated with euchromatic genes, the br...

Omnibus Tests for Interactions in Repeated Measures Designs with Dichotomous Dependent Variables.

ERIC Educational Resources Information Center

Serlin, Ronald C.; Marascuilo, Leonard A.

When examining a repeated measures design with independent groups for a significant group by trial interaction, classical analysis of variance or multivariate procedures can be used if the assumptions underlying the tests are met. Neither procedure may be justified for designs with small sample sizes and dichotomous dependent variables. An omnibus…

Reciprocal Peer Tutoring and Repeated Reading: Increasing Practicality Using Student Groups

ERIC Educational Resources Information Center

Oddo, Maria; Barnett, David W.; Hawkins, Renee O.; Musti-Rao, Shobana

2010-01-01

Previous research has investigated the efficacy of peer-mediated repeated reading (RR) interventions carried out by student dyads. This research extends the existing research by investigating the impact of RR on oral reading fluency and comprehension when carried out by a teacher in small groups of fourth-grade students. Outcomes were analyzed…

Development and characterization of simple sequence repeats for Bipolaris sokiniana and cross transferability to related species

USDA-ARS?s Scientific Manuscript database

Simple sequence repeats (SSR) markers were developed from a small insert genomic library for Bipolaris sorokiniana, a mitosporic fungal pathogen that causes spot blotch and root rot in switchgrass. About 59% of sequenced clones (n=384) harbored various SSR motifs. After eliminating the redundant seq...

The Influence of Non-Nociceptive Factors on Hot Plate Latency in Rats

PubMed Central

Gunn, Amanda; Bobeck, Erin N.; Weber, Ceri; Morgan, Michael M.

2010-01-01

The hot plate is a widely used test to assess nociception. The effect of non-nociceptive factors (weight, sex, activity, habituation, and repeated testing) on hot plate latency was examined. Comparison of body weight and hot plate latency revealed a small but significant inverse correlation (light rats had longer latencies). Habituating rats to the test room for 1 hr prior to testing did not decrease hot plate latency except for female rats tested on Days 2 - 4. Hot plate latency decreased with repeated daily testing, but this was not caused by a decrease in locomotor activity or learning to respond. Activity on the hot plate was consistent across all four trials, and prior exposure to a room temperature plate caused a similar decrease in latency as rats tested repeatedly on the hot plate. Despite this decrease in baseline hot plate latency, there was no difference in morphine antinociceptive potency. The present study shows that weight, habituation to the test room, and repeated testing can alter baseline hot plate latency, but these effects are small and have relatively little impact on morphine antinociception. PMID:20797920

Insertion device and method for accurate and repeatable target insertion

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

Gubeli, III, Joseph F.; Shinn, Michelle D.; Bevins, Michael E.

The present invention discloses a device and a method for inserting and positioning a target within a free electron laser, particle accelerator, or other such device that generates or utilizes a beam of energy or particles. The system includes a three-point registration mechanism that insures angular and translational accuracy and repeatability of positioning upon multiple insertions within the same structure.

Antibiotic Susceptibility and Molecular Diversity of Bacillus anthracis Strains in Chad: Detection of a New Phylogenetic Subgroup

PubMed Central

Maho, Angaya; Rossano, Alexandra; Hächler, Herbert; Holzer, Anita; Schelling, Esther; Zinsstag, Jakob; Hassane, Mahamat H.; Toguebaye, Bhen S.; Akakpo, Ayayi J.; Van Ert, Matthew; Keim, Paul; Kenefic, Leo; Frey, Joachim; Perreten, Vincent

2006-01-01

We genotyped 15 Bacillus anthracis isolates from Chad, Africa, using multiple-locus variable-number tandem repeat analysis and three additional direct-repeat markers. We identified two unique genotypes that represent a novel genetic lineage in the A cluster. Chadian isolates were susceptible to 11 antibiotics and free of 94 antibiotic resistance genes. PMID:16954291

Battered Women's Perceptions of Risk Versus Risk Factors and Instruments in Predicting Repeat Reassault

ERIC Educational Resources Information Center

Heckert, D. Alex; Gondolf, Edward W.

2004-01-01

This study partially replicates and expands on a previous study that showed women's perceptions of risk to be a strong predictor of reassault among batterers. The current study employed a larger and multisite sample, a longer follow-up period of 15 months, and multiple outcomes including "repeated reassault" (n = 499). According to the multinomial…

Effects of "D"-Amphetamine and Ethanol on Variable and Repetitive Key-Peck Sequences in Pigeons

ERIC Educational Resources Information Center

Ward, Ryan D.; Bailey, Ericka M.; Odum, Amy L.

2006-01-01

This experiment assessed the effects of "d"-Amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component,…

Retail clinic visits: are resident paneled patients more likely to make multiple visits?

PubMed

Angstman, Kurt B; Garrison, Gregory M; Rohrer, James E; Dupras, Denise M; O'Grady, Jason S

2012-04-01

Primary care resident physicians generally have significantly fewer hours in outpatient clinic per week than staff physicians. With the transient nature of a primary care resident's practice, do the patients of residents utilize the health care system differently? Our hypothesis was that patients paneled with a resident physician would be more likely to utilize retail clinics with repeat week day visits than those patients paneled with a staff primary care physician. A retrospective review of 16,318 retail clinic visits made in 2009 was studied. Since the patient making a repeat retail clinic visit had experience with the services available, they were making an informed decision on the type of care desired (their primary care provider or not). The patients who made repeat retail clinical visits were divided into groups by age, those younger than 18 years and those 18 years and older. Via multiple logistic regression, patients under 18 years demonstrated that a patient paneled with a resident physician was no more likely to have repeat visits to the retail clinic than a staff physician's patient, when controlling for all other variables. Similarly, those ages 18 years and older also demonstrated no differences in resident or staff paneled patients in utilization of retail clinics during the work day. Multivariate analysis found no difference in the utilization of repeat retail clinic visits during 2009 with resident paneled patients as compared to staff physician patients.

Peutz-Jeghers syndrome: Diagnostic and therapeutic approach

PubMed Central

Kopacova, Marcela; Tacheci, Ilja; Rejchrt, Stanislav; Bures, Jan

2009-01-01

Peutz-Jeghers syndrome (PJS) is an inherited, autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions. Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals. PJS predisposes sufferers to various malignancies (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular tumors). Bleeding, obstruction and intussusception are common complications in patients with PJS. Double balloon enteroscopy (DBE) allows examination and treatment of the small bowel. Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome. Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients. Intraoperative enteroscopy (IOE) was the only possibility for endoscopic treatment of patients with PJS before the DBE era. Both DBE and IOE facilitate exploration and treatment of the small intestine. DBE is less invasive and more convenient for the patient. Both procedures are generally safe and useful. An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution, but also regular lifelong cancer screening (colonoscopy, upper endoscopy, computed tomography, magnetic resonance imaging or ultrasound of the pancreas, chest X-ray, mammography and pelvic examination with ultrasound in women, and testicular examination in men). Although the incidence of PJS is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in the first-degree relatives of PJS patients. PMID:19916169

A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

PubMed Central

Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

2013-01-01

One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

Body shape convergence driven by small size optimum in marine angelfishes.

PubMed

Frédérich, Bruno; Santini, Francesco; Konow, Nicolai; Schnitzler, Joseph; Lecchini, David; Alfaro, Michael E

2017-06-01

Convergent evolution of small body size occurs across many vertebrate clades and may reflect an evolutionary response to shared selective pressures. However it remains unclear if other aspects of phenotype undergo convergent evolution in miniaturized lineages. Here we present a comparative analysis of body size and shape evolution in marine angelfishes (Pomacanthidae), a reef fish family characterized by repeated transitions to small body size. We ask if lineages that evolve small sizes show convergent evolution in body shape. Our results reveal that angelfish lineages evolved three different stable size optima with one corresponding to the group of pygmy angelfishes ( Centropyge ). Then, we test if the observed shifts in body size are associated with changes to new adaptive peaks in shape. Our data suggest that independent evolution to small size optima have induced repeated convergence upon deeper body and steeper head profile in Centropyge These traits may favour manoeuvrability and visual awareness in these cryptic species living among corals, illustrating that functional demands on small size may be related to habitat specialization and predator avoidance. The absence of shape convergence in large marine angelfishes also suggests that more severe requirements exist for small than for large size optima. © 2017 The Author(s).

Effects of Functional Mobility Skills Training for Adults with Severe Multiple Disabilities

ERIC Educational Resources Information Center

Whinnery, Stacie B.; Whinnery, Keith W.

2011-01-01

This study investigated the effects of a functional mobility program on the functional standing and walking skills of five adults with developmental disabilities. The Mobility Opportunities Via Education (MOVE) Curriculum was implemented using a multiple-baseline across subjects design. Repeated measures were taken during baseline, intervention…

Accuracy and repeatability of long-bone replicas of small animals fabricated by use of low-end and high-end commercial three-dimensional printers.

PubMed

Cone, Jamie A; Martin, Thomas M; Marcellin-Little, Denis J; Harrysson, Ola L A; Griffith, Emily H

2017-08-01

OBJECTIVE To assess the repeatability and accuracy of polymer replicas of small, medium, and large long bones of small animals fabricated by use of 2 low-end and 2 high-end 3-D printers. SAMPLE Polymer replicas of a cat femur, dog radius, and dog tibia were fabricated in triplicate by use of each of four 3-D printing methods. PROCEDURES 3-D renderings of the 3 bones reconstructed from CT images were prepared, and length, width of the proximal aspect, and width of the distal aspect of each CT image were measured in triplicate. Polymer replicas were fabricated by use of a high-end system that relied on jetting of curable liquid photopolymer, a high-end system that relied on polymer extrusion, a triple-nozzle polymer extrusion low-end system, and a dual-nozzle polymer extrusion low-end system. Polymer replicas were scanned by use of a laser-based coordinate measurement machine. Length, width of the proximal aspect, and width of the distal aspect of the scans of replicas were measured and compared with measurements for the 3-D renderings. RESULTS 129 measurements were collected for 34 replicas (fabrication of 1 large long-bone replica was unsuccessful on each of the 2 low-end printers). Replicas were highly repeatable for all 3-D printers. The 3-D printers overestimated dimensions of large replicas by approximately 1%. CONCLUSIONS AND CLINICAL RELEVANCE Low-end and high-end 3-D printers fabricated CT-derived replicas of bones of small animals with high repeatability. Replicas were slightly larger than the original bones.

Comparative Chloroplast Genomes of Photosynthetic Orchids: Insights into Evolution of the Orchidaceae and Development of Molecular Markers for Phylogenetic Applications

PubMed Central

Niu, Zhi-Tao; Liu, Wei; Xue, Qing-Yun; Ding, Xiao-Yu

2014-01-01

The orchid family Orchidaceae is one of the largest angiosperm families, including many species of important economic value. While chloroplast genomes are very informative for systematics and species identification, there is very limited information available on chloroplast genomes in the Orchidaceae. Here, we report the complete chloroplast genomes of the medicinal plant Dendrobium officinale and the ornamental orchid Cypripedium macranthos, demonstrating their gene content and order and potential RNA editing sites. The chloroplast genomes of the above two species and five known photosynthetic orchids showed similarities in structure as well as gene order and content, but differences in the organization of the inverted repeat/small single-copy junction and ndh genes. The organization of the inverted repeat/small single-copy junctions in the chloroplast genomes of these orchids was classified into four types; we propose that inverted repeats flanking the small single-copy region underwent expansion or contraction among Orchidaceae. The AT-rich regions of the ycf1 gene in orchids could be linked to the recombination of inverted repeat/small single-copy junctions. Relative species in orchids displayed similar patterns of variation in ndh gene contents. Furthermore, fifteen highly divergent protein-coding genes were identified, which are useful for phylogenetic analyses in orchids. To test the efficiency of these genes serving as markers in phylogenetic analyses, coding regions of four genes (accD, ccsA, matK, and ycf1) were used as a case study to construct phylogenetic trees in the subfamily Epidendroideae. High support was obtained for placement of previously unlocated subtribes Collabiinae and Dendrobiinae in the subfamily Epidendroideae. Our findings expand understanding of the diversity of orchid chloroplast genomes and provide a reference for study of the molecular systematics of this family. PMID:24911363

Comparative chloroplast genomes of photosynthetic orchids: insights into evolution of the Orchidaceae and development of molecular markers for phylogenetic applications.

PubMed

Luo, Jing; Hou, Bei-Wei; Niu, Zhi-Tao; Liu, Wei; Xue, Qing-Yun; Ding, Xiao-Yu

2014-01-01

The orchid family Orchidaceae is one of the largest angiosperm families, including many species of important economic value. While chloroplast genomes are very informative for systematics and species identification, there is very limited information available on chloroplast genomes in the Orchidaceae. Here, we report the complete chloroplast genomes of the medicinal plant Dendrobium officinale and the ornamental orchid Cypripedium macranthos, demonstrating their gene content and order and potential RNA editing sites. The chloroplast genomes of the above two species and five known photosynthetic orchids showed similarities in structure as well as gene order and content, but differences in the organization of the inverted repeat/small single-copy junction and ndh genes. The organization of the inverted repeat/small single-copy junctions in the chloroplast genomes of these orchids was classified into four types; we propose that inverted repeats flanking the small single-copy region underwent expansion or contraction among Orchidaceae. The AT-rich regions of the ycf1 gene in orchids could be linked to the recombination of inverted repeat/small single-copy junctions. Relative species in orchids displayed similar patterns of variation in ndh gene contents. Furthermore, fifteen highly divergent protein-coding genes were identified, which are useful for phylogenetic analyses in orchids. To test the efficiency of these genes serving as markers in phylogenetic analyses, coding regions of four genes (accD, ccsA, matK, and ycf1) were used as a case study to construct phylogenetic trees in the subfamily Epidendroideae. High support was obtained for placement of previously unlocated subtribes Collabiinae and Dendrobiinae in the subfamily Epidendroideae. Our findings expand understanding of the diversity of orchid chloroplast genomes and provide a reference for study of the molecular systematics of this family.

Multiple zeros of polynomials

NASA Technical Reports Server (NTRS)

Wood, C. A.

1974-01-01

For polynomials of higher degree, iterative numerical methods must be used. Four iterative methods are presented for approximating the zeros of a polynomial using a digital computer. Newton's method and Muller's method are two well known iterative methods which are presented. They extract the zeros of a polynomial by generating a sequence of approximations converging to each zero. However, both of these methods are very unstable when used on a polynomial which has multiple zeros. That is, either they fail to converge to some or all of the zeros, or they converge to very bad approximations of the polynomial's zeros. This material introduces two new methods, the greatest common divisor (G.C.D.) method and the repeated greatest common divisor (repeated G.C.D.) method, which are superior methods for numerically approximating the zeros of a polynomial having multiple zeros. These methods were programmed in FORTRAN 4 and comparisons in time and accuracy are given.

Repeated Cross-Sectional Assessment of Commercial Truck Driver Health.

PubMed

Thiese, Matthew S; Moffitt, Gary; Hanowski, Richard J; Kales, Stefanos N; Porter, Richard J; Hegmann, Kurt T

2015-09-01

To assess relationships and trends over time in individual conditions and multiple conditions among a large sample of independent, nonoverlapping truck drivers using a repeated cross-sectional study design. Commercial driver medical examinations were conducted on 95,567 commercial drivers between January 1, 2005, and October 31, 2012. Specific medical conditions that have been identified by the Federal Motor Carrier Safety Administration's Medical Review Board as possibly increasing crash risk were examined. Prevalence and trends over time were analyzed. A total of 8 of the 13 conditions significantly increased from 2005 to 2012. Prevalence of multiple concomitant conditions also increased, with prevalence odds ratios as high as 7.39 (95% confidence interval, 3.92 to 13.98) for four or more conditions in 2012 as compared with 2005. Individual and multiple conditions thought to be associated with increased crash risk significantly increased between 2005 and 2012.

Comprehensive analysis of all triple helical repeats in beta-spectrins reveals patterns of selective evolutionary conservation.

PubMed

Baines, Anthony J

2003-01-01

The spectrin superfamily (spectrin, alpha-actinin, utrophin and dystrophin) has in common a triple helical repeating unit of ~106 amino acid residues. In spectrin, alpha and beta chains contain multiple copies of this repeat. beta-spectrin chains contain the majority of binding activities in spectrin and are essential for animal life. Canonical beta-spectrins have 17 repeats; beta-heavy spectrins have 30. Here, the repeats of five human beta-spectrins, plus beta-spectrins from several other vertebrates and invertebrates, have been analysed. Repeats 1, 2, 14 and 17 in canonical beta are highly conserved between invertebrates and vertebrates, and repeat 8 in some isoforms. This is consistent with conservation of critical functions, since repeats 1, 2 and 17 bind alpha-spectrin. Repeats 1 of beta-spectrins are not always detected by SMART or Pfam tools. A profile hidden Markov model of beta-spectrin repeat 1 detects alpha-actinins, but not utrophin or dystrophin. Novel examples of repeat 1 were detected in the spectraplakins MACF1, BPAG1 and plectin close to the actin-binding domain. Ankyrin binds to the C-terminal portion of repeat 14; the high conservation of this entire repeat may point to additional, undiscovered ligand-binding activities. This analysis indicates that the basic triple helical repeat pattern was adapted early in the evolution of the spectrin superfamily to encompass essential binding activities, which characterise individual repeats in proteins extant today.

IMPLANTABLE RESONATORS – A TECHNIQUE FOR REPEATED MEASUREMENT OF OXYGEN AT MULTIPLE DEEP SITES WITH IN VIVO EPR

PubMed Central

Li, Hongbin; Hou, Huagang; Sucheta, Artur; Williams, Benjamin B.; Lariviere, Jean P.; Khan, Nadeem; Lesniewski, Piotr N.; Swartz, Harold M.

2013-01-01

EPR oximetry using implantable resonators allow measurements at much deeper sites than are possible with surface resonators (> 80 mm vs. 10 mm) and have greater sensitivity at any depth. We report here the development of an improvement of the technique that now enables us to obtain the information from multiple sites and at a variety of depths. The measurements from the various sites are resolved using a simple magnetic field gradient. In the rat brain multi-probe implanted resonators measured pO2 at several sites simultaneously for over 6 months to record under normoxic, hypoxic and hyperoxic conditions. This technique also facilitates measurements in moving parts of the animal such as the heart, because the orientation of the paramagnetic material relative to the sensitive small loop is not altered by the motion. The measured response is very fast, enabling measurements in real time of physiological and pathological changes such as experimental cardiac ischemia in the mouse heart. The technique also is quite useful for following changes in tumor pO2, including applications with simultaneous measurements in tumors and adjacent normal tissues. PMID:20204802

Repeated bubble breakup and coalescence in perturbed Hele-Shaw channels

NASA Astrophysics Data System (ADS)

Thompson, Alice; Franco-Gomez, Andres; Hazel, Andrew; Juel, Anne

2017-11-01

The introduction of an axially-uniform, centred constriction in a Hele-Shaw channel leads to multiple propagation modes for both air fingers and bubbles, including symmetric and asymmetric steadily propagating modes along with oscillations. These multiple modes correspond to a non-trivial bifurcation structure, and relate to the plethora of steadily propagating bubbles and fingers which exist in the Saffman-Taylor system. In both experiments and depth-averaged computations, a very small centred occlusion can be enough to trigger bubble breakup, with a single large centred bubble splitting into two smaller bubbles which propagate along each side of the channel. We present numerical simulations for the depth-averaged model, implementing geometric criteria for pinchoff and coalescence in order to track the bubble before and beyond breakup. We find that the two-bubble state is itself unstable, with finger competition causing one bubble to move ahead; the trailing bubble then moves across the channel to merge with the leading bubble. However, the story is not always so simple, enabling complicated cascades of splitting and merging bubbles. We compare the general dynamical behaviour, basins of attraction, and the details of merging and splitting, to experimental observations.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue

NASA Astrophysics Data System (ADS)

Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

2010-05-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

Quantitative polarized Raman spectroscopy in highly turbid bone tissue.

PubMed

Raghavan, Mekhala; Sahar, Nadder D; Wilson, Robert H; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H; Morris, Michael D

2010-01-01

Polarized Raman spectroscopy allows measurement of molecular orientation and composition and is widely used in the study of polymer systems. Here, we extend the technique to the extraction of quantitative orientation information from bone tissue, which is optically thick and highly turbid. We discuss multiple scattering effects in tissue and show that repeated measurements using a series of objectives of differing numerical apertures can be employed to assess the contributions of sample turbidity and depth of field on polarized Raman measurements. A high numerical aperture objective minimizes the systematic errors introduced by multiple scattering. We test and validate the use of polarized Raman spectroscopy using wild-type and genetically modified (oim/oim model of osteogenesis imperfecta) murine bones. Mineral orientation distribution functions show that mineral crystallites are not as well aligned (p<0.05) in oim/oim bones (28+/-3 deg) compared to wild-type bones (22+/-3 deg), in agreement with small-angle X-ray scattering results. In wild-type mice, backbone carbonyl orientation is 76+/-2 deg and in oim/oim mice, it is 72+/-4 deg (p>0.05). We provide evidence that simultaneous quantitative measurements of mineral and collagen orientations on intact bone specimens are possible using polarized Raman spectroscopy.

An algorithm for separation of mixed sparse and Gaussian sources

PubMed Central

Akkalkotkar, Ameya

2017-01-01

Independent component analysis (ICA) is a ubiquitous method for decomposing complex signal mixtures into a small set of statistically independent source signals. However, in cases in which the signal mixture consists of both nongaussian and Gaussian sources, the Gaussian sources will not be recoverable by ICA and will pollute estimates of the nongaussian sources. Therefore, it is desirable to have methods for mixed ICA/PCA which can separate mixtures of Gaussian and nongaussian sources. For mixtures of purely Gaussian sources, principal component analysis (PCA) can provide a basis for the Gaussian subspace. We introduce a new method for mixed ICA/PCA which we call Mixed ICA/PCA via Reproducibility Stability (MIPReSt). Our method uses a repeated estimations technique to rank sources by reproducibility, combined with decomposition of multiple subsamplings of the original data matrix. These multiple decompositions allow us to assess component stability as the size of the data matrix changes, which can be used to determinine the dimension of the nongaussian subspace in a mixture. We demonstrate the utility of MIPReSt for signal mixtures consisting of simulated sources and real-word (speech) sources, as well as mixture of unknown composition. PMID:28414814

An algorithm for separation of mixed sparse and Gaussian sources.

PubMed

Akkalkotkar, Ameya; Brown, Kevin Scott

2017-01-01

Independent component analysis (ICA) is a ubiquitous method for decomposing complex signal mixtures into a small set of statistically independent source signals. However, in cases in which the signal mixture consists of both nongaussian and Gaussian sources, the Gaussian sources will not be recoverable by ICA and will pollute estimates of the nongaussian sources. Therefore, it is desirable to have methods for mixed ICA/PCA which can separate mixtures of Gaussian and nongaussian sources. For mixtures of purely Gaussian sources, principal component analysis (PCA) can provide a basis for the Gaussian subspace. We introduce a new method for mixed ICA/PCA which we call Mixed ICA/PCA via Reproducibility Stability (MIPReSt). Our method uses a repeated estimations technique to rank sources by reproducibility, combined with decomposition of multiple subsamplings of the original data matrix. These multiple decompositions allow us to assess component stability as the size of the data matrix changes, which can be used to determinine the dimension of the nongaussian subspace in a mixture. We demonstrate the utility of MIPReSt for signal mixtures consisting of simulated sources and real-word (speech) sources, as well as mixture of unknown composition.

Comparison of stethoscope bell and diaphragm, and of stethoscope tube length, for clinical blood pressure measurement.

PubMed

Liu, Chengyu; Griffiths, Clive; Murray, Alan; Zheng, Dingchang

2016-06-01

This study investigated the effect of stethoscope side and tube length on auscultatory blood pressure (BP) measurement. Thirty-two healthy participants were studied. For each participant, four measurements with different combinations of stethoscope characteristics (bell or diaphragm side, standard or short tube length) were each recorded at two repeat sessions, and eight Korotkoff sound recordings were played twice on separate days to one experienced listener to determine the systolic and diastolic BPs (SBP and DBP). Analysis of variance was carried out to study the measurement repeatability between the two repeat sessions and between the two BP determinations on separate days, as well as the effects of stethoscope side and tube length. There was no significant paired difference between the repeat sessions and between the repeat determinations for both SBP and DBP (all P-values>0.10, except the repeat session for SBP using short tube and diaphragm). The key result was that there was a small but significantly higher DBP on using the bell in comparison with the diaphragm (0.66 mmHg, P=0.007), and a significantly higher SBP on using the short tube in comparison with the standard length (0.77 mmHg, P=0.008). This study shows that stethoscope characteristics have only a small, although statistically significant, influence on clinical BP measurement. Although this helps understand the measurement technique and resolves questions in the published literature, the influence is not clinically significant.

Comparison of stethoscope bell and diaphragm, and of stethoscope tube length, for clinical blood pressure measurement

PubMed Central

Griffiths, Clive; Murray, Alan; Zheng, Dingchang

2016-01-01

Objective This study investigated the effect of stethoscope side and tube length on auscultatory blood pressure (BP) measurement. Methods Thirty-two healthy participants were studied. For each participant, four measurements with different combinations of stethoscope characteristics (bell or diaphragm side, standard or short tube length) were each recorded at two repeat sessions, and eight Korotkoff sound recordings were played twice on separate days to one experienced listener to determine the systolic and diastolic BPs (SBP and DBP). Analysis of variance was carried out to study the measurement repeatability between the two repeat sessions and between the two BP determinations on separate days, as well as the effects of stethoscope side and tube length. Results There was no significant paired difference between the repeat sessions and between the repeat determinations for both SBP and DBP (all P-values>0.10, except the repeat session for SBP using short tube and diaphragm). The key result was that there was a small but significantly higher DBP on using the bell in comparison with the diaphragm (0.66 mmHg, P=0.007), and a significantly higher SBP on using the short tube in comparison with the standard length (0.77 mmHg, P=0.008). Conclusion This study shows that stethoscope characteristics have only a small, although statistically significant, influence on clinical BP measurement. Although this helps understand the measurement technique and resolves questions in the published literature, the influence is not clinically significant. PMID:26741415

MSDB: A Comprehensive Database of Simple Sequence Repeats.

PubMed

Avvaru, Akshay Kumar; Saxena, Saketh; Sowpati, Divya Tej; Mishra, Rakesh Kumar

2017-06-01

Microsatellites, also known as Simple Sequence Repeats (SSRs), are short tandem repeats of 1-6 nt motifs present in all genomes, particularly eukaryotes. Besides their usefulness as genome markers, SSRs have been shown to perform important regulatory functions, and variations in their length at coding regions are linked to several disorders in humans. Microsatellites show a taxon-specific enrichment in eukaryotic genomes, and some may be functional. MSDB (Microsatellite Database) is a collection of >650 million SSRs from 6,893 species including Bacteria, Archaea, Fungi, Plants, and Animals. This database is by far the most exhaustive resource to access and analyze SSR data of multiple species. In addition to exploring data in a customizable tabular format, users can view and compare the data of multiple species simultaneously using our interactive plotting system. MSDB is developed using the Django framework and MySQL. It is freely available at http://tdb.ccmb.res.in/msdb. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Molecular typing of Chinese Streptococcus pyogenes isolates.

PubMed

You, Yuanhai; Wang, Haibin; Bi, Zhenwang; Walker, Mark; Peng, Xianhui; Hu, Bin; Zhou, Haijian; Song, Yanyan; Tao, Xiaoxia; Kou, Zengqiang; Meng, Fanliang; Zhang, Menghan; Bi, Zhenqiang; Luo, Fengji; Zhang, Jianzhong

2015-06-01

Streptococcus pyogenes causes human infections ranging from mild pharyngitis and impetigo to serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. The objective of this study was to compare molecular emm typing and pulsed field gel electrophoresis (PFGE) with multiple-locus variable-number tandem-repeat analysis (MLVA) for genotyping of Chinese S. pyogenes isolates. Molecular emm typing and PFGE were performed using standard protocols. Seven variable number tandem repeat (VNTR) loci reported in a previous study were used to genotype 169 S. pyogenes geographically-diverse isolates from China isolated from a variety of disease syndromes. Multiple-locus variable-number tandem-repeat analysis provided greater discrimination between isolates when compared to emm typing and PFGE. Removal of a single VNTR locus (Spy2) reduced the sensitivity by only 0.7%, which suggests that Spy2 was not informative for the isolates screened. The results presented support the use of MLVA as a powerful epidemiological tool for genotyping S. pyogenes clinical isolates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple-locus variable-number tandem repeat analysis of Salmonella Enteritidis isolates from human and non-human sources using a single multiplex PCR

PubMed Central

Cho, Seongbeom; Boxrud, David J; Bartkus, Joanne M; Whittam, Thomas S; Saeed, Mahdi

2007-01-01

Simplified multiple-locus variable-number tandem repeat analysis (MLVA) was developed using one-shot multiplex PCR for seven variable-number tandem repeats (VNTR) markers with high diversity capacity. MLVA, phage typing, and PFGE methods were applied on 34 diverse Salmonella Enteritidis isolates from human and non-human sources. MLVA detected allelic variations that helped to classify the S. Enteritidis isolates into more evenly distributed subtypes than other methods. MLVA-based S. Enteritidis clonal groups were largely associated with sources of the isolates. Nei's diversity indices for polymorphism ranged from 0.25 to 0.70 for seven VNTR loci markers. Based on Simpson's and Shannon's diversity indices, MLVA had a higher discriminatory power than pulsed field gel electrophoresis (PFGE), phage typing, or multilocus enzyme electrophoresis. Therefore, MLVA may be used along with PFGE to enhance the effectiveness of the molecular epidemiologic investigation of S. Enteritidis infections. PMID:17692097

Improving the Medical Assessment of Patients Before Electroconvulsive Therapy: An Audit Across Two Sites.

PubMed

Driver, Hannah R

2016-06-01

It is essential that a medical assessment is completed before commencing electroconvulsive therapy (ECT) to identify possible risk factors that may complicate anesthesia. This audit aimed to improve the physical examination and documented medical history of this assessment usually performed by referring psychiatrists. Patients from 2 sites (A and B) were retrospectively audited against standards from the Scottish ECT Accreditation Network. The timing and systems examined for the physical examination were noted. Site A used an examination sheet; at site B there was no standard way of recording examination. Documented medical histories were compared with comprehensive histories obtained using multiple sources. Discrepancies were noted. Site A was reaudited after amending the examination sheet and adding prompts to use multiple sources when gathering histories. There were repeat examinations for ECT in 30 patients (100%) at site A and 6 (23%) of 26 at site B. Physical examinations were incomplete in 47% of patients at A and 100% at B. Oral examination was frequently missed at both sites. Medical histories were accurate in 20% at A and 38% at B. In the reaudit of site A, all 12 patients had a complete repeat examination; histories were accurate in 8 (67%), with multiple sources used in 11 (92%). Incomplete or inaccurate assessments put patients at risk. Oral examinations should be part of initial medical assessments. This audit shows the benefits of using a physical examination sheet to ensure a repeat complete examination. Using multiple sources to gather medical histories is encouraged.

Multiple-Ring Digital Communication Network

NASA Technical Reports Server (NTRS)

Kirkham, Harold

1992-01-01

Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

A simple technic for repeated collection of blood samples from mice.

PubMed

Stoltz, D R; Bendall, R D

1975-06-01

A device for repeated collection of small blood samples from mice was constructed from a plastic syringe. Blood was collected into a 3.33 lambda capillary tube. Bleeding was stopped by a hemostat made from a rubber stopper. This technic allows easy collection of approximately 20 serial samples within an 8-hr period.

Risk Factors of Repeated Infectious Disease Incidence among Substance Dependent Girls and Boys Court-Referred to Treatment

ERIC Educational Resources Information Center

Pagano, Maria E.; Maietti, Candice M.; Levine, Alan D.

2015-01-01

A small portion of Americans account for a disproportionate amount of the incidences of sexually transmitted infection observed over a short period of time. Studies with adults have begun to characterize this population, yet there is very little data on adolescent sexually transmitted infection repeaters (STIR). This study explores characteristics…

Subtle impacts of repeated glyphosate use on wheat-associated bacteria are small and depend on glyphosate use history

USDA-ARS?s Scientific Manuscript database

Glyphosate (Roundup) is the most widely used herbicide in the world and a critical tool for weed control in no-till wheat cropping systems. However, there are persistent concerns about non-target impacts of long-term glyphosate use on soil communities. We investigated the impacts of repeated glyphos...

Joking Culture: The Role of Repeated Humorous Interactions on Group Processes during Challenge Course Experiences

ERIC Educational Resources Information Center

Rothwell, Erin; Siharath, Kassidy; Bell, Steven; Nguyen, Kim; Baker, Carla

2011-01-01

When groups form, they develop their own culture from the shared meaning created from their interactions. Humor is part of every social group, and when repeatedly referenced, it forms a joking culture. The joking culture of small groups influences group processes by smoothing group interaction, forming a collective identity, separating the group…

Formation of peptides from amino acids by single or multiple additions of ATP to suspensions of nucleoproteinoid microparticles

NASA Technical Reports Server (NTRS)

Nakashima, T.; Fox, S. W.

1981-01-01

The synthesis of peptides from individual amino acids or pairs of amino acids and ATP in the presence of catalysis by nucleoproteinoid microparticles is investigated. Experiments were performed with suspensions formed from the condensation of lysine-rich and acidic proteinoids with polyadenylic acid, to which were added glycine, phenylalanine, proline, lysine or glycine-phenylalanine mixtures, and ATP either at once or serially. Peptide yields are found to be greatest for equal amounts of acidic and basic proteinoids. The addition of imidazole is found to alter the preference of glycine-phenylalanine mixtures to form mixed heteropeptides rather than homopeptides. A rapid ATP decay in the peptide synthesis reaction is observed, and a greater yield is obtained for repeated small additions than for a single addition of ATP. The experimental system has properties similar to modern cells, and represents an organizational unit ready for the evolution of associated biochemical pathways.

Network pharmacology of JAK inhibitors

PubMed Central

Moodley, Devapregasan; Yoshida, Hideyuki; Mostafavi, Sara; Asinovski, Natasha; Ortiz-Lopez, Adriana; Symanowicz, Peter; Telliez, Jean-Baptiste; Hegen, Martin; Clark, James D.; Mathis, Diane; Benoist, Christophe

2016-01-01

Small-molecule inhibitors of the Janus kinase family (JAKis) are clinically efficacious in multiple autoimmune diseases, albeit with increased risk of certain infections. Their precise mechanism of action is unclear, with JAKs being signaling hubs for several cytokines. We assessed the in vivo impact of pan- and isoform-specific JAKi in mice by immunologic and genomic profiling. Effects were broad across the immunogenomic network, with overlap between inhibitors. Natural killer (NK) cell and macrophage homeostasis were most immediately perturbed, with network-level analysis revealing a rewiring of coregulated modules of NK cell transcripts. The repression of IFN signature genes after repeated JAKi treatment continued even after drug clearance, with persistent changes in chromatin accessibility and phospho-STAT responsiveness to IFN. Thus, clinical use and future development of JAKi might need to balance effects on immunological networks, rather than expect that JAKis affect a particular cytokine response and be cued to long-lasting epigenomic modifications rather than by short-term pharmacokinetics. PMID:27516546

Small molecule kinase inhibitors for LRRK2 and their application to Parkinson's disease models.

PubMed

Kramer, Thomas; Lo Monte, Fabio; Göring, Stefan; Okala Amombo, Ghislaine Marlyse; Schmidt, Boris

2012-03-21

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Several single gene mutations have been linked to this disease. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) indicate LRRK2 as promising therapeutic target for the treatment of PD. LRRK2 mutations were observed in sporadic as well as familial PD patients and have been investigated intensively. LRRK2 is a large and complex protein, with multiple enzymatic and protein-interaction domains, each of which is effected by mutations. The most common mutation in PD patients is G2019S. Several LRRK2 inhibitors have been reported already, although the crystal structure of LRRK2 has not yet been determined. This review provides a summary of known LRRK2 inhibitors and will discuss recent in vitro and in vivo results of these inhibitors.

Computer Simulation Shows the Effect of Communication on Day of Surgery Patient Flow.

PubMed

Taaffe, Kevin; Fredendall, Lawrence; Huynh, Nathan; Franklin, Jennifer

2015-07-01

To improve patient flow in a surgical environment, practitioners and academicians often use process mapping and simulation as tools to evaluate and recommend changes. We used simulations to help staff visualize the effect of communication and coordination delays that occur on the day of surgery. Perioperative services staff participated in tabletop exercises in which they chose the delays that were most important to eliminate. Using a day-of-surgery computer simulation model, the elimination of delays was tested and the results were shared with the group. This exercise, repeated for multiple groups of staff, provided an understanding of not only the dynamic events taking place, but also how small communication delays can contribute to a significant loss in efficiency and the ability to provide timely care. Survey results confirmed these understandings. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Automated mask and wafer defect classification using a novel method for generalized CD variation measurements

NASA Astrophysics Data System (ADS)

Verechagin, V.; Kris, R.; Schwarzband, I.; Milstein, A.; Cohen, B.; Shkalim, A.; Levy, S.; Price, D.; Bal, E.

2018-03-01

Over the years, mask and wafers defects dispositioning has become an increasingly challenging and time consuming task. With design rules getting smaller, OPC getting complex and scanner illumination taking on free-form shapes - the probability of a user to perform accurate and repeatable classification of defects detected by mask inspection tools into pass/fail bins is reducing. The critical challenging of mask defect metrology for small nodes ( < 30 nm) was reviewed in [1]. While Critical Dimension (CD) variation measurement is still the method of choice for determining a mask defect future impact on wafer, the high complexity of OPCs combined with high variability in pattern shapes poses a challenge for any automated CD variation measurement method. In this study, a novel approach for measurement generalization is presented. CD variation assessment performance is evaluated on multiple different complex shape patterns, and is benchmarked against an existing qualified measurement methodology.

Armc5 deletion causes developmental defects and compromises T-cell immune responses

PubMed Central

Hu, Yan; Lao, Linjiang; Mao, Jianning; Jin, Wei; Luo, Hongyu; Charpentier, Tania; Qi, Shijie; Peng, Junzheng; Hu, Bing; Marcinkiewicz, Mieczyslaw Martin; Lamarre, Alain; Wu, Jiangping

2017-01-01

Armadillo repeat containing 5 (ARMC5) is a cytosolic protein with no enzymatic activities. Little is known about its function and mechanisms of action, except that gene mutations are associated with risks of primary macronodular adrenal gland hyperplasia. Here we map Armc5 expression by in situ hybridization, and generate Armc5 knockout mice, which are small in body size. Armc5 knockout mice have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. These mice also develop adrenal gland hyperplasia in old age. Yeast 2-hybrid assays identify 16 ARMC5-binding partners. Together these data indicate that ARMC5 is crucial in fetal development, T-cell function and adrenal gland growth homeostasis, and that the functions of ARMC5 probably depend on interaction with multiple signalling pathways. PMID:28169274

A Tool for Medical Research

NASA Technical Reports Server (NTRS)

1992-01-01

California Measurements, Inc.'s PC-2 Aerosol Particle Analyzer, developed by William Chiang, a former Jet Propulsion Laboratory (JPL) engineer, was used in a study to measure the size of particles in the medical environment. Chiang has a NASA license for the JPL crystal oscillator technology and originally built the instrument for atmospheric research. In the operating room, it enabled researchers from the University of California to obtain multiple sets of data repeatedly and accurately. The study concluded that significant amounts of aerosols are generated during surgery when power tools are employed, and most of these are in the respirable size. Almost all contain blood and are small enough to pass through surgical masks. Research on the presence of blood aerosols during oral surgery had similar results. Further studies are planned to determine the possibility of HIV transmission during surgery, and the PC-2H will be used to quantify blood aerosols.

Rapid Characterization of Shorelines using a Georeferenced Video Mapping System

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

Anderson, Michael G.; Judd, Chaeli; Marcoe, K.

Increased understanding of shoreline conditions is needed, yet current approaches are limited in ability to characterize remote areas or document features at a finer resolution. Documentation using video mapping may provide a rapid and repeatable method for assessing the current state of the environment and determining changes to the shoreline over time. In this study, we compare two studies using boat-based, georeferenced video mapping in coastal Washington and the Columbia River Estuary to map and characterize coastal stressors and functional data. In both areas, mapping multiple features along the shoreline required approximation of the coastline. However, characterization of vertically orientedmore » features such as shoreline armoring and small features such as pilings and large woody debris was possible. In addition, end users noted that geovideo provides a permanent record to allow a user to examine recorded video anywhere along a transect or at discrete points.« less

Microseismic Monitoring of the Mounds Drill Cuttings Injection Tests

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

Branagan, P.T.; Mahrer, K.D.; Moschovidis, Z.A.

This paper describes the microseismic mapping of repeated injections of drill cuttings into two separate formations at a test site near Mounds, OK. Injections were performed in sandstone and shale formations at depths of 830 and 595 m, respectively. Typical injection disposal was simulated using multiple small-volume injections over a three-day period, with long shut-in periods interspersed between the injections. Microseismic monitoring was achieved using a 5-level array of wireline-run, triaxial- accelerometer receivers in a monitor well 76 m from the disposed well. Results of the mapped microseismic locations showed that the disposal domti W= generally aligns with the majormore » horizontal stress with some variations in azimuth and that wide variations in height and length growth occurred with continued injections. These experiments show that the cuttings injection process cm be adequately monitored from a downhole, wireline-run receiver array, thus providing process control and environmental assurance.« less

Repeated cis-regulatory tuning of a metabolic bottleneck gene during evolution.

PubMed

Kuang, Meihua Christina; Kominek, Jacek; Alexander, William G; Cheng, Jan-Fang; Wrobel, Russell L; Hittinger, Chris Todd

2018-05-21

Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.

Repeating Patterns and Multiplicative Thinking: Analysis of Classroom Interactions with 9-Year-Old Students that Support the Transition from the Known to the Novel

ERIC Educational Resources Information Center

Warren, Elizabeth; Cooper, Tom

2007-01-01

In early years' (primary grade) classrooms in Australia repeated patterns are commonly explored as an early introductory activity to mathematics. Most young students have an extensive knowledge of and exhibit success in copying, continuing, creating and transferring patterns into other media. By contrast, research indicates one of the most…

Variable Effects of Exposure to Formulated Microbicides on Antibiotic Susceptibility in Firmicutes and Proteobacteria

PubMed Central

Forbes, Sarah; Knight, Christopher G.; Cowley, Nicola L.; Amézquita, Alejandro; McClure, Peter; Humphreys, Gavin

2016-01-01

ABSTRACT Microbicides are broad-spectrum antimicrobial agents that generally interact with multiple pharmacological targets. While they are widely deployed in disinfectant, antiseptic, and preservative formulations, data relating to their potential to select for microbicide or antibiotic resistance have been generated mainly by testing the compounds in much simpler aqueous solutions. In the current investigation, antibiotic susceptibility was determined for bacteria that had previously exhibited decreased microbicide susceptibility following repeated exposure to microbicides either in formulation with sequestrants and surfactants or in simple aqueous solution. Statistically significant increases in antibiotic susceptibility occurred for 12% of bacteria after exposure to microbicides in formulation and 20% of bacteria after exposure to microbicides in aqueous solutions, while 22% became significantly less susceptible to the antibiotics, regardless of formulation. Of the combinations of a bacterium and an antibiotic for which British Society for Antimicrobial Chemotherapy breakpoints are available, none became resistant. Linear modeling taking into account phylogeny, microbicide, antibiotic, and formulation identified small but significant effects of formulation that varied depending on the bacterium and microbicide. Adaptation to formulated benzalkonium chloride in particular was more likely to increase antibiotic susceptibility than adaptation to the simple aqueous solution. In conclusion, bacterial adaptation through repeated microbicide exposure was associated with both increases and decreases in antibiotic susceptibility. Formulation of the microbicide to which the bacteria had previously adapted had an identifiable effect on antibiotic susceptibility, but it effect was typically small relative to the differences observed among microbicides. Susceptibility changes resulting in resistance were not observed. IMPORTANCE The safety of certain microbicide applications has been questioned due to the possibility that microbicide exposure could select for microbicide and antibiotic resistance. Evidence that this may happen is based mainly on in vitro experiments where bacteria have been exposed to microbicides in aqueous solution. Microbicides are, however, normally deployed in products formulated with surfactants, sequestrants, and other compounds. While this may influence the frequency and extent of susceptibility changes, few studies reported in the literature have assessed this. In the current investigation, therefore, we have investigated changes in antibiotic susceptibility in bacteria which exhibited decreased microbicide susceptibility following repeated exposure to microbicides in simple aqueous solutions and in formulation. We report that the microbicide formulation had an identifiable effect on antibiotic susceptibility, but it was typically small relative to the differences observed among microbicides. We did not observe susceptibility changes resulting in resistance. PMID:27060123

Tracheobronchial Polyflex stents for the management of benign refractory hypopharyngeal strictures.

PubMed

Silva, Rui Almeida; Mesquita, Nuno; Nunes, Pedro Pimentel; Cardoso, Elisabete; Pinto, Ricardo Marcos; Dias, Luís Moreira

2012-02-14

To describe a modified technique for placement of a tracheobronchial self-expanding plastic stent (SEPS) in patients with benign refractory hypopharyngeal strictures in order to improve dysphagia and allow stricture remodeling. A case series of four consecutive patients with complex hypopharyngeal strictures after combined therapy for laryngeal cancer, previously submitted to multiple sessions of dilation without lasting improvement, is presented. All patients underwent placement of a small diameter and unflared tracheobronchial SEPS. Main outcome measurements were improvement of dysphagia and avoiding of repeated dilation. The modified introducer system allowed an easy and technically successful deployment of the tracheobronchial Polyflex stent through the stricture. All four patients developed complications related to stent placement. Two patients had stent migration (one proximal and one distal), two patients developed phanryngocutaneous fistulas and all patients with stents in situ for more than 8 wk had hyperplastic tissue growth at the upper end of the stent. Stricture recurrence was observed at 4 wk follow-up after stent removal in all patients. Although technically feasible, placement of a tracheobronchial SEPS is associated with a high risk of complications. Small diameter stents must be kept in place for longer than 3 mo to allow adequate time for stricture remodeling.

Stretch-induced contraction in pulmonary arteries.

PubMed

Kulik, T J; Evans, J N; Gamble, W J

1988-12-01

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.

Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells.

PubMed

Kwon, ChangHyuk; Tak, Hyosun; Rho, Mina; Chang, Hae Ryung; Kim, Yon Hui; Kim, Kyung Tae; Balch, Curt; Lee, Eun Kyung; Nam, Seungyoon

2014-03-28

Piwi-interacting RNAs (piRNAs) are 26-31 nt small noncoding RNAs that are processed from their longer precursor transcripts by Piwi proteins. Localization of Piwi and piRNA has been reported mostly in nucleus and cytoplasm of higher eukaryotes germ-line cells, where it is believed that known piRNA sequences are located in repeat regions of nuclear genome in germ-line cells. However, localization of PIWI and piRNA in mammalian somatic cell mitochondria yet remains largely unknown. We identified 29 piRNA sequence alignments from various regions of the human mitochondrial genome. Twelve out 29 piRNA sequences matched stem-loop fragment sequences of seven distinct tRNAs. We observed their actual expression in mitochondria subcellular fractions by inspecting mitochondrial-specific small RNA-Seq datasets. Of interest, the majority of the 29 piRNAs overlapped with multiple longer transcripts (expressed sequence tags) that are unique to the human mitochondrial genome. The presence of mature piRNAs in mitochondria was detected by qRT-PCR of mitochondrial subcellular RNAs. Further validation showed detection of Piwi by colocalization using anti-Piwil1 and mitochondria organelle-specific protein antibodies. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Reduced genetic influence on childhood obesity in small for gestational age children

PubMed Central

2013-01-01

Background Children born small-for-gestational-age (SGA) are at increased risk of developing obesity and metabolic diseases later in life, a risk which is magnified if followed by accelerated postnatal growth. We investigated whether common gene variants associated with adult obesity were associated with increased postnatal growth, as measured by BMI z-score, in children born SGA and appropriate for gestational age (AGA) in the Auckland Birthweight Collaborative. Methods A total of 37 candidate SNPs were genotyped on 547 European children (228 SGA and 319 AGA). Repeated measures of BMI (z-score) were used for assessing obesity status, and results were corrected for multiple testing using the false discovery rate. Results SGA children had a lower BMI z-score than non-SGA children at assessment age 3.5, 7 and 11 years. We confirmed 27 variants within 14 obesity risk genes to be individually associated with increasing early childhood BMI, predominantly in those born AGA. Conclusions Genetic risk variants are less important in influencing early childhood BMI in those born SGA than in those born AGA, suggesting that non-genetic or environmental factors may be more important in influencing childhood BMI in those born SGA. PMID:23339409

Multiple injection mode with or without repeated sample injections: Strategies to enhance productivity in countercurrent chromatography.

PubMed

Müller, Marco; Wasmer, Katharina; Vetter, Walter

2018-06-29

Countercurrent chromatography (CCC) is an all liquid based separation technique typically used for the isolation and purification of natural compounds. The simplicity of the method makes it easy to scale up CCC separations from analytical to preparative and even industrial scale. However, scale-up of CCC separations requires two different instruments with varying coil dimensions. Here we developed two variants of the CCC multiple injection mode as an alternative to increase the throughput and enhance productivity of a CCC separation when using only one instrument. The concept is based on the parallel injection of samples at different points in the CCC column system and the simultaneous separation using one pump only. The wiring of the CCC setup was modified by the insertion of a 6-port selection valve, multiple T-pieces and sample loops. Furthermore, the introduction of storage sample loops enabled the CCC system to be used with repeated injection cycles. Setup and advantages of both multiple injection modes were shown by the isolation of the furan fatty acid 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5-EE) from an ethyl ester oil rich in 4,7,10,13,16,19-docosahexaenoic acid (DHA-EE). 11D5-EE was enriched in one step from 1.9% to 99% purity. The solvent consumption per isolated amount of analyte could be reduced by ∼40% compared to increased throughput CCC and by ∼5% in the repeated multiple injection mode which also facilitated the isolation of the major compound (DHA-EE) in the sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Feedback produces divergence from prospect theory in descriptive choice.

PubMed

Jessup, Ryan K; Bishara, Anthony J; Busemeyer, Jerome R

2008-10-01

A recent study demonstrated that individuals making experience-based choices underweight small probabilities, in contrast to the overweighting observed in a typical descriptive paradigm. We tested whether trial-by-trial feedback in a repeated descriptive paradigm would engender choices more correspondent with experiential or descriptive paradigms. The results of a repeated gambling task indicated that individuals receiving feedback underweighted small probabilities, relative to their no-feedback counterparts. These results implicate feedback as a critical component during the decision-making process, even in the presence of fully specified descriptive information. A model comparison at the individual-subject level suggested that feedback drove individuals' decision weights toward objective probability weighting.

Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome.

PubMed

Yang, Wang-Yong; He, Fang; Strack, Rita L; Oh, Seok Yoon; Frazer, Michelle; Jaffrey, Samie R; Todd, Peter K; Disney, Matthew D

2016-09-16

RNA transcripts containing expanded nucleotide repeats cause many incurable diseases via various mechanisms. One such disorder, fragile X-associated tremor ataxia syndrome (FXTAS), is caused by a noncoding r(CGG) repeat expansion (r(CGG)(exp)) that (i) sequesters proteins involved in RNA metabolism in nuclear foci, causing dysregulation of alternative pre-mRNA splicing, and (ii) undergoes repeat associated non-ATG translation (RANT), which produces toxic homopolymeric proteins without using a start codon. Here, we describe the design of two small molecules that inhibit both modes of toxicity and the implementation of various tools to study perturbation of these cellular events. Competitive Chemical Cross Linking and Isolation by Pull Down (C-Chem-CLIP) established that compounds bind r(CGG)(exp) and defined small molecule occupancy of r(CGG)(exp) in cells, the first approach to do so. Using an RNA GFP mimic, r(CGG)(exp)-Spinach2, we observe that our optimal designed compound binds r(CGG)(exp) and affects RNA localization by disrupting preformed RNA foci. These events correlate with an improvement of pre-mRNA splicing defects caused by RNA gain of function. In addition, the compounds reduced levels of toxic homopolymeric proteins formed via RANT. Polysome profiling studies showed that small molecules decreased loading of polysomes onto r(CGG)(exp), explaining decreased translation.

Extending substructure based iterative solvers to multiple load and repeated analyses

NASA Technical Reports Server (NTRS)

Farhat, Charbel

1993-01-01

Direct solvers currently dominate commercial finite element structural software, but do not scale well in the fine granularity regime targeted by emerging parallel processors. Substructure based iterative solvers--often called also domain decomposition algorithms--lend themselves better to parallel processing, but must overcome several obstacles before earning their place in general purpose structural analysis programs. One such obstacle is the solution of systems with many or repeated right hand sides. Such systems arise, for example, in multiple load static analyses and in implicit linear dynamics computations. Direct solvers are well-suited for these problems because after the system matrix has been factored, the multiple or repeated solutions can be obtained through relatively inexpensive forward and backward substitutions. On the other hand, iterative solvers in general are ill-suited for these problems because they often must restart from scratch for every different right hand side. In this paper, we present a methodology for extending the range of applications of domain decomposition methods to problems with multiple or repeated right hand sides. Basically, we formulate the overall problem as a series of minimization problems over K-orthogonal and supplementary subspaces, and tailor the preconditioned conjugate gradient algorithm to solve them efficiently. The resulting solution method is scalable, whereas direct factorization schemes and forward and backward substitution algorithms are not. We illustrate the proposed methodology with the solution of static and dynamic structural problems, and highlight its potential to outperform forward and backward substitutions on parallel computers. As an example, we show that for a linear structural dynamics problem with 11640 degrees of freedom, every time-step beyond time-step 15 is solved in a single iteration and consumes 1.0 second on a 32 processor iPSC-860 system; for the same problem and the same parallel processor, a pair of forward/backward substitutions at each step consumes 15.0 seconds.

Effective screen of CRISPR/Cas9-induced mutants in rice by single-strand conformation polymorphism.

PubMed

Zheng, Xuelian; Yang, Shixin; Zhang, Dengwei; Zhong, Zhaohui; Tang, Xu; Deng, Kejun; Zhou, Jianping; Qi, Yiping; Zhang, Yong

2016-07-01

A method based on DNA single-strand conformation polymorphism is demonstrated for effective genotyping of CRISPR/Cas9-induced mutants in rice. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) has been widely adopted for genome editing in many organisms. A large proportion of mutations generated by CRISPR/Cas9 are very small insertions and deletions (indels), presumably because Cas9 generates blunt-ended double-strand breaks which are subsequently repaired without extensive end-processing. CRISPR/Cas9 is highly effective for targeted mutagenesis in the important crop, rice. For example, homozygous mutant seedlings are commonly recovered from CRISPR/Cas9-treated calli. However, many current mutation detection methods are not very suitable for screening homozygous mutants that typically carry small indels. In this study, we tested a mutation detection method based on single-strand conformational polymorphism (SSCP). We found it can effectively detect small indels in pilot experiments. By applying the SSCP method for CRISRP-Cas9-mediated targeted mutagenesis in rice, we successfully identified multiple mutants of OsROC5 and OsDEP1. In conclusion, the SSCP analysis will be a useful genotyping method for rapid identification of CRISPR/Cas9-induced mutants, including the most desirable homozygous mutants. The method also has high potential for similar applications in other plant species.

High-output stoma after small-bowel resections for Crohn's disease.

PubMed

Tsao, Stephen K K; Baker, Melanie; Nightingale, Jeremy M D

2005-12-01

A 56-year-old Caucasian woman with a history of Crohn's disease and multiple bowel resections resulting in a loop jejunostomy was referred to our Nutritional Unit from a neighboring district general hospital for further management. She was first seen in October 2001, and initial assessment indicated that she was malnourished with fluid depletion, evidenced by the high volume of stomal fluid produced. There had been no sudden change in her medication, her Crohn's disease was quiescent and there was no evidence of any intra-abdominal sepsis. Despite a high calorific intake through her diet, she continued to lose weight. Serum urea and electrolytes; magnesium; C-reactive protein; full blood count; urinary spot sodium; anthropometric measurements. High-output stoma with malabsorption as a consequence of repeated small-bowel surgery. The patient was treated with oral hypotonic fluid restriction (0.5 l/day), 2 l of oral glucose-saline solution per day, high-dose oral antimotility agents (loperamide and codeine phosphate), a proton-pump inhibitor (omeprazole) and oral magnesium replacement. A year later, the patient's loop jejunostomy was closed and an end ileostomy fashioned, bringing an additional 35 cm of small bowel into continuity; macronutrient absorption improved but her problem of dehydration was only slightly reduced. She was stabilized on a twice-weekly subcutaneous magnesium and saline infusion and daily oral 1alpha-hydroxycholecalciferol.

Controls of repeating earthquakes' location from a- and b- values imaging

NASA Astrophysics Data System (ADS)

Chen, K. H.; Kawamura, M.

2017-12-01

The locations where creeping and locked fault areas abut have commonly found to be delineated by the foci of small repeating earthquakes (REs). REs not only represent the finer structure of high creep-rate location, they also function as fault slip-rate indicators. Knowledge of the expected location of REs therefore, is crucial for fault deformation monitoring and assessment of earthquake potential. However, a precise description of factors determining REs locations is lacking. To explore where earthquakes tend to recur, we statistically investigated repeating earthquake catalogs and background seismicity from different regions including six fault segments in California and Taiwan. We show that the location of repeating earthquakes can be mapped using the spatial distribution of the seismic a- and b-values obtained from the background seismicity. Molchan's error diagram statistically confirmed that repeating earthquakes occur within areas with high a-values (2.8-3.8) and high b-values (0.9-1.1) on both strike-slip and thrust fault segments. However, no significant association held true for fault segments with more complicated geometry or for wider areas with a complex fault network. The productivity of small earthquakes responsible for high a- and b-values may thus be the most important factor controlling the location of repeating earthquakes. We hypothesize that, given that the deformation conditions within a fault zone are suitable for a planar fault plane, the location of repeating earthquakes can be best described by a-value 3 and b-value 1. This feature of a- and b-values may be useful for foresee the location of REs for measuring creep rate at depth. Further investigation of REs-rich areas may allow testing of this hypothesis.

Tandem repeat regions within the Burkholderia pseudomallei genome and their application for high resolution genotyping.

PubMed

U'Ren, Jana M; Schupp, James M; Pearson, Talima; Hornstra, Heidie; Friedman, Christine L Clark; Smith, Kimothy L; Daugherty, Rebecca R Leadem; Rhoton, Shane D; Leadem, Ben; Georgia, Shalamar; Cardon, Michelle; Huynh, Lynn Y; DeShazer, David; Harvey, Steven P; Robison, Richard; Gal, Daniel; Mayo, Mark J; Wagner, David; Currie, Bart J; Keim, Paul

2007-03-30

The facultative, intracellular bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. We identified and categorized tandem repeat arrays and their distribution throughout the genome of B. pseudomallei strain K96243 in order to develop a genetic typing method for B. pseudomallei. We then screened 104 of the potentially polymorphic loci across a diverse panel of 31 isolates including B. pseudomallei, B. mallei and B. thailandensis in order to identify loci with varying degrees of polymorphism. A subset of these tandem repeat arrays were subsequently developed into a multiple-locus VNTR analysis to examine 66 B. pseudomallei and 21 B. mallei isolates from around the world, as well as 95 lineages from a serial transfer experiment encompassing ~18,000 generations. B. pseudomallei contains a preponderance of tandem repeat loci throughout its genome, many of which are duplicated elsewhere in the genome. The majority of these loci are composed of repeat motif lengths of 6 to 9 bp with 4 to 10 repeat units and are predominately located in intergenic regions of the genome. Across geographically diverse B. pseudomallei and B.mallei isolates, the 32 VNTR loci displayed between 7 and 28 alleles, with Nei's diversity values ranging from 0.47 and 0.94. Mutation rates for these loci are comparable (>10-5 per locus per generation) to that of the most diverse tandemly repeated regions found in other less diverse bacteria. The frequency, location and duplicate nature of tandemly repeated regions within the B. pseudomallei genome indicate that these tandem repeat regions may play a role in generating and maintaining adaptive genomic variation. Multiple-locus VNTR analysis revealed extensive diversity within the global isolate set containing B. pseudomallei and B. mallei, and it detected genotypic differences within clonal lineages of both species that were identical using previous typing methods. Given the health threat to humans and livestock and the potential for B. pseudomallei to be released intentionally, MLVA could prove to be an important tool for fine-scale epidemiological or forensic tracking of this increasingly important environmental pathogen.

No impact of repeated extinction exposures on operant responding maintained by different reinforcer rates.

PubMed

Bai, John Y H; Podlesnik, Christopher A

2017-05-01

Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests. Copyright © 2017 Elsevier B.V. All rights reserved.

Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1×1 Nucleotide UU Internal Loop Conformations⊥

PubMed Central

Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D.

2011-01-01

RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5′CUG/3′GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures are disclosed of a model DM1 triplet repeating construct, 5′r(UUGGGC(CUG)3GUCC)2, refined to 2.20 Å and 1.52 Å resolution. Here, differences in orientation of the 5′ dangling UU end between the two structures induce changes in the backbone groove width, which reveals that non-canonical 1×1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 Å structure, CUGa, the 5′UU forms one hydrogen-bonded pairs with a 5′UU of a neighboring helix in the unit cell to form a pseudo-infinite helix. The central 1×1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1×1 nucleotide UU internal loops each form a one hydrogen-bonded pair. In the 1.52 Å structure, CUGb, the 5′ UU dangling end is tucked into the major groove of the duplex. While the canonical paired bases show no change in base pairing, in CUGb the terminal 1×1 nucleotide UU internal loops form now two hydrogen-bonded pairs. Thus, the shift in major groove induced by the 5′UU dangling end alters non-canonical base patterns. Collectively, these structures indicate that 1×1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands. PMID:21988728

Myotonic dystrophy type 1 RNA crystal structures reveal heterogeneous 1 × 1 nucleotide UU internal loop conformations.

PubMed

Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W; Disney, Matthew D

2011-11-15

RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[UUGGGC(CUG)(3)GUCC](2), refined to 2.20 and 1.52 Å resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 × 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 Å structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 × 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 × 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 Å structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 × 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 × 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

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

Kumar, Amit; Park, HaJeung; Fang, Pengfei

2012-03-27

RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations.more » In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.« less

Examining Spillovers between Long and Short Repeated Prisoner's Dilemma Games Played in the Laboratory.

PubMed

Arechar, Antonio A; Kouchaki, Maryam; Rand, David G

2018-03-01

We had participants play two sets of repeated Prisoner's Dilemma (RPD) games, one with a large continuation probability and the other with a small continuation probability, as well as Dictator Games (DGs) before and after the RPDs. We find that, regardless of which is RPD set is played first, participants typically cooperate when the continuation probability is large and defect when the continuation probability is small. However, there is an asymmetry in behavior when transitioning from one continuation probability to the other. When switching from large to small, transient higher levels of cooperation are observed in the early games of the small continuation set. Conversely, when switching from small to large, cooperation is immediately high in the first game of the large continuation set. We also observe that response times increase when transitioning between sets of RPDs, except for altruistic participants transitioning into the set of RPDs with long continuation probabilities. These asymmetries suggest a bias in favor of cooperation. Finally, we examine the link between altruism and RPD play. We find that small continuation probability RPD play is correlated with giving in DGs played before and after the RPDs, whereas high continuation probability RPD play is not.

A Method for WD40 Repeat Detection and Secondary Structure Prediction

PubMed Central

Wang, Yang; Jiang, Fan; Zhuo, Zhu; Wu, Xian-Hui; Wu, Yun-Dong

2013-01-01

WD40-repeat proteins (WD40s), as one of the largest protein families in eukaryotes, play vital roles in assembling protein-protein/DNA/RNA complexes. WD40s fold into similar β-propeller structures despite diversified sequences. A program WDSP (WD40 repeat protein Structure Predictor) has been developed to accurately identify WD40 repeats and predict their secondary structures. The method is designed specifically for WD40 proteins by incorporating both local residue information and non-local family-specific structural features. It overcomes the problem of highly diversified protein sequences and variable loops. In addition, WDSP achieves a better prediction in identifying multiple WD40-domain proteins by taking the global combination of repeats into consideration. In secondary structure prediction, the average Q3 accuracy of WDSP in jack-knife test reaches 93.7%. A disease related protein LRRK2 was used as a representive example to demonstrate the structure prediction. PMID:23776530

A Correction for the Epsilon Approximate Test in Repeated Measures Designs with Two or More Independent Groups.

ERIC Educational Resources Information Center

Lecoutre, Bruno

1991-01-01

The routine epsilon approximate test in repeated measures designs when the condition of circularity is unfulfilled uses an erroneous formula in the case of two or more groups. Because this may lead to underestimation of the deviation from circularity when the subject number is small, a correction is proposed. (Author/SLD)

Analysis of the repeatability of the exhaust pollutants emission research results for cold and hot starts under controlled driving cycle conditions.

PubMed

Jaworski, Artur; Kuszewski, Hubert; Ustrzycki, Adam; Balawender, Krzysztof; Lejda, Kazimierz; Woś, Paweł

2018-04-20

Measurement of car engines exhaust pollutants emissions is very important because of their harmful effects on the environment. This article presents the assessment of repeatability of the passenger car engine exhaust pollutants emission research results obtained in the conditions of a chassis dynamometer. The research was conducted in a climate chamber, enabling the temperature conditions to be determined from - 20 to + 30 °C. The emission of CO, CH 4 , CO 2 , NO X , THC, and NMHC was subjected to the analysis. The aim of the research is to draw attention to the accuracy of the pollutant emission research results in driving cycles, and the comparison of pollutant emission results and their repeatability obtained in successive NEDC cycles under cold and hot start conditions. The results of the analysis show that, in the case of a small number of measurements, the results repeatability analysis is necessary for a proper interpretation of the pollutant emission results on the basis of the mean value. According to the authors' judgment, it is beneficial to determine the coefficient of variation for a more complete assessment of exhaust emission result repeatability obtained from a small number of measurements. This parameter is rarely presented by the authors of papers on exhaust components emission research.

Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.

PubMed

Murmann, Andrea E; Gao, Quan Q; Putzbach, William E; Patel, Monal; Bartom, Elizabeth T; Law, Calvin Y; Bridgeman, Bryan; Chen, Siquan; McMahon, Kaylin M; Thaxton, C Shad; Peter, Marcus E

2018-03-01

Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents. © 2018 The Authors.

Repetition of Deliberate Self-Harm: A Study of the Characteristics and Subsequent Deaths in Patients Presenting to a General Hospital According to Extent of Repetition

ERIC Educational Resources Information Center

Haw, Camilla; Bergen, Helen; Casey, Deborah; Hawton, Keith

2007-01-01

Repetition of deliberate self-harm (DSH) is common. Some patients repeat multiple times. We have investigated the characteristics of repeaters, and mortality in three groups of DSH patients by repetition status. Data collected by the Oxford Monitoring System for Attempted Suicide were used to examine the pattern of repetition of DSH patients…

Heterogeneity of the Epstein-Barr Virus (EBV) Major Internal Repeat Reveals Evolutionary Mechanisms of EBV and a Functional Defect in the Prototype EBV Strain B95-8.

PubMed

Ba Abdullah, Mohammed M; Palermo, Richard D; Palser, Anne L; Grayson, Nicholas E; Kellam, Paul; Correia, Samantha; Szymula, Agnieszka; White, Robert E

2017-12-01

Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types of lymphoma and carcinoma. Like other herpesviruses, EBV has diversified through both coevolution with its host and genetic exchange between virus strains. Sequence analysis of the EBV genome is unusually challenging because of the large number and lengths of repeat regions within the virus. Here we describe the sequence assembly and analysis of the large internal repeat 1 of EBV (IR1; also known as the BamW repeats) for more than 70 strains. The diversity of the latency protein EBV nuclear antigen leader protein (EBNA-LP) resides predominantly within the exons downstream of IR1. The integrity of the putative BWRF1 open reading frame (ORF) is retained in over 80% of strains, and deletions truncating IR1 always spare BWRF1. Conserved regions include the IR1 latency promoter (Wp) and one zone upstream of and two within BWRF1. IR1 is heterogeneous in 70% of strains, and this heterogeneity arises from sequence exchange between strains as well as from spontaneous mutation, with interstrain recombination being more common in tumor-derived viruses. This genetic exchange often incorporates regions of <1 kb, and allelic gene conversion changes the frequency of small regions within the repeat but not close to the flanks. These observations suggest that IR1-and, by extension, EBV-diversifies through both recombination and breakpoint repair, while concerted evolution of IR1 is driven by gene conversion of small regions. Finally, the prototype EBV strain B95-8 contains four nonconsensus variants within a single IR1 repeat unit, including a stop codon in the EBNA-LP gene. Repairing IR1 improves EBNA-LP levels and the quality of transformation by the B95-8 bacterial artificial chromosome (BAC). IMPORTANCE Epstein-Barr virus (EBV) infects the majority of the world population but causes illness in only a small minority of people. Nevertheless, over 1% of cancers worldwide are attributable to EBV. Recent sequencing projects investigating virus diversity to see if different strains have different disease impacts have excluded regions of repeating sequence, as they are more technically challenging. Here we analyze the sequence of the largest repeat in EBV (IR1). We first characterized the variations in protein sequences encoded across IR1. In studying variations within the repeat of each strain, we identified a mutation in the main laboratory strain of EBV that impairs virus function, and we suggest that tumor-associated viruses may be more likely to contain DNA mixed from two strains. The patterns of this mixing suggest that sequences can spread between strains (and also within the repeat) by copying sequence from another strain (or repeat unit) to repair DNA damage. Copyright © 2017 Ba abdullah et al.

Development of Multiple-Locus Variable-Number Tandem-Repeat Analysis for Molecular Subtyping of Campylobacter jejuni by Using Capillary Electrophoresis

PubMed Central

Techaruvichit, Punnida; Vesaratchavest, Mongkol; Keeratipibul, Suwimon; Kuda, Takashi; Kimura, Bon

2015-01-01

Campylobacter jejuni is a common cause of the frequently reported food-borne diseases in developed and developing nations. This study describes the development of multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) using capillary electrophoresis as a novel typing method for microbial source tracking and epidemiological investigation of C. jejuni. Among 36 tandem repeat loci detected by the Tandem Repeat Finder program, 7 VNTR loci were selected and used for characterizing 60 isolates recovered from chicken meat samples from retail shops, samples from chicken meat processing factory, and stool samples. The discrimination ability of MLVA was compared with that of multilocus sequence typing (MLST). MLVA (diversity index of 0.97 with 31 MLVA types) provided slightly higher discrimination than MLST (diversity index of 0.95 with 25 MLST types). The overall concordance between MLVA and MLST was estimated at 63% by adjusted Rand coefficient. MLVA predicted MLST type better than MLST predicted MLVA type, as reflected by Wallace coefficient (Wallace coefficient for MLVA to MLST versus MLST to MLVA, 86% versus 51%). MLVA is a useful tool and can be used for effective monitoring of C. jejuni and investigation of epidemics caused by C. jejuni. PMID:26025899

Tandem Repeated Irritation Test (TRIT) Studies and Clinical Relevance: Post 2006.

PubMed

Reddy, Rasika; Maibach, Howard

2018-06-11

Single or multiple applications of irritants can lead to occupational contact dermatitis, and most commonly irritant contact dermatitis (ICD). Tandem irritation, the sequential application of two irritants to a target skin area, has been studied using the Tandem Repeated Irritation Test (TRIT) to provide a more accurate representation of skin irritation. Here we present an update to Kartono's review on tandem irritation studies since 2006 [1]. We surveyed the literature available on PubMed, Embase, Google Scholar, and the UCSF Dermatology library databases since 2006. The studies included discuss the tandem effects of common chemical irritants, organic solvents, occlusion as well as clinical relevance - and enlarge our ability to discern whether multiple chemical exposures are more or less likely to enhance irritation.

Patient-Delivered Partner Treatment and Trichomonas vaginalis Repeat Infection Among Human Immunodeficiency Virus-Infected Women

PubMed Central

Gatski, Megan; Mena, Leandro; Levison, Judy; Clark, Rebecca A.; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L.; Martin, David H.; Kissinger, Patricia

2013-01-01

Background Repeat infections with Trichomonas vaginalis (TV) among human immunodeficiency virus (HIV)-infected women are common and may increase the risk of HIV transmission. Patient delivered partner treatment (PDPT) has been shown to reduce repeat infections of other sexually transmitted diseases. The purpose of this study was to evaluate adherence to PDPT and possible causes of repeat TV infection among HIV-infected women. Methods A multicentered cohort study was conducted in 3 US cities. Women coinfected with HIV and TV were treated with metro-nidazole and given treatment to deliver to all reported sex partners. A test-of-cure visit was conducted 6 to 12 days post index treatment completion and behavioral data were collected. Results Of 252 women (mean age = 40 years, s.d. 9.1) enrolled, 92.5% were black, 26.2% had CD4 cell counts <200/mm3, 34.1% had plasma viral loads >10,000 copies, 58.3% were taking antiretrovial therapy, and 15.1% had multiple partners. Of the 183 women with partners at baseline, 75.4% provided PDPT to all partners and 61.7% reported they were sure all of their partners took the medication. Factors associated with not giving medications to all partner(s) were multiple sex partners, being single, and having at least one partner unaware of the index woman’s HIV status. At test-of-cure, 10.3% were TV-positive and 16.7% reported having sex since baseline. Of the 24 repeat infections, 21 (87.5%) reported adherence to medication and no sexual exposure. Conclusion HIV-infected women with TV reported high adherence to PDPT, and treatment failure was the most common probable cause of repeat infection. PMID:20502393

Mutation supply and the repeatability of selection for antibiotic resistance

NASA Astrophysics Data System (ADS)

van Dijk, Thomas; Hwang, Sungmin; Krug, Joachim; de Visser, J. Arjan G. M.; Zwart, Mark P.

2017-10-01

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 β-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. We show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes.

Development of a Multiple-Locus Variable number of tandem repeat Analysis (MLVA) for Leptospira interrogans and its application to Leptospira interrogans serovar Australis isolates from Far North Queensland, Australia

PubMed Central

Slack, Andrew T; Dohnt, Michael F; Symonds, Meegan L; Smythe, Lee D

2005-01-01

Background Leptospirosis is a zoonotic disease caused by the genus, Leptospira. Leptospira interrogans is the most common genomospecies implicated in the disease. Epidemiological investigations are needed to distinguish outbreak situations or to trace reservoirs of the organisms. Current methodologies used for typing Leptospira have significant drawbacks. The development of an easy to perform yet high resolution method is needed for this organism. Methods In this study we have searched the available genomic sequence of L. interrogans serovar Copenhageni strain Fiocruz L1-130 for the presence of tandem repeats [1]. These repeats were evaluated against reference strains for diversity. Six loci were selected to create a Multiple Locus Variable Number of Tandem Repeats (VNTR) Analysis (MLVA) to explore the genetic diversity within L. interrogans serovar Australis clinical isolates from Far North Queensland. Results The 39 reference strains used for the development of the method displayed 39 distinct patterns. Diversity Indexes for the loci varied between 0.80 and 0.93 and the number of repeat units at each locus varied between less than one to 52 repeats. When the MLVA was applied to serovar Australis isolates three large clusters were distinguishable, each comprising various hosts including Rattus species, human and canines. Conclusion The MLVA described in this report, was easy to perform, analyse and was reproducible. The loci selected had high diversity allowing discrimination between serovars and also between strains within a serovar. This method provides a starting point on which improvements to the method and comparisons to other techniques can be made. PMID:15987533

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

PubMed

White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).

Effects of rearing environment and population origin on responses to repeated behavioural trials in cane toads (Rhinella marina).

PubMed

Gruber, Jodie; Whiting, Martin J; Brown, Gregory; Shine, Richard

2018-05-02

Behavioural response to repeated trials in captivity can be driven by many factors including rearing environment, population of origin, habituation to captivity/trial conditions and an individual's behavioural type (e.g., bold versus shy). We tested the effect of rearing environment (captive raised common-garden versus wild-caught) and population origin (range-edge versus range-front) on the responses of invasive cane toads (Rhinella marina) to repeated exploration and risk-taking assays in captivity. We found that behavioural responses to identical assays performed on two occasions were complex and showed few consistent patterns based on rearing environment or population of origin. However, behavioural traits were repeatable across Trial Blocks when all sample populations were grouped together, indicating general consistency in individual toad behaviour across repeated behavioural assays. Our findings exemplify the complexity and unpredictability of behavioural responses and their effects on the repeatability and interpretation of behavioural traits across repeated behavioural assays in captivity. To meaningfully interpret the results from repeated behavioural assays, we need to consider how multiple factors may affect behavioural responses to these tests and importantly, how these responses may affect the repeatability of behavioural traits across time. Copyright © 2018. Published by Elsevier B.V.

Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology.

PubMed

Hazrati, Lili-Naz; Tartaglia, Maria C; Diamandis, Phedias; Davis, Karen D; Green, Robin E; Wennberg, Richard; Wong, Janice C; Ezerins, Leo; Tator, Charles H

2013-01-01

Chronic traumatic encephalopathy (CTE) is the term coined for the neurodegenerative disease often suspected in athletes with histories of repeated concussion and progressive dementia. Histologically, CTE is defined as a tauopathy with a distribution of tau-positive neurofibrillary tangles (NFTs) that is distinct from other tauopathies, and usually shows an absence of beta-amyloid deposits, in contrast to Alzheimer's disease (AD). Although the connection between repeated concussions and CTE-type neurodegeneration has been recently proposed, this causal relationship has not yet been firmly established. Also, the prevalence of CTE among athletes with multiple concussions is unknown. We performed a consecutive case series brain autopsy study on six retired professional football players from the Canadian Football League (CFL) with histories of multiple concussions and significant neurological decline. All participants had progressive neurocognitive decline prior to death; however, only 3 cases had post-mortem neuropathological findings consistent with CTE. The other 3 participants had pathological diagnoses of AD, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Moreover, the CTE cases showed co-morbid pathology of cancer, vascular disease, and AD. Our case studies highlight that not all athletes with history of repeated concussions and neurological symptomology present neuropathological changes of CTE. These preliminary findings support the need for further research into the link between concussion and CTE as well as the need to expand the research to other possible causes of taupathy in athletes. They point to a critical need for prospective studies with good sampling methods to allow us to understand the relationship between multiple concussions and the development of CTE.

3D high-resolution radar imaging of small body interiors

NASA Astrophysics Data System (ADS)

Sava, Paul; Asphaug, Erik

2017-10-01

Answering fundamental questions about the origin and evolution of small planetary bodies hinges on our ability to image their interior structure in detail and at high resolution (Asphaug, 2009). We often infer internal structure from surface observations, e.g. that comet 67P/Churyumov-Gerasimenko is a primordial agglomeration of cometesimals (Massironi et al., 2015). However, the interior structure is not easily accessible without systematic imaging using, e.g., radar transmission and reflection data, as suggested by the CONSERT experiment on Rosetta. Interior imaging depends on observations from multiple viewpoints, as in medical tomography.We discuss radar imaging using methodology adapted from terrestrial exploration seismology (Sava et al., 2015). We primarily focus on full wavefield methods that facilitate high quality imaging of small body interiors characterized by complex structure and large contrasts of physical properties. We consider the case of a monostatic system (co-located transmitters and receivers) operated at two frequency bands, centered around 5 and 15 MHz, from a spacecraft in slow polar orbit around a spinning comet nucleus. Assuming that the spin period is significantly (e.g. 5x) faster than the orbital period, this configuration allows repeated views from multiple directions (Safaeinili et al., 2002)Using realistic numerical experiments, we argue that (1) the comet/asteroid imaging problem is intrinsically 3D and conventional SAR methodology does not satisfy imaging, sampling and resolution requirements; (2) imaging at different frequency bands can provide information about internal surfaces (through migration) and internal volumes (through tomography); (3) interior imaging can be accomplished progressively as data are being acquired through successive orbits around the studied object; (4) imaging resolution can go beyond the apparent radar frequency band by deconvolution of the point-spread-function characterizing the imaging system; and (5) exploiting the known (and complex) exterior shape of the studied body facilitates high-resolution imaging and tomography comparable with what could be accomplished by bi/multi-static systems.

Time Dependence of Collision Probabilities During Satellite Conjunctions

NASA Technical Reports Server (NTRS)

Hall, Doyle T.; Hejduk, Matthew D.; Johnson, Lauren C.

2017-01-01

The NASA Conjunction Assessment Risk Analysis (CARA) team has recently implemented updated software to calculate the probability of collision (P (sub c)) for Earth-orbiting satellites. The algorithm can employ complex dynamical models for orbital motion, and account for the effects of non-linear trajectories as well as both position and velocity uncertainties. This “3D P (sub c)” method entails computing a 3-dimensional numerical integral for each estimated probability. Our analysis indicates that the 3D method provides several new insights over the traditional “2D P (sub c)” method, even when approximating the orbital motion using the relatively simple Keplerian two-body dynamical model. First, the formulation provides the means to estimate variations in the time derivative of the collision probability, or the probability rate, R (sub c). For close-proximity satellites, such as those orbiting in formations or clusters, R (sub c) variations can show multiple peaks that repeat or blend with one another, providing insight into the ongoing temporal distribution of risk. For single, isolated conjunctions, R (sub c) analysis provides the means to identify and bound the times of peak collision risk. Additionally, analysis of multiple actual archived conjunctions demonstrates that the commonly used “2D P (sub c)” approximation can occasionally provide inaccurate estimates. These include cases in which the 2D method yields negligibly small probabilities (e.g., P (sub c)) is greater than 10 (sup -10)), but the 3D estimates are sufficiently large to prompt increased monitoring or collision mitigation (e.g., P (sub c) is greater than or equal to 10 (sup -5)). Finally, the archive analysis indicates that a relatively efficient calculation can be used to identify which conjunctions will have negligibly small probabilities. This small-P (sub c) screening test can significantly speed the overall risk analysis computation for large numbers of conjunctions.

Snake and Bird Predation Drive the Repeated Convergent Evolution of Correlated Life History Traits and Phenotype in the Izu Island Scincid Lizard (Plestiodon latiscutatus)

PubMed Central

Brandley, Matthew C.; Kuriyama, Takeo; Hasegawa, Masami

2014-01-01

Predation may create strong natural selection pressure on the phenotype and life history characteristics of prey species. The Izu scincid lizards (Plestiodon latiscutatus) that inhabit the four Japanese Izu Islands with only bird predators are drab brown, mature later, lay small clutches of large eggs, and hatch large neonates. In contrast, skinks on seven islands with both snake and bird predators are conspicuously colored, mature early, lay large clutches of small eggs, and hatch small neonates. We test the hypothesis that these suites of traits have evolved independently on each island via natural selection pressures from one of two predator regimes – birds-only and birds + snakes. Using two mtDNA genes and a nuclear locus, we infer a time-calibrated phylogeny of P. latiscutatus that reveals a basal split between Mikura and all islands south, and Miyake, all islands north, and the Izu Peninsula. Populations inhabiting Miyake, Niijima, Shikine, and Toshima are not monophyletic, suggesting either multiple colonizations or an artifact of incomplete lineage sorting (ILS). We therefore developed novel phylogenetic comparative analyses that assume either a multiple colonization or more restrictive single colonization ILS scenario and found 1) statistically significant support for the of different suites of phenotypic and life history characteristics with the presence of bird-only or bird + snake predator assemblages, and 2) strong phylogenetic support for at least two independent derivations of either the “bird-only” or “snakes + birds” phenotypes regardless of colonization scenario. Finally, our time-calibrated phylogeographic analysis supports the conclusion that the ancestor to modern Izu Island P. latiscutatus dispersed from the mainland to the Izu proto-islands between 3–7.6 million years ago (Ma). These lineages remained present in the area during successive formation of the islands, with one lineage re-colonizing the mainland 0.24-0.7 Ma. PMID:24667496

Measuring joint kinematics of treadmill walking and running: Comparison between an inertial sensor based system and a camera-based system.

PubMed

Nüesch, Corina; Roos, Elena; Pagenstert, Geert; Mündermann, Annegret

2017-05-24

Inertial sensor systems are becoming increasingly popular for gait analysis because their use is simple and time efficient. This study aimed to compare joint kinematics measured by the inertial sensor system RehaGait® with those of an optoelectronic system (Vicon®) for treadmill walking and running. Additionally, the test re-test repeatability of kinematic waveforms and discrete parameters for the RehaGait® was investigated. Twenty healthy runners participated in this study. Inertial sensors and reflective markers (PlugIn Gait) were attached according to respective guidelines. The two systems were started manually at the same time. Twenty consecutive strides for walking and running were recorded and each software calculated sagittal plane ankle, knee and hip kinematics. Measurements were repeated after 20min. Ensemble means were analyzed calculating coefficients of multiple correlation for waveforms and root mean square errors (RMSE) for waveforms and discrete parameters. After correcting the offset between waveforms, the two systems/models showed good agreement with coefficients of multiple correlation above 0.950 for walking and running. RMSE of the waveforms were below 5° for walking and below 8° for running. RMSE for ranges of motion were between 4° and 9° for walking and running. Repeatability analysis of waveforms showed very good to excellent coefficients of multiple correlation (>0.937) and RMSE of 3° for walking and 3-7° for running. These results indicate that in healthy subjects sagittal plane joint kinematics measured with the RehaGait® are comparable to those using a Vicon® system/model and that the measured kinematics have a good repeatability, especially for walking. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should it be classified together as traumatic encephalopathy?

PubMed Central

Washington, Patricia M.; Villapol, Sonia; Burns, Mark P.

2015-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer’s disease (AD), while mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position—examining epidemiological and case-control human studies, neuropathological evidence, and preclinical studies. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson’s disease. Further, human post-mortem studies on either single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a ‘polypathology’. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI are viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

Identification of Variable-Number Tandem-Repeat (VNTR) Sequences in Acinetobacter baumannii and Interlaboratory Validation of an Optimized Multiple-Locus VNTR Analysis Typing Scheme▿†

PubMed Central

Pourcel, Christine; Minandri, Fabrizia; Hauck, Yolande; D'Arezzo, Silvia; Imperi, Francesco; Vergnaud, Gilles; Visca, Paolo

2011-01-01

Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial outbreaks, mostly occurring in intensive care units. Due to the multiplicity of infection sources, reliable molecular fingerprinting techniques are needed to establish epidemiological correlations among A. baumannii isolates. Multiple-locus variable-number tandem-repeat analysis (MLVA) has proven to be a fast, reliable, and cost-effective typing method for several bacterial species. In this study, an MLVA assay compatible with simple PCR- and agarose gel-based electrophoresis steps as well as with high-throughput automated methods was developed for A. baumannii typing. Preliminarily, 10 potential polymorphic variable-number tandem repeats (VNTRs) were identified upon bioinformatic screening of six annotated genome sequences of A. baumannii. A collection of 7 reference strains plus 18 well-characterized isolates, including unique types and representatives of the three international A. baumannii lineages, was then evaluated in a two-center study aimed at validating the MLVA assay and comparing it with other genotyping assays, namely, macrorestriction analysis with pulsed-field gel electrophoresis (PFGE) and PCR-based sequence group (SG) profiling. The results showed that MLVA can discriminate between isolates with identical PFGE types and SG profiles. A panel of eight VNTR markers was selected, all showing the ability to be amplified and good amounts of polymorphism in the majority of strains. Independently generated MLVA profiles, composed of an ordered string of allele numbers corresponding to the number of repeats at each VNTR locus, were concordant between centers. Typeability, reproducibility, stability, discriminatory power, and epidemiological concordance were excellent. A database containing information and MLVA profiles for several A. baumannii strains is available from http://mlva.u-psud.fr/. PMID:21147956

Changes in seismic velocity during the first 14 months of the 2004-2008 eruption of Mount St. Helens, Washington

NASA Astrophysics Data System (ADS)

Hotovec-Ellis, A. J.; Vidale, J. E.; Gomberg, J.; Thelen, W.; Moran, S. C.

2015-09-01

Mount St. Helens began erupting in late 2004 following an 18 year quiescence. Swarms of repeating earthquakes accompanied the extrusion of a mostly solid dacite dome over the next 4 years. In some cases the waveforms from these earthquakes evolved slowly, likely reflecting changes in the properties of the volcano that affect seismic wave propagation. We use coda-wave interferometry to quantify small changes in seismic velocity structure (usually <1%) between two similar earthquakes and employed waveforms from several hundred families of repeating earthquakes together to create a continuous function of velocity change observed at permanent stations operated within 20 km of the volcano. The high rate of earthquakes allowed tracking of velocity changes on an hourly time scale. Changes in velocity were largest near the newly extruding dome and likely related to shallow deformation as magma first worked its way to the surface. We found strong correlation between velocity changes and the inverse of real-time seismic amplitude measurements during the first 3 weeks of activity, suggesting that fluctuations of pressure in the shallow subsurface may have driven both seismicity and velocity changes. Velocity changes during the remainder of the eruption likely result from a complex interplay of multiple effects and are not well explained by any single factor alone, highlighting the need for complementary geophysical data when interpreting velocity changes.

Donating blood: a meta-analytic review of self-reported motivators and deterrents.

PubMed

Bednall, Timothy C; Bove, Liliana L

2011-10-01

Although research on blood donor motivation abounds, most studies have typically focused on small sets of variables, used different terminology to label equivalent constructs, and have not attempted to generalize findings beyond their individual settings. The current study sought to synthesize past findings into a unified taxonomy of blood donation drivers and deterrents and to estimate the prevalence of each factor across the worldwide population of donors and eligible nondonors. Primary studies were collected, and cross-validated categories of donation motivators and deterrents were developed. Proportions of first-time, repeat, lapsed, apheresis, and eligible nondonors endorsing each category were calculated. In terms of motivators, first-time and repeat donors most frequently cited convenience, prosocial motivation, and personal values; apheresis donors similarly cited the latter 2 motivators and money. Conversely, lapsed donors more often cited collection agency reputation, perceived need for donation, and marketing communication as motivators. In terms of deterrents, both donors and nondonors most frequently referred to low self-efficacy to donate, low involvement, inconvenience, absence of marketing communication, ineffective incentives, lack of knowledge about donating, negative service experiences, and fear. The integration of past findings has yielded a comprehensive taxonomy of factors influencing blood donation and has provided insight into the prevalence of each factor across multiple stages of donors' careers. Implications for collection agencies are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Stakeholder-focused evaluation of an online course for health care providers.

PubMed

Dunet, Diane O; Reyes, Michele

2006-01-01

Different people who have a stake or interest in a training course (stakeholders) may have markedly different definitions of what constitutes "training success" and how they will use evaluation results. Stakeholders at multiple levels within and outside of the organization guided the development of an evaluation plan for a Web-based training course on hemochromatosis. Stakeholder interests and values were reflected in the type, level, and rigor of evaluation methods selected. Our mixed-method evaluation design emphasized small sample sizes and repeated measures. Limited resources for evaluation were leveraged by focusing on the data needs of key stakeholders, understanding how they wanted to use evaluation results, and collecting data needed for stakeholder decision making. Regular feedback to key stakeholders provided opportunities for updating the course evaluation plan to meet emerging needs for new or different information. Early and repeated involvement of stakeholders in the evaluation process also helped build support for the final product. Involving patient advocacy groups, managers, and representative course participants improved the course and enhanced product dissemination. For training courses, evaluation planning is an opportunity to tailor methods and data collection to meet the information needs of particular stakeholders. Rigorous evaluation research of every training course may be infeasible or unwarranted; however, course evaluations can be improved by good planning. A stakeholder-focused approach can build a picture of the results and impact of training while fostering the practical use of evaluation data.

Computerized ionospheric tomography based on geosynchronous SAR

NASA Astrophysics Data System (ADS)

Hu, Cheng; Tian, Ye; Dong, Xichao; Wang, Rui; Long, Teng

2017-02-01

Computerized ionospheric tomography (CIT) based on spaceborne synthetic aperture radar (SAR) is an emerging technique to construct the three-dimensional (3-D) image of ionosphere. The current studies are all based on the Low Earth Orbit synthetic aperture radar (LEO SAR) which is limited by long repeat period and small coverage. In this paper, a novel ionospheric 3-D CIT technique based on geosynchronous SAR (GEO SAR) is put forward. First, several influences of complex atmospheric environment on GEO SAR focusing are detailedly analyzed, including background ionosphere and multiple scattering effects (induced by turbulent ionosphere), tropospheric effects, and random noises. Then the corresponding GEO SAR signal model is constructed with consideration of the temporal-variant background ionosphere within the GEO SAR long integration time (typically 100 s to 1000 s level). Concurrently, an accurate total electron content (TEC) retrieval method based on GEO SAR data is put forward through subband division in range and subaperture division in azimuth, obtaining variant TEC value with respect to the azimuth time. The processing steps of GEO SAR CIT are given and discussed. Owing to the short repeat period and large coverage area, GEO SAR CIT has potentials of covering the specific space continuously and completely and resultantly has excellent real-time performance. Finally, the TEC retrieval and GEO SAR CIT construction are performed by employing a numerical study based on the meteorological data. The feasibility and correctness of the proposed methods are verified.

Changes in seismic velocity during the first 14 months of the 2004–2008 eruption of Mount St. Helens, Washington

USGS Publications Warehouse

Hotovec-Ellis, A.J.; Vidale, J.E.; Gomberg, Joan S.; Thelen, Weston A.; Moran, Seth C.

2015-01-01

Mount St. Helens began erupting in late 2004 following an 18 year quiescence. Swarms of repeating earthquakes accompanied the extrusion of a mostly solid dacite dome over the next 4 years. In some cases the waveforms from these earthquakes evolved slowly, likely reflecting changes in the properties of the volcano that affect seismic wave propagation. We use coda-wave interferometry to quantify small changes in seismic velocity structure (usually <1%) between two similar earthquakes and employed waveforms from several hundred families of repeating earthquakes together to create a continuous function of velocity change observed at permanent stations operated within 20 km of the volcano. The high rate of earthquakes allowed tracking of velocity changes on an hourly time scale. Changes in velocity were largest near the newly extruding dome and likely related to shallow deformation as magma first worked its way to the surface. We found strong correlation between velocity changes and the inverse of real-time seismic amplitude measurements during the first 3 weeks of activity, suggesting that fluctuations of pressure in the shallow subsurface may have driven both seismicity and velocity changes. Velocity changes during the remainder of the eruption likely result from a complex interplay of multiple effects and are not well explained by any single factor alone, highlighting the need for complementary geophysical data when interpreting velocity changes.

Experimental creation of quantum Zeno subspaces by repeated multi-spin projections in diamond

NASA Astrophysics Data System (ADS)

Kalb, N.; Cramer, J.; Twitchen, D. J.; Markham, M.; Hanson, R.; Taminiau, T. H.

2016-10-01

Repeated observations inhibit the coherent evolution of quantum states through the quantum Zeno effect. In multi-qubit systems this effect provides opportunities to control complex quantum states. Here, we experimentally demonstrate that repeatedly projecting joint observables of multiple spins creates quantum Zeno subspaces and simultaneously suppresses the dephasing caused by a quasi-static environment. We encode up to two logical qubits in these subspaces and show that the enhancement of the dephasing time with increasing number of projections follows a scaling law that is independent of the number of spins involved. These results provide experimental insight into the interplay between frequent multi-spin measurements and slowly varying noise and pave the way for tailoring the dynamics of multi-qubit systems through repeated projections.

Extraction and utilization of the repeating patterns for CP writing in mask making

NASA Astrophysics Data System (ADS)

Shoji, Masahiro; Inoue, Tadao; Yamabe, Masaki

2010-05-01

In May 2006, the Mask Design, Drawing, and Inspection Technology Research Department (Mask D2I) at the Association of Super-Advanced Electronics Technologies (ASET) launched a 4-year program for reducing mask manufacturing cost and TAT by concurrent optimization of Mask Data Preparation (MDP), mask writing, and mask inspection [1]. Figure 1 shows an outline of the project at Mask D2I at ASET. As one of the tasks being pursued at the Mask Design Data Technology Research Laboratory we have evaluated the effect of reducing the writing shot counts by utilizing the repeating patterns, and that showed positive impact on mask making by using CP writing. During the past four years, we have developed a software to extract repeating patterns from fractured OPCed mask data and have evaluated the efficiency of reducing the writing shot counts using the repeating patterns with this software. In this evaluation, we have used many actual device production data obtained from the member companies of Mask D2I. To the extraction software, we added new functions for extracting common repeating patterns from a set of multiple masks, and studied how this step affects the ratio of reducing the shot counts in comparison to the case of utilization of the repeating patterns for single mask. We have also developed a software that uses the result of extracting repeating patterns and prepares writing-data for the MCC/CP writing system which has been developed at the Mask Writing Equipment Technology Research Laboratory. With this software, we have examined how EB proximity effect on CP writing affects in reducing the shot count where CP shots with large CD errors have to be divided into VSB shots. In this paper we will report on making common CP mask from a set of multiple actual device data by using these software, and will also report on the results of CP writing and calculation of writing-TAT by MCC/CP writing system.

Relations among Multiple Types of Peer Victimization, Reactivity to Peer Victimization, and Academic Achievement in Fifth-Grade Goys and Girls

ERIC Educational Resources Information Center

Morrow, Michael T.; Hubbard, Julie A.; Swift, Lauren E.

2014-01-01

This study examined the relations between multiple types of peer victimization, affective reactivity to victimization, and academic achievement. Participants (179 fifth-grade boys and girls) completed repeated daily measures of peer victimization and negative affect; a standardized measure of achievement was collected concurrently. The daily…

R-loops: targets for nuclease cleavage and repeat instability.

PubMed

Freudenreich, Catherine H

2018-01-11

R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

A subcontinental view of forest plant invasions

Treesearch

Christopher M. Oswalt; Songlin Fei; Qinfeng Guo; Basil V. Iannone III; Sonja N. Oswalt; Bryan C. Pijanowski; Kevin M. Potter

2015-01-01

Over the last few decades, considerable attention has focused on small-scale studies of invasive plants and invaded systems. Unfortunately, small scale studies rarely provide comprehensive insight into the complexities of biological invasions at macroscales. Systematic and repeated monitoring of biological invasions at broad scales are rare. In this report, we...

RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 1: Evidence analysis and consensus process: collaborative path toward small animal CPR guidelines.

PubMed

Boller, Manuel; Fletcher, Daniel J

2012-06-01

To describe the methodology used by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) to evaluate the scientific evidence relevant to small animal CPR and to compose consensus-based clinical CPR guidelines for dogs and cats. This report is part of a series of 7 articles on the RECOVER evidence and knowledge gap analysis and consensus-based small animal CPR guidelines. It describes the organizational structure of RECOVER, the evaluation process employed, consisting of standardized literature searches, the analysis of relevant articles according to study design, species and predefined quality markers, and the drafting of clinical CPR guidelines based on these data. Therefore, this article serves as the methodology section for the subsequent 6 RECOVER articles. Academia, referral practice. RECOVER is a collaborative initiative that systematically evaluated the evidence on 74 topics relevant to small animal CPR and generated 101 clinical CPR guidelines from this analysis. All primary contributors were veterinary specialists, approximately evenly split between academic institutions and private referral practices. The evidence evaluation and guideline drafting processes were conducted according to a predefined sequence of steps designed to reduce bias and increase the repeatability of the findings, including multiple levels of review, culminating in a consensus process. Many knowledge gaps were identified that will allow prioritization of research efforts in veterinary CPR. Collaborative systematic evidence review is organizationally challenging but feasible and effective in veterinary medicine. More experience is needed to refine the process. © Veterinary Emergency and Critical Care Society 2012.

[The effect of self-foot reflexology on the relief of premenstrual syndrome and dysmenorrhea in high school girls].

PubMed

Kim, Yi-Soon; Kim, Min-Za; Jeong, Ihn-Sook

2004-08-01

This study was aimed to identify the effect of self-foot reflexology on the relief of premenstrual syndrome and dysmenorrhea in high school girls. Study subjects was 236 women residing in the community, teachers and nurses who were older than 45 were recruited. Data was collected with self administered questionnaires from July 1st to August 31st, 2003 and analysed using SPSS/WIN 10.0 with Xtest, t-test, and stepwise multiple logistic regression at a significant level of =.05. The breast cancer screening rate was 57.2%, and repeat screening rate was 15.3%. With the multiple logistic regression analysis, factors associated with mammography screening were age and perceived barriers of action, and factors related to the repeat mammography screening were education level and other cancer screening experience. Based on the results, we recommend the development of an intervention program to decrease the perceived barrier of action, to regard mammography as an essential test in regular check-up, and to give active advertisement and education to the public to improve the rates of breast cancer screening and repeat screening.

MULTIPLE-LOCUS VARIABLE-NUMBER TANDEM REPEAT ANALYSIS OF BRUCELLA ISOLATES FROM THAILAND.

PubMed

Kumkrong, Khurawan; Chankate, Phanita; Tonyoung, Wittawat; Intarapuk, Apiradee; Kerdsin, Anusak; Kalambaheti, Thareerat

2017-01-01

Brucellosis-induced abortion can result in significant economic loss to farm animals. Brucellosis can be transmitted to humans during slaughter of infected animals or via consumption of contaminated food products. Strain identification of Brucella isolates can reveal the route of transmission. Brucella strains were isolated from vaginal swabs of farm animal, cow milk and from human blood cultures. Multiplex PCR was used to identify Brucella species, and owing to high DNA homology among Brucella isolates, multiple-locus variable-number tandem repeat analysis (MLVA) based on the number of tandem repeats at 16 different genomic loci was used for strain identification. Multiplex PCR categorized the isolates into B. abortus (n = 7), B. melitensis (n = 37), B. suis (n = 3), and 5 of unknown Brucella spp. MLVA-16 clustering analysis differentiated the strains into various genotypes, with Brucella isolates from the same geographic region being closely related, and revealed that the Thai isolates were phylogenetically distinct from those in other countries, including within the Southeast Asian region. Thus, MLVA-16 typing has utility in epidemiological studies.

Brilliant Blue G double staining enhances successful internal limiting membrane peeling with minimal adverse effect by low cellular permeability into live cells.

PubMed

Hisatomi, Toshio; Notomi, Shoji; Tachibana, Takashi; Oishi, Seiichiro; Asato, Ryo; Yamashita, Takehiro; Murakami, Yusuke; Ikeda, Yasuhiro; Enaida, Hiroshi; Sakamoto, Taiji; Ishibashi, Tatsuro

2015-02-01

Brilliant Blue G is used as a surgical adjuvant for retinal surgery. Although BBG double or multiple staining was reported, the effectiveness and safety of repeated staining is still elusive. To further examine the effectiveness and safety, we examined BBG in clinical cases in vivo, primary cell culture in vitro, and surgically resected specimen ex vivo. A retrospective interventional case series with in vitro and ex vivo studies were performed. Vitrectomy was performed in 28 cases of epiretinal membrane with BBG single to multiple staining. The surgically resected membranes were stained by BBG with or without cellular fixation. Primary cell cultures were examined with BBG and live/death cell markers, such as Calcein AM and TUNEL. Single staining provided satisfactory staining in seven cases. Double or multiple staining substantially visualized internal limiting membrane (21 cases), especially the edges of remaining internal limiting membrane (11 cases). Adverse retinal staining was not noted and the final visual acuity showed no difference with multiple staining. The live cells barely stained with BBG, while some dead cells were stained. Brilliant Blue G multiple staining substantially enhanced the visualization of internal limiting membrane. The absence of abnormal staining supports the safety of repeated BBG staining.

Mechanical unfolding of an ankyrin repeat protein.

PubMed

Serquera, David; Lee, Whasil; Settanni, Giovanni; Marszalek, Piotr E; Paci, Emanuele; Itzhaki, Laura S

2010-04-07

Ankryin repeat proteins comprise tandem arrays of a 33-residue, predominantly alpha-helical motif that stacks roughly linearly to produce elongated and superhelical structures. They function as scaffolds mediating a diverse range of protein-protein interactions, and some have been proposed to play a role in mechanical signal transduction processes in the cell. Here we use atomic force microscopy and molecular-dynamics simulations to investigate the natural 7-ankyrin repeat protein gankyrin. We find that gankyrin unfolds under force via multiple distinct pathways. The reactions do not proceed in a cooperative manner, nor do they always involve fully stepwise unfolding of one repeat at a time. The peeling away of half an ankyrin repeat, or one or more ankyrin repeats, occurs at low forces; however, intermediate species are formed that are resistant to high forces, and the simulations indicate that in some instances they are stabilized by nonnative interactions. The unfolding of individual ankyrin repeats generates a refolding force, a feature that may be more easily detected in these proteins than in globular proteins because the refolding of a repeat involves a short contraction distance and incurs a low entropic cost. We discuss the origins of the differences between the force- and chemical-induced unfolding pathways of ankyrin repeat proteins, as well as the differences between the mechanics of natural occurring ankyrin repeat proteins and those of designed consensus ankyin repeat and globular proteins. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Identification of critical functional residues of receptor-like kinase ERECTA.

PubMed

Kosentka, Pawel Z; Zhang, Liang; Simon, Yonas A; Satpathy, Binita; Maradiaga, Richard; Mitoubsi, Omar; Shpak, Elena D

2017-03-01

In plants, extracellular signals are primarily sensed by plasma membrane-localized receptor-like kinases (RLKs). ERECTA is a leucine-rich repeat RLK that together with its paralogs ERECTA-like 1 (ERL1) and ERL2 regulates multiple aspects of plant development. ERECTA forms complexes with a range of co-receptors and senses secreted cysteine-rich small proteins from the EPF/EPFL family. Currently the mechanism of the cytoplasmic domain activation and transmission of the signal by ERECTA is unclear. To gain a better understanding we performed a structure-function analysis by introducing altered ERECTA genes into erecta and erecta erl1 erl2 mutants. These experiments indicated that ERECTA's ability to phosphorylate is functionally significant, and that while the cytoplasmic juxtamembrane domain is important for ERECTA function, the C-terminal tail is not. An analysis of multiple putative phosphorylation sites identified four amino acids in the activation segment of the kinase domain as functionally important. Homology of those residues to functionally significant amino acids in multiple other plant RLKs emphasizes similarities in RLK function. Specifically, our data predicts Thr812 as a primary site of phosphor-activation and potential inhibitory phosphorylation of Tyr815 and Tyr820. In addition, our experiments suggest that there are differences in the molecular mechanism of ERECTA function during regulation of stomata development and in elongation of above-ground organs. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Comparative Analysis of User-Generated Online Yelp Reviews for Periodontal Practices in Multiple Metropolitan Markets.

PubMed

Holtzclaw, Dan J

2017-02-01

Previously published research for a single metropolitan market (Austin, Texas) found that periodontists fare poorly on the Yelp website for nearly all measured metrics, including average star ratings, number of reviews, review removal rate, and evaluations by "elite" Yelp users. The purpose of the current study is to confirm or refute these findings by expanding datasets to additional metropolitan markets of various sizes and geographic locations. A total of 6,559 Yelp reviews were examined for general dentists, endodontists, pediatric dentists, oral surgeons, orthodontists, and periodontists in small (Austin, Texas), medium (Seattle, Washington), and large (New York City, New York) metropolitan markets. Numerous review characteristics were evaluated, including: 1) total number of reviews; 2) average star rating; 3) review filtering rate; and 4) number of reviews by Yelp members with elite status. Results were compared in multiple ways to determine whether statistically significant differences existed. In all metropolitan markets, periodontists were outperformed by all other dental specialties for all measured Yelp metrics in this study. Intermetropolitan comparisons of periodontal practices showed no statistically significant differences. Periodontists were outperformed consistently by all other dental specialties in every measured metric on the Yelp website. These results were consistent and repeated in all three metropolitan markets evaluated in this study. Poor performance of periodontists on Yelp may be related to the age profile of patients in the typical periodontal practice. This may result in inadvertently biased filtering of periodontal reviews and subsequently poor performance in multiple other categories.

Cognitive status in patients with multiple sclerosis in Lanzarote.

PubMed

Pérez-Martín, María Yaiza; Eguia-Del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Cognitive impairment is a common feature in multiple sclerosis affecting ~43%-72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety.

Cognitive status in patients with multiple sclerosis in Lanzarote

PubMed Central

Pérez-Martín, María Yaiza; Eguia-del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Objectives Cognitive impairment is a common feature in multiple sclerosis affecting ~43%–72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. Patients and methods In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Results Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Conclusion Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety. PMID:27418825

Photogrammetric discharge monitoring of small tropical mountain rivers - A case study at Rivière des Pluies, Réunion island

NASA Astrophysics Data System (ADS)

Stumpf, André; Augereau, Emmanuel; Delacourt, Christophe; Bonnier, Julien

2016-04-01

Reliable discharge measurements are indispensable for an effective management of natural water resources and floods. Limitations of classical current meter profiling and stage-discharge ratings have stimulated the development of more accurate and efficient gauging techniques. While new discharge measurements technologies such as acoustic doppler current profilers and large-scale image particle velocimetry (LSPIV) have been developed and tested in numerous studies, the continuous monitoring of small mountain rivers and discharge dynamics during strong meteorological events remains challenging. More specifically LSPIV studies are often focused on short-term measurements during flood events and there are still very few studies that address its use for long-term monitoring of small mountain rivers. To fill this gap this study targets the development and testing of largely autonomous photogrammetric discharge measurement system with a special focus on the application to small mountain river with high discharge variability and a mobile riverbed in the tropics. It proposes several enhancements among previous LSPIV methods regarding camera calibration, more efficient processing in image geometry, the automatic detection of the water level as well as the statistical calibration and estimation of the discharge from multiple profiles. To account for changes in the bed topography the riverbed is surveyed repeatedly during the dry seasons using multi-view photogrammetry or terrestrial laser scanners. The presented case study comprises the analysis of several thousand videos spanning over two and a half year (2013-2015) to test the robustness and accuracy of different processing steps. An analysis of the obtained results suggests that the quality of the camera calibration reaches a sub-pixel accuracy. The median accuracy of the watermask detections is F1=0.82, whereas the precision is systematically higher than the recall. The resulting underestimation of the water surface area and level leads to a systematic underestimation of the discharge and error rates of up to 25 %. However, the bias can be effectively removed using a least-square cross-calibration which reduces the error to a MAE of 6.39% and a maximum error of 16.18%. Those error rates are significantly lower than the uncertainties among multiple profiles (30%) and illustrate the importance of the spatial averaging from multiple measurements. The study suggests that LSPIV can already be considered as a valuable tool for the monitoring of torrential flows, whereas further research is still needed to fully integrate night-time observation and stereo-photogrammetric capabilities.

Multi-dimensional photonic states from a quantum dot

NASA Astrophysics Data System (ADS)

Lee, J. P.; Bennett, A. J.; Stevenson, R. M.; Ellis, D. J. P.; Farrer, I.; Ritchie, D. A.; Shields, A. J.

2018-04-01

Quantum states superposed across multiple particles or degrees of freedom offer an advantage in the development of quantum technologies. Creating these states deterministically and with high efficiency is an ongoing challenge. A promising approach is the repeated excitation of multi-level quantum emitters, which have been shown to naturally generate light with quantum statistics. Here we describe how to create one class of higher dimensional quantum state, a so called W-state, which is superposed across multiple time bins. We do this by repeated Raman scattering of photons from a charged quantum dot in a pillar microcavity. We show this method can be scaled to larger dimensions with no reduction in coherence or single-photon character. We explain how to extend this work to enable the deterministic creation of arbitrary time-bin encoded qudits.

Barrier function and natural moisturizing factor levels after cumulative exposure to a fruit-derived organic acid and a detergent: different outcomes in atopic and healthy skin and relevance for occupational contact dermatitis in the food industry.

PubMed

Angelova-Fischer, Irena; Hoek, Anne-Karin; Dapic, Irena; Jakasa, Ivone; Kezic, Sanja; Fischer, Tobias W; Zillikens, Detlef

2015-12-01

Fruit-derived organic compounds and detergents are relevant exposure factors for occupational contact dermatitis in the food industry. Although individuals with atopic dermatitis (AD) are at risk for development of occupational contact dermatitis, there have been no controlled studies on the effects of repeated exposure to multiple irritants, relevant for the food industry, in atopic skin. The aim of the study was to investigate the outcomes of repeated exposure to a fruit-derived organic acid and a detergent in AD compared to healthy volunteers. The volunteers were exposed to 2.0% acetic acid (AcA) and/or 0.5% sodium lauryl sulfate (SLS) in controlled tandem repeated irritation test. The outcomes were assessed by measurements of erythema, transepidermal water loss (TEWL) and natural moisturizing factor (NMF) levels. In the AD volunteers, repeated AcA exposure led to barrier disruption and significant TEWL increase; no significant differences after the same exposure in the healthy controls were found. Repeated exposure to SLS and the irritant tandems enhanced the reactions and resulted in a significantly higher increase in TEWL in the AD compared to the control group. Cumulative irritant exposure reduced the NMF levels in both groups. Differences in the severity of irritant-induced barrier impairment in atopic individuals contribute to the risk for occupational contact dermatitis in result of multiple exposures to food-derived irritants and detergents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

PubMed

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

Variability in Prefrontal Hemodynamic Response during Exposure to Repeated Self-Selected Music Excerpts, a Near-Infrared Spectroscopy Study

PubMed Central

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes. PMID:25837268

Roles of pro-angiogenic and anti-angiogenic factors as well as matrix metalloproteinases in healing of NSAID-induced small intestinal ulcers in rats.

PubMed

Gyenge, Melinda; Amagase, Kikuko; Kunimi, Shino; Matsuoka, Rie; Takeuchi, Koji

2013-10-06

We examined changes in the expression of a pro-angiogenic factor, vascular endothelial growth factor (VEGF), and an anti-angiogenic factor, endostatin, as well as matrix metalloproteinase (MMP)-2 and MMP-9 in the rat small intestine after administration of indomethacin and investigated the roles of these factors in the healing of indomethacin-induced small intestinal ulcers. Male SD rats were given indomethacin (10mg/kg) p.o. and euthanized at various time points (3-24h and 2-7days) after the administration. To impair the healing of these lesions, low-dose of indomethacin (2mg/kg) was given p.o. once daily for 6days starting 1day after ulceration. Levels of VEGF, endostatin, MMP-2 and MMP-9 were determined by Western blotting. The expression of both VEGF and endostatin was upregulated after the ulceration. Repeated administration of low-dose indomethacin impaired the ulcer healing with a decrease of VEGF expression and a further increase of endostatin expression, resulting in a marked decrease in the ratio of VEGF/endostatin expression. The levels of MMP-2 and MMP-9 were both significantly increased after the ulceration, but these responses were suppressed by the repeated indomethacin treatment. The healing of these ulcers was significantly delayed by the repeated administration of MMP inhibitors such as ARP-101 and SB-3CT. The results confirm the importance of the balance between pro-angiogenic and anti-angiogenic activities in the healing of indomethacin-induced small intestinal damage and further suggest that the increased expression of MMP-2 and MMP-9 is another important factor for ulcer healing in the small intestine. © 2013.

The influence of non-nociceptive factors on hot-plate latency in rats.

PubMed

Gunn, Amanda; Bobeck, Erin N; Weber, Ceri; Morgan, Michael M

2011-02-01

The hot plate is a widely used test to assess nociception. The effect of non-nociceptive factors (weight, sex, activity, habituation, and repeated testing) on hot-plate latency was examined. Comparison of body weight and hot-plate latency revealed a small but significant inverse correlation (light rats had longer latencies). Habituating rats to the test room for 1 hour prior to testing did not decrease hot-plate latency except for female rats tested on days 2 to 4. Hot-plate latency decreased with repeated daily testing, but this was not caused by a decrease in locomotor activity or learning to respond. Activity on the hot plate was consistent across all 4 trials, and prior exposure to a room-temperature plate caused a similar decrease in latency as rats tested repeatedly on the hot plate. Despite this decrease in baseline hot-plate latency, there was no difference in morphine antinociceptive potency. The present study shows that weight, habituation to the test room, and repeated testing can alter baseline hot-plate latency, but these effects are small and have relatively little impact on morphine antinociception. This manuscript shows that non-nociceptive factors such as body weight, habituation, and repeated testing can alter hot-plate latency, but these factors do not alter morphine potency. In sum, the hot-plate test is an easy to use and reliable method to assess supraspinally organized nociceptive responses. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Geometric Positioning for Satellite Imagery without Ground Control Points by Exploiting Repeated Observation.

PubMed

Ma, Zhenling; Wu, Xiaoliang; Yan, Li; Xu, Zhenliang

2017-01-26

With the development of space technology and the performance of remote sensors, high-resolution satellites are continuously launched by countries around the world. Due to high efficiency, large coverage and not being limited by the spatial regulation, satellite imagery becomes one of the important means to acquire geospatial information. This paper explores geometric processing using satellite imagery without ground control points (GCPs). The outcome of spatial triangulation is introduced for geo-positioning as repeated observation. Results from combining block adjustment with non-oriented new images indicate the feasibility of geometric positioning with the repeated observation. GCPs are a must when high accuracy is demanded in conventional block adjustment; the accuracy of direct georeferencing with repeated observation without GCPs is superior to conventional forward intersection and even approximate to conventional block adjustment with GCPs. The conclusion is drawn that taking the existing oriented imagery as repeated observation enhances the effective utilization of previous spatial triangulation achievement, which makes the breakthrough for repeated observation to improve accuracy by increasing the base-height ratio and redundant observation. Georeferencing tests using data from multiple sensors and platforms with the repeated observation will be carried out in the follow-up research.

Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

PubMed

Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

2016-06-01

Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. Copyright © 2016. Published by Elsevier Ltd.

Examining Spillovers between Long and Short Repeated Prisoner’s Dilemma Games Played in the Laboratory

PubMed Central

Arechar, Antonio A.; Kouchaki, Maryam; Rand, David G.

2018-01-01

We had participants play two sets of repeated Prisoner’s Dilemma (RPD) games, one with a large continuation probability and the other with a small continuation probability, as well as Dictator Games (DGs) before and after the RPDs. We find that, regardless of which is RPD set is played first, participants typically cooperate when the continuation probability is large and defect when the continuation probability is small. However, there is an asymmetry in behavior when transitioning from one continuation probability to the other. When switching from large to small, transient higher levels of cooperation are observed in the early games of the small continuation set. Conversely, when switching from small to large, cooperation is immediately high in the first game of the large continuation set. We also observe that response times increase when transitioning between sets of RPDs, except for altruistic participants transitioning into the set of RPDs with long continuation probabilities. These asymmetries suggest a bias in favor of cooperation. Finally, we examine the link between altruism and RPD play. We find that small continuation probability RPD play is correlated with giving in DGs played before and after the RPDs, whereas high continuation probability RPD play is not. PMID:29809199

Environmental stress induces trinucleotide repeat mutagenesis in human cells

PubMed Central

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

2015-01-01

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

PubMed

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Modeling Life-Span Growth Curves of Cognition Using Longitudinal Data with Multiple Samples and Changing Scales of Measurement

ERIC Educational Resources Information Center

McArdle, John J.; Grimm, Kevin J.; Hamagami, Fumiaki; Bowles, Ryan P.; Meredith, William

2009-01-01

The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs…

"I Don't Know" and Multiple Choice Analysis of Pre- and Post-Tests

ERIC Educational Resources Information Center

Spears, Karen; Wilson, Mary

2010-01-01

Evaluation is an essential component of any Extension education program. One tool, the pre- and post-test, provides measurable evaluation data. Yet often the answer "I don't know" or all possible answers to a multiple choice question are not included in the repeated measure analysis. Because more than two answers are offered, the test of marginal…

Multiple-Locus Variable-Number Tandem-Repeats Analysis of Escherichia coli O157 using PCR multiplexing and multi-colored capillary electrophoresis.

PubMed

Lindstedt, Bjørn-Arne; Vardund, Traute; Kapperud, Georg

2004-08-01

The Multiple-Locus Variable-Number Tandem-Repeats Analysis (MLVA) method is currently being used as the primary typing tool for Shiga-toxin-producing Escherichia coli (STEC) O157 isolates in our laboratory. The initial assay was performed using a single fluorescent dye and the different patterns were assigned using a gel image. Here, we present a significantly improved assay using multiple dye colors and enhanced PCR multiplexing to increase speed, and ease the interpretation of the results. The different MLVA patterns are now based on allele sizes entered as character values, thus removing the uncertainties introduced when analyzing band patterns from the gel image. We additionally propose an easy numbering scheme for the identification of separate isolates that will facilitate exchange of typing data. Seventy-two human and animal strains of Shiga-toxin-producing E. coli O157 were used for the development of the improved MLVA assay. The method is based on capillary separation of multiplexed PCR products of VNTR loci in the E. coli O157 genome labeled with multiple fluorescent dyes. The different alleles at each locus were then assigned to allele numbers, which were used for strain comparison.

Do repeated wildfires change homebuyers' demand for homes in high-risk areas?

Treesearch

Julie M. Mueller; John D. Loomis; Armando González-Cabán

2009-01-01

Unlike most hedonic studies that analyze the effects of a one-time event, this paper analyzes the effects of forest fires that are several years apart in a small geographical area. We find that repeated forest fires cause house prices to decrease for houses located near the fires. We test and reject the hypothesis that the house price reduction from the first fire is...

Topical photodynamic therapy of squamous cell carcinomas in a hairless mouse model

NASA Astrophysics Data System (ADS)

Wang, Hong-Wei; Lv, Ting; Li, Jing-Jing; Tu, Qingfeng; Huang, Zheng; Wang, Xiu-Li

2013-02-01

Objectives: To examine therapeutic effects of 5-aminolevulinate (ALA)-mediated photodynamic therapy (PDT) on UVB-induced cutaneous squamous cell carcinomas (SCCs) in a mouse model. Materials and methods: Cutaneous SCCs were established by UVB (280-320 nm) irradiation of hairless mice. In situ fluorescence measurement was used to monitor PpIX formation after the topical application of various concentrations of ALA cream to determine the optimal ALA dose. Therapeutic responses of SCCs to multiple sessions of ALA PDT were examined histologically and quantitatively. TUNEL staining was used to examine apoptosis caused by PDT. Results: After repeated exposure for 18 to 22 weeks (4-5 days/week), multiple nodular and verrucous hyperplasia lesions of various sizes developed at the exposed area. After four sessions of ALA PDT (8% ALA, 3 h incubation, 30 J/cm2 at 20 mW/cm2) a total of 84% of complete response was achieved for small SCCs (1-4 mm, thickness <2.5 mm). TUNEL staining showed that PDT-induced apoptotic cells were distributed evenly from the basal to stratum corneum layers. Conclusions: Topical ALA PDT can trigger apoptosis in SCCs, inhibit SCC growth, and reduce the size and number of tumors in the hairless mouse model. The true clinical value of ALA PDT for the treatment of cutaneous SCC deserves further investigation.

The Heterogeneity in Retrieved Relations between the Personality Trait ‘Harm Avoidance’ and Gray Matter Volumes Due to Variations in the VBM and ROI Labeling Processing Settings

PubMed Central

Van Schuerbeek, Peter; Baeken, Chris; De Mey, Johan

2016-01-01

Concerns are raising about the large variability in reported correlations between gray matter morphology and affective personality traits as ‘Harm Avoidance’ (HA). A recent review study (Mincic 2015) stipulated that this variability could come from methodological differences between studies. In order to achieve more robust results by standardizing the data processing procedure, as a first step, we repeatedly analyzed data from healthy females while changing the processing settings (voxel-based morphology (VBM) or region-of-interest (ROI) labeling, smoothing filter width, nuisance parameters included in the regression model, brain atlas and multiple comparisons correction method). The heterogeneity in the obtained results clearly illustrate the dependency of the study outcome to the opted analysis settings. Based on our results and the existing literature, we recommended the use of VBM over ROI labeling for whole brain analyses with a small or intermediate smoothing filter (5-8mm) and a model variable selection step included in the processing procedure. Additionally, it is recommended that ROI labeling should only be used in combination with a clear hypothesis and that authors are encouraged to report their results uncorrected for multiple comparisons as supplementary material to aid review studies. PMID:27096608

MicroRNA-155 expression and function in AML: An evolving paradigm.

PubMed

Narayan, Nisha; Bracken, Cameron P; Ekert, Paul G

2018-06-01

Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. Acute leukemia is the most common form of pediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) noncoding RNAs that posttranscriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML, which may prove useful for the purposes of disease classification, prognosis, and future therapeutic approaches. MicroRNA expression profiles are associated with patient prognosis and responses to standard chemotherapy, including predicting therapy resistance in AML. miR-155 is the primary focus of this review because it has been repeatedly associated with poorer survival across multiple cohorts of adult and pediatric AML. We discuss some novel features of miR-155 expression in AML, in particular how the levels of expression can critically influence function. Understanding the role of microRNAs in AML and the ways in which microRNA expression influences AML biology is one means to develop novel and more targeted therapies. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Plug-and-play, infrared, laser-mediated PCR in a microfluidic chip.

PubMed

Pak, Nikita; Saunders, D Curtis; Phaneuf, Christopher R; Forest, Craig R

2012-04-01

Microfluidic polymerase chain reaction (PCR) systems have set milestones for small volume (100 nL-5 μL), amplification speed (100-400 s), and on-chip integration of upstream and downstream sample handling including purification and electrophoretic separation functionality. In practice, the microfluidic chips in these systems require either insertion of thermocouples or calibration prior to every amplification. These factors can offset the speed advantages of microfluidic PCR and have likely hindered commercialization. We present an infrared, laser-mediated, PCR system that features a single calibration, accurate and repeatable precision alignment, and systematic thermal modeling and management for reproducible, open-loop control of PCR in 1 μL chambers of a polymer microfluidic chip. Total cycle time is less than 12 min: 1 min to fill and seal, 10 min to amplify, and 1 min to recover the sample. We describe the design, basis for its operation, and the precision engineering in the system and microfluidic chip. From a single calibration, we demonstrate PCR amplification of a 500 bp amplicon from λ-phage DNA in multiple consecutive trials on the same instrument as well as multiple identical instruments. This simple, relatively low-cost plug-and-play design is thus accessible to persons who may not be skilled in assembly and engineering.

Ant-inspired density estimation via random walks.

PubMed

Musco, Cameron; Su, Hsin-Hao; Lynch, Nancy A

2017-10-03

Many ant species use distributed population density estimation in applications ranging from quorum sensing, to task allocation, to appraisal of enemy colony strength. It has been shown that ants estimate local population density by tracking encounter rates: The higher the density, the more often the ants bump into each other. We study distributed density estimation from a theoretical perspective. We prove that a group of anonymous agents randomly walking on a grid are able to estimate their density within a small multiplicative error in few steps by measuring their rates of encounter with other agents. Despite dependencies inherent in the fact that nearby agents may collide repeatedly (and, worse, cannot recognize when this happens), our bound nearly matches what would be required to estimate density by independently sampling grid locations. From a biological perspective, our work helps shed light on how ants and other social insects can obtain relatively accurate density estimates via encounter rates. From a technical perspective, our analysis provides tools for understanding complex dependencies in the collision probabilities of multiple random walks. We bound the strength of these dependencies using local mixing properties of the underlying graph. Our results extend beyond the grid to more general graphs, and we discuss applications to size estimation for social networks, density estimation for robot swarms, and random walk-based sampling for sensor networks.

Variability of pulsed energy outputs from three dermatology lasers during multiple simulated treatments.

PubMed

Britton, Jason

2018-01-20

Dermatology laser treatments are undertaken at regional departments using lasers of different powers and wavelengths. In order to achieve good outcomes, there needs to be good consistency of laser output across different weeks as it is custom and practice to break down the treatments into individual fractions. Departments will also collect information from test patches to help decide on the most appropriate treatment parameters for individual patients. The objective of these experiments is to assess the variability of the energy outputs from a small number of lasers across multiple weeks at realistic parameters. The energy outputs from 3 lasers were measured at realistic treatment parameters using a thermopile detector across a period of 6 weeks. All lasers fired in single-pulse mode demonstrated good repeatability of energy output. In spite of one of the lasers being scheduled for a dye canister change in the next 2 weeks, there was good energy matching between the two devices with only a 4%-5% variation in measured energies. Based on the results presented, clinical outcomes should not be influenced by variability in the energy outputs of the dermatology lasers used as part of the treatment procedure. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repeat Syphilis Among Men Who Have Sex With Men in California, 2002–2006: Implications for Syphilis Elimination Efforts

PubMed Central

Chew Ng, Rilene A.; Katz, Kenneth A.; Bernstein, Kyle T.; Samuel, Michael C.; Kerndt, Peter R.; Bolan, Gail

2012-01-01

Objectives. We examined rates of and risk factors for repeat syphilis infection among men who have sex with men (MSM) in California. Methods. We analyzed 2002 to 2006 California syphilis surveillance system data. Results. During the study period, a mean of 5.9% (range: 4.9%–7.1% per year) of MSM had a repeat primary or secondary (PS) syphilis infection within 2 years of an initial infection. There was no significant increase in the annual proportion of MSM with a repeat syphilis infection (P = .42). In a multivariable model, factors associated with repeat syphilis infection were HIV infection (odds ratio [OR] = 1.65; 95% confidence interval [CI] = 1.14, 2.37), Black race (OR = 1.84; 95% CI = 1.12, 3.04), and 10 or more recent sex partners (OR = 1.99; 95% CI = 1.12, 3.50). Conclusions. Approximately 6% of MSM in California have a repeat PS syphilis infection within 2 years of an initial infection. HIV infection, Black race, and having multiple sex partners are associated with increased odds of repeat infection. Syphilis elimination efforts should include messages about the risk for repeat infection and the importance of follow-up testing. Public health attention to individuals repeatedly infected with syphilis may help reduce local disease burdens. PMID:22095364

A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family1[w

PubMed Central

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L.; Salt, Jennifer N.; Goring, Daphne R.

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis. PMID:14657406

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

PubMed

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L; Salt, Jennifer N; Goring, Daphne R

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

PubMed

Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

2015-06-01

Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biophysical characterization of soluble Pseudomonas syringae ice nucleation protein InaZ fragments.

PubMed

Han, Yu Jin; Song, HyoJin; Lee, Chang Woo; Ly, Nguyễn Hoàng; Joo, Sang-Woo; Lee, Jun Hyuck; Kim, Soon-Jong; Park, SangYoun

2017-01-01

Ice nucleation protein (INP) with its functional domain consisting of multiple 48-residue repeat units effectively induces super-cooled water into ice. Circular dichroism and infrared deconvolution analyses on a soluble 240-residue fragment of Pseudomonas syringae InaZ (InaZ240) containing five 48-residue repeat units indicated that it is mostly composed of β-sheet and random coil. Analytical ultracentrifugation suggested that InaZ240 behaves as a monomer of an elongated ellipsoid. However, InaZ240 showed only minimum ice binding compared to anti-freeze proteins. Other P. syringae InaZ proteins with more 48-residue repeat units were made, in which the largest soluble fragment obtainable was an InaZ with twelve 48-residue repeat units. Size-exclusion chromatography analyses further suggested that the overall shape of the expressed InaZ fragments is pH-dependent, which becomes compact as the numbers of 48-residue repeat unit increase. Copyright © 2016 Elsevier B.V. All rights reserved.

[Skills lab training in veterinary medicine. Effective preparation for clinical work at the small animal clinic of the University for Veterinary Medicine Hannover, Foundation].

PubMed

Engelskirchen, Simon; Ehlers, Jan; Kirk, Ansgar T; Tipold, Andrea; Dilly, Marc

2017-09-20

During five and a half years of studying veterinary medicine, students should in addition to theoretical knowledge acquire sufficient practical skills. Considering animal welfare and ethical aspects, opportunities for hands-on learning on living animals are limited because of the high annual number of students. The first German veterinary clinical-skills lab, established in 2013 at the University for Veterinary Medicine Hannover, Foundation (TiHo), offers opportunities for all students to learn, train and repeat clinical skills on simulators and models as frequently as they would like, until they feel sufficiently confident to transfer these skills to living animals. This study describes the establishment of clinical-skills lab training within the students' practical education, using the example of the small-animal clinic of the TiHo. Two groups of students were compared: without skills lab training (control group K) and with skills lab training (intervention group I). At the end of both the training and a subsequent 10-week clinical rotation in different sections of the clinic, an objective structured clinical examination (OSCE) was performed, testing the students' practical skills at 15 stations. An additional multiple-choice test was performed before and after the clinical rotation to evaluate the increased theoretical knowledge. Students of group I achieved significantly (p ≤ 0.05) better results in eight of the 15 tested skills. The multiple-choice test revealed a significant (p ≤ 0.05) gain of theoretical knowledge in both groups without any differences between the groups. Students displayed a high degree of acceptance of the skills lab training. Using simulators and models in veterinary education is an efficient teaching concept, and should be used continually and integrated in the curriculum.

Spatial and Temporal Dynamics of Pacific Oyster Hemolymph Microbiota across Multiple Scales

PubMed Central

Lokmer, Ana; Goedknegt, M. Anouk; Thieltges, David W.; Fiorentino, Dario; Kuenzel, Sven; Baines, John F.; Wegner, K. Mathias

2016-01-01

Unveiling the factors and processes that shape the dynamics of host associated microbial communities (microbiota) under natural conditions is an important part of understanding and predicting an organism's response to a changing environment. The microbiota is shaped by host (i.e., genetic) factors as well as by the biotic and abiotic environment. Studying natural variation of microbial community composition in multiple host genetic backgrounds across spatial as well as temporal scales represents a means to untangle this complex interplay. Here, we combined a spatially-stratified with a longitudinal sampling scheme within differentiated host genetic backgrounds by reciprocally transplanting Pacific oysters between two sites in the Wadden Sea (Sylt and Texel). To further differentiate contingent site from host genetic effects, we repeatedly sampled the same individuals over a summer season to examine structure, diversity and dynamics of individual hemolymph microbiota following experimental removal of resident microbiota by antibiotic treatment. While a large proportion of microbiome variation could be attributed to immediate environmental conditions, we observed persistent effects of antibiotic treatment and translocation suggesting that hemolymph microbial community dynamics is subject to within-microbiome interactions and host population specific factors. In addition, the analysis of spatial variation revealed that the within-site microenvironmental heterogeneity resulted in high small-scale variability, as opposed to large-scale (between-site) stability. Similarly, considerable within-individual temporal variability was in contrast with the overall temporal stability at the site level. Overall, our longitudinal, spatially-stratified sampling design revealed that variation in hemolymph microbiota is strongly influenced by site and immediate environmental conditions, whereas internal microbiome dynamics and oyster-related factors add to their long-term stability. The combination of small and large scale resolution of spatial and temporal observations therefore represents a crucial but underused tool to study host-associated microbiome dynamics. PMID:27630625

Borderline Personality Disorder

MedlinePlus

... It can negatively affect intimate relationships, jobs, school, social activities and self-image, resulting in: Repeated job changes or losses Not completing an education Multiple legal issues, such as jail time Conflict-filled relationships, marital ...

SU-F-T-495: Method for Simultaneous Commissioning of Multiple Truebeam (TB) Linacs: Small Field Data and the Choice of Dosimetric Lead Gap (DLG)

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

Mihailidis, D; Mallah, J

2016-06-15

Purpose: Many times a set of multiple Varian-Truebeam (TB) linacs are acquired by an institution. Since “beam matching” is an important requirement for many facilities, we developed a strategy to perform a “simultaneous” commissioning between multiple linacs.Methods and Materials: We first commissioned the required photon beam data for eclipse on the 1st TB for all the energy modalities with a beam scanning system, while integrated measurements for output factors, of all field sizes (from 1×1 to 40×40cm{sup 2}) were conducted on the 2nd TB. Care was exercised during small field dosimetry so the appropriate detectors were used with data takenmore » between two detectors be “linked” to a larger field size (4×4cm{sup 2}) with the “daisy-chaining” technique via: OF=[M-PTW(fs)×(M-PTW(4×4))-1]×[MA12s(4×4)×(M-A12S(10×10))−1]. For all energy modalities, data that span the entire range of field size, was repeated on the next TB linac, for verification. The primarily energy-dependent dosimetric leaf gap (DLG) which was measured separately on each TB. The modeled data was validated with special measurements conducted on both linacs during commissioning. Results: Our data agreed with the “TB representative beam data” to within 0.5% for all energy modalities and field sizes ≥3×3cm2. Sample depth-doses and cross-profiles of a 3×3cm2 between the linacs agreeing to within 1% between linacs. The measured DLGs were quite different with a uniform difference of 1.3% between the two linacs. The measured DLG values are independent of the average dose rate and medium used for the measurements. Conclusion: A comprehensive method of commissioning identical Varian-TB linacs, outlining the critical issues, especially small field dosimetry and DLG. The dosimetric effect of different DLG values, when it comes to, dynamic delivery and data comparisons will be presented. The dependence of DLG value on the measurement medium (in-air vs. water) or dose rate used will also be discussed. This work was supported by CAMC Cancer Center and Alliance Oncology.« less

Optimized Heat Pipe Backup Cooling System Tested with a Stirling Convertor

NASA Technical Reports Server (NTRS)

Schwendeman, Carl L.; Tarau, Calin; Schifer, Nicholas A.; Anderson, William G.; Garner, Scott

2016-01-01

In a Stirling Radioisotope Power System (RPS), heat must be continuously removed from the General Purpose Heat Source (GPHS) modules to maintain the modules and surrounding insulation at acceptable temperatures. The Stirling convertor normally provides this cooling. If the Stirling convertor stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS at the cost of an early termination of the mission. An alkali-metal variable conductance heat pipe (VCHP) can be used to passively allow multiple stops and restarts of the Stirling convertor by bypassing the heat during stops. In a previous NASA Small Business Innovation Research (SBIR) Program, Advanced Cooling Technologies, Inc. (ACT) developed a series of sodium VCHPs as backup cooling systems for the Stirling RPS. In 2012, one of these VCHPs was successfully tested at NASA Glenn Research Center with a Stirling convertor as an Advanced Stirling Radioisotope Generator (ASRG) backup cooling system. The prototype; however, was not optimized and did not reflect the final heat rejection path. ACT through further funding has developed a semioptimized prototype with the finalized heat path for testing at Glenn with a Stirling convertor. The semioptimized system features a two-phase radiator and is significantly smaller and lighter than the prior prototype to reflect a higher level of flight readiness. The VCHP is designed to activate and remove heat from the GPHS during stoppage with a small temperature increase from the nominal vapor temperature. This small temperature increase from nominal is low enough to avoid risking standard ASRG operation and spoiling of the multilayer insulation (MLI). The VCHP passively allows the Stirling convertor to be turned off multiple times during a mission with potentially unlimited off durations. Having the ability to turn the Stirling off allows for the Stirling to be reset and reduces vibrations on the platform during sensitive measurements or procedures. This paper presents the design of the VCHP and its test results with a Stirling convertor at Glenn. Tests were carried for multiple on and off cycles to demonstrate repeatability. The impacts associated with the addition of the VCHP to the system are also addressed in terms of mass and additional heat losses due to the presence of the VCHP.

Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology

PubMed Central

Hazrati, Lili-Naz; Tartaglia, Maria C.; Diamandis, Phedias; Davis, Karen D.; Green, Robin E.; Wennberg, Richard; Wong, Janice C.; Ezerins, Leo; Tator, Charles H.

2013-01-01

Background: Chronic traumatic encephalopathy (CTE) is the term coined for the neurodegenerative disease often suspected in athletes with histories of repeated concussion and progressive dementia. Histologically, CTE is defined as a tauopathy with a distribution of tau-positive neurofibrillary tangles (NFTs) that is distinct from other tauopathies, and usually shows an absence of beta-amyloid deposits, in contrast to Alzheimer's disease (AD). Although the connection between repeated concussions and CTE-type neurodegeneration has been recently proposed, this causal relationship has not yet been firmly established. Also, the prevalence of CTE among athletes with multiple concussions is unknown. Methods: We performed a consecutive case series brain autopsy study on six retired professional football players from the Canadian Football League (CFL) with histories of multiple concussions and significant neurological decline. Results: All participants had progressive neurocognitive decline prior to death; however, only 3 cases had post-mortem neuropathological findings consistent with CTE. The other 3 participants had pathological diagnoses of AD, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Moreover, the CTE cases showed co-morbid pathology of cancer, vascular disease, and AD. Discussion: Our case studies highlight that not all athletes with history of repeated concussions and neurological symptomology present neuropathological changes of CTE. These preliminary findings support the need for further research into the link between concussion and CTE as well as the need to expand the research to other possible causes of taupathy in athletes. They point to a critical need for prospective studies with good sampling methods to allow us to understand the relationship between multiple concussions and the development of CTE. PMID:23745112

Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells

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

Kwon, ChangHyuk, E-mail: netbuyer@hanmail.net; Tak, Hyosun, E-mail: chuberry@naver.com; Rho, Mina, E-mail: minarho@hanyang.ac.kr

2014-03-28

Highlights: • piRNA sequences were mapped to human mitochondrial (mt) genome. • We inspected small RNA-Seq datasets from somatic cell mt subcellular fractions. • Piwi and piRNA transcripts are present in mammalian somatic cancer cell mt fractions. - Abstract: Piwi-interacting RNAs (piRNAs) are 26–31 nt small noncoding RNAs that are processed from their longer precursor transcripts by Piwi proteins. Localization of Piwi and piRNA has been reported mostly in nucleus and cytoplasm of higher eukaryotes germ-line cells, where it is believed that known piRNA sequences are located in repeat regions of nuclear genome in germ-line cells. However, localization of PIWImore » and piRNA in mammalian somatic cell mitochondria yet remains largely unknown. We identified 29 piRNA sequence alignments from various regions of the human mitochondrial genome. Twelve out 29 piRNA sequences matched stem-loop fragment sequences of seven distinct tRNAs. We observed their actual expression in mitochondria subcellular fractions by inspecting mitochondrial-specific small RNA-Seq datasets. Of interest, the majority of the 29 piRNAs overlapped with multiple longer transcripts (expressed sequence tags) that are unique to the human mitochondrial genome. The presence of mature piRNAs in mitochondria was detected by qRT-PCR of mitochondrial subcellular RNAs. Further validation showed detection of Piwi by colocalization using anti-Piwil1 and mitochondria organelle-specific protein antibodies.« less

Tandem-repeat protein domains across the tree of life.

PubMed

Jernigan, Kristin K; Bordenstein, Seth R

2015-01-01

Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20-40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

The relationship of social support concept and repeat mammography among Iranian women.

PubMed

Farhadifar, Fariba; Taymoori, Parvaneh; Bahrami, Mitra; Zarea, Shamsy

2015-10-24

Breast cancer ranks as the first most common cancer among the Iranian women. The regular repeat of mammography with 1-2 year intervals leads to the increased efficiency of early detection of breast cancer. The present study examined the predictors of repeat mammography. It was hypothesized that higher social support is connected with mammography repeat. A cross-sectional study was carried out among 400 women 50 years and older in Sanandaj, Iran. Data was collected by the questionnaire including information on socio demographical variables and measuring social support level. Data was analyzed by SPSS16 software. Multiple logistic regression was used to determine the predictive power of demographic variables and dimensions of social support for repeat mammography. Women aged 50-55 years had three times odds of repeat mammography compared to women aged 56-60 years) OR, 3.02). Married women had greater odds of repeat mammography compared to single women (P < 0.006). The probability of repeat mammography in women with higher social support was 0.93 times greater than the women with lower social support (OR, 0.93; 95 % CI, 0.91-0.95; P < 0.0001). Iranian women are less likely repeat mammography than other Asian women. Identifying the associations between perceived social support and repeat mammography may offer detailed information to allow for future study and guide the development of interventions not only for Iranian women but also for similar cultural that received pay too little attention to date in the breast cancer literature.

ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

PubMed

Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

2006-06-16

The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

Informed actions: where to cost effectively manage multiple threats to species to maximize return on investment.

PubMed

Auerbach, Nancy A; Tulloch, Ayesha I T; Possingham, Hugh P

Conservation practitioners, faced with managing multiple threats to biodiversity and limited funding, must prioritize investment in different management actions. From an economic perspective, it is routine practice to invest where the highest rate of return is expected. This return-on-investment (ROI) thinking can also benefit species conservation, and researchers are developing sophisticated approaches to support decision-making for cost-effective conservation. However, applied use of these approaches is limited. Managers may be wary of “black-box” algorithms or complex methods that are difficult to explain to funding agencies. As an alternative, we demonstrate the use of a basic ROI analysis for determining where to invest in cost-effective management to address threats to species. This method can be applied using basic geographic information system and spreadsheet calculations. We illustrate the approach in a management action prioritization for a biodiverse region of eastern Australia. We use ROI to prioritize management actions for two threats to a suite of threatened species: habitat degradation by cattle grazing, and predation by invasive red foxes (Vulpes vulpes). We show how decisions based on cost-effective threat management depend upon how expected benefits to species are defined and how benefits and costs co-vary. By considering a combination of species richness, restricted habitats, species vulnerability, and costs of management actions, small investments can result in greater expected benefit compared with management decisions that consider only species richness. Furthermore, a landscape management strategy that implements multiple actions is more efficient than managing only for one threat, or more traditional approaches that don't consider ROI. Our approach provides transparent and logical decision support for prioritizing different actions intended to abate threats associated with multiple species; it is of use when managers need a justifiable and repeatable approach to investment.

Testing an empirically derived mental health training model featuring small groups, distributed practice and patient discussion.

PubMed

Murrihy, Rachael C; Byrne, Mitchell K; Gonsalvez, Craig J

2009-02-01

Internationally, family doctors seeking to enhance their skills in evidence-based mental health treatment are attending brief training workshops, despite clear evidence in the literature that short-term, massed formats are not likely to improve skills in this complex area. Reviews of the educational literature suggest that an optimal model of training would incorporate distributed practice techniques; repeated practice over a lengthy time period, small-group interactive learning, mentoring relationships, skills-based training and an ongoing discussion of actual patients. This study investigates the potential role of group-based training incorporating multiple aspects of good pedagogy for training doctors in basic competencies in brief cognitive behaviour therapy (BCBT). Six groups of family doctors (n = 32) completed eight 2-hour sessions of BCBT group training over a 6-month period. A baseline control design was utilised with pre- and post-training measures of doctors' BCBT skills, knowledge and engagement in BCBT treatment. Family doctors' knowledge, skills in and actual use of BCBT with patients improved significantly over the course of training compared with the control period. This research demonstrates preliminary support for the efficacy of an empirically derived group training model for family doctors. Brief CBT group-based training could prove to be an effective and viable model for future doctor training.

Repetitive sequences and epigenetic modification: inseparable partners play important roles in the evolution of plant sex chromosomes.

PubMed

Li, Shu-Fen; Zhang, Guo-Jun; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

2016-05-01

The present review discusses the roles of repetitive sequences played in plant sex chromosome evolution, and highlights epigenetic modification as potential mechanism of repetitive sequences involved in sex chromosome evolution. Sex determination in plants is mostly based on sex chromosomes. Classic theory proposes that sex chromosomes evolve from a specific pair of autosomes with emergence of a sex-determining gene(s). Subsequently, the newly formed sex chromosomes stop recombination in a small region around the sex-determining locus, and over time, the non-recombining region expands to almost all parts of the sex chromosomes. Accumulation of repetitive sequences, mostly transposable elements and tandem repeats, is a conspicuous feature of the non-recombining region of the Y chromosome, even in primitive one. Repetitive sequences may play multiple roles in sex chromosome evolution, such as triggering heterochromatization and causing recombination suppression, leading to structural and morphological differentiation of sex chromosomes, and promoting Y chromosome degeneration and X chromosome dosage compensation. In this article, we review the current status of this field, and based on preliminary evidence, we posit that repetitive sequences are involved in sex chromosome evolution probably via epigenetic modification, such as DNA and histone methylation, with small interfering RNAs as the mediator.

Molecular Epidemiology of Leptospira Serogroup Pomona Infections Among Wild and Domestic Animals in Spain.

PubMed

Arent, Z J; Gilmore, C; San-Miguel Ayanz, J M; Neyra, L Quevedo; García-Peña, F J

2017-03-01

Strains of Leptospira serogroup Pomona are known to cause widespread animal infections in many parts of the world. Forty-three isolates retrieved from domestic animals and wild small mammals suggest that serogroup Pomona is epidemiologically relevant in Spain. This is supported by the high prevalence of serovar Pomona antibodies in livestock and wild animals. In this study, the strains were serologically and genetically characterized in an attempt to elucidate their epidemiology. Serological typing was based on the microscopic agglutination test but molecular typing involved species-specific polymerase chain reaction, restriction endonuclease analysis, and multiple-locus variable-number tandem repeat analysis. The study revealed that the infections are caused by two serovars, namely Pomona and Mozdok. Serovar Pomona was derived only from farm animals and may be adapted to pigs, which are recognized as the maintenance host. The results demonstrated that serovar Pomona is genetically heterogeneous and three different types were recognized. This heterogeneity was correlated with different geographical distributions of the isolates. All strains derived from small wild mammals were identified as serovar Mozdok. Some isolates of this serovar retrieved from cattle confirm that this serovar may also be the cause of infections in food-producing animals for which these wild species may be source of infection.

Improving Correlation Algorithms to Detect and Characterize Smaller Magnitude Induced Seismicity Swarms

NASA Astrophysics Data System (ADS)

Skoumal, R.; Brudzinski, M.; Currie, B.

2015-12-01

Induced seismic sequences often occur as swarms that can include thousands of small (< M 2) earthquakes. While the identification of this microseismicity would invariably aid in the characterization and modeling of induced sequences, traditional earthquake detection techniques often provide incomplete catalogs, even when local networks are deployed. Because induced sequences often include scores of micro-earthquakes that prelude larger magnitude events, the identification of these small magnitude events would be crucial for the early identification of induced sequences. By taking advantage of the repeating, swarm-like nature of induced seismicity, a more robust catalog can be created using complementary correlation algorithms in near real-time without the reliance on traditional earthquake detection and association routines. Since traditional earthquake catalog methodologies using regional networks have a relatively high detection threshold (M 2+), we have sought to develop correlation routines that can detect smaller magnitude sequences. While short-term/long-term amplitude average detection algorithms requires significant signal-to-noise ratio at multiple stations for confident identification, a correlation detector is capable of identifying earthquakes with high confidence using just a single station. The result is an embarrassingly parallel task that can be employed for a network to be used as an early warning system for potentially induced seismicity while also better characterizing tectonic sequences beyond what traditional methods allow.

Rapid-Response or Repeat-Mode Topography from Aerial Structure from Motion

NASA Astrophysics Data System (ADS)

Nissen, E.; Johnson, K. L.; Fitzgerald, F. S.; Morgan, M.; White, J.

2014-12-01

This decade has seen a surge of interest in Structure-from-Motion (SfM) as a means of generating high-resolution topography and coregistered texture maps from stereo digital photographs. Using an unstructured set of overlapping photographs captured from multiple viewpoints and minimal GPS ground control, SfM solves simultaneously for scene topography and camera positions, orientations and lens parameters. The use of cheap unmanned aerial vehicles or tethered helium balloons as camera platforms expedites data collection and overcomes many of the cost, time and logistical limitations of LiDAR surveying, making it a potentially valuable tool for rapid response mapping and repeat monitoring applications. We begin this presentation by assessing what data resolutions and precisions are achievable using a simple aerial camera platform and commercial SfM software (we use the popular Agisoft Photoscan package). SfM point clouds generated at two small (~0.1 km2), sparsely-vegetated field sites in California compare favorably with overlapping airborne and terrestrial LiDAR surveys, with closest point distances of a few centimeters between the independent datasets. Next, we go on to explore the method in more challenging conditions, in response to a major landslide in Mesa County, Colorado, on 25th May 2014. Photographs collected from a small UAV were used to generate a high-resolution model of the 4.5 x 1 km landslide several days before an airborne LiDAR survey could be organized and flown. An initial estimate of the mass balance of the landslide could quickly be made by differencing this model against pre-event topography generated using stereo photographs collected in 2009 as part of the National Agricultural Imagery Program (NAIP). This case study therefore demonstrates the rich potential offered by this technique, as well as some of the challenges, particularly with respect to the treatment of vegetation.

Effects of long-term grassland management on the carbon and nitrogen pools of different soil aggregate fractions.

PubMed

Egan, Gary; Crawley, Michael J; Fornara, Dario A

2018-02-01

Common grassland management practices include animal grazing and the repeated addition of lime and nutrient fertilizers to soils. These practices can greatly influence the size and distribution of different soil aggregate fractions, thus altering the cycling and storage of carbon (C) and nitrogen (N) in grassland soils. So far, very few studies have simultaneously addressed the potential long-term effect that multiple management practices might have on soil physical aggregation. Here we specifically ask whether and how grazing, liming and nutrient fertilization might influence C and N content (%) as well as C and N pools of different soil aggregate fractions in a long-term grassland experiment established in 1991 at Silwood Park, Berkshire, UK. We found that repeated liming applications over 23years significantly decreased the C pool (i.e. gCKg -1 soil) of Large Macro Aggregate (LMA>2mm) fractions and increased C pools within three smaller soil aggregate fractions: Small Macro Aggregate (SMA, 250μm-2mm), Micro Aggregate (MiA, 53-250μm), and Silt Clay Aggregate (SCA<53μm). Soil C (and N) accrual in smaller fractions was mainly caused by positive liming effects on aggregate fraction mass rather than on changes in soil C (and N) content (%). Liming effects could be explained by increases in soil pH, as this factor was significantly positively related to greater soil C and N pools of smaller aggregate fractions. Long-term grazing and inorganic nutrient fertilization had much weaker effects on both soil aggregate-fraction mass and on soil C and N concentrations, however, our evidence is that these practices could also contribute to greater C and N pools of smaller soil fractions. Overall our study demonstrates how agricultural liming can contribute to increase C pools of small (more stable) soil fractions with potential significant benefits for the long-term C balance of human-managed grassland soils. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing Toy Play among Toddlers with Multiple Disabilities in an Inclusive Classroom: A More-to-Less, Child-Directed Intervention Continuum.

ERIC Educational Resources Information Center

DiCarlo, Cynthia F.; Reid, Dennis H.; Stricklin, Sarintha B.

2003-01-01

A study evaluated a more-to-less, child-directed continuum of intervention to increase toy play among six toddlers with multiple disabilities. Toddlers were provided with repeated choices of preferred toys in a child-directed manner. Nonprompted toy play for two toddlers increased. Toy play also increased for another child after staff prompts and…

Passenger comfort during terminal-area flight maneuvers. M.S. Thesis.

NASA Technical Reports Server (NTRS)

Schoonover, W. E., Jr.

1976-01-01

A series of flight experiments was conducted to obtain passenger subjective responses to closely controlled and repeatable flight maneuvers. In 8 test flights, reactions were obtained from 30 passenger subjects to a wide range of terminal-area maneuvers, including descents, turns, decelerations, and combinations thereof. Analysis of the passenger rating variance indicated that the objective of a repeatable flight passenger environment was achieved. Multiple linear regression models developed from the test data were used to define maneuver motion boundaries for specified degrees of passenger acceptance.

[Reinfections and the development of schistosomal periportal fibrosis in the murine model].

PubMed

Santos, A B; de Souza, M M; Andrade, Z A

2000-01-01

Experimental pipestem fibrosis of the liver developed more frequently (69.2%) in mice submitted to repeated infections with Schistosoma mansoni, than with single infection (11.1%). The counting of eggs in the liver revealed no significant differences between the two experimental groups. Although the reason why multiple infections favor the development of pipestem fibrosis has not been elucidated, the data obtained represent an experimental support to clinico-epidemiological claims that repeated infections play a role in pathogenesis of hepatosplenic schistosomiasis

Making assessments while taking repeated risks: a pattern of multiple response pathways.

PubMed

Pleskac, Timothy J; Wershbale, Avishai

2014-02-01

Beyond simply a decision process, repeated risky decisions also require a number of cognitive processes including learning, search and exploration, and attention. In this article, we examine how multiple response pathways develop over repeated risky decisions. Using the Balloon Analogue Risk Task (BART) as a case study, we show that 2 different response pathways emerge over the course of the task. The assessment pathway is a slower, more controlled pathway where participants deliberate over taking a risk. The 2nd pathway is a faster, more automatic process where no deliberation occurs. Results imply the slower assessment pathway is taken as choice conflict increases and that the faster automatic response is a learned response. Based on these results, we modify an existing formal cognitive model of decision making during the BART to account for these dual response pathways. The slower more deliberative response process is modeled with a sequential sampling process where evidence is accumulated to a threshold, while the other response is given automatically. We show that adolescents with conduct disorder and substance use disorder symptoms not only evaluate risks differently during the BART but also differ in the rate at which they develop the more automatic response. More broadly, our results suggest cognitive models of judgment decision making need to transition from treating observed decisions as the result of a single response pathway to the result of multiple response pathways that change and develop over time.

The role of diffusive architectural surfaces on auditory spatial discrimination in performance venues.

PubMed

Robinson, Philip W; Pätynen, Jukka; Lokki, Tapio; Jang, Hyung Suk; Jeon, Jin Yong; Xiang, Ning

2013-06-01

In musical or theatrical performance, some venues allow listeners to individually localize and segregate individual performers, while others produce a well blended ensemble sound. The room acoustic conditions that make this possible, and the psycho-acoustic effects at work are not fully understood. This research utilizes auralizations from measured and simulated performance venues to investigate spatial discrimination of multiple acoustic sources in rooms. Signals were generated from measurements taken in a small theater, and listeners in the audience area were asked to distinguish pairs of speech sources on stage with various spatial separations. This experiment was repeated with the proscenium splay walls treated to be flat, diffusive, or absorptive. Similar experiments were conducted in a simulated hall, utilizing 11 early reflections with various characteristics, and measured late reverberation. The experiments reveal that discriminating the lateral arrangement of two sources is possible at narrower separation angles when reflections come from flat or absorptive rather than diffusive surfaces.

A statistical approach to combining multisource information in one-class classifiers

DOE PAGES

Simonson, Katherine M.; Derek West, R.; Hansen, Ross L.; ...

2017-06-08

A new method is introduced in this paper for combining information from multiple sources to support one-class classification. The contributing sources may represent measurements taken by different sensors of the same physical entity, repeated measurements by a single sensor, or numerous features computed from a single measured image or signal. The approach utilizes the theory of statistical hypothesis testing, and applies Fisher's technique for combining p-values, modified to handle nonindependent sources. Classifier outputs take the form of fused p-values, which may be used to gauge the consistency of unknown entities with one or more class hypotheses. The approach enables rigorousmore » assessment of classification uncertainties, and allows for traceability of classifier decisions back to the constituent sources, both of which are important for high-consequence decision support. Application of the technique is illustrated in two challenge problems, one for skin segmentation and the other for terrain labeling. Finally, the method is seen to be particularly effective for relatively small training samples.« less

A statistical approach to combining multisource information in one-class classifiers

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

Simonson, Katherine M.; Derek West, R.; Hansen, Ross L.

A new method is introduced in this paper for combining information from multiple sources to support one-class classification. The contributing sources may represent measurements taken by different sensors of the same physical entity, repeated measurements by a single sensor, or numerous features computed from a single measured image or signal. The approach utilizes the theory of statistical hypothesis testing, and applies Fisher's technique for combining p-values, modified to handle nonindependent sources. Classifier outputs take the form of fused p-values, which may be used to gauge the consistency of unknown entities with one or more class hypotheses. The approach enables rigorousmore » assessment of classification uncertainties, and allows for traceability of classifier decisions back to the constituent sources, both of which are important for high-consequence decision support. Application of the technique is illustrated in two challenge problems, one for skin segmentation and the other for terrain labeling. Finally, the method is seen to be particularly effective for relatively small training samples.« less

The Next-Generation PCR-Based Quantification Method for Ambient Waters: Digital PCR.

PubMed

Cao, Yiping; Griffith, John F; Weisberg, Stephen B

2016-01-01

Real-time quantitative PCR (qPCR) is increasingly being used for ambient water monitoring, but development of digital polymerase chain reaction (digital PCR) has the potential to further advance the use of molecular techniques in such applications. Digital PCR refines qPCR by partitioning the sample into thousands to millions of miniature reactions that are examined individually for binary endpoint results, with DNA density calculated from the fraction of positives using Poisson statistics. This direct quantification removes the need for standard curves, eliminating the labor and materials associated with creating and running standards with each batch, and removing biases associated with standard variability and mismatching amplification efficiency between standards and samples. Confining reactions and binary endpoint measurements to small partitions also leads to other performance advantages, including reduced susceptibility to inhibition, increased repeatability and reproducibility, and increased capacity to measure multiple targets in one analysis. As such, digital PCR is well suited for ambient water monitoring applications and is particularly advantageous as molecular methods move toward autonomous field application.

A LDR-PCR approach for multiplex polymorphisms genotyping of severely degraded DNA with fragment sizes <100 bp.

PubMed

Zhang, Zhen; Wang, Bao-Jie; Guan, Hong-Yu; Pang, Hao; Xuan, Jin-Feng

2009-11-01

Reducing amplicon sizes has become a major strategy for analyzing degraded DNA typical of forensic samples. However, amplicon sizes in current mini-short tandem repeat-polymerase chain reaction (PCR) and mini-sequencing assays are still not suitable for analysis of severely degraded DNA. In this study, we present a multiplex typing method that couples ligase detection reaction with PCR that can be used to identify single nucleotide polymorphisms and small-scale insertion/deletions in a sample of severely fragmented DNA. This method adopts thermostable ligation for allele discrimination and subsequent PCR for signal enhancement. In this study, four polymorphic loci were used to assess the ability of this technique to discriminate alleles in an artificially degraded sample of DNA with fragment sizes <100 bp. Our results showed clear allelic discrimination of single or multiple loci, suggesting that this method might aid in the analysis of extremely degraded samples in which allelic drop out of larger fragments is observed.

Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales

NASA Astrophysics Data System (ADS)

Bhérer, Claude; Campbell, Christopher L.; Auton, Adam

2017-04-01

In humans, males have lower recombination rates than females over the majority of the genome, but the opposite is usually true near the telomeres. These broad-scale differences have been known for decades, yet little is known about differences at the fine scale. By combining data sets, we have collected recombination events from over 100,000 meioses and have constructed sex-specific genetic maps at a previously unachievable resolution. Here we show that, although a substantial fraction of the genome shows some degree of sexually dimorphic recombination, the vast majority of hotspots are shared between the sexes, with only a small number of putative sex-specific hotspots. Wavelet analysis indicates that most of the differences can be attributed to the fine scale, and that variation in rate between the sexes can mostly be explained by differences in hotspot magnitude, rather than location. Nonetheless, known recombination-associated genomic features, such as THE1B repeat elements, show systematic differences between the sexes.

Precision Spectrophotometric Calibration System for Dark Energy Instruments

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

Schubnell, Michael S.

2015-06-30

For this research we build a precision calibration system and carried out measurements to demonstrate the precision that can be achieved with a high precision spectrometric calibration system. It was shown that the system is capable of providing a complete spectrophotometric calibration at the sub-pixel level. The calibration system uses a fast, high precision monochromator that can quickly and efficiently scan over an instrument’s entire spectral range with a spectral line width of less than 0.01 nm corresponding to a fraction of a pixel on the CCD. The system was extensively evaluated in the laboratory. Our research showed that amore » complete spectrophotometric calibration standard for spectroscopic survey instruments such as DESI is possible. The monochromator precision and repeatability to a small fraction of the DESI spectrograph LSF was demonstrated with re-initialization on every scan and thermal drift compensation by locking to multiple external line sources. A projector system that mimics telescope aperture for point source at infinity was demonstrated.« less

[Case of CNS-limited ANCA-associated vasculitis presenting as recurrent ischemic stroke].

PubMed

Wakisaka, Kayo; Hagiwara, Noriko; Kanazawa, Yuka; Arakawa, Shuji; Ago, Tetsuro; Kitazono, Takanari

2014-01-01

A 73-year-old man was admitted to our hospital because of a decrease in spontaneity. His medical history included two stroke episodes, probably related to hypertension. Brain MRI on admission demonstrated acute infarction in the right caudate nucleus and left putamen. Intravenous infusion of a low molecular-weight heparin added to oral antiplatelets was started. Following admission, he developed a low grade fever and severe inflammatory reaction. The focus of infection was not evident, and none of the antibiotics tried were effective. Ten days after admission, he developed right hemiparesis, and an additional brain MRI showed new multiple infarctions. We also determined the presence of a high MPO-ANCA titer (57 EU), and we diagnosed the patient's condition to be ANCA-associated vasculitis (AAV). Steroid therapy improved his inflammatory reaction and stroke recurrence was not observed. We suggest that vasculitis should be considered as a potential risk factor for repeated small infarctions with fever of unknown origin, especially those of perforating artery territories.

Genotypes of pathogenic Leptospira spp isolated from rodents in Argentina

PubMed Central

Loffler, Sylvia Grune; Pavan, Maria Elisa; Vanasco, Bibiana; Samartino, Luis; Suarez, Olga; Auteri, Carmelo; Romero, Graciela; Brihuega, Bibiana

2014-01-01

Leptospirosis is the most widespread zoonosis in the world and significant efforts have been made to determine and classify pathogenic Leptospira strains. This zoonosis is maintained in nature through chronic renal infections of carrier animals, with rodents and other small mammals serving as the most important reservoirs. Additionally, domestic animals, such as livestock and dogs, are significant sources of human infection. In this study, a multiple-locus variable-number tandem repeat analysis (MLVA) was applied to genotype 22 pathogenic Leptospira strains isolated from urban and periurban rodent populations from different regions of Argentina. Three MLVA profiles were identified in strains belonging to the species Leptospira interrogans (serovars Icterohaemorrhagiae and Canicola); one profile was observed in serovar Icterohaemorrhagiae and two MLVA profiles were observed in isolates of serovars Canicola and Portlandvere. All strains belonging to Leptospira borgpetersenii serovar Castellonis exhibited the same MLVA profile. Four different genotypes were isolated from urban populations of rodents, including both mice and rats and two different genotypes were isolated from periurban populations. PMID:24676656

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

Andrew, S.E.; Goldberg, Y.P.; Squitieri, F.

Huntington disease (HD) is one of 7 disorders now known to be caused by expansion of a trinucleotide repeat. The HD mutation is a polymorphic trinucleotide (CAG) repeat in the 5{prime} region of a novel gene that expands beyond the normal range of 10-35 repeats in persons destined to develop the disease. Haplotype analysis of other dynamic mutation disorders such as myotonic dystrophy and Fragil X have suggested that a rare ancestral expansion event on a normal chromosome is followed by subsequent expansion events, resulting in a pool of chromosomes in the premutation range, which is inherently unstable and pronemore » to further multiple expansion events leading to disease range chromosomes. Haplotype analysis of 67 HD and 84 control chromosomes using 5 polymorphic markers, both intragenic and 5{prime} to the disease mutation, demonstrate that multiple haplotypes underlie HD. However, 94% of the chromosomes can be grouped under two major haplotypes. These two haplotypes are also present in the normal population. A third major haplotype is seen on 38% of normal chromosomes but rarely on HD chromosomes (6%). CAG lengths on the normal chromosomes with the two haplotypes seen in the HD population are higher than those seen on the normal chromosomes with the haplotype rarely seen on HD chromosomes. Furthermore, in populations with a diminished frequency of HD, CAG length on normal chromosomes is significantly less than other populations with higher prevalence rates for HD. These data suggest that CAG length on normal chromosomes may be a significant factor contributing to repeat instability that eventually leads to chromosomes with CAG repeat lengths in the HD range. Haplotypes on the HD chromosomes are identical to those normal chromosomes which have CAG lengths in the high range of normal, suggesting that further expansions of this pool of chromosomes leads to chromosomes with CAG repeat sizes within the disease range, consistent with a multistep model.« less

Structure of the Myotonic Dystrophy Type 2 RNA and Designed Small Molecules That Reduce Toxicity

PubMed Central

Park, HaJeung; Lohman, Jeremy R.; Guan, Lirui; Tran, Tuan; Sarkar, Partha; Schatz, George C.; Disney, Matthew D.

2014-01-01

Myotonic dystrophy type 2 (DM2) is an untreatable neuromuscular disorder caused by a r(CCUG) expansion (r(CCUG)exp) that folds into an extended hairpin with periodically repeating 2×2 nucleotide internal loops (5’CCUG/3’GUCC). We designed multivalent compounds that improve DM2-associated defects using information about RNA-small molecule interactions. We also report the first crystal structure of r(CCUG)exp refined to 2.35 Å. Structural analysis of the three 5’CCUG/3’GUCC repeat internal loops (L) reveals that the CU pairs in L1 are each stabilized by one hydrogen bond and a water-mediated hydrogen bond while CU pairs in L2 and L3 are stabilized by two hydrogen bonds. Molecular dynamics (MD) simulations reveal that the CU pairs are dynamic and stabilized by Na+ and water molecules. MD simulations of the binding of the small molecule to r(CCUG) repeats reveal that the lowest free energy binding mode occurs via the major groove, in which one C residue is unstacked and the cross-strand nucleotides are displaced. Moreover, we modeled the binding of our dimeric compound to two 5’CCUG/3’GUCC motifs, which shows that the scaffold on which the RNA-binding modules are displayed provides an optimal distance to span two adjacent loops. PMID:24341895

About-face on face recognition ability and holistic processing

PubMed Central

Richler, Jennifer J.; Floyd, R. Jackie; Gauthier, Isabel

2015-01-01

Previous work found a small but significant relationship between holistic processing measured with the composite task and face recognition ability measured by the Cambridge Face Memory Test (CFMT; Duchaine & Nakayama, 2006). Surprisingly, recent work using a different measure of holistic processing (Vanderbilt Holistic Face Processing Test [VHPT-F]; Richler, Floyd, & Gauthier, 2014) and a larger sample found no evidence for such a relationship. In Experiment 1 we replicate this unexpected result, finding no relationship between holistic processing (VHPT-F) and face recognition ability (CFMT). A key difference between the VHPT-F and other holistic processing measures is that unique face parts are used on each trial in the VHPT-F, unlike in other tasks where a small set of face parts repeat across the experiment. In Experiment 2, we test the hypothesis that correlations between the CFMT and holistic processing tasks are driven by stimulus repetition that allows for learning during the composite task. Consistent with our predictions, CFMT performance was correlated with holistic processing in the composite task when a small set of face parts repeated over trials, but not when face parts did not repeat. A meta-analysis confirms that relationships between the CFMT and holistic processing depend on stimulus repetition. These results raise important questions about what is being measured by the CFMT, and challenge current assumptions about why faces are processed holistically. PMID:26223027

About-face on face recognition ability and holistic processing.

PubMed

Richler, Jennifer J; Floyd, R Jackie; Gauthier, Isabel

2015-01-01

Previous work found a small but significant relationship between holistic processing measured with the composite task and face recognition ability measured by the Cambridge Face Memory Test (CFMT; Duchaine & Nakayama, 2006). Surprisingly, recent work using a different measure of holistic processing (Vanderbilt Holistic Face Processing Test [VHPT-F]; Richler, Floyd, & Gauthier, 2014) and a larger sample found no evidence for such a relationship. In Experiment 1 we replicate this unexpected result, finding no relationship between holistic processing (VHPT-F) and face recognition ability (CFMT). A key difference between the VHPT-F and other holistic processing measures is that unique face parts are used on each trial in the VHPT-F, unlike in other tasks where a small set of face parts repeat across the experiment. In Experiment 2, we test the hypothesis that correlations between the CFMT and holistic processing tasks are driven by stimulus repetition that allows for learning during the composite task. Consistent with our predictions, CFMT performance was correlated with holistic processing in the composite task when a small set of face parts repeated over trials, but not when face parts did not repeat. A meta-analysis confirms that relationships between the CFMT and holistic processing depend on stimulus repetition. These results raise important questions about what is being measured by the CFMT, and challenge current assumptions about why faces are processed holistically.

Regression Models for the Analysis of Longitudinal Gaussian Data from Multiple Sources

PubMed Central

O’Brien, Liam M.; Fitzmaurice, Garrett M.

2006-01-01

We present a regression model for the joint analysis of longitudinal multiple source Gaussian data. Longitudinal multiple source data arise when repeated measurements are taken from two or more sources, and each source provides a measure of the same underlying variable and on the same scale. This type of data generally produces a relatively large number of observations per subject; thus estimation of an unstructured covariance matrix often may not be possible. We consider two methods by which parsimonious models for the covariance can be obtained for longitudinal multiple source data. The methods are illustrated with an example of multiple informant data arising from a longitudinal interventional trial in psychiatry. PMID:15726666

Identification and Analysis of Novel Amino-Acid Sequence Repeats in Bacillus anthracis str. Ames Proteome Using Computational Tools

PubMed Central

Hemalatha, G. R.; Rao, D. Satyanarayana; Guruprasad, L.

2007-01-01

We have identified four repeats and ten domains that are novel in proteins encoded by the Bacillus anthracis str. Ames proteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure. PMID:17538688

A novel magnet based 3D printed marker wand as basis for repeated in-shoe multi segment foot analysis: a proof of concept.

PubMed

Eerdekens, Maarten; Staes, Filip; Pilkington, Thomas; Deschamps, Kevin

2017-01-01

Application of in-shoe multi-segment foot kinematic analyses currently faces a number of challenges, including: (i) the difficulty to apply regular markers onto the skin, (ii) the necessity for an adequate shoe which fits various foot morphologies and (iii) the need for adequate repeatability throughout a repeated measure condition. The aim of this study therefore was to design novel magnet based 3D printed markers for repeated in-shoe measurements while using accordingly adapted modified shoes for a specific multi-segment foot model. Multi-segment foot kinematics of ten participants were recorded and kinematics of hindfoot, midfoot and forefoot were calculated. Dynamic trials were conducted to check for intra and inter-session repeatability when combining novel markers and modified shoes in a repeated measures design. Intraclass correlation coefficients were calculated to determine reliability. Both repeatability and reliability were proven to be good to excellent with maximum joint angle deviations of 1.11° for intra-session variability and 1.29° for same-day inter-session variability respectively and ICC values of >0.91. The novel markers can be reliably used in future research settings using in-shoe multi-segment foot kinematic analyses with multiple shod conditions.

Multiple context mere exposure: Examining the limits of liking.

PubMed

de Zilva, Daniel; Newell, Ben R; Mitchell, Chris J

2016-01-01

Recent evidence suggests that increased liking of exposed stimuli-a phenomenon known as the mere exposure effect-is dependent on experiencing the stimuli in the same context at exposure and test. Three experiments extended this work by examining the effect of presenting target stimuli in single and multiple exposure contexts. Target face stimuli were repeatedly paired with nonsense words, which took the role of contexts, across exposure. On test, the mere exposure effect was found only when the target face stimuli were presented with nonsense word cues (contexts) with which they had been repeatedly paired. The mere exposure effect was eliminated when exposure to target face stimuli with the nonsense word cues (contexts) was minimal, despite the overall number of exposures to the target face being equated across single- and multiple-context exposure conditions. The results suggest that familiarity of the relationship between stimuli and their context, not simply familiarity of the stimuli themselves, leads to liking. The finding supports a broader framework, which suggests that liking is partly a function of the consistency between past and present experiences with a target stimulus.

Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

PubMed

O'Flynn, E A M; Currie, R J; Mohammed, K; Allen, S D; Michell, M J

2013-02-01

We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multimodal MRI in cerebral small vessel disease: its relationship with cognition and sensitivity to change over time.

PubMed

Nitkunan, Arani; Barrick, Tom R; Charlton, Rebecca A; Clark, Chris A; Markus, Hugh S

2008-07-01

Cerebral small vessel disease is the most common cause of vascular dementia. Interest in using MRI parameters as surrogate markers of disease to assess therapies is increasing. In patients with symptomatic sporadic small vessel disease, we determined which MRI parameters best correlated with cognitive function on cross-sectional analysis and which changed over a period of 1 year. Thirty-five patients with lacunar stroke and leukoaraiosis were recruited. They underwent multimodal MRI (brain volume, fluid-attenuated inversion recovery lesion load, lacunar infarct number, fractional anisotropy, and mean diffusivity from diffusion tensor imaging) and neuropsychological testing. Twenty-seven agreed to reattend for repeat MRI and neuropsychology at 1 year. An executive function score correlated most strongly with diffusion tensor imaging (fractional anisotropy histogram, r=-0.640, P=0.004) and brain volume (r=0.501, P=0.034). Associations with diffusion tensor imaging were stronger than with all other MRI parameters. On multiple regression of all imaging parameters, a model that contained brain volume and fractional anisotropy, together with age, gender, and premorbid IQ, explained 74% of the variance of the executive function score (P=0.0001). Changes in mean diffusivity and fractional anisotropy were detectable over the 1-year follow-up; in contrast, no change in other MRI parameters was detectable over this time period. A multimodal MRI model explains a large proportion of the variation in executive function in cerebral small vessel disease. In particular, diffusion tensor imaging correlates best with executive function and is the most sensitive to change. This supports the use of MRI, in particular diffusion tensor imaging, as a surrogate marker in treatment trials.

Secretion of CyaA-PrtB and HlyA-PrtB fusion proteins in Escherichia coli: involvement of the glycine-rich repeat domain of Erwinia chrysanthemi protease B.

PubMed Central

Létoffé, S; Wandersman, C

1992-01-01

Protease B from Erwinia chrysanthemi was shown previously to have a C-terminal secretion signal located downstream of a domain that contains six glycine-rich repeats. This domain is conserved in all known bacterial proteins secreted by the signal peptide-independent pathway. The role of these repeats in the secretion process is controversial. We compared the secretion processes of various heterologous polypeptides fused either directly to the signal or separated from it by the glycine-rich domain. Although the repeats are not involved in the secretion of small truncated protease B carboxy-terminal peptides, they are required for the secretion of higher-molecular-weight fusion proteins. Secretion efficiency was also dependent on the size of the passenger polypeptide. Images PMID:1629152

Rational design of alpha-helical tandem repeat proteins with closed architectures

PubMed Central

Doyle, Lindsey; Hallinan, Jazmine; Bolduc, Jill; Parmeggiani, Fabio; Baker, David; Stoddard, Barry L.; Bradley, Philip

2015-01-01

Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials1,2. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks3,4. The overall architecture of tandem repeat protein structures – which is dictated by the internal geometry and local packing of the repeat building blocks – is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners5–9, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis10. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed alpha-solenoid11 repeat structures (alpha-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the N- and C-termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering12–20, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed alpha-solenoid repeats with a left-handed helical architecture that – to our knowledge – is not yet present in the protein structure database21. PMID:26675735

Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis.

PubMed

Vogler, Amy J; Keys, Christine E; Allender, Christopher; Bailey, Ira; Girard, Jessica; Pearson, Talima; Smith, Kimothy L; Wagner, David M; Keim, Paul

2007-03-01

VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing approximately 96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database.

The effect of pain on task switching: pain reduces accuracy and increases reaction times across multiple switching paradigms.

PubMed

Attridge, Nina; Keogh, Edmund; Eccleston, Christopher

2016-10-01

Pain disrupts attention, which may have negative consequences for daily life for people with acute or chronic pain. It has been suggested that switching between tasks may leave us particularly susceptible to pain-related attentional disruption, because we need to disengage our attention from one task before shifting it onto another. Switching tasks typically elicit lower accuracies and/or longer reaction times when participants switch to a new task compared with repeating the same task, and pain may exacerbate this effect. We present 3 studies to test this hypothesis. In study 1, participants completed 2 versions of an alternating runs switching task under pain-free and thermal pain-induction conditions. Pain did not affect performance on either task. In studies 2 and 3, we examined 7 versions of the switching task using large general population samples, experiencing a variety of naturally occurring pain conditions, recruited and tested on the internet. On all tasks, participants with pain had longer reaction times on both switch and repeat trials compared with participants without pain, but pain did not increase switch costs. In studies 2 and 3, we also investigated the effects of type of pain, duration of pain, and analgesics on task performance. We conclude that pain has a small dampening effect on performance overall on switching tasks. This suggests that pain interrupts attention even when participants are engaged in a trial, not only when attention has been disengaged for shifting to a new task set.

Multiple-trait structured antedependence model to study the relationship between litter size and birth weight in pigs and rabbits.

PubMed

David, Ingrid; Garreau, Hervé; Balmisse, Elodie; Billon, Yvon; Canario, Laurianne

2017-01-20

Some genetic studies need to take into account correlations between traits that are repeatedly measured over time. Multiple-trait random regression models are commonly used to analyze repeated traits but suffer from several major drawbacks. In the present study, we developed a multiple-trait extension of the structured antedependence model (SAD) to overcome this issue and validated its usefulness by modeling the association between litter size (LS) and average birth weight (ABW) over parities in pigs and rabbits. The single-trait SAD model assumes that a random effect at time [Formula: see text] can be explained by the previous values of the random effect (i.e. at previous times). The proposed multiple-trait extension of the SAD model consists in adding a cross-antedependence parameter to the single-trait SAD model. This model can be easily fitted using ASReml and the OWN Fortran program that we have developed. In comparison with the random regression model, we used our multiple-trait SAD model to analyze the LS and ABW of 4345 litters from 1817 Large White sows and 8706 litters from 2286 L-1777 does over a maximum of five successive parities. For both species, the multiple-trait SAD fitted the data better than the random regression model. The difference between AIC of the two models (AIC_random regression-AIC_SAD) were equal to 7 and 227 for pigs and rabbits, respectively. A similar pattern of heritability and correlation estimates was obtained for both species. Heritabilities were lower for LS (ranging from 0.09 to 0.29) than for ABW (ranging from 0.23 to 0.39). The general trend was a decrease of the genetic correlation for a given trait between more distant parities. Estimates of genetic correlations between LS and ABW were negative and ranged from -0.03 to -0.52 across parities. No correlation was observed between the permanent environmental effects, except between the permanent environmental effects of LS and ABW of the same parity, for which the estimate of the correlation was strongly negative (ranging from -0.57 to -0.67). We demonstrated that application of our multiple-trait SAD model is feasible for studying several traits with repeated measurements and showed that it provided a better fit to the data than the random regression model.

Non-radioactive detection of trinucleotide repeat size variability.

PubMed

Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

2014-03-06

Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitative data. The method relies on the amplification of a very low number of DNA molecules, through sucessive dilution of a stock genomic DNA solution. Radioactive Southern blot hybridization is sensitive enough to detect SP-PCR products derived from single template molecules, separated by agarose gel electrophoresis and transferred onto DNA membranes. We describe a variation of the detection method that uses digoxigenin-labelled locked nucleic acid probes. This protocol keeps the sensitivity of the original method, while eliminating the health risks associated with the manipulation of radiolabelled probes, and the burden associated with their regulation, manipulation and waste disposal.

Tandem-repeat protein domains across the tree of life

PubMed Central

Jernigan, Kristin K.

2015-01-01

Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species. PMID:25653910

Classification Systems for Individual Differences in Multiple-task Performance and Subjective Estimates of Workload

NASA Technical Reports Server (NTRS)

Damos, D. L.

1984-01-01

Human factors practitioners often are concerned with mental workload in multiple-task situations. Investigations of these situations have demonstrated repeatedly that individuals differ in their subjective estimates of workload. These differences may be attributed in part to individual differences in definitions of workload. However, after allowing for differences in the definition of workload, there are still unexplained individual differences in workload ratings. The relation between individual differences in multiple-task performance, subjective estimates of workload, information processing abilities, and the Type A personality trait were examined.

SERT 2 hollow cathode multiple restarts in space

NASA Technical Reports Server (NTRS)

Kerslake, W. R.; Finke, R. C.

1973-01-01

Future missions, both station keeping and primary electric propulsion, will require multiple thrust restarts after periods of inactivity from a few hours to over one year. Although not a part of the original SERT 2 (Space Electric Rocket Test) flight objective, the opportunity to demonstrate multiple cathode restarts in space became available following completion of thruster running. Both neutralizer and main cathodes of each flight thruster were restarted repeatedly following storage periods up to 490 days. No deterioration of cathode heaters was noted nor was any change required in starting voltages or currents.

Photomask repeater strategy for high-quality and low-cost reticle fabrication

NASA Astrophysics Data System (ADS)

Kyoh, Suigen; Inoue, Soichi; Ikenaga, Osamu; Higaki, Tomotaka; Shigemitsu, Fumiaki; Mori, Ichiro; Kokubo, Haruo; Hayashi, Naoya; Irie, Nobuyuki; Ishii, Yuki; Umatate, Toshikazu

2003-08-01

The severe mask specification makes mask cost increase drastically. Especially, the increase in the mask cost deals ASIC businesses a fatal blow due to its small chip volume per product. Pattern writing cost has always occupied the main part of the prime mask cost and the emphasis of this is still increasing. This paper reports on a Photomask Repeater strategy to be a solution for reducing mask cost in pattern writing, comparing with conventional EB system.

Construction of a small Mus musculus repetitive DNA library: identification of a new satellite sequence in Mus musculus.

PubMed Central

Pietras, D F; Bennett, K L; Siracusa, L D; Woodworth-Gutai, M; Chapman, V M; Gross, K W; Kane-Haas, C; Hastie, N D

1983-01-01

We report the construction of a small library of recombinant plasmids containing Mus musculus repetitive DNA inserts. The repetitive cloned fraction was derived from denatured genomic DNA by reassociation to a Cot value at which repetitive, but not unique, sequences have reannealed followed by exhaustive S1 nuclease treatment to degrade single stranded DNA. Initial characterizations of this library by colony filter hybridizations have led to the identification of a previously undetected M. musculus minor satellite as well as to clones containing M. musculus major satellite sequences. This new satellite is repeated 10-20 times less than the major satellite in the M. musculus genome. It has a repeat length of 130 nucleotides compared with the M. musculus major satellite with a repeat length of 234 nucleotides. Sequence analysis of the minor satellite has shown that it has a 29 base pair region with extensive homology to one of the major satellite repeating subunits. We also show by in situ hybridization that this minor satellite sequence is located at the centromeres and possibly the arms of at least half the M musculus chromosomes. Sequences related to the minor satellite have been found in the DNA of a related Mus species, Mus spretus, and may represent the major satellite of that species. Images PMID:6314268

A standardized tritrophic small-scale system (TriCosm) for the assessment of stressor-induced effects on aquatic community dynamics.

PubMed

Riedl, Verena; Agatz, Annika; Benstead, Rachel; Ashauer, Roman

2018-04-01

Chemical impacts on the environment are routinely assessed in single-species tests. They are employed to measure direct effects on nontarget organisms, but indirect effects on ecological interactions can only be detected in multispecies tests. Micro- and mesocosms are more complex and environmentally realistic, yet they are less frequently used for environmental risk assessment because resource demand is high, whereas repeatability and statistical power are often low. Test systems fulfilling regulatory needs (i.e., standardization, repeatability, and replication) and the assessment of impacts on species interactions and indirect effects are lacking. In the present study we describe the development of the TriCosm, a repeatable aquatic multispecies test with 3 trophic levels and increased statistical power. High repeatability of community dynamics of 3 interacting aquatic populations (algae, Ceriodaphnia, and Hydra) was found with an average coefficient of variation of 19.5% and the ability to determine small effect sizes. The TriCosm combines benefits of both single-species tests (fulfillment of regulatory requirements) and complex multispecies tests (ecological relevance) and can be used, for instance, at an intermediate tier in environmental risk assessment. Furthermore, comparatively quickly generated population and community toxicity data can be useful for the development and testing of mechanistic effect models. Environ Toxicol Chem 2018;37:1051-1060. © 2017 SETAC. © 2017 SETAC.

The complete chloroplast genome of Cinnamomum camphora and its comparison with related Lauraceae species.

PubMed

Chen, Caihui; Zheng, Yongjie; Liu, Sian; Zhong, Yongda; Wu, Yanfang; Li, Jiang; Xu, Li-An; Xu, Meng

2017-01-01

Cinnamomum camphora , a member of the Lauraceae family, is a valuable aromatic and timber tree that is indigenous to the south of China and Japan. All parts of Cinnamomum camphora have secretory cells containing different volatile chemical compounds that are utilized as herbal medicines and essential oils. Here, we reported the complete sequencing of the chloroplast genome of Cinnamomum camphora using illumina technology. The chloroplast genome of Cinnamomum camphora is 152,570 bp in length and characterized by a relatively conserved quadripartite structure containing a large single copy region of 93,705 bp, a small single copy region of 19,093 bp and two inverted repeat (IR) regions of 19,886 bp. Overall, the genome contained 123 coding regions, of which 15 were repeated in the IR regions. An analysis of chloroplast sequence divergence revealed that the small single copy region was highly variable among the different genera in the Lauraceae family. A total of 40 repeat structures and 83 simple sequence repeats were detected in both the coding and non-coding regions. A phylogenetic analysis indicated that Calycanthus is most closely related to Lauraceae , both being members of Laurales , which forms a sister group to Magnoliids . The complete sequence of the chloroplast of Cinnamomum camphora will aid in in-depth taxonomical studies of the Lauraceae family in the future. The genetic sequence information will also have valuable applications for chloroplast genetic engineering.

Universal strategies for the DNA-encoding of libraries of small molecules using the chemical ligation of oligonucleotide tags

PubMed Central

Litovchick, Alexander; Clark, Matthew A; Keefe, Anthony D

2014-01-01

The affinity-mediated selection of large libraries of DNA-encoded small molecules is increasingly being used to initiate drug discovery programs. We present universal methods for the encoding of such libraries using the chemical ligation of oligonucleotides. These methods may be used to record the chemical history of individual library members during combinatorial synthesis processes. We demonstrate three different chemical ligation methods as examples of information recording processes (writing) for such libraries and two different cDNA-generation methods as examples of information retrieval processes (reading) from such libraries. The example writing methods include uncatalyzed and Cu(I)-catalyzed alkyne-azide cycloadditions and a novel photochemical thymidine-psoralen cycloaddition. The first reading method “relay primer-dependent bypass” utilizes a relay primer that hybridizes across a chemical ligation junction embedded in a fixed-sequence and is extended at its 3′-terminus prior to ligation to adjacent oligonucleotides. The second reading method “repeat-dependent bypass” utilizes chemical ligation junctions that are flanked by repeated sequences. The upstream repeat is copied prior to a rearrangement event during which the 3′-terminus of the cDNA hybridizes to the downstream repeat and polymerization continues. In principle these reading methods may be used with any ligation chemistry and offer universal strategies for the encoding (writing) and interpretation (reading) of DNA-encoded chemical libraries. PMID:25483841

Myricetin Reduces Toxic Level of CAG Repeats RNA in Huntington's Disease (HD) and Spino Cerebellar Ataxia (SCAs).

PubMed

Khan, Eshan; Tawani, Arpita; Mishra, Subodh Kumar; Verma, Arun Kumar; Upadhyay, Arun; Kumar, Mohit; Sandhir, Rajat; Mishra, Amit; Kumar, Amit

2018-01-19

Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of muscle blind like-1 splicing factor (MBNL1), and thus both of these elicit the pathogenesis of HD. Targeting the onset as well as progression of HD by small molecules could be a potent therapeutic approach. We have screened a set of small molecules to target this transcript and found Myricetin, a flavonoid, as a lead molecule that interacts with the CAG motif and thus prevents the translation of mutant huntingtin protein as well as sequestration of MBNL1. Here, we report the first solution structure of the complex formed between Myricetin and RNA containing the 5'CAG/3'GAC motif. Myricetin interacts with this RNA via base stacking at the AA mismatch. Moreover, Myricetin was also found reducing the proteo-toxicity generated due to the aggregation of polyglutamine, and further, its supplementation also improves neurobehavioral deficits in the HD mouse model. Our study provides the structural and mechanistic basis of Myricetin as an effective therapeutic candidate for HD and other polyQ related disorders.

Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei

PubMed Central

2012-01-01

Background At the core of the RNA interference (RNAi) pathway in Trypanosoma brucei is a single Argonaute protein, TbAGO1, with an established role in controlling retroposon and repeat transcripts. Recent evidence from higher eukaryotes suggests that a variety of genomic sequences with the potential to produce double-stranded RNA are sources for small interfering RNAs (siRNAs). Results To test whether such endogenous siRNAs are present in T. brucei and to probe the individual role of the two Dicer-like enzymes, we affinity purified TbAGO1 from wild-type procyclic trypanosomes, as well as from cells deficient in the cytoplasmic (TbDCL1) or nuclear (TbDCL2) Dicer, and subjected the bound RNAs to Illumina high-throughput sequencing. In wild-type cells the majority of reads originated from two classes of retroposons. We also considerably expanded the repertoire of trypanosome siRNAs to encompass a family of 147-bp satellite-like repeats, many of the regions where RNA polymerase II transcription converges, large inverted repeats and two pseudogenes. Production of these newly described siRNAs is strictly dependent on the nuclear DCL2. Notably, our data indicate that putative centromeric regions, excluding the CIR147 repeats, are not a significant source for endogenous siRNAs. Conclusions Our data suggest that endogenous RNAi targets may be as evolutionarily old as the mechanism itself. PMID:22925482

Strategies for longitudinal neuroimaging studies of overt language production.

PubMed

Meltzer, Jed A; Postman-Caucheteux, Whitney A; McArdle, Joseph J; Braun, Allen R

2009-08-15

Longitudinal fMRI studies of language production are of interest for evaluating recovery from post-stroke aphasia, but numerous methodological issues remain unresolved, particularly regarding strategies for evaluating single subjects at multiple timepoints. To address these issues, we studied overt picture naming in eleven healthy subjects, scanned four times each at one-month intervals. To evaluate the natural variability present across repeated sessions, repeated scans were directly contrasted in a unified statistical framework on a per-voxel basis. The effect of stimulus familiarity was evaluated using explicitly overtrained pictures, novel pictures, and untrained pictures that were repeated across sessions. For untrained pictures, we found that activation declined across multiple sessions, equally for both novel and repeated stimuli. Thus, no repetition priming for individual stimuli at one-month intervals was found, but rather a general effect of task habituation was present. Using a set of overtrained pictures identical in each session, no decline was found, but activation was minimized and produced less consistent patterns across participants, as measured by intra-class correlation coefficients. Subtraction of a baseline task, in which subjects produced a stereotyped utterance to scrambled pictures, resulted in specific activations in the left inferior frontal gyrus and other language areas for untrained items, while overlearned stimuli relative to pseudo pictures activated only the fusiform gyrus and supplementary motor area. These findings indicate that longitudinal fMRI is an effective means of detecting changes in neural activation magnitude over time, as long as the effect of task habituation is taken into account.

Multiple-Locus Variable-Number Tandem-Repeat Analysis in Genotyping Yersinia enterocolitica Strains from Human and Porcine Origins

PubMed Central

Laukkanen-Ninios, R.; Ortiz Martínez, P.; Siitonen, A.; Fredriksson-Ahomaa, M.; Korkeala, H.

2013-01-01

Sporadic and epidemiologically linked Yersinia enterocolitica strains (n = 379) isolated from fecal samples from human patients, tonsil or fecal samples from pigs collected at slaughterhouses, and pork samples collected at meat stores were genotyped using multiple-locus variable-number tandem-repeat analysis (MLVA) with six loci, i.e., V2A, V4, V5, V6, V7, and V9. In total, 312 different MLVA types were found. Similar types were detected (i) in fecal samples collected from human patients over 2 to 3 consecutive years, (ii) in samples from humans and pigs, and (iii) in samples from pigs that originated from the same farms. Among porcine strains, we found farm-specific MLVA profiles. Variations in the numbers of tandem repeats from one to four for variable-number tandem-repeat (VNTR) loci V2A, V5, V6, and V7 were observed within a farm. MLVA was applicable for serotypes O:3, O:5,27, and O:9 and appeared to be a highly discriminating tool for distinguishing sporadic and outbreak-related strains. With long-term use, interpretation of the results became more challenging due to variations in more-discriminating loci, as was observed for strains originating from pig farms. Additionally, we encountered unexpectedly short V2A VNTR fragments and sequenced them. According to the sequencing results, updated guidelines for interpreting V2A VNTR results were prepared. PMID:23637293

Performing Repeated Quantitative Small-Animal PET with an Arterial Input Function Is Routinely Feasible in Rats.

PubMed

Huang, Chi-Cheng; Wu, Chun-Hu; Huang, Ya-Yao; Tzen, Kai-Yuan; Chen, Szu-Fu; Tsai, Miao-Ling; Wu, Hsiao-Ming

2017-04-01

Performing quantitative small-animal PET with an arterial input function has been considered technically challenging. Here, we introduce a catheterization procedure that keeps a rat physiologically stable for 1.5 mo. We demonstrated the feasibility of quantitative small-animal 18 F-FDG PET in rats by performing it repeatedly to monitor the time course of variations in the cerebral metabolic rate of glucose (CMR glc ). Methods: Aseptic surgery was performed on 2 rats. Each rat underwent catheterization of the right femoral artery and left femoral vein. The catheters were sealed with microinjection ports and then implanted subcutaneously. Over the next 3 wk, each rat underwent 18 F-FDG quantitative small-animal PET 6 times. The CMR glc of each brain region was calculated using a 3-compartment model and an operational equation that included a k* 4 Results: On 6 mornings, we completed 12 18 F-FDG quantitative small-animal PET studies on 2 rats. The rats grew steadily before and after the 6 quantitative small-animal PET studies. The CMR glc of the conscious brain (e.g., right parietal region, 99.6 ± 10.2 μmol/100 g/min; n = 6) was comparable to that for 14 C-deoxyglucose autoradiographic methods. Conclusion: Maintaining good blood patency in catheterized rats is not difficult. Longitudinal quantitative small-animal PET imaging with an arterial input function can be performed routinely. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Regulation of cell fate determination by single-repeat R3 MYB transcription factors in Arabidopsis

PubMed Central

Wang, Shucai; Chen, Jin-Gui

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYBs are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulation of cell type specification in the model plant Arabidopsis. PMID:24782874

Regulation of Cell Fate Determination by Single-Repeat R3 MYB Transcription Factors in Arabidopsis

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

Wang, Shucai; Chen, Jay

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYB are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulationmore » of cell type specification in the model plant Arabidopsis.« less

High speed polling protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1995-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs a remote node polling process performed by a master node by transmitting a polling message generically addressed to all remote nodes associated with the master node. Each remote node responds upon receipt of the generically addressed polling message by transmitting a poll-answering informational message and by relaying the polling message to other adjacent remote nodes.

Homology-integrated CRISPR-Cas (HI-CRISPR) system for one-step multigene disruption in Saccharomyces cerevisiae.

PubMed

Bao, Zehua; Xiao, Han; Liang, Jing; Zhang, Lu; Xiong, Xiong; Sun, Ning; Si, Tong; Zhao, Huimin

2015-05-15

One-step multiple gene disruption in the model organism Saccharomyces cerevisiae is a highly useful tool for both basic and applied research, but it remains a challenge. Here, we report a rapid, efficient, and potentially scalable strategy based on the type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas) system to generate multiple gene disruptions simultaneously in S. cerevisiae. A 100 bp dsDNA mutagenizing homologous recombination donor is inserted between two direct repeats for each target gene in a CRISPR array consisting of multiple donor and guide sequence pairs. An ultrahigh copy number plasmid carrying iCas9, a variant of wild-type Cas9, trans-encoded RNA (tracrRNA), and a homology-integrated crRNA cassette is designed to greatly increase the gene disruption efficiency. As proof of concept, three genes, CAN1, ADE2, and LYP1, were simultaneously disrupted in 4 days with an efficiency ranging from 27 to 87%. Another three genes involved in an artificial hydrocortisone biosynthetic pathway, ATF2, GCY1, and YPR1, were simultaneously disrupted in 6 days with 100% efficiency. This homology-integrated CRISPR (HI-CRISPR) strategy represents a powerful tool for creating yeast strains with multiple gene knockouts.

Molecular characterization of enterohemorrhagic Escherichia coli O157:H7 isolates dispersed across Japan by pulsed-field gel electrophoresis and multiple-locus variable-number tandem repeat analysis.

PubMed

Pei, Yingxin; Terajima, Jun; Saito, Yasunori; Suzuki, Reiko; Takai, Nobuko; Izumiya, Hidemasa; Morita-Ishihara, Tomoko; Ohnishi, Makoto; Miura, Masashi; Iyoda, Sunao; Mitobe, Jiro; Wang, Binyou; Watanabe, Haruo

2008-01-01

We identified seven distinct subtypes of enterohemorrhagic Escherichia coli (EHEC) O157:H7 isolates that were derived from sporadic cases and outbreaks from multiple prefectures in Japan in 2005. A surveillance system utilizing pulsed-field gel electrophoresis (PFGE), PulseNet Japan, was used. Some strains showed indistinguishable PFGE patterns using another restriction enzyme (BlnI or SpeI) in each subtype of EHEC O157:H7 isolates that were routinely subtyped by the XbaI PFGE pattern. In order to examine the genotypic relatedness of these strains, we carried out a multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA). By using the MLVA system, we found that three of seven subtypes of EHEC O157:H7 strains that were isolated from sporadic cases dispersed across multiple prefectures within a few months showed indistinguishable PFGE patterns and identical MLVA types. Strains belonging to the other four subtypes of EHEC O157:H7 in the PFGE analysis were further classified into different clusters of EHEC O157:H7. Therefore, compared to PFGE, MLVA showed greater discriminatory power with respect to analysis of the isolates in this study.

Photoacoustics of disperse systems: Below cavitation threshold

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

Egerev, Sergey; Ovchinnikov, Oleg

2012-05-24

The paper considers photoacoustic (PA) conversion while irradiating suspensions in extra-small volume probes with laser pulses having small fluence values. Only linear and nonlinear thermooptical laser sound generation regimes were observed. Thus, good repeatability of acoustic signal parameters informative about probe content was achieved. The experiment conducted has shown how one can avoid the decrease of particles detection sensitivity for the thermooptical mode.

Multibaseline interferometric SAR at millimeterwaves test of an algorithm on real data and a synthetic scene

NASA Astrophysics Data System (ADS)

Essen, Helmut; Brehm, Thorsten; Boehmsdorff, Stephan

2007-10-01

Interferometric Synthetic Aperture Radar has the capability to provide the user with the 3-D-Information of land surfaces. To gather data with high height estimation accuracy it is necessary to use a wide interferometric baseline or a high radar frequency. However the problem of resolving the phase ambiguity at smaller wavelengths is more critical than at longer wavelengths, as the unambiguous height interval is inversely proportional to the radar wavelength. To solve this shortcoming, a multiple baseline approach can be used with a number of neighbouring horns and an increasing baselength going from narrow to wide. The narrowest, corresponding to adjacent horns, is then assumed to be unambiguous in phase. This initial interferogram is used as a starting point for the algorithm, which in the next step, unwraps the interferogram with the next wider baseline using the coarse height information to solve the phase ambiguities. This process is repeated consecutively until the interferogram with highest precision is unwrapped. On the expense of this multi-channel-approach the algorithm is simple and robust, and even the amount of processing time is reduced considerably, compared to traditional methods. The multiple baseline approach is especially adequate for millimeterwave radars as antenna horns with relatively small aperture can be used, while a sufficient 3-dB beamwidth is maintained. The paper describes the multiple baseline algorithm and shows the results of tests on real data and a synthetic area. Possibilities and limitations of this approach are discussed. Examples of digital elevation maps derived from measured data at millimeterwaves are shown.

Development of pharmacophore models for small molecules targeting RNA: Application to the RNA repeat expansion in myotonic dystrophy type 1.

PubMed

Angelbello, Alicia J; González, Àlex L; Rzuczek, Suzanne G; Disney, Matthew D

2016-12-01

RNA is an important drug target, but current approaches to identify bioactive small molecules have been engineered primarily for protein targets. Moreover, the identification of small molecules that bind a specific RNA target with sufficient potency remains a challenge. Computer-aided drug design (CADD) and, in particular, ligand-based drug design provide a myriad of tools to identify rapidly new chemical entities for modulating a target based on previous knowledge of active compounds without relying on a ligand complex. Herein we describe pharmacophore virtual screening based on previously reported active molecules that target the toxic RNA that causes myotonic dystrophy type 1 (DM1). DM1-associated defects are caused by sequestration of muscleblind-like 1 protein (MBNL1), an alternative splicing regulator, by expanded CUG repeats (r(CUG) exp ). Several small molecules have been found to disrupt the MBNL1-r(CUG) exp complex, ameliorating DM1 defects. Our pharmacophore model identified a number of potential lead compounds from which we selected 11 compounds to evaluate. Of the 11 compounds, several improved DM1 defects both in vitro and in cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparing Dynamic Treatment Regimes Using Repeated-Measures Outcomes: Modeling Considerations in SMART Studies

PubMed Central

Lu, Xi; Nahum-Shani, Inbal; Kasari, Connie; Lynch, Kevin G.; Oslin, David W.; Pelham, William E.; Fabiano, Gregory; Almirall, Daniel

2016-01-01

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient’s past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder (ADHD), and adult alcoholism. In all three SMARTs we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome. PMID:26638988

Comparing dynamic treatment regimes using repeated-measures outcomes: modeling considerations in SMART studies.

PubMed

Lu, Xi; Nahum-Shani, Inbal; Kasari, Connie; Lynch, Kevin G; Oslin, David W; Pelham, William E; Fabiano, Gregory; Almirall, Daniel

2016-05-10

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient's past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder, and adult alcoholism. In all three SMARTs, we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome. Copyright © 2015 John Wiley & Sons, Ltd.

Amount of fear extinction changes its underlying mechanisms.

PubMed

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-07-03

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

Bayesian function-on-function regression for multilevel functional data.

PubMed

Meyer, Mark J; Coull, Brent A; Versace, Francesco; Cinciripini, Paul; Morris, Jeffrey S

2015-09-01

Medical and public health research increasingly involves the collection of complex and high dimensional data. In particular, functional data-where the unit of observation is a curve or set of curves that are finely sampled over a grid-is frequently obtained. Moreover, researchers often sample multiple curves per person resulting in repeated functional measures. A common question is how to analyze the relationship between two functional variables. We propose a general function-on-function regression model for repeatedly sampled functional data on a fine grid, presenting a simple model as well as a more extensive mixed model framework, and introducing various functional Bayesian inferential procedures that account for multiple testing. We examine these models via simulation and a data analysis with data from a study that used event-related potentials to examine how the brain processes various types of images. © 2015, The International Biometric Society.

Repeated readings and science: Fluency with expository passages

NASA Astrophysics Data System (ADS)

Kostewicz, Douglas E.

The current study investigated the effects of repeated readings to a fluency criterion (RRFC) for seven students with disabilities using science text. The study employed a single subject design, specifically, two multiple probe multiple baselines across subjects, to evaluate the effects of the RRFC intervention. Results indicated that students met criterion (200 or more correct words per minute with 2 or fewer errors) on four consecutive passages. A majority of students displayed accelerations to correct words per minute and decelerations to incorrect words per minute on successive initial, intervention readings suggesting reading transfer. Students' reading scores during posttest and maintenance out performed pre-test and baseline readings provided additional measures of reading transfer. For a relationship to comprehension, students scored higher on oral retell measures after meeting criterion as compared to initial readings. Overall, the research findings suggested that the RRFC intervention improves science reading fluency for students with disabilities, and may also indirectly benefit comprehension.

Impaired face recognition is associated with social inhibition

PubMed Central

Avery, Suzanne N; VanDerKlok, Ross M; Heckers, Stephan; Blackford, Jennifer U

2016-01-01

Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety. PMID:26776300

Impaired face recognition is associated with social inhibition.

PubMed

Avery, Suzanne N; VanDerKlok, Ross M; Heckers, Stephan; Blackford, Jennifer U

2016-02-28

Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hot Fusion: an efficient method to clone multiple DNA fragments as well as inverted repeats without ligase.

PubMed

Fu, Changlin; Donovan, William P; Shikapwashya-Hasser, Olga; Ye, Xudong; Cole, Robert H

2014-01-01

Molecular cloning is utilized in nearly every facet of biological and medical research. We have developed a method, termed Hot Fusion, to efficiently clone one or multiple DNA fragments into plasmid vectors without the use of ligase. The method is directional, produces seamless junctions and is not dependent on the availability of restriction sites for inserts. Fragments are assembled based on shared homology regions of 17-30 bp at the junctions, which greatly simplifies the construct design. Hot Fusion is carried out in a one-step, single tube reaction at 50 °C for one hour followed by cooling to room temperature. In addition to its utility for multi-fragment assembly Hot Fusion provides a highly efficient method for cloning DNA fragments containing inverted repeats for applications such as RNAi. The overall cloning efficiency is in the order of 90-95%.

Hot Fusion: An Efficient Method to Clone Multiple DNA Fragments as Well as Inverted Repeats without Ligase

PubMed Central

Fu, Changlin; Donovan, William P.; Shikapwashya-Hasser, Olga; Ye, Xudong; Cole, Robert H.

2014-01-01

Molecular cloning is utilized in nearly every facet of biological and medical research. We have developed a method, termed Hot Fusion, to efficiently clone one or multiple DNA fragments into plasmid vectors without the use of ligase. The method is directional, produces seamless junctions and is not dependent on the availability of restriction sites for inserts. Fragments are assembled based on shared homology regions of 17–30 bp at the junctions, which greatly simplifies the construct design. Hot Fusion is carried out in a one-step, single tube reaction at 50°C for one hour followed by cooling to room temperature. In addition to its utility for multi-fragment assembly Hot Fusion provides a highly efficient method for cloning DNA fragments containing inverted repeats for applications such as RNAi. The overall cloning efficiency is in the order of 90–95%. PMID:25551825

Multi-sensor field trials for detection and tracking of multiple small unmanned aerial vehicles flying at low altitude

NASA Astrophysics Data System (ADS)

Laurenzis, Martin; Hengy, Sebastien; Hommes, Alexander; Kloeppel, Frank; Shoykhetbrod, Alex; Geibig, Thomas; Johannes, Winfried; Naz, Pierre; Christnacher, Frank

2017-05-01

Small unmanned aerial vehicles (UAV) flying at low altitude are becoming more and more a serious threat in civilian and military scenarios. In recent past, numerous incidents have been reported where small UAV were flying in security areas leading to serious danger to public safety or privacy. The detection and tracking of small UAV is a widely discussed topic. Especially, small UAV flying at low altitude in urban environment or near background structures and the detection of multiple UAV at the same time is challenging. Field trials were carried out to investigate the detection and tracking of multiple UAV flying at low altitude with state of the art detection technologies. Here, we present results which were achieved using a heterogeneous sensor network consisting of acoustic antennas, small frequency modulated continuous wave (FMCW) RADAR systems and optical sensors. While acoustics, RADAR and LiDAR were applied to monitor a wide azimuthal area (360°) and to simultaneously track multiple UAV, optical sensors were used for sequential identification with a very narrow field of view.

In-Situ Observation of Undisturbed Surface Layer Scaler Profiles for Characterizing Evaporative Duct Properties

DTIC Science & Technology

2016-06-01

lowest tens of meters of the MASL from a small Rigid Hull Inflatable Boat (RHIB), or a small work boat, equipped with a tethered profiling system and...ducting Research (CASPER) project. It is capable of making repeated measurements of the lowest tens of meters of the MASL from a small Rigid Hull ...Naval Postgraduate School ONR Office of Naval Research PJ Paulus-Jeske RHIB rigid- hulled inflatable boat R/V research vessel SST sea

Characterization of two genes encoding leucine-rich repeat-containing proteins in grass carp Ctenopharyngodon idellus.

PubMed

Chang, M X; Nie, P; Xie, H X; Sun, B J; Gao, Q

2005-01-01

The cDNAs and genes of two different types of leucine-rich repeat-containing proteins from grass carp (Ctenopharyngodon idellus) were cloned. Homology search revealed that the two genes, designated as GC-GARP and GC-LRG, have 37% and 32% deduced amino-acid sequence similarities with human glycoprotein A repetitions predominant precursor (GARP) and leucine-rich alpha2-glycoprotein (LRG), respectively. The cDNAs of GC-GARP and GC-LRG encoded 664 and 339 amino acid residues, respectively. GC-GARP and GC-LRG contain many distinct structural and/or functional motifs of the leucine-rich repeat (LRR) subfamily, such as multiple conserved 11-residue segments with the consensus sequence LxxLxLxxN/CxL (x can be any amino acid). The genes GC-GARP and GC-LRG consist of two exons, with 4,782 bp and 2,119 bp in total length, respectively. The first exon of each gene contains a small 5'-untranslated region and partial open reading frame. The putative promoter region of GC-GARP was found to contain transcription factor binding sites for GATA-1, IRF4, Oct-1, IRF-7, IRF-1, AP1, GATA-box and NFAT, and the promoter region of GC-LRG for MYC-MAX, MEIS1, ISRE, IK3, HOXA9 and C/EBP alpha. Phylogenetic analysis showed that GC-GARP and mammalian GARPs were clustered into one branch, while GC-LRG and mammalian LRGs were in another branch. The GC-GARP gene was only detected in head kidney, and GC-LRG in the liver, spleen and heart in the copepod (Sinergasilus major)-infected grass carp, indicating the induction of gene expression by the parasite infection. The results obtained in the present study provide insight into the structure of fish LRR genes, and further study should be carried out to understand the importance of LRR proteins in host-pathogen interactions.

CRISPRDetect: A flexible algorithm to define CRISPR arrays.

PubMed

Biswas, Ambarish; Staals, Raymond H J; Morales, Sergio E; Fineran, Peter C; Brown, Chris M

2016-05-17

CRISPR (clustered regularly interspaced short palindromic repeats) RNAs provide the specificity for noncoding RNA-guided adaptive immune defence systems in prokaryotes. CRISPR arrays consist of repeat sequences separated by specific spacer sequences. CRISPR arrays have previously been identified in a large proportion of prokaryotic genomes. However, currently available detection algorithms do not utilise recently discovered features regarding CRISPR loci. We have developed a new approach to automatically detect, predict and interactively refine CRISPR arrays. It is available as a web program and command line from bioanalysis.otago.ac.nz/CRISPRDetect. CRISPRDetect discovers putative arrays, extends the array by detecting additional variant repeats, corrects the direction of arrays, refines the repeat/spacer boundaries, and annotates different types of sequence variations (e.g. insertion/deletion) in near identical repeats. Due to these features, CRISPRDetect has significant advantages when compared to existing identification tools. As well as further support for small medium and large repeats, CRISPRDetect identified a class of arrays with 'extra-large' repeats in bacteria (repeats 44-50 nt). The CRISPRDetect output is integrated with other analysis tools. Notably, the predicted spacers can be directly utilised by CRISPRTarget to predict targets. CRISPRDetect enables more accurate detection of arrays and spacers and its gff output is suitable for inclusion in genome annotation pipelines and visualisation. It has been used to analyse all complete bacterial and archaeal reference genomes.

Solar Electricity

NASA Technical Reports Server (NTRS)

1988-01-01

ARCO Solar manufactures PV Systems tailored to a broad variety of applications. PV arrays are routinely used at remote communications installations to operate large microwave repeaters, TV and radio repeaters rural telephone, and small telemetry systems that monitor environmental conditions. Also used to power agricultural water pumping systems, to provide electricity for isolated villages and medical clinics, for corrosion protection for pipelines and bridges, to power railroad signals, air/sea navigational aids, and for many types of military systems. ARCO is now moving into large scale generation for utilities.

Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

DTIC Science & Technology

2015-11-01

in 2D and Xenografts . B) Panel of cancer cell lines grown in 2D or 3D culture. 5 cancers (Fig. 3). We have completed RNA-seq analysis of 2D and 3D...reverse transcribed (RT) as a means to expand these regions in tumor genomes. We evaluated the presence of HSATII RT products by treating xenograft small...specific for satellite repeats in human cells. These RNA derived DNAs (rdDNA) are found in primary tumors, xenografts , and tumorspheres in large

Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

PubMed

Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

2016-09-01

4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Long-Term Immunization with Multiple Antigens.

DTIC Science & Technology

1980-01-01

to infectious mononucleosis . Proc. Natl. Acad. Sci. USA 59:94-101, 1968. 23. Holt, S., D. Hudgins, K. R. Krishnan, and E. M. R. Critchley. Diffuse...and J. C. Bausher. Epstein-Barr virus infection in relation to infectious mononucleosis and Burkitt’s lymphoma. Annu. Rev. Med. 23:39-56, 1972. 54...Army Biological Laboratory at Fort Detrick, Maryland, it had been the prac- tice to immunize workers repeatedly with multiple antigens of infectious

What Does Division Mean?

ERIC Educational Resources Information Center

Burton, Grace M.; Knifong, J. Dan

1983-01-01

Models for division are discussed: counting, repeated subtraction, inverse of multiplication, sets, number line, balance beam, arrays, and cross product of sets. Expressing the remainder using various models is then presented, followed by comments on why all the models should be taught. (MNS)

CT fluoroscopy-guided renal tumour cutting needle biopsy: retrospective evaluation of diagnostic yield, safety, and risk factors for diagnostic failure.

PubMed

Iguchi, Toshihiro; Hiraki, Takao; Matsui, Yusuke; Fujiwara, Hiroyasu; Sakurai, Jun; Masaoka, Yoshihisa; Gobara, Hideo; Kanazawa, Susumu

2018-01-01

To evaluate retrospectively the diagnostic yield, safety, and risk factors for diagnostic failure of computed tomography (CT) fluoroscopy-guided renal tumour biopsy. Biopsies were performed for 208 tumours (mean diameter 2.3 cm; median diameter 2.1 cm; range 0.9-8.5 cm) in 199 patients. One hundred and ninety-nine tumours were ≤4 cm. All 208 initial procedures were divided into diagnostic success and failure groups. Multiple variables related to the patients, lesions, and procedures were assessed to determine the risk factors for diagnostic failure. After performing 208 initial and nine repeat biopsies, 180 malignancies and 15 benign tumours were pathologically diagnosed, whereas 13 were not diagnosed. In 117 procedures, 118 Grade I and one Grade IIIa adverse events (AEs) occurred. Neither Grade ≥IIIb AEs nor tumour seeding were observed within a median follow-up period of 13.7 months. Logistic regression analysis revealed only small tumour size (≤1.5 cm; odds ratio 3.750; 95% confidence interval 1.362-10.326; P = 0.011) to be a significant risk factor for diagnostic failure. CT fluoroscopy-guided renal tumour biopsy is a safe procedure with a high diagnostic yield. A small tumour size (≤1.5 cm) is a significant risk factor for diagnostic failure. • CT fluoroscopy-guided renal tumour biopsy has a high diagnostic yield. • CT fluoroscopy-guided renal tumour biopsy is safe. • Small tumour size (≤1.5 cm) is a risk factor for diagnostic failure.

How do repeat suicide attempters differ from first timers? An exploratory record based analysis

PubMed Central

Menon, Vikas; Kattimani, Shivanand; Sarkar, Siddharth; Mathan, Kaliaperumal

2016-01-01

Background: Evidence indicates that repeat suicide attempters, as a group, may differ from 1st time attempters. The identification of repeat attempters is a powerful but underutilized clinical variable. Aims: In this research, we aimed to compare individuals with lifetime histories of multiple attempts with 1st time attempters to identify factors predictive of repeat attempts. Setting and Design: This was a retrospective record based study carried out at a teaching cum Tertiary Care Hospital in South India. Methods: Relevant data was extracted from the clinical records of 1st time attempters (n = 362) and repeat attempters (n = 61) presenting to a single Tertiary Care Center over a 4½ year period. They were compared on various sociodemographic and clinical parameters. The clinical measures included Presumptive Stressful Life Events Scale, Beck Hopelessness Scale, Coping Strategies Inventory – Short Form, and the Global Assessment of Functioning Scale. Statistical Analysis Used: First time attempters and repeaters were compared using appropriate inferential statistics. Logistic regression was used to identify independent predictors of repeat attempts. Results: The two groups did not significantly differ on sociodemographic characteristics. Repeat attempters were more likely to have given prior hints about their act (χ2 = 4.500, P = 0.034). In the final regression model, beck hopelessness score emerged as a significant predictor of repeat suicide attempts (odds ratio = 1.064, P = 0.020). Conclusion: Among suicide attempters presenting to the hospital, the presence of hopelessness is a predictor of repeat suicide attempts, independent of clinical depression. This highlights the importance of considering hopelessness in the assessment of suicidality with a view to minimize the risk of future attempts. PMID:26933353

The multiple roles of epidermal growth factor repeat O-glycans in animal development

PubMed Central

Haltom, Amanda R; Jafar-Nejad, Hamed

2015-01-01

The epidermal growth factor (EGF)-like repeat is a common, evolutionarily conserved motif found in secreted proteins and the extracellular domain of transmembrane proteins. EGF repeats harbor six cysteine residues which form three disulfide bonds and help generate the three-dimensional structure of the EGF repeat. A subset of EGF repeats harbor consensus sequences for the addition of one or more specific O-glycans, which are initiated by O-glucose, O-fucose or O-N-acetylglucosamine. These glycans are relatively rare compared to mucin-type O-glycans. However, genetic experiments in model organisms and cell-based assays indicate that at least some of the glycosyltransferases involved in the addition of O-glycans to EGF repeats play important roles in animal development. These studies, combined with state-of-the-art biochemical and structural biology experiments have started to provide an in-depth picture of how these glycans regulate the function of the proteins to which they are linked. In this review, we will discuss the biological roles assigned to EGF repeat O-glycans and the corresponding glycosyltransferases. Since Notch receptors are the best studied proteins with biologically-relevant O-glycans on EGF repeats, a significant part of this review is devoted to the role of these glycans in the regulation of the Notch signaling pathway. We also discuss recently identified proteins other than Notch which depend on EGF repeat glycans to function properly. Several glycosyltransferases involved in the addition or elongation of O-glycans on EGF repeats are mutated in human diseases. Therefore, mechanistic understanding of the functional roles of these carbohydrate modifications is of interest from both basic science and translational perspectives. PMID:26175457

The Influence of Primary and Secondary DNA Structure in Deletion and Duplication between Direct Repeats in Escherichia Coli

PubMed Central

Trinh, T. Q.; Sinden, R. R.

1993-01-01

We describe a system to measure the frequency of both deletions and duplications between direct repeats. Short 17- and 18-bp palindromic and nonpalindromic DNA sequences were cloned into the EcoRI site within the chloramphenicol acetyltransferase gene of plasmids pBR325 and pJT7. This creates an insert between direct repeated EcoRI sites and results in a chloramphenicol-sensitive phenotype. Selection for chloramphenicol resistance was utilized to select chloramphenicol resistant revertants that included those with precise deletion of the insert from plasmid pBR325 and duplication of the insert in plasmid pJT7. The frequency of deletion or duplication varied more than 500-fold depending on the sequence of the short sequence inserted into the EcoRI site. For the nonpalindromic inserts, multiple internal direct repeats and the length of the direct repeats appear to influence the frequency of deletion. Certain palindromic DNA sequences with the potential to form DNA hairpin structures that might stabilize the misalignment of direct repeats had a high frequency of deletion. Other DNA sequences with the potential to form structures that might destabilize misalignment of direct repeats had a very low frequency of deletion. Duplication mutations occurred at the highest frequency when the DNA between the direct repeats contained no direct or inverted repeats. The presence of inverted repeats dramatically reduced the frequency of duplications. The results support the slippage-misalignment model, suggesting that misalignment occurring during DNA replication leads to deletion and duplication mutations. The results also support the idea that the formation of DNA secondary structures during DNA replication can facilitate and direct specific mutagenic events. PMID:8325478

Effects of Active Sting Damping on Common Research Model Data Quality

NASA Technical Reports Server (NTRS)

Acheson, Michael J.; Balakrishna, S.

2011-01-01

Recent tests using the Common Research Model (CRM) at the Langley National Transonic Facility (NTF) and the Ames 11-foot Transonic Wind Tunnel (11' TWT) produced large sets of data that have been used to examine the effects of active damping on transonic tunnel aerodynamic data quality. In particular, large statistically significant sets of repeat data demonstrate that the active damping system had no apparent effect on drag, lift and pitching moment repeatability during warm testing conditions, while simultaneously enabling aerodynamic data to be obtained post stall. A small set of cryogenic (high Reynolds number) repeat data was obtained at the NTF and again showed a negligible effect on data repeatability. However, due to a degradation of control power in the active damping system cryogenically, the ability to obtain test data post-stall was not achieved during cryogenic testing. Additionally, comparisons of data repeatability between NTF and 11-ft TWT CRM data led to further (warm) testing at the NTF which demonstrated that for a modest increase in data sampling time, a 2-3 factor improvement in drag, and pitching moment repeatability was readily achieved not related with the active damping system.

Ligand-Binding Properties and Conformational Dynamics of Autolysin Repeat Domains in Staphylococcal Cell Wall Recognition

PubMed Central

Zoll, Sebastian; Schlag, Martin; Shkumatov, Alexander V.; Rautenberg, Maren; Svergun, Dmitri I.; Götz, Friedrich

2012-01-01

The bifunctional major autolysin Atl plays a key role in staphylococcal cell separation. Processing of Atl yields catalytically active amidase (AM) and glucosaminidase (GL) domains that are each fused to repeating units. The two repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves murein between dividing cells. We have determined the crystal structure of R2, which reveals that each repeat folds into two half-open β-barrel subunits. We further demonstrate that lipoteichoic acid serves as a receptor for the repeats and that this interaction depends on conserved surfaces in each subunit. Small-angle X-ray scattering of the mature amidase reveals the presence of flexible linkers separating the AM, R1, and R2 units. Different levels of flexibility for each linker provide mechanistic insights into the conformational dynamics of the full-length protein and the roles of its components in cell wall association and catalysis. Our analysis supports a model in which the repeats direct the catalytic AM domain to the septum, where it can optimally perform the final step of cell division. PMID:22609916

The complete chloroplast genome sequence of Cephalotaxus oliveri (Cephalotaxaceae): evolutionary comparison of cephalotaxus chloroplast DNAs and insights into the loss of inverted repeat copies in gymnosperms.

PubMed

Yi, Xuan; Gao, Lei; Wang, Bo; Su, Ying-Juan; Wang, Ting

2013-01-01

We have determined the complete chloroplast (cp) genome sequence of Cephalotaxus oliveri. The genome is 134,337 bp in length, encodes 113 genes, and lacks inverted repeat (IR) regions. Genome-wide mutational dynamics have been investigated through comparative analysis of the cp genomes of C. oliveri and C. wilsoniana. Gene order transformation analyses indicate that when distinct isomers are considered as alternative structures for the ancestral cp genome of cupressophyte and Pinaceae lineages, it is not possible to distinguish between hypotheses favoring retention of the same IR region in cupressophyte and Pinaceae cp genomes from a hypothesis proposing independent loss of IRA and IRB. Furthermore, in cupressophyte cp genomes, the highly reduced IRs are replaced by short repeats that have the potential to mediate homologous recombination, analogous to the situation in Pinaceae. The importance of repeats in the mutational dynamics of cupressophyte cp genomes is also illustrated by the accD reading frame, which has undergone extreme length expansion in cupressophytes. This has been caused by a large insertion comprising multiple repeat sequences. Overall, we find that the distribution of repeats, indels, and substitutions is significantly correlated in Cephalotaxus cp genomes, consistent with a hypothesis that repeats play a role in inducing substitutions and indels in conifer cp genomes.

DNA CTG triplet repeats involved in dynamic mutations of neurologically related gene sequences form stable duplexes

NASA Technical Reports Server (NTRS)

Smith, G. K.; Jie, J.; Fox, G. E.; Gao, X.

1995-01-01

DNA triplet repeats, 5'-d(CTG)n and 5'-d(CAG)n, are present in genes which have been implicated in several neurodegenerative disorders. To investigate possible stable structures formed by these repeating sequences, we have examined d(CTG)n, d(CAG)n and d(CTG).d(CAG)n (n = 2 and 3) using NMR and UV optical spectroscopy. These studies reveal that single stranded (CTG)n (n > 2) forms stable, antiparallel helical duplexes, while the single stranded (CAG)n requires at least three repeating units to form a duplex. NMR and UV melting experiments show that the Tm increases in the order of [(CAG)3]2 < [(CTG)3]2 << (CAG)3.(CTG)3. The (CTG)3 duplex is stable and exhibits similar NMR spectra in solutions containing 0.1-4 M NaCl and at a pH range from 4.6 to 8.8. The (CTG)3 duplex, which contains multiple-T.T mismatches, displays many NMR spectral characteristics similar to those of B-form DNA. However, unique NOE and 1H-31P coupling patterns associated with the repetitive T.T mismatches in the CTG repeats are discerned. These results, in conjunction with recent in vitro studies suggest that longer CTG repeats may form hairpin structures, which can potentially cause interruption in replication, leading to dynamic expansion or deletion of triplet repeats.

Schema therapy for chronic depression: Results of a multiple single case series.

PubMed

Renner, Fritz; Arntz, Arnoud; Peeters, Frenk P M L; Lobbestael, Jill; Huibers, Marcus J H

2016-06-01

The aim of this study was to test the effects of individual schema therapy (ST) for patients with chronic depression. Using a multiple-baseline single case series design, patients with chronic major depressive disorder (N = 25) first entered a 6-24 weeks baseline phase; this phase functioned as a no-treatment control condition. Then, patients started a 12 week exploration phase during which symptoms and underlying schemas were explored; this phase functioned as an attention control condition. Next, patients received up to 65 sessions of individual ST. The Beck Depression Inventory II (BDI-II) and the Quick Inventory of Depressive Symptomatology (QIDS) were the primary outcome measures. The BDI-II was assessed once a week during all phases of the study resulting in 100 repeated assessments per participant on average. Mixed regression analysis was used to contrast change in symptoms during the intervention with change in symptoms during the baseline and exploration control phases. When compared to the no-treatment control period, the intervention had a significant, large effect on depressive symptoms (Cohen's d BDI-II = 1.30; Cohen's d QIDS = 1.22). Effects on secondary continuous outcomes were moderate to large. The small sample size and lack of a control group. These findings provide evidence that ST might be an effective treatment for patients with chronic depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ant-inspired density estimation via random walks

PubMed Central

Musco, Cameron; Su, Hsin-Hao

2017-01-01

Many ant species use distributed population density estimation in applications ranging from quorum sensing, to task allocation, to appraisal of enemy colony strength. It has been shown that ants estimate local population density by tracking encounter rates: The higher the density, the more often the ants bump into each other. We study distributed density estimation from a theoretical perspective. We prove that a group of anonymous agents randomly walking on a grid are able to estimate their density within a small multiplicative error in few steps by measuring their rates of encounter with other agents. Despite dependencies inherent in the fact that nearby agents may collide repeatedly (and, worse, cannot recognize when this happens), our bound nearly matches what would be required to estimate density by independently sampling grid locations. From a biological perspective, our work helps shed light on how ants and other social insects can obtain relatively accurate density estimates via encounter rates. From a technical perspective, our analysis provides tools for understanding complex dependencies in the collision probabilities of multiple random walks. We bound the strength of these dependencies using local mixing properties of the underlying graph. Our results extend beyond the grid to more general graphs, and we discuss applications to size estimation for social networks, density estimation for robot swarms, and random walk-based sampling for sensor networks. PMID:28928146

Pre-natal exposures to cocaine and alcohol and physical growth patterns to age 8 years

PubMed Central

Lumeng, Julie C.; Cabral, Howard J.; Gannon, Katherine; Heeren, Timothy; Frank, Deborah A.

2007-01-01

Two hundred and two primarily African American/Caribbean children (classified by maternal report and infant meconium as 38 heavier, 74 lighter and 89 not cocaine-exposed) were measured repeatedly from birth to age 8 years to assess whether there is an independent effect of prenatal cocaine exposure on physical growth patterns. Children with fetal alcohol syndrome identifiable at birth were excluded. At birth, cocaine and alcohol exposures were significantly and independently associated with lower weight, length and head circumference in cross-sectional multiple regression analyses. The relationship over time of pre-natal exposures to weight, height, and head circumference was then examined by multiple linear regression using mixed linear models including covariates: child’s gestational age, gender, ethnicity, age at assessment, current caregiver, birth mother’s use of alcohol, marijuana and tobacco during the pregnancy and pre-pregnancy weight (for child’s weight) and height (for child’s height and head circumference). The cocaine effects did not persist beyond infancy in piecewise linear mixed models, but a significant and independent negative effect of pre-natal alcohol exposure persisted for weight, height, and head circumference. Catch-up growth in cocaine-exposed infants occurred primarily by 6 months of age for all growth parameters, with some small fluctuations in growth rates in the preschool age range but no detectable differences between heavier versus unexposed nor lighter versus unexposed thereafter. PMID:17412558

Long-term serum bile acid concentrations in 51 dogs after complete extrahepatic congenital portosystemic shunt ligation.

PubMed

Bristow, P; Tivers, M; Packer, R; Brockman, D; Ortiz, V; Newson, K; Lipscomb, V

2017-08-01

To report the long-term bile acid stimulation test results for dogs that have undergone complete suture ligation of a single congenital extrahepatic portosystemic shunt. Data were collected from the hospital records of all dogs that had undergone a complete suture ligation of a single congenital extrahepatic portosystemic shunt. Owners were invited to return to the referral centre or their local veterinarian for repeat serum bile acid measurement. Dogs diagnosed with idiopathic epilepsy and undergoing bile acid stimulation tests were used as a comparison population. Fifty-one study dogs were included, with a mean follow-up time of 62 months. 48 dogs had no evidence of multiple acquired shunts and a significant reduction in the pre- and post-prandial serum bile acid concentrations at long-term follow-up compared with pre-operative measurements. Pre- and post-prandial serum bile acids were statistically significantly greater for dogs that had undergone a full ligation (with no evidence of multiple acquired shunts) at all time points compared to the control dogs (P<0·001 for all comparisons). The results suggest that in dogs treated with complete suture ligation mild increases in serum bile acids are not clinically relevant if there are no physical examination abnormalities, a normal body condition score and no relapse in clinical signs. © 2017 British Small Animal Veterinary Association.

Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

PubMed Central

Guaitoli, Giambattista; Raimondi, Francesco; Gilsbach, Bernd K.; Gómez-Llorente, Yacob; Deyaert, Egon; Renzi, Fabiana; Li, Xianting; Schaffner, Adam; Jagtap, Pravin Kumar Ankush; Boldt, Karsten; von Zweydorf, Felix; Gotthardt, Katja; Lorimer, Donald D.; Yue, Zhenyu; Burgin, Alex; Janjic, Nebojsa; Sattler, Michael; Versées, Wim; Ueffing, Marius; Ubarretxena-Belandia, Iban; Kortholt, Arjan; Gloeckner, Christian Johannes

2016-01-01

Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson’s disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity—together with the LRR domain—to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD. PMID:27357661

Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules

DOEpatents

Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E

2014-01-14

Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

Longitudinal Monitoring of Successive Commercial Layer Flocks for Salmonella enterica Serovar Enteritidis.

PubMed

Denagamage, Thomas N; Patterson, Paul; Wallner-Pendleton, Eva; Trampel, Darrell; Shariat, Nikki; Dudley, Edward G; Jayarao, Bhushan M; Kariyawasam, Subhashinie

2016-11-01

The Pennsylvania Egg Quality Assurance Program (EQAP) provided the framework for Salmonella Enteritidis (SE) control programs, including the Food and Drug Administration (FDA) mandated Final Egg Rule, for commercial layer facilities throughout the United States. Although flocks with ≥3000 birds must comply with the FDA Final Egg Rule, smaller flocks are exempted from the rule. As a result, eggs produced by small layer flocks may pose a greater public health risk than those from larger flocks. It is also unknown if the EQAPs developed with large flocks in mind are suitable for small- and medium-sized flocks. Therefore, a study was performed to evaluate the effectiveness of best management practices included in EQAPs in reducing SE contamination of small- and medium-sized flocks by longitudinal monitoring of their environment and eggs. A total of 59 medium-sized (3000 to 50,000 birds) and small-sized (<3000 birds) flocks from two major layer production states of the United States were enrolled and monitored for SE by culturing different types of environmental samples and shell eggs for two consecutive flock cycles. Isolated SE was characterized by phage typing, pulsed-field gel electrophoresis (PFGE), and clustered regularly interspaced short palindromic repeats-multi-virulence-locus sequence typing (CRISPR-MVLST). Fifty-four Salmonella isolates belonging to 17 serovars, 22 of which were SE, were isolated from multiple sample types. Typing revealed that SE isolates belonged to three phage types (PTs), three PFGE fingerprint patterns, and three CRISPR-MVLST SE Sequence Types (ESTs). The PT8 and JEGX01.0004 PFGE pattern, the most predominant SE types associated with foodborne illness in the United States, were represented by a majority (91%) of SE. Of the three ESTs observed, 85% SE were typed as EST4. The proportion of SE-positive hen house environment during flock cycle 2 was significantly less than the flock cycle 1, demonstrating that current EQAP practices were effective in reducing SE contamination of medium and small layer flocks.

Optimal periodic binary codes of lengths 28 to 64

NASA Technical Reports Server (NTRS)

Tyler, S.; Keston, R.

1980-01-01

Results from computer searches performed to find repeated binary phase coded waveforms with optimal periodic autocorrelation functions are discussed. The best results for lengths 28 to 64 are given. The code features of major concern are where (1) the peak sidelobe in the autocorrelation function is small and (2) the sum of the squares of the sidelobes in the autocorrelation function is small.

An Examination of a Small-Group Decoding Intervention for Struggling Readers: Comparing Accuracy and Automaticity Criteria

ERIC Educational Resources Information Center

Hudson, Roxanne F.; Isakson, Carole; Richman, Taylor; Lane, Holly B.; Arriaza-Allen, Stephanie

2011-01-01

In this study, we compared methods to improve the decoding and reading fluency of struggling readers. Second-grade poor readers were randomly assigned to one of the two practice conditions within a repeated reading intervention. Both interventions were in small groups, were 20-28 min long, took place 2-4 days per week, and consisted of phonemic…

Detecting small-scale spatial heterogeneity and temporal dynamics of soil organic carbon (SOC) stocks: a comparison between automatic chamber-derived C budgets and repeated soil inventories

NASA Astrophysics Data System (ADS)

Hoffmann, Mathias; Jurisch, Nicole; Garcia Alba, Juana; Albiac Borraz, Elisa; Schmidt, Marten; Huth, Vytas; Rogasik, Helmut; Rieckh, Helene; Verch, Gernot; Sommer, Michael; Augustin, Jürgen

2017-03-01

Carbon (C) sequestration in soils plays a key role in the global C cycle. It is therefore crucial to adequately monitor dynamics in soil organic carbon (ΔSOC) stocks when aiming to reveal underlying processes and potential drivers. However, small-scale spatial (10-30 m) and temporal changes in SOC stocks, particularly pronounced in arable lands, are hard to assess. The main reasons for this are limitations of the well-established methods. On the one hand, repeated soil inventories, often used in long-term field trials, reveal spatial patterns and trends in ΔSOC but require a longer observation period and a sufficient number of repetitions. On the other hand, eddy covariance measurements of C fluxes towards a complete C budget of the soil-plant-atmosphere system may help to obtain temporal ΔSOC patterns but lack small-scale spatial resolution. To overcome these limitations, this study presents a reliable method to detect both short-term temporal dynamics as well as small-scale spatial differences of ΔSOC using measurements of the net ecosystem carbon balance (NECB) as a proxy. To estimate the NECB, a combination of automatic chamber (AC) measurements of CO2 exchange and empirically modeled aboveground biomass development (NPPshoot) were used. To verify our method, results were compared with ΔSOC observed by soil resampling. Soil resampling and AC measurements were performed from 2010 to 2014 at a colluvial depression located in the hummocky ground moraine landscape of northeastern Germany. The measurement site is characterized by a variable groundwater level (GWL) and pronounced small-scale spatial heterogeneity regarding SOC and nitrogen (Nt) stocks. Tendencies and magnitude of ΔSOC values derived by AC measurements and repeated soil inventories corresponded well. The period of maximum plant growth was identified as being most important for the development of spatial differences in annual ΔSOC. Hence, we were able to confirm that AC-based C budgets are able to reveal small-scale spatial differences and short-term temporal dynamics of ΔSOC.

Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) length is measured by a ruler mechanism anchored at the precursor processing site.

PubMed

Hatoum-Aslan, Asma; Maniv, Inbal; Marraffini, Luciano A

2011-12-27

Precise RNA processing is fundamental to all small RNA-mediated interference pathways. In prokaryotes, clustered, regularly interspaced, short palindromic repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against invasive genetic elements by antisense targeting. CRISPR loci are transcribed as a long precursor that is cleaved within repeat sequences by CRISPR-associated (Cas) proteins. In many organisms, this primary processing generates crRNA intermediates that are subject to additional nucleolytic trimming to render mature crRNAs of specific lengths. The molecular mechanisms underlying this maturation event remain poorly understood. Here, we defined the genetic requirements for crRNA primary processing and maturation in Staphylococcus epidermidis. We show that changes in the position of the primary processing site result in extended or diminished maturation to generate mature crRNAs of constant length. These results indicate that crRNA maturation occurs by a ruler mechanism anchored at the primary processing site. We also show that maturation is mediated by specific cas genes distinct from those genes involved in primary processing, showing that this event is directed by CRISPR/Cas loci.

Toward an MRI-based method to measure non-uniform cartilage deformation: an MRI-cyclic loading apparatus system and steady-state cyclic displacement of articular cartilage under compressive loading.

PubMed

Neu, C P; Hull, M L

2003-04-01

Recent magnetic resonance imaging (MRI) techniques have shown potential for measuring non-uniform deformations throughout the volume (i.e. three-dimensional (3D) deformations) in small orthopedic tissues such as articular cartilage. However, to analyze cartilage deformation using MRI techniques, a system is required which can construct images from multiple acquisitions of MRI signals from the cartilage in both the underformed and deformed states. The objectives of the work reported in this article were to 1) design an apparatus that could apply highly repeatable cyclic compressive loads of 400 N and operate in the bore of an MRI scanner, 2) demonstrate that the apparatus and MRI scanner can be successfully integrated to observe 3D deformations in a phantom material, 3) use the apparatus to determine the load cycle necessary to achieve a steady-state deformation response in normal bovine articular cartilage samples using a flat-surfaced and nonporous indentor in unconfined compression. Composed of electronic and pneumatic components, the apparatus regulated pressure to a double-acting pneumatic cylinder so that (1) load-controlled compression cycles were applied to cartilage samples immersed in a saline bath, (2) loading and recovery periods within a cycle varied in time duration, and (3) load magnitude varied so that the stress applied to cartilage samples was within typical physiological ranges. In addition the apparatus allowed gating for MR image acquisition, and operation within the bore of an MRI scanner without creating image artifacts. The apparatus demonstrated high repeatability in load application with a standard deviation of 1.8% of the mean 400 N load applied. When the apparatus was integrated with an MRI scanner programmed with appropriate pulse sequences, images of a phantom material in both the underformed and deformed states were constructed by assembling data acquired through multiple signal acquisitions. Additionally, the number of cycles to reach a steady-state response in normal bovine articular cartilage was 49 for a total cycle duration of 5 seconds, but decreased to 33 and 27 for increasing total cycle durations of 10 and 15 seconds, respectively. Once the steady-state response was achieved, 95% of all displacements were within +/- 7.42 microns of the mean displacement, indicating that the displacement response to the cyclic loads was highly repeatable. With this performance, the MRI-loading apparatus system meets the requirements to create images of articular cartilage from which 3D deformation can be determined.

Evolution of genes and repeats in the Nimrod superfamily.

PubMed

Somogyi, Kálmán; Sipos, Botond; Pénzes, Zsolt; Kurucz, Eva; Zsámboki, János; Hultmark, Dan; Andó, István

2008-11-01

The recently identified Nimrod superfamily is characterized by the presence of a special type of EGF repeat, the NIM repeat, located right after a typical CCXGY/W amino acid motif. On the basis of structural features, nimrod genes can be divided into three types. The proteins encoded by Draper-type genes have an EMI domain at the N-terminal part and only one copy of the NIM motif, followed by a variable number of EGF-like repeats. The products of Nimrod B-type and Nimrod C-type genes (including the eater gene) have different kinds of N-terminal domains, and lack EGF-like repeats but contain a variable number of NIM repeats. Draper and Nimrod C-type (but not Nimrod B-type) proteins carry a transmembrane domain. Several members of the superfamily were claimed to function as receptors in phagocytosis and/or binding of bacteria, which indicates an important role in the cellular immunity and the elimination of apoptotic cells. In this paper, the evolution of the Nimrod superfamily is studied with various methods on the level of genes and repeats. A hypothesis is presented in which the NIM repeat, along with the EMI domain, emerged by structural reorganizations at the end of an EGF-like repeat chain, suggesting a mechanism for the formation of novel types of repeats. The analyses revealed diverse evolutionary patterns in the sequences containing multiple NIM repeats. Although in the Nimrod B and Nimrod C proteins show characteristics of independent evolution, many internal NIM repeats in Eater sequences seem to have undergone concerted evolution. An analysis of the nimrod genes has been performed using phylogenetic and other methods and an evolutionary scenario of the origin and diversification of the Nimrod superfamily is proposed. Our study presents an intriguing example how the evolution of multigene families may contribute to the complexity of the innate immune response.

Repeatability of three-dimensional thorax and pelvis kinematics in the golf swing measured using a field-based motion capture system.

PubMed

Evans, Kerrie; Horan, Sean A; Neal, Robert J; Barrett, Rod S; Mills, Peter M

2012-06-01

Field-based methods of evaluating three-dimensional (3D) swing kinematics offer coaches and researchers the opportunity to assess golfers in context-specific environments. The purpose of this study was to establish the inter-trial, between-tester, between-location, and between-day repeatability of thorax and pelvis kinematics during the downswing using an electromagnetic motion capture system. Two experienced testers measured swing kinematics in 20 golfers (handicap < or =14 strokes) on consecutive days in an indoor and outdoor location. Participants performed five swings with each of two clubs (five-iron and driver) at each test condition. Repeatability of 3D kinematic data was evaluated by computing the coefficient of multiple determination (CMD) and the systematic error (SE). With the exception of pelvis forward bend for between-day and between-tester conditions, CMDs exceeded 0.854 for all variables, indicating high levels of overall waveform repeatability across conditions. When repeatability was compared across conditions using MANOVA, the lowest CMDs and highest SEs were found for the between-tester and between-day conditions. The highest CMDs were for the inter-trial and between-location conditions. The absence of significant differences in CMDs between these two conditions supports this method of analysing pelvis and thorax kinematics in different environmental settings without unduly affecting repeatability.

Repeated Solid-state Dewetting of Thin Gold Films for Nanogap-rich Plasmonic Nanoislands.

PubMed

Kang, Minhee; Park, Sang-Gil; Jeong, Ki-Hun

2015-10-15

This work reports a facile wafer-level fabrication for nanogap-rich gold nanoislands for highly sensitive surface enhanced Raman scattering (SERS) by repeating solid-state thermal dewetting of thin gold film. The method provides enlarged gold nanoislands with small gap spacing, which increase the number of electromagnetic hotspots and thus enhance the extinction intensity as well as the tunability for plasmon resonance wavelength. The plasmonic nanoislands from repeated dewetting substantially increase SERS enhancement factor over one order-of-magnitude higher than those from a single-step dewetting process and they allow ultrasensitive SERS detection of a neurotransmitter with extremely low Raman activity. This simple method provides many opportunities for engineering plasmonics for ultrasensitive detection and highly efficient photon collection.

Repeated Solid-state Dewetting of Thin Gold Films for Nanogap-rich Plasmonic Nanoislands

PubMed Central

Kang, Minhee; Park, Sang-Gil; Jeong, Ki-Hun

2015-01-01

This work reports a facile wafer-level fabrication for nanogap-rich gold nanoislands for highly sensitive surface enhanced Raman scattering (SERS) by repeating solid-state thermal dewetting of thin gold film. The method provides enlarged gold nanoislands with small gap spacing, which increase the number of electromagnetic hotspots and thus enhance the extinction intensity as well as the tunability for plasmon resonance wavelength. The plasmonic nanoislands from repeated dewetting substantially increase SERS enhancement factor over one order-of-magnitude higher than those from a single-step dewetting process and they allow ultrasensitive SERS detection of a neurotransmitter with extremely low Raman activity. This simple method provides many opportunities for engineering plasmonics for ultrasensitive detection and highly efficient photon collection. PMID:26469768

Holocentromeres in Rhynchospora are associated with genome-wide centromere-specific repeat arrays interspersed among euchromatin.

PubMed

Marques, André; Ribeiro, Tiago; Neumann, Pavel; Macas, Jiří; Novák, Petr; Schubert, Veit; Pellino, Marco; Fuchs, Jörg; Ma, Wei; Kuhlmann, Markus; Brandt, Ronny; Vanzela, André L L; Beseda, Tomáš; Šimková, Hana; Pedrosa-Harand, Andrea; Houben, Andreas

2015-11-03

Holocentric chromosomes lack a primary constriction, in contrast to monocentrics. They form kinetochores distributed along almost the entire poleward surface of the chromatids, to which spindle fibers attach. No centromere-specific DNA sequence has been found for any holocentric organism studied so far. It was proposed that centromeric repeats, typical for many monocentric species, could not occur in holocentrics, most likely because of differences in the centromere organization. Here we show that the holokinetic centromeres of the Cyperaceae Rhynchospora pubera are highly enriched by a centromeric histone H3 variant-interacting centromere-specific satellite family designated "Tyba" and by centromeric retrotransposons (i.e., CRRh) occurring as genome-wide interspersed arrays. Centromeric arrays vary in length from 3 to 16 kb and are intermingled with gene-coding sequences and transposable elements. We show that holocentromeres of metaphase chromosomes are composed of multiple centromeric units rather than possessing a diffuse organization, thus favoring the polycentric model. A cell-cycle-dependent shuffling of multiple centromeric units results in the formation of functional (poly)centromeres during mitosis. The genome-wide distribution of centromeric repeat arrays interspersing the euchromatin provides a previously unidentified type of centromeric chromatin organization among eukaryotes. Thus, different types of holocentromeres exist in different species, namely with and without centromeric repetitive sequences.

Factitious panniculitis induced by cupping therapy.

PubMed

Moon, Suk-Ho; Han, Hyun-Ho; Rhie, Jong-Won

2011-11-01

Cupping therapy is an alternative medical procedure that has been widely performed in Asian countries to relieve pain. It is known that there is no complication to this therapy, so many non-health care professionals have performed this procedure. However, there have been few reports on complications, such as iron deficiency anemia, hemorrhagic bullae, kelloids, vasovagal syncope, and foreign body reactions. Masses associated with panniculitis induced by cupping are extremely rare, and they require a unique approach.A 56-year-old woman presented with a 10-month history of multiple masses in the posterior neck and right shoulder areas. The patient repeatedly attempted cupping therapy by herself, and multiple palpable masses developed in the posterior neck and right shoulder area where cupping therapy had been performed. The masses were enlarged by repeated cupping, and they decreased in size when cupping was stopped. Among all lesions, the 2 masses with tenderness were surgically excised. The remaining masses resolved after cupping therapy was ceased. When a patient with subcutaneous mass has a history of cupping or trace of cupping marks, panniculitis induced by cupping should be suspected. The lesion seems to spontaneously resolve unless they are repeatedly stimulated. However, surgical resection is considered in patients with infections or severe tenderness as a complication.

A repeatedly refuelable mediated biofuel cell based on a hierarchical porous carbon electrode

NASA Astrophysics Data System (ADS)

Fujita, Shuji; Yamanoi, Shun; Murata, Kenichi; Mita, Hiroki; Samukawa, Tsunetoshi; Nakagawa, Takaaki; Sakai, Hideki; Tokita, Yuichi

2014-05-01

Biofuel cells that generate electricity from renewable fuels, such as carbohydrates, must be reusable through repeated refuelling, should these devices be used in consumer electronics. We demonstrate the stable generation of electricity from a glucose-powered mediated biofuel cell through multiple refuelling cycles. This refuelability is achieved by immobilizing nicotinamide adenine dinucleotide (NAD), an electron-transfer mediator, and redox enzymes in high concentrations on porous carbon particles constituting an anode while maintaining their electrochemical and enzymatic activities after the immobilization. This bioanode can be refuelled continuously for more than 60 cycles at 1.5 mA cm-2 without significant potential drop. Cells assembled with these bioanodes and bilirubin-oxidase-based biocathodes can be repeatedly used to power a portable music player at 1 mW cm-3 through 10 refuelling cycles. This study suggests that the refuelability within consumer electronics should facilitate the development of long and repeated use of the mediated biofuel cells as well as of NAD-based biosensors, bioreactors, and clinical applications.

The molecular mechanism of nuclear transport revealed by atomic-scale measurements

PubMed Central

Hough, Loren E; Dutta, Kaushik; Sparks, Samuel; Temel, Deniz B; Kamal, Alia; Tetenbaum-Novatt, Jaclyn; Rout, Michael P; Cowburn, David

2015-01-01

Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC. DOI: http://dx.doi.org/10.7554/eLife.10027.001 PMID:26371551

A repeatedly refuelable mediated biofuel cell based on a hierarchical porous carbon electrode.

PubMed

Fujita, Shuji; Yamanoi, Shun; Murata, Kenichi; Mita, Hiroki; Samukawa, Tsunetoshi; Nakagawa, Takaaki; Sakai, Hideki; Tokita, Yuichi

2014-05-13

Biofuel cells that generate electricity from renewable fuels, such as carbohydrates, must be reusable through repeated refuelling, should these devices be used in consumer electronics. We demonstrate the stable generation of electricity from a glucose-powered mediated biofuel cell through multiple refuelling cycles. This refuelability is achieved by immobilizing nicotinamide adenine dinucleotide (NAD), an electron-transfer mediator, and redox enzymes in high concentrations on porous carbon particles constituting an anode while maintaining their electrochemical and enzymatic activities after the immobilization. This bioanode can be refuelled continuously for more than 60 cycles at 1.5 mA cm(-2) without significant potential drop. Cells assembled with these bioanodes and bilirubin-oxidase-based biocathodes can be repeatedly used to power a portable music player at 1 mW cm(-3) through 10 refuelling cycles. This study suggests that the refuelability within consumer electronics should facilitate the development of long and repeated use of the mediated biofuel cells as well as of NAD-based biosensors, bioreactors, and clinical applications.

A repeatedly refuelable mediated biofuel cell based on a hierarchical porous carbon electrode

PubMed Central

Fujita, Shuji; Yamanoi, Shun; Murata, Kenichi; Mita, Hiroki; Samukawa, Tsunetoshi; Nakagawa, Takaaki; Sakai, Hideki; Tokita, Yuichi

2014-01-01

Biofuel cells that generate electricity from renewable fuels, such as carbohydrates, must be reusable through repeated refuelling, should these devices be used in consumer electronics. We demonstrate the stable generation of electricity from a glucose-powered mediated biofuel cell through multiple refuelling cycles. This refuelability is achieved by immobilizing nicotinamide adenine dinucleotide (NAD), an electron-transfer mediator, and redox enzymes in high concentrations on porous carbon particles constituting an anode while maintaining their electrochemical and enzymatic activities after the immobilization. This bioanode can be refuelled continuously for more than 60 cycles at 1.5 mA cm−2 without significant potential drop. Cells assembled with these bioanodes and bilirubin-oxidase-based biocathodes can be repeatedly used to power a portable music player at 1 mW cm−3 through 10 refuelling cycles. This study suggests that the refuelability within consumer electronics should facilitate the development of long and repeated use of the mediated biofuel cells as well as of NAD-based biosensors, bioreactors, and clinical applications. PMID:24820210

Repeatability of nest morphology in African weaver birds.

PubMed

Walsh, Patrick T; Hansell, Mike; Borello, Wendy D; Healy, Susan D

2010-04-23

It is generally assumed that birds build nests according to a genetic 'template', little influenced by learning or memory. One way to confirm the role of genetics in nest building is to assess the repeatability of nest morphology with repeated nest attempts. Solitary weaver birds, which build multiple nests in a single breeding season, are a useful group with which to do this. Here we show that repeatability of nest morphology was low, but significant, in male Southern Masked weaver birds and not significant in the Village weavers. The larger bodied Village weavers built larger nests than did Southern Masked weavers, but body size did not explain variation in Southern Masked weaver nest dimensions. Nests built by the same male in both species got shorter and lighter as more nests were constructed. While these data demonstrate the potential for a genetic component of variation in nest building in solitary weavers, it is also clear that there remains plenty of scope in both of these species for experience to shape nest construction.

Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions

PubMed Central

Wang, Chao; Wei, Zhiyi

2017-01-01

Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches. We discovered that the entire ANK repeats are inhibited by combinatorial and quasi-independent bindings of multiple disordered segments located in the ankyrin-B/G linkers and tails, suggesting a mechanistic basis for differential regulations of membrane target bindings by ankyrins. In addition to elucidating the autoinhibition mechanisms of ankyrins, our study may also shed light on regulations on target bindings by other long repeat-containing proteins. PMID:28841137

Integration of promoters, inverted repeat sequences and proteomic data into a model for high silencing efficiency of coeliac disease related gliadins in bread wheat

PubMed Central

2013-01-01

Background Wheat gluten has unique nutritional and technological characteristics, but is also a major trigger of allergies and intolerances. One of the most severe diseases caused by gluten is coeliac disease. The peptides produced in the digestive tract by the incomplete digestion of gluten proteins trigger the disease. The majority of the epitopes responsible reside in the gliadin fraction of gluten. The location of the multiple gliadin genes in blocks has to date complicated their elimination by classical breeding techniques or by the use of biotechnological tools. As an approach to silence multiple gliadin genes we have produced 38 transgenic lines of bread wheat containing combinations of two endosperm-specific promoters and three different inverted repeat sequences to silence three fractions of gliadins by RNA interference. Results The effects of the RNA interference constructs on the content of the gluten proteins, total protein and starch, thousand seed weights and SDSS quality tests of flour were analyzed in these transgenic lines in two consecutive years. The characteristics of the inverted repeat sequences were the main factor that determined the efficiency of silencing. The promoter used had less influence on silencing, although a synergy in silencing efficiency was observed when the two promoters were used simultaneously. Genotype and the environment also influenced silencing efficiency. Conclusions We conclude that to obtain wheat lines with an optimum reduction of toxic gluten epitopes one needs to take into account the factors of inverted repeat sequences design, promoter choice and also the wheat background used. PMID:24044767

A multi-segment foot model based on anatomically registered technical coordinate systems: method repeatability and sensitivity in pediatric planovalgus feet.

PubMed

Saraswat, Prabhav; MacWilliams, Bruce A; Davis, Roy B; D'Astous, Jacques L

2013-01-01

Several multisegment foot models have been proposed and some have been used to study foot pathologies. These models have been tested and validated on typically developed populations; however application of such models to feet with significant deformities presents an additional set of challenges. For the first time, in this study, a multisegment foot model is tested for repeatability in a population of children with symptomatic abnormal feet. The results from this population are compared to the same metrics collected from an age matched (8-14 years) typically developing population. The modified Shriners Hospitals for Children, Greenville (mSHCG) foot model was applied to ten typically developing children and eleven children with planovalgus feet by two clinicians. Five subjects in each group were retested by both clinicians after 4-6 weeks. Both intra-clinician and inter-clinician repeatability were evaluated using static and dynamic measures. A plaster mold method was used to quantify variability arising from marker placement error. Dynamic variability was measured by examining trial differences from the same subjects when multiple clinicians carried out the data collection multiple times. For hindfoot and forefoot angles, static and dynamic variability in both groups was found to be less than 4° and 6° respectively. The mSHCG model strategy of minimal reliance on anatomical markers for dynamic measures and inherent flexibility enabled by separate anatomical and technical coordinate systems resulted in a model equally repeatable in typically developing and planovalgus populations. Copyright © 2012 Elsevier B.V. All rights reserved.

Energetic consequences of repeated and prolonged dehydration in the Antarctic midge, Belgica antarctica.

PubMed

Teets, Nicholas M; Kawarasaki, Yuta; Lee, Richard E; Denlinger, David L

2012-04-01

Larvae of the Antarctic midge, Belgica antarctica, routinely face periods of limited water availability in their natural environments on the Antarctic Peninsula. As a result, B. antarctica is one of the most dehydration-tolerant insects studied, surviving up to 70% loss of its body water. While previous studies have characterized the physiological effects of a single bout of dehydration, in nature larvae are likely to experience multiple bouts of dehydration throughout their lifetime. Thus, we examined the physiological consequences of repeated dehydration and compared results to larvae exposed to a single, prolonged period of dehydration. For the repeated dehydration experiment, larvae were exposed to 1-5 cycles of 24 h dehydration at 75% RH followed by 24 h rehydration. Each bout of dehydration resulted in 30-40% loss of body water, with a concomitant 2- to 3-fold increase in body fluid osmolality. While nearly 100% of larvae survived a single bout of dehydration, <65% of larvae survived five such cycles. Larvae subjected to multiple bouts of dehydration also experienced severe depletion of carbohydrate energy reserves; glycogen and trehalose content decreased with each successive cycle, with larvae losing 89% and 48% of their glycogen and trehalose, respectively, after five cycles of dehydration/rehydration. Larvae exposed to prolonged dehydration (99% RH for 10d) had 26% less water, 43% less glycogen, and 27% less lipid content than controls, but did not experience any mortality. Thus, both repeated and prolonged dehydration results in substantial energetic costs that are likely to negatively impact fitness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Photopic Negative Response Obtained Using a Handheld Electroretinogram Device: Determining the Optimal Measure and Repeatability

PubMed Central

Wu, Zhichao; Hadoux, Xavier; Hui, Flora; Sarossy, Marc G.; Crowston, Jonathan G.

2016-01-01

Purpose To determine the measure of the photopic negative response (PhNR) of the full-field electroretinogram (ERG) that exhibits the optimal level of test-retest repeatability, and examine its repeatability under different conditions using a handheld, nonmydriatic ERG system and self-adhering skin electrodes. Methods Multiple ERG recordings (using 200 sweeps each) were performed in both eyes of 20 normal participants at two different sessions to compare its coefficient of repeatability (CoR; where 95% of the test-retest difference is expected to lie) between different PhNR measures and under different testing conditions (within and between examiners, and between sessions). Results The ratio between the PhNR trough to b-wave peak and b-wave peak to a-wave trough amplitude (PhNR/B ratio) exhibited the lowest CoR relative to its effective dynamic range (30 ± 4%) when including three recordings. There were no significant changes in the PhNR/B ratio over seven measurements (4 right and 3 left eyes) at either session (P ≥ 0.100), or significant difference in its CoR between different testing conditions (P = 0.314). Conclusion The PhNR/B ratio was the measure that minimized variability, and its measurements using a novel handheld ERG system with self-adhering skin electrodes and the protocols described in this study were comparable under different testing conditions and over multiple recordings. Translational Relevance The PhNR can be measured for clinical and research purposes using a simple-to-implement technique that is consistent within and between visits, and also between examiners. PMID:27540494

Repeats of base oligomers as the primordial coding sequences of the primeval earth and their vestiges in modern genes.

PubMed

Ohno, S

1984-01-01

Three outstanding properties uniquely qualify repeats of base oligomers as the primordial coding sequences of all polypeptide chains. First, when compared with randomly generated base sequences in general, they are more likely to have long open reading frames. Second, periodical polypeptide chains specified by such repeats are more likely to assume either alpha-helical or beta-sheet secondary structures than are polypeptide chains of random sequence. Third, provided that the number of bases in the oligomeric unit is not a multiple of 3, these internally repetitious coding sequences are impervious to randomly sustained base substitutions, deletions, and insertions. This is because the recurring periodicity of their polypeptide chains is given by three consecutive copies of the oligomeric unit translated in three different reading frames. Accordingly, when one reading frame is open, the other two are automatically open as well, all three being capable of coding for polypeptide chains of identical periodicity. Under this circumstance, a frame shift due to the deletion or insertion of a number of bases that is not a multiple of 3 fails to alter the down-stream amino acid sequence, and even a base change causing premature chain-termination can silence only one of the three potential coding units. Newly arisen coding sequences in modern organisms are oligomeric repeats, and most of the older genes retain various vestiges of their original internal repetitions. Some of the genes (e.g., oncogenes) have even inherited the property of being impervious to randomly sustained base changes.

A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed in Echinococcus multilocularis Stem Cells

PubMed Central

Koziol, Uriel; Radio, Santiago; Smircich, Pablo; Zarowiecki, Magdalena; Fernández, Cecilia; Brehm, Klaus

2015-01-01

Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. PMID:26133390

Bilateral sacroiliac luxation fixation using a single transiliosacral pin: surgical technique and clinical outcomes in eight cats.

PubMed

Parslow, A; Simpson, D J

2017-06-01

A very limited safe anatomical window for transiliosacral implant placement exists in cats (<0·5 cm 2 ). Lag screw fixation requires multiple bilateral implants thus increasing the risk of iatrogenic trauma and implant interference. We describe a safe and effective method for bilateral sacroiliac fixation in cats using a single implant to minimise inadvertent iatrogenic damage to local structures and restore pelvic canal diameter. Eight cats underwent surgical fixation for traumatic bilateral sacroiliac luxation using a single smooth intramedullary pin. The pin spanned both ilial wings and sacrum. Implants were applied using a Universal C-guide. Pre- and postsurgery pelvic canal diameter ratios were calculated. Short-term follow-up was performed at 10 to 14 days postoperatively. Long-term follow-up was performed using the Feline Musculoskeletal Pain Index Questionnaire. Long-term radiographic assessment was available in two cases. The technique achieved safe and accurate implant position with precise sacroiliac joint reduction. Pelvic canal diameter ratios were restored to normal in all cases. Rapid return to normal hind leg function and excellent long-term clinical outcomes were achieved. This technique offers a simple, safe, repeatable and affordable technique for treating bilateral sacroiliac luxations in the cat without the aid of fluoroscopy. The procedure can be performed using surgical tools and inventory readily available in general small animal practices. © 2017 British Small Animal Veterinary Association.

A case report of apatinib in treating osteosarcoma with pulmonary metastases.

PubMed

Zhou, Yong; Zhang, Wengeng; Tang, Fan; Luo, Yi; Min, Li; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

2017-04-01

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Pulmonary metastases lead to a significantly increased risk of death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast cancer. However, its efficacy in metastatic osteosarcoma has not been reported yet. Herein, we presented a 50-year-old man patient who visited hospital due to local bone pain in the left leg. He was initially diagnosed with osteoblastic osteosarcoma. The patient suffered repeated resection surgeries but developed multiple lung metastases. Positive staining for CD31, CD34, and VEGFR-2 were detected in the tumor section. As he refused to receive chemotherapy due to concerns regarding the chemotherapy toxicities and sorafenib due to high cost, apatinib was given at a dose of 500 mg daily. Eleven months following apatinib administration, the patient achieved a partial response according to the RECIST 1.1 standard. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of metastatic osteosarcoma. Clinical trials are required to further confirm the efficacy and safety of apatinib in treating pulmonary metastases from osteosarcoma.

A case report of apatinib in treating osteosarcoma with pulmonary metastases

PubMed Central

Zhou, Yong; Zhang, Wengeng; Tang, Fan; Luo, Yi; Min, Li; Zhang, Wenli; Shi, Rui; Duan, Hong; Tu, Chongqi

2017-01-01

Abstract Rationale: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Pulmonary metastases lead to a significantly increased risk of death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast cancer. However, its efficacy in metastatic osteosarcoma has not been reported yet. Patient concerns: Herein, we presented a 50-year-old man patient who visited hospital due to local bone pain in the left leg. Diagnoses: He was initially diagnosed with osteoblastic osteosarcoma. Interventions: The patient suffered repeated resection surgeries but developed multiple lung metastases. Positive staining for CD31, CD34, and VEGFR-2 were detected in the tumor section. As he refused to receive chemotherapy due to concerns regarding the chemotherapy toxicities and sorafenib due to high cost, apatinib was given at a dose of 500 mg daily. Outcomes: Eleven months following apatinib administration, the patient achieved a partial response according to the RECIST 1.1 standard. No severe toxicity or drug-related side effect was observed during the treatment. Lessons: Therefore, apatinib could be a new option for the treatment of metastatic osteosarcoma. Clinical trials are required to further confirm the efficacy and safety of apatinib in treating pulmonary metastases from osteosarcoma. PMID:28403086

Numerous Transitions of Sex Chromosomes in Diptera

PubMed Central

Vicoso, Beatriz; Bachtrog, Doris

2015-01-01

Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot), but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes). Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa. PMID:25879221

Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review.

PubMed

Liu, Yangyang

2018-06-03

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs. The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural metastasis after successful treatment with surgery and adjuvant treatment. So, erlotinib was administered with 18 months. Because of enlarged pleural nodule, repeat biopsy identified an SCLC and chemotherapy was started. However, despite the brief success of chemotherapy, our patient suffered brain metastasis. Our case emaphsizes both the profile of transformation from NSCLC to SCLC and the importance of repeat biopsy dealing with drug resistance. We also summarize the clinical characteristics, mechanisms, predictors of SCLC transformation, treatment after transformation and other types of transformation to SCLC.

Targeting the r(CGG) repeats that cause FXTAS with modularly assembled small molecules and oligonucleotides.

PubMed

Tran, Tuan; Childs-Disney, Jessica L; Liu, Biao; Guan, Lirui; Rzuczek, Suzanne; Disney, Matthew D

2014-04-18

We designed small molecules that bind the structure of the RNA that causes fragile X-associated tremor ataxia syndrome (FXTAS), an incurable neuromuscular disease. FXTAS is caused by an expanded r(CGG) repeat (r(CGG)(exp)) that inactivates a protein regulator of alternative pre-mRNA splicing. Our designed compounds modulate r(CGG)(exp) toxicity in cellular models of FXTAS, and pull-down experiments confirm that they bind r(CGG)(exp) in vivo. Importantly, compound binding does not affect translation of the downstream open reading frame (ORF). We compared molecular recognition properties of our optimal compound to oligonucleotides. Studies show that r(CGG)(exp)'s self-structure is a significant energetic barrier for oligonucleotide binding. A fully modified 2'-OMethyl phosphorothioate is incapable of completely reversing an FXTAS-associated splicing defect and inhibits translation of the downstream ORF, which could have deleterious effects. Taken together, these studies suggest that a small molecule that recognizes structure may be more well suited for targeting highly structured RNAs that require strand invasion by a complementary oligonucleotide.

Targeting the r(CGG) Repeats That Cause FXTAS with Modularly Assembled Small Molecules and Oligonucleotides

PubMed Central

2015-01-01

We designed small molecules that bind the structure of the RNA that causes fragile X-associated tremor ataxia syndrome (FXTAS), an incurable neuromuscular disease. FXTAS is caused by an expanded r(CGG) repeat (r(CGG)exp) that inactivates a protein regulator of alternative pre-mRNA splicing. Our designed compounds modulate r(CGG)exp toxicity in cellular models of FXTAS, and pull-down experiments confirm that they bind r(CGG)expin vivo. Importantly, compound binding does not affect translation of the downstream open reading frame (ORF). We compared molecular recognition properties of our optimal compound to oligonucleotides. Studies show that r(CGG)exp’s self-structure is a significant energetic barrier for oligonucleotide binding. A fully modified 2′-OMethyl phosphorothioate is incapable of completely reversing an FXTAS-associated splicing defect and inhibits translation of the downstream ORF, which could have deleterious effects. Taken together, these studies suggest that a small molecule that recognizes structure may be more well suited for targeting highly structured RNAs that require strand invasion by a complementary oligonucleotide. PMID:24506227

Semiparametric Thurstonian Models for Recurrent Choices: A Bayesian Analysis

ERIC Educational Resources Information Center

Ansari, Asim; Iyengar, Raghuram

2006-01-01

We develop semiparametric Bayesian Thurstonian models for analyzing repeated choice decisions involving multinomial, multivariate binary or multivariate ordinal data. Our modeling framework has multiple components that together yield considerable flexibility in modeling preference utilities, cross-sectional heterogeneity and parameter-driven…

Photometric Repeatability of Scanned Imagery: UVIS

NASA Astrophysics Data System (ADS)

Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

2017-08-01

We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

A preliminary estimate of geoid-induced variations in repeat orbit satellite altimeter observations

NASA Technical Reports Server (NTRS)

Brenner, Anita C.; Beckley, B. D.; Koblinsky, C. J.

1990-01-01

Altimeter satellites are often maintained in a repeating orbit to facilitate the separation of sea-height variations from the geoid. However, atmospheric drag and solar radiation pressure cause a satellite orbit to drift. For Geosat this drift causes the ground track to vary by + or - 1 km about the nominal repeat path. This misalignment leads to an error in the estimates of sea surface height variations because of the local slope in the geoid. This error has been estimated globally for the Geosat Exact Repeat Mission using a mean sea surface constructed from Geos 3 and Seasat altimeter data. Over most of the ocean the geoid gradient is small, and the repeat-track misalignment leads to errors of only 1 to 2 cm. However, in the vicinity of trenches, continental shelves, islands, and seamounts, errors can exceed 20 cm. The estimated error is compared with direct estimates from Geosat altimetry, and a strong correlation is found in the vicinity of the Tonga and Aleutian trenches. This correlation increases as the orbit error is reduced because of the increased signal-to-noise ratio.

Simultaneous entanglement swapping of multiple orbital angular momentum states of light.

PubMed

Zhang, Yingwen; Agnew, Megan; Roger, Thomas; Roux, Filippus S; Konrad, Thomas; Faccio, Daniele; Leach, Jonathan; Forbes, Andrew

2017-09-21

High-bit-rate long-distance quantum communication is a proposed technology for future communication networks and relies on high-dimensional quantum entanglement as a core resource. While it is known that spatial modes of light provide an avenue for high-dimensional entanglement, the ability to transport such quantum states robustly over long distances remains challenging. To overcome this, entanglement swapping may be used to generate remote quantum correlations between particles that have not interacted; this is the core ingredient of a quantum repeater, akin to repeaters in optical fibre networks. Here we demonstrate entanglement swapping of multiple orbital angular momentum states of light. Our approach does not distinguish between different anti-symmetric states, and thus entanglement swapping occurs for several thousand pairs of spatial light modes simultaneously. This work represents the first step towards a quantum network for high-dimensional entangled states and provides a test bed for fundamental tests of quantum science.Entanglement swapping in high dimensions requires large numbers of entangled photons and consequently suffers from low photon flux. Here the authors demonstrate entanglement swapping of multiple spatial modes of light simultaneously, without the need for increasing the photon numbers with dimension.

[Multiple mere exposure effect: category evaluation measured in the Go/No-go association task (GNAT)].

PubMed

Kawakami, Naoaki; Yoshida, Fujio

2011-12-01

The effect on likability of multiple subliminal exposures to the same person was investigated. Past studies on the mere exposure effect indicated a correlation between the frequency of repeated exposure to the same stimulus and likability. We proposed that exposure to various stimuli of the same person would have a stronger effect on likability. Participants were subliminally exposed to photographs of a person's face taken from seven angles (multi-angle-exposure) three times each (Experiment 1), or photographs of a person with seven facial expressions (multi-expression-exposure) three times each (Experiment 2). Then, the likability toward the exposed person was measured using the Go/No-go Association Task. The results indicated that the effect of the multiple exposures from various angles was equivalent to exposure to only one full-face photograph shown 21 times (Experiment 1). Moreover, likability was significantly higher in the case of exposure to various facial expressions than for exposure to only a single facial expression (Experiment 2). The results suggest that exposure to various stimuli in a category is more effective than repeated exposure to a single stimulus for increasing likability.

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

PubMed

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

2013-11-01

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

Electromagnetic fields in small systems from a multiphase transport model

NASA Astrophysics Data System (ADS)

Zhao, Xin-Li; Ma, Yu-Gang; Ma, Guo-Liang

2018-02-01

We calculate the electromagnetic fields generated in small systems by using a multiphase transport (AMPT) model. Compared to A +A collisions, we find that the absolute electric and magnetic fields are not small in p +Au and d +Au collisions at energies available at the BNL Relativistic Heavy Ion Collider and in p +Pb collisions at energies available at the CERN Large Hadron Collider. We study the centrality dependencies and the spatial distributions of electromagnetic fields. We further investigate the azimuthal fluctuations of the magnetic field and its correlation with the fluctuating geometry using event-by-event simulations. We find that the azimuthal correlation 〈" close="〉cos(ϕα+ϕβ-2 ΨRP)〉">cos2 (ΨB-Ψ2) between the magnetic field direction and the second-harmonic participant plane is almost zero in small systems with high multiplicities, but not in those with low multiplicities. This indicates that the charge azimuthal correlation is not a valid probe to study the chiral magnetic effect (CME) in small systems with high multiplicities. However, we suggest searching for possible CME effects in small systems with low multiplicities.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans.

PubMed

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q; Otrakji, Alexi; Kalra, Mannudeep K; Xu, X George; Liu, Bob

2014-09-01

To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8%-25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2±3.3 and 16.5±2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.

Pharmacological enhancement of calcium-activated potassium channel function reduces the effects of repeated stress on fear memory

PubMed Central

Atchley, Derek; Hankosky, Emily R.; Gasparotto, Kaylyn; Rosenkranz, J. Amiel

2012-01-01

Repeated stress impacts emotion, and can induce mood and anxiety disorders. These disorders are characterized by imbalance of emotional responses. The amygdala is fundamental in expression of emotion, and is hyperactive in many patients with mood or anxiety disorders. Stress also leads to hyperactivity of the amygdala in humans. In rodent studies, repeated stress causes hyperactivity of the amygdala, and increases fear conditioning behavior that is mediated by the basolateral amygdala (BLA). Calcium-activated potassium (KCa) channels regulate BLA neuronal activity, and evidence suggests reduced small conductance KCa (SK) channel function in male rats exposed to repeated stress. Pharmacological enhancement of SK channels reverses the BLA neuronal hyperexcitability caused by repeated stress. However, it is not known if pharmacological targeting of SK channels can repair the effects of repeated stress on amygdala-dependent behaviors. The purpose of this study was to test whether enhancement of SK channel function reverses the effects of repeated restraint on BLA-dependent auditory fear conditioning. We found that repeated restraint stress increased the expression of cued conditioned fear in male rats. However, 1-EBIO (1 or 10 mg/kg) or CyPPA (5 mg/kg) administered 30 minutes prior to testing of fear expression brought conditioned freezing to control levels, with little impact on fear expression in control handled rats. These results demonstrate that enhancement of SK channel function can reduce the abnormalities of BLA-dependent fear memory caused by repeated stress. Furthermore, this indicates that pharmacological targeting of SK channels may provide a novel target for alleviation of psychiatric symptoms associated with amygdala hyperactivity. PMID:22487247

Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

PubMed

van den Broek, Walther J A A; Nelen, Marcel R; Wansink, Derick G; Coerwinkel, Marga M; te Riele, Hein; Groenen, Patricia J T A; Wieringa, Bé

2002-01-15

The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown. Most likely, long repeats exert toxicity at the level of nuclear RNA transport or splicing. Here, we analyse cis- and trans-acting parameters that determine repeat behaviour in novel mouse models for DM1. Our mice carry 'humanized' myotonic dystrophy protein kinase (Dmpk) allele(s) with either a (CTG)84 or a (CTG)11 repeat, inserted at the correct position into the endogenous DM locus. Unlike in the human situation, the (CTG)84 repeat in the syntenic mouse environment was relatively stable during intergenerational segregation. However, somatic tissues showed substantial repeat expansions which were progressive upon aging and prominent in kidney, and in stomach and small intestine, where it was cell-type restricted. Other tissues examined showed only marginal size changes. The (CTG)11 allele was completely stable, as anticipated. Introducing the (CTG)84 allele into an Msh3-deficient background completely blocked the somatic repeat instability. In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions. Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6.

Human telomeres that contain (CTAGGG)n repeats show replication dependent instability in somatic cells and the male germline

PubMed Central

Mendez-Bermudez, Aaron; Hills, Mark; Pickett, Hilda A.; Phan, Anh Tuân; Mergny, Jean-Louis; Riou, Jean-François; Royle, Nicola J.

2009-01-01

A number of different processes that impact on telomere length dynamics have been identified but factors that affect the turnover of repeats located proximally within the telomeric DNA are poorly defined. We have identified a particular repeat type (CTAGGG) that is associated with an extraordinarily high mutation rate (20% per gamete) in the male germline. The mutation rate is affected by the length and sequence homogeneity of the (CTAGGG)n array. This level of instability was not seen with other sequence-variant repeats, including the TCAGGG repeat type that has the same composition. Telomeres carrying a (CTAGGG)n array are also highly unstable in somatic cells with the mutation process resulting in small gains or losses of repeats that also occasionally result in the deletion of the whole (CTAGGG)n array. These sequences are prone to quadruplex formation in vitro but adopt a different topology from (TTAGGG)n (see accompanying article). Interestingly, short (CTAGGG)2 oligonucleotides induce a DNA damage response (γH2AX foci) as efficiently as (TTAGGG)2 oligos in normal fibroblast cells, suggesting they recruit POT1 from the telomere. Moreover, in vitro assays show that (CTAGGG)n repeats bind POT1 more efficiently than (TTAGGG)n or (TCAGGG)n. We estimate that 7% of human telomeres contain (CTAGGG)n repeats and when present, they create additional problems that probably arise during telomere replication. PMID:19656953

Characterization of small RNA populations in non-transgenic and aflatoxin-reducing-transformed peanut.

PubMed

Power, Imana L; Dang, Phat M; Sobolev, Victor S; Orner, Valerie A; Powell, Joseph L; Lamb, Marshall C; Arias, Renee S

2017-04-01

Aflatoxin contamination is a major constraint in food production worldwide. In peanut (Arachis hypogaea L.), these toxic and carcinogenic aflatoxins are mainly produced by Aspergillus flavus Link and A. parasiticus Speare. The use of RNA interference (RNAi) is a promising method to reduce or prevent the accumulation of aflatoxin in peanut seed. In this study, we performed high-throughput sequencing of small RNA populations in a control line and in two transformed peanut lines that expressed an inverted repeat targeting five genes involved in the aflatoxin-biosynthesis pathway and that showed up to 100% less aflatoxin B 1 than the controls. The objective was to determine the putative involvement of the small RNA populations in aflatoxin reduction. In total, 41 known microRNA (miRNA) families and many novel miRNAs were identified. Among those, 89 known and 10 novel miRNAs were differentially expressed in the transformed lines. We furthermore found two small interfering RNAs derived from the inverted repeat, and 39 sRNAs that mapped without mismatches to the genome of A. flavus and were present only in the transformed lines. This information will increase our understanding of the effectiveness of RNAi and enable the possible improvement of the RNAi technology for the control of aflatoxins. Copyright © 2017 Elsevier B.V. All rights reserved.

Validity of four approaches of using repeaters' MCAT scores in medical school admissions to predict USMLE Step 1 total scores.

PubMed

Zhao, Xiaohui; Oppler, Scott; Dunleavy, Dana; Kroopnick, Marc

2010-10-01

This study investigated the validity of four approaches (the average, most recent, highest-within-administration, and highest-across-administration approaches) of using repeaters' Medical College Admission Test (MCAT) scores to predict Step 1 scores. Using the differential predication method, this study investigated the magnitude of differences in the expected Step 1 total scores between MCAT nonrepeaters and three repeater groups (two-time, three-time, and four-time test takers) for the four scoring approaches. For the average score approach, matriculants with the same MCAT average are expected to achieve similar Step 1 total scores regardless of whether the individual attempted the MCAT exam one or multiple times. For the other three approaches, repeaters are expected to achieve lower Step 1 scores than nonrepeaters; for a given MCAT score, as the number of attempts increases, the expected Step 1 decreases. The effect was strongest for the highest-across-administration approach, followed by the highest-within-administration approach, and then the most recent approach. Using the average score is the best approach for considering repeaters' MCAT scores in medical school admission decisions.

Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip

PubMed Central

Nelson, Gregory M.; Huffman, Holly; Smith, David F.

2003-01-01

Functional steroid receptor complexes are assembled and maintained by an ordered pathway of interactions involving multiple components of the cellular chaperone machinery. Two of these components, Hop and Hip, serve as co-chaperones to the major heat shock proteins (Hsps), Hsp70 and Hsp90, and participate in intermediate stages of receptor assembly. In an effort to better understand the functions of Hop and Hip in the assembly process, we focused on a region of similarity located near the C-terminus of each co-chaperone. Contained within this region is a repeated sequence motif we have termed the DP repeat. Earlier mutagenesis studies implicated the DP repeat of either Hop or Hip in Hsp70 binding and in normal assembly of the co-chaperones with progesterone receptor (PR) complexes. We report here that the DP repeat lies within a protease-resistant domain that extends to or is near the C-terminus of both co-chaperones. Point mutations in the DP repeats render the C-terminal regions hypersensitive to proteolysis. In addition, a Hop DP mutant displays altered proteolytic digestion patterns, which suggest that the DP-repeat region influences the folding of other Hop domains. Although the respective DP regions of Hop and Hip share sequence and structural similarities, they are not functionally interchangeable. Moreover, a double-point mutation within the second DP-repeat unit of Hop that converts this to the sequence found in Hip disrupts Hop function; however, the corresponding mutation in Hip does not alter its function. We conclude that the DP repeats are important structural elements within a C-terminal domain, which is important for Hop and Hip function. PMID:14627198

Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip.

PubMed

Nelson, Gregory M; Huffman, Holly; Smith, David F

2003-01-01

Functional steroid receptor complexes are assembled and maintained by an ordered pathway of interactions involving multiple components of the cellular chaperone machinery. Two of these components, Hop and Hip, serve as co-chaperones to the major heat shock proteins (Hsps), Hsp70 and Hsp90, and participate in intermediate stages of receptor assembly. In an effort to better understand the functions of Hop and Hip in the assembly process, we focused on a region of similarity located near the C-terminus of each co-chaperone. Contained within this region is a repeated sequence motif we have termed the DP repeat. Earlier mutagenesis studies implicated the DP repeat of either Hop or Hip in Hsp70 binding and in normal assembly of the co-chaperones with progesterone receptor (PR) complexes. We report here that the DP repeat lies within a protease-resistant domain that extends to or is near the C-terminus of both co-chaperones. Point mutations in the DP repeats render the C-terminal regions hypersensitive to proteolysis. In addition, a Hop DP mutant displays altered proteolytic digestion patterns, which suggest that the DP-repeat region influences the folding of other Hop domains. Although the respective DP regions of Hop and Hip share sequence and structural similarities, they are not functionally interchangeable. Moreover, a double-point mutation within the second DP-repeat unit of Hop that converts this to the sequence found in Hip disrupts Hop function; however, the corresponding mutation in Hip does not alter its function. We conclude that the DP repeats are important structural elements within a C-terminal domain, which is important for Hop and Hip function.