Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.

PubMed

Di Giovanni, Valeria; Walker, Kenneth A; Bushnell, Daniel; Schaefer, Caitlin; Sims-Lucas, Sunder; Puri, Pawan; Bates, Carlton M

2015-04-01

Previous studies using transgenic Pax3cre mice have revealed roles for fibroblast growth factor receptors (Fgfrs) and Fgfr substrate 2α (Frs2α) signaling in early metanephric mesenchyme patterning and in ureteric morphogenesis. The role of Fgfr/Frs2α signaling in nephron progenitors is unknown. Thus, we generated mouse models using BAC transgenic Six2EGFPcre (Six2cre) mediated deletion of Fgfrs and/or Frs2α in nephron progenitors. Six2cre mediated deletion of Fgfr1 or Fgfr2 alone led to no obvious kidney defects. Six2creFgfr1(flox/flox)Fgfr2(flox/flox) (Fgfr1/2(NP-/-)) mice generate a discernable kidney; however, they develop nephron progenitor depletion starting at embryonic day 12.5 (E12.5) and later demonstrate severe cystic dysplasia. To determine the role of Frs2α signaling downstream of Fgfr2 in Fgfr1/2(NP-/-) mice, we generated Six2cre(,)Fgfr1(flox/flox)Fgfr2(LR/LR) (Fgfr1(NP-/-)Fgfr2(LR/LR)) mice that have point mutations in the Frs2α binding site of Fgfr2. Like Fgfr1/2(NP-/-) mice, Fgfr1(NP-/-)Fgfr2(LR/LR) develop nephron progenitor depletion, but it does not start until E14.5 and older mice have less severe cystic dysplasia than Fgfr1/2(NP-/-) To determine the role of Frs2α alone in nephron progenitors, we generated Six2creFrs2'A(flox/flox) (Frs2a(NP-/-)) mice. Frs2a(NP-/-)mice also develop nephron progenitor depletion and renal cysts, although these occurred later and were less severe than in the other Six2cre mutant mice. The nephron progenitor loss in all Six2cre mutant lines was associated with decreased Cited1 expression and increased apoptosis versus controls. FAC-sorted nephron progenitors in Six2cre Frs2'A(flox/flox) mice demonstrated evidence of increased Notch activity versus controls, which likely drives the progenitor defects. Thus, Fgfr1 and Fgfr2 have synergistic roles in maintaining nephron progenitors; furthermore, Fgfr signaling in nephron progenitors appears to be mediated predominantly by Frs2α. Copyright © 2015 Elsevier Inc. All rights reserved.

Corona Enhancement and Mosaic Architecture for Prognosis and Selection Between of Liver Resection Versus Transcatheter Arterial Chemoembolization in Single Hepatocellular Carcinomas >5 cm Without Extrahepatic Metastases

PubMed Central

Li, Meng; Xin, Yongjie; Fu, Sirui; Liu, Zaiyi; Li, Yong; Hu, Baoshan; Chen, Shuting; Liang, Changhong; Lu, Ligong

2016-01-01

Abstract Corona enhancement and mosaic architecture are 2 radiologic features of hepatocellular carcinoma (HCC). However, neither their prognostic values nor their impacts on the selection of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) as treatment modalities have been established. We retrospectively analyzed 275 patients with a single HCC lesion >5 cm without extrahepatic metastasis treated with LR or TACE. In LR patients, the overall survival (OS) and time to progression (TTP) were compared between corona enhancement negative (corona−) versus positive (corona+) and mosaic architecture negative (mosaic−) versus positive (mosaic+) patients. Furthermore, by the combination of corona and mosaic, LR patients were divided into negative for both corona and mosaic patterns (LR−/−), positive for only 1 feature (LR+/−), and positive for both (LR+/+); their OS and TTP were compared to those of the TACE group. Cox regression was performed to identify independent factors for OS. In the survival plots for LR, corona− had better OS and TTP than corona+, and mosaic− had better OS than mosaic+. There was no significant difference in TTP between the subgroups. On Cox regression analysis, corona enhancement, but not mosaic architecture, was a significant factor for OS, whereas neither were a significant factor for TTP. In TACE patients, neither corona nor mosaic patterns had significant correlations with OS or TTP. In the whole population, LR−/ and LR+/− subgroups had similar OS, which was better than the LR+/+ and TACE groups. Moreover, LR−/− and LR+/− patients had better TTP than TACE patients, but there were no differences between the LR−/− versus LR+/−, LR−/ versus LR+/+, LR+/− versus LR+/+, and LR+/+ versus TACE groups. On Cox regression analysis, the presence of corona/mosaic patterns was an independent prognostic factor for OS. Our results showed that, for patients with a single HCC >5 cm without extrahepatic metastasis, corona and mosaic patterns are indicators of limited LR efficacy. When both of the features are present, TACE can be used instead of LR with no negative influence on survival. PMID:26765441

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

CONSERVED ROLES FOR CYTOSKELETAL COMPONENTS IN DETERMINING LATERALITY

PubMed Central

McDowell, Gary S.; Lemire, Joan M.; Paré, Jean-Francois; Cammarata, Garrett; Lowery, Laura Anne; Levin, Michael

2016-01-01

SUMMARY Consistently-biased left-right (LR) patterning is required for the proper placement of organs including the heart and viscera. The LR axis is especially fascinating as an example of multi-scale pattern formation, since here chiral events at the subcellular level are integrated and amplified into asymmetric transcriptional cascades and ultimately into the anatomical patterning of the entire body. In contrast to the other two body axes, there is considerable controversy about the earliest mechanisms of embryonic laterality. Many molecular components of asymmetry have not been widely tested among phyla with diverse bodyplans, and it is unknown whether parallel (redundant) pathways may exist that could reverse abnormal asymmetry states at specific checkpoints in development. To address conservation of the early steps of LR patterning, we used the Xenopus laevis (frog) embryo to functionally test a number of protein targets known to direct asymmetry in plants, fruit fly, and rodent. Using the same reagents that randomize asymmetry in Arabidopsis, Drosophila, and mouse embryos, we show that manipulation of the microtubule and actin cytoskeleton immediately post-fertilization, but not later, results in laterality defects in Xenopus embryos. Moreover, we observed organ-specific randomization effects and a striking dissociation of organ situs from effects on the expression of left side control genes, which parallel data from Drosophila and mouse. Remarkably, some early manipulations that disrupt laterality of transcriptional asymmetry determinants can be subsequently “rescued” by the embryo, resulting in normal organ situs. These data reveal the existence of novel corrective mechanisms, demonstrate that asymmetric expression of Nodal is not a definitive marker of laterality, and suggest the existence of amplification pathways that connect early cytoskeletal processes to control of organ situs bypassing Nodal. Counter to alternative models of symmetry breaking during neurulation (via ciliary structures absent in many phyla), our data suggest a widely-conserved role for the cytoskeleton in regulating left-right axis formation immediately after fertilization of the egg. The novel mechanisms that rescue organ situs, even after incorrect expression of genes previously considered to be left-side master regulators, suggest LR patterning as a new context in which to explore multi-scale redundancy and integration of patterning from the subcellular structure to the entire bodyplan. PMID:26928161

Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

PubMed Central

Vandenberg, Laura N.; Pennarola, Brian W.; Levin, Michael

2011-01-01

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs. PMID:21826245

Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

PubMed

Lenhart, Kari F; Holtzman, Nathalia G; Williams, Jessica R; Burdine, Rebecca D

2013-01-01

Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

Cilia in vertebrate left–right patterning

PubMed Central

Dasgupta, Agnik

2016-01-01

Understanding how left–right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left–right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic ‘left–right organizer’. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left–right organizer, both of which are critical for effective cilia function during left–right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left–right organizer. This suggests the possibility that these cells acquire left–right positional information prior to the appearance of cilia. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821522

Cilia in vertebrate left-right patterning.

PubMed

Dasgupta, Agnik; Amack, Jeffrey D

2016-12-19

Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease.

PubMed

Kathiriya, I S; Srivastava, D

2000-01-01

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

Lateral Root Initiation in Arabidopsis: Developmental Window, Spatial Patterning, Density and Predictability

PubMed Central

DUBROVSKY, J. G.; GAMBETTA, G. A.; HERNÁNDEZ-BARRERA, A.; SHISHKOVA, S.; GONZÁLEZ, I.

2006-01-01

• Background and Aims The basic regulatory mechanisms that control lateral root (LR) initiation are still poorly understood. An attempt is made to characterize the pattern and timing of LR initiation, to define a developmental window in which LR initiation takes place and to address the question of whether LR initiation is predictable. • Methods The spatial patterning of LRs and LR primordia (LRPs) on cleared root preparations were characterized. New measures of LR and LRP densities (number of LRs and/or LRPs divided by the length of the root portions where they are present) were introduced and illustrate the shortcomings of the more customarily used measure through a comparative analysis of the mutant aux1-7. The enhancer trap line J0121 was used to monitor LR initiation in time-lapse experiments and a plasmolysis-based method was developed to determine the number of pericycle cells between successive LRPs. • Key Results LRP initiation occurred strictly acropetally and no de novo initiation events were found between already developed LRs or LRPs. However, LRPs did not become LRs in a similar pattern. The longitudinal spacing of lateral organs was variable and the distance between lateral organs was proportional to the number of cells and the time between initiations of successive LRPs. There was a strong tendency towards alternation in LR initiation between the two pericycle cell files adjacent to the protoxylem poles. LR density increased with time due to the emergence of slowly developing LRPs and appears to be unique for individual Arabidopsis accessions. • Conclusions. In Arabidopsis there is a narrow developmental window for LR initiation, and no specific cell-count or distance-measuring mechanisms have been found that determine the site of successive initiation events. Nevertheless, the branching density and lateral organ density (density of LRs and LRPs) are accession-specific, and based on the latter density the average distance between successive LRs can be predicted. PMID:16390845

Genome-wide association study using deregressed breeding values for cryptorchidism and scrotal/inguinal hernia in two pig lines.

PubMed

Sevillano, Claudia A; Lopes, Marcos S; Harlizius, Barbara; Hanenberg, Egiel H A T; Knol, Egbert F; Bastiaansen, John W M

2015-03-21

Cryptorchidism and scrotal/inguinal hernia are the most frequent congenital defects in pigs. Identification of genomic regions that control these congenital defects is of great interest to breeding programs, both from an animal welfare point of view as well as for economic reasons. The aim of this genome-wide association study (GWAS) was to identify single nucleotide polymorphisms (SNPs) that are strongly associated with these congenital defects. Genotypes were available for 2570 Large White (LW) and 2272 Landrace (LR) pigs. Breeding values were estimated based on 1 359 765 purebred and crossbred male offspring, using a binary trait animal model. Estimated breeding values were deregressed (DEBV) and taken as the response variable in the GWAS. Heritability estimates were equal to 0.26 ± 0.02 for cryptorchidism and to 0.31 ± 0.01 for scrotal/inguinal hernia. Seven and 31 distinct QTL regions were associated with cryptorchidism in the LW and LR datasets, respectively. The top SNP per region explained between 0.96% and 1.10% and between 0.48% and 2.77% of the total variance of cryptorchidism incidence in the LW and LR populations, respectively. Five distinct QTL regions associated with scrotal/inguinal hernia were detected in both LW and LR datasets. The top SNP per region explained between 1.22% and 1.60% and between 1.15% and 1.46% of the total variance of scrotal/inguinal hernia incidence in the LW and LR populations, respectively. For each trait, we identified one overlapping region between the LW and LR datasets, i.e. a region on SSC8 (Sus scrofa chromosome) between 65 and 73 Mb for cryptorchidism and a region on SSC13 between 34 and 37 Mb for scrotal/inguinal hernia. The use of DEBV in combination with a binary trait model was a powerful approach to detect regions associated with difficult traits such as cryptorchidism and scrotal/inguinal hernia that have a low incidence and for which affected animals are generally not available for genotyping. Several novel QTL regions were detected for cryptorchidism and scrotal/inguinal hernia, and for several previously known QTL regions, the confidence interval was narrowed down.

IFT46 plays an essential role in cilia development

PubMed Central

Lee, Mi-Sun; Hwang, Kyu-Seok; Oh, Hyun-Woo; Ji-Ae, Kim; Kim, Hyun-Taek; Cho, Hyun-Soo; Lee, Jeong-Ju; Ko, Je Yeong; Choi, Jung-Hwa; Jeong, Yun-Mi; You, Kwan-Hee; Kim, Joon; Park, Doo-Sang; Nam, Ki-Hoan; Aizawa, Shinichi; Kiyonari, Hiroshi; Shioi, Go; Park, Jong-Hoon; Zhou, Weibin; Kim, Nam-Soon; Kim, Cheol-Hee

2015-01-01

Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer’s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer’s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(−/−) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left-right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development. PMID:25722189

A prospective validation of the IOTA logistic regression models (LR1 and LR2) in comparison to subjective pattern recognition for the diagnosis of ovarian cancer.

PubMed

Nunes, Natalie; Ambler, Gareth; Hoo, Wee-Liak; Naftalin, Joel; Foo, Xulin; Widschwendter, Martin; Jurkovic, Davor

2013-11-01

This study aimed to assess the accuracy of the International Ovarian Tumour Analysis (IOTA) logistic regression models (LR1 and LR2) and that of subjective pattern recognition (PR) for the diagnosis of ovarian cancer. This was a prospective single-center study in a general gynecology unit of a tertiary hospital during 33 months. There were 292 consecutive women who underwent surgery after an ultrasound diagnosis of an adnexal tumor. All examinations were by a single level 2 ultrasound operator, according to the IOTA guidelines. The malignancy likelihood was calculated using the IOTA LR1 and LR2. The women were then examined separately by an expert operator using subjective PR. These were compared to operative findings and histology. The sensitivity, specificity, area under the curve (AUC), and accuracy of the 3 methods were calculated and compared. The AUCs for LR1 and LR2 were 0.94 [95% confidence interval (CI), 0.92-0.97] and 0.93 (95% CI, 0.90-0.96), respectively. Subjective PR gave a positive likelihood ratio (LR+ve) of 13.9 (95% CI, 7.84-24.6) and a LR-ve of 0.049 (95% CI, 0.022-0.107). The corresponding LR+ve and LR-ve for LR1 were 3.33 (95% CI, 2.85-3.55) and 0.03 (95% CI, 0.01-0.10), and for LR2 were 3.58 (95% CI, 2.77-4.63) and 0.052 (95% CI, 0.022-0.123). The accuracy of PR was 0.942 (95% CI, 0.908-0.966), which was significantly higher when compared with 0.829 (95% CI, 0.781-0.870) for LR1 and 0.836 (95% CI, 0.788-0.872) for LR2 (P < 0.001). The AUC of the IOTA LR1 and LR2 were similar in nonexpert's hands when compared to the original and validation IOTA studies. The PR method was the more accurate test to diagnose ovarian cancer than either of the IOTA models.

The V-ATPase accessory protein Atp6ap1b mediates dorsal forerunner cell proliferation and left-right asymmetry in zebrafish.

PubMed

Gokey, Jason J; Dasgupta, Agnik; Amack, Jeffrey D

2015-11-01

Asymmetric fluid flows generated by motile cilia in a transient 'organ of asymmetry' are involved in establishing the left-right (LR) body axis during embryonic development. The vacuolar-type H(+)-ATPase (V-ATPase) proton pump has been identified as an early factor in the LR pathway that functions prior to cilia, but the role(s) for V-ATPase activity are not fully understood. In the zebrafish embryo, the V-ATPase accessory protein Atp6ap1b is maternally supplied and expressed in dorsal forerunner cells (DFCs) that give rise to the ciliated organ of asymmetry called Kupffer's vesicle (KV). V-ATPase accessory proteins modulate V-ATPase activity, but little is known about their functions in development. We investigated Atp6ap1b and V-ATPase in KV development using morpholinos, mutants and pharmacological inhibitors. Depletion of both maternal and zygotic atp6ap1b expression reduced KV organ size, altered cilia length and disrupted LR patterning of the embryo. Defects in other ciliated structures-neuromasts and olfactory placodes-suggested a broad role for Atp6ap1b during development of ciliated organs. V-ATPase inhibitor treatments reduced KV size and identified a window of development in which V-ATPase activity is required for proper LR asymmetry. Interfering with Atp6ap1b or V-ATPase function reduced the rate of DFC proliferation, which resulted in fewer ciliated cells incorporating into the KV organ. Analyses of pH and subcellular V-ATPase localizations suggested Atp6ap1b functions to localize the V-ATPase to the plasma membrane where it regulates proton flux and cytoplasmic pH. These results uncover a new role for the V-ATPase accessory protein Atp6ap1b in early development to maintain the proliferation rate of precursor cells needed to construct a ciliated KV organ capable of generating LR asymmetry. Copyright © 2015 Elsevier Inc. All rights reserved.

The V-ATPase accessory protein Atp6ap1b mediates dorsal forerunner cell proliferation and left-right asymmetry in zebrafish

PubMed Central

Gokey, Jason J.; Dasgupta, Agnik; Amack, Jeffrey D.

2015-01-01

Asymmetric fluid flows generated by motile cilia in a transient ‘organ of asymmetry’ are involved in establishing the left-right (LR) body axis during embryonic development. The vacuolar-type H+-ATPase (V-ATPase) proton pump has been identified as an early factor in the LR pathway that functions prior to cilia, but the role(s) for V-ATPase activity are not fully understood. In the zebrafish embryo, the V-ATPase accessory protein Atp6ap1b is maternally supplied and expressed in dorsal forerunner cells (DFCs) that give rise to the ciliated organ of asymmetry called Kupffer’s vesicle (KV). V-ATPase accessory proteins modulate V-ATPase activity, but little is known about their functions in development. We investigated Atp6ap1b and V-ATPase in KV development using morpholinos, mutants and pharmacological inhibitors. Depletion of both maternal and zygotic atp6ap1b expression reduced KV organ size, altered cilia length and disrupted LR patterning of the embryo. Defects in other ciliated structures—neuromasts and olfactory placodes—suggested a broad role for Atp6ap1b during development of ciliated organs. V-ATPase inhibitor treatments reduced KV size and identified a window of development in which V-ATPase activity is required for proper LR asymmetry. Interfering with Atp6ap1b or V-ATPase function reduced the rate of DFC proliferation, which resulted in fewer ciliated cells incorporating into the KV organ. Analyses of pH and subcellular V-ATPase localizations suggested Atp6ap1b functions to localize the V-ATPase to the plasma membrane where it regulates proton flux and cytoplasmic pH. These results uncover a new role for the V-ATPase accessory protein Atp6ap1b in early development to maintain the proliferation rate of precursor cells needed to construct a ciliated KV organ capable of generating LR asymmetry. PMID:26254189

The signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis

PubMed Central

Gao, Qian; Zhang, Junfeng; Wang, Xiumei; Liu, Ying; He, Rongqiao; Liu, Xingfeng; Wang, Fei; Feng, Jing; Yang, Dongling; Wang, Zhaoqing; Meng, Anming; Yan, Xiyun

2017-01-01

The apical–basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK. We find that MCAM-mediated vesicular trafficking towards FGF4, while generating a priority-grade transcriptional response of NFAT determines lumenogenesis. We demonstrate that MCAM plays indispensable roles in ciliogenesis through activating JNK independently of FGF signals. Furthermore, mcam-deficient zebrafish and Xenopus exhibit a global defect in left-right (LR) asymmetric establishment as a result of morphogenetic failure of their LR organizers. Therefore, MCAM coordination of AB polarity and PCP provides insight into the general mechanisms of morphogenesis. PMID:28589943

Solar photo-Fenton treatment of microcystin-LR in aqueous environment: Transformation products and toxicity in different water matrices

EPA Science Inventory

Transformation products and toxicity patterns of microcystin-LR (MC-LR), a common cyanotoxin in freshwaters, during degradation by solar photo-Fenton process were studied in the absence and presence of two major water components, namely fulvic acid and alkalinity. The transformat...

DNA damage inhibits lateral root formation by up-regulating cytokinin biosynthesis genes in Arabidopsis thaliana.

PubMed

Davis, La Ode Muhammad Muchdar; Ogita, Nobuo; Inagaki, Soichi; Takahashi, Naoki; Umeda, Masaaki

2016-11-01

Lateral roots (LRs) are an important organ for water and nutrient uptake from soil. Thus, control of LR formation is crucial in the adaptation of plant growth to environmental conditions. However, the underlying mechanism controlling LR formation in response to external factors has remained largely unknown. Here, we found that LR formation was inhibited by DNA damage. Treatment with zeocin, which causes DNA double-strand breaks, up-regulated several DNA repair genes in the LR primordium (LRP) through the signaling pathway mediated by the transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1). Cell division was severely inhibited in the LRP of zeocin-treated sog1-1 mutant, which in turn inhibited LR formation. This result suggests that SOG1-mediated maintenance of genome integrity is crucial for proper cell division during LRP development. Furthermore, zeocin induced several cytokinin biosynthesis genes in a SOG1-dependent manner, thereby activating cytokinin signaling in the LRP. LR formation was less inhibited by zeocin in mutants defective in cytokinin biosynthesis or signaling, suggesting that elevated cytokinin signaling is crucial for the inhibition of LR formation in response to DNA damage. We conclude that SOG1 regulates DNA repair and cytokinin signaling separately and plays a key role in controlling LR formation under genotoxic stress. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination

PubMed Central

Grimes, Daniel T.; Keynton, Jennifer L.; Buenavista, Maria T.; Jin, Xingjian; Patel, Saloni H.; Kyosuke, Shinohara; Williams, Debbie J.; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M.; Norris, Dominic P.

2016-01-01

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo. PMID:27272319

The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis Formation and Heart Development

PubMed Central

2017-01-01

The formation of the asymmetric left-right (LR) body axis is one of the fundamental aspects of vertebrate embryonic development, and one still raising passionate discussions among scientists. Although the conserved role of nodal is unquestionable in this process, several of the details around this signaling cascade are still unanswered. To further understand this mechanism, we have been studying Cerberus-like 2 (Cerl2), an inhibitor of Nodal, and its role in the generation of asymmetries in the early vertebrate embryo. The absence of Cerl2 results in a wide spectrum of malformations commonly known as heterotaxia, which comprises defects in either global organ position (e.g., situs inversus totalis), reversed orientation of at least one organ (e.g., situs ambiguus), and mirror images of usually asymmetric paired organs (e.g., left or right isomerisms of the lungs). Moreover, these laterality defects are frequently associated with congenital heart diseases (e.g., transposition of the great arteries, or atrioventricular septal defects). Here, reviewing the knowledge on the establishment of LR asymmetry in mouse embryos, the emerging conclusion is that as necessary as is the activation of the Nodal signaling cascade, the tight control that Cerl2-mediates on Nodal signaling is equally important, and that generates a further regionalized LR genetic program in the proper time and space. PMID:29367552

Intramuscular Distribution of the Abducens Nerve in the Lateral Rectus Muscle for the Management of Strabismus.

PubMed

Shin, Hyun Jin; Lee, Shin-Hyo; Shin, Kang-Jae; Koh, Ki-Seok; Song, Wu-Chul

2018-06-01

To elucidate the intramuscular distribution and branching patterns of the abducens nerve in the lateral rectus (LR) muscle so as to provide anatomical confirmation of the presence of compartmentalization, including for use in clinical applications such as botulinum toxin injections. Thirty whole-mount human cadaver specimens were dissected and then Sihler's stain was applied. The basic dimensions of the LR and its intramuscular nerve distribution were investigated. The distances from the muscle insertion to the point at which the abducens nerve enters the LR and to the terminal nerve plexus were also measured. The LR was 46.0 mm long. The abducens nerve enters the muscle on the posterior one-third of the LR and then typically divides into a few branches (average of 1.8). This supports a segregated abducens nerve selectively innervating compartments of the LR. The intramuscular nerve distribution showed a Y-shaped ramification with root-like arborization. The intramuscular nerve course finished around the middle of the LR (24.8 mm posterior to the insertion point) to form the terminal nerve plexus. This region should be considered the optimal target site for botulinum toxin injections. We have also identified the presence of an overlapping zone and communicating nerve branches between the neighboring LR compartments. Sihler's staining is a useful technique for visualizing the entire nerve network of the LR. Improving the knowledge of the nerve distribution patterns is important not only for researchers but also clinicians to understand the functions of the LR and the diverse pathophysiology of strabismus.

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning

PubMed Central

Fakhro, Khalid A.; Choi, Murim; Ware, Stephanie M.; Belmont, John W.; Towbin, Jeffrey A.; Lifton, Richard P.; Khokha, Mustafa K.; Brueckner, Martina

2011-01-01

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10−4). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10−6). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning. PMID:21282601

Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning.

PubMed

Fakhro, Khalid A; Choi, Murim; Ware, Stephanie M; Belmont, John W; Towbin, Jeffrey A; Lifton, Richard P; Khokha, Mustafa K; Brueckner, Martina

2011-02-15

Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10(-4)). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10(-6)). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning.

[Analysis of methylation-sensitive amplified polymorphism in wheat genome under the wheat leaf rust stress].

PubMed

Fu, Sheng-Jie; Wang, Hui; Feng, Li-Na; Sun, Yi; Yang, Wen-Xiang; Liu, Da-Qun

2009-03-01

Intrinsic DNA methylation pattern is an integral component of the epigenetic network in many eukaryotes. DNA methylation plays an important role in regulating gene expression in eukaryotes. Biological stress in plant provides an inherent epigenetic driving force of evolution. Study of DNA methylation patterns arising from biological stress will help us fully understand the epigenetic regulation of gene expression and DNA methylation of biological functions. The wheat near-isogenic lines TcLr19 and TcLr41 were resistant to races THTT and TKTJ, respectively, and Thatcher is compatible in the interaction with Puccinia triticina THTT and TKTJ, respectively. By means of methylation-sensitive amplified polymorphism (MSAP) analysis, the patterns of cytosine methylation in TcLr19, TcLr41, and Thatcher inoculated with P. triticina THTT and TKTJ were compared with those of the untreated samples. All the DNA fragments, each representing a recognition site cleaved by each or both of isoschizomers, were amplified using 60 pairs of selective primers. The results indicated that there was no significant difference between the challenged and unchallenged plants at DNA methylation level. However, epigenetic difference between the near-isogenic line for wheat leaf rust resistance gene Lr41 and Thatcher was present.

Elimination patterns

MedlinePlus

... urethra. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... disorders. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Left‐right asymmetry in the light of TOR: An update on what we know so far

PubMed Central

Casar Tena, Teresa

2015-01-01

The internal left‐right (LR) asymmetry is a characteristic that exists throughout the animal kingdom from roundworms over flies and fish to mammals. Cilia, which are antenna‐like structures protruding into the extracellular space, are involved in establishing LR asymmetry during early development. Humans who suffer from dysfunctional cilia often develop conditions such as heterotaxy, where internal organs appear to be placed randomly. As a consequence to this failure in asymmetry development, serious complications such as congenital heart defects (CHD) occur. The mammalian (or mechanistic) target of rapamycin (mTOR) pathway has recently emerged as an important regulator regarding symmetry breaking. The mTOR pathway governs fundamental processes such as protein translation or metabolism. Its activity can be transduced by two complexes, which are called TORC1 and TORC2, respectively. So far, only TORC1 has been implicated with asymmetry development and appears to require very precise regulation. A number of recent papers provided evidence that dysregulated TORC1 results in alterations of motile cilia and asymmetry defects. In here, we give an update on what we know so far of mTORC1 in LR asymmetry development. PMID:25943139

Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality

PubMed Central

Raymond, Michael J.; Ray, Poulomi; Kaur, Gurleen; Fredericks, Michael; Singh, Ajay V.; Wan, Leo Q.

2016-01-01

Intrinsic cell chirality has been implicated in the left-right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels. PMID:28360944

Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality.

PubMed

Raymond, Michael J; Ray, Poulomi; Kaur, Gurleen; Fredericks, Michael; Singh, Ajay V; Wan, Leo Q

2017-02-01

Intrinsic cell chirality has been implicated in the left-right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels.

The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ.

PubMed

Compagnon, Julien; Barone, Vanessa; Rajshekar, Srivarsha; Kottmeier, Rita; Pranjic-Ferscha, Kornelija; Behrndt, Martin; Heisenberg, Carl-Philipp

2014-12-22

Kupffer's vesicle (KV) is the zebrafish organ of laterality, patterning the embryo along its left-right (LR) axis. Regional differences in cell shape within the lumen-lining KV epithelium are essential for its LR patterning function. However, the processes by which KV cells acquire their characteristic shapes are largely unknown. Here, we show that the notochord induces regional differences in cell shape within KV by triggering extracellular matrix (ECM) accumulation adjacent to anterior-dorsal (AD) regions of KV. This localized ECM deposition restricts apical expansion of lumen-lining epithelial cells in AD regions of KV during lumen growth. Our study provides mechanistic insight into the processes by which KV translates global embryonic patterning into regional cell shape differences required for its LR symmetry-breaking function. Copyright © 2014 Elsevier Inc. All rights reserved.

Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells.

PubMed

Takumi, Shota; Ikema, Satoshi; Hanyu, Tamami; Shima, Yusuke; Kurimoto, Takashi; Shiozaki, Kazuhiro; Sugiyama, Yasumasa; Park, Ho-Dong; Ando, Seiichi; Furukawa, Tatsuhiko; Komatsu, Masaharu

2015-03-01

Microcystin-LR, which is an inhibitor of serine/threonine protein phosphatase (PP)1 and PP2A, induces liver injury by its selective uptake system into the hepatocyte. It is also thought that microcystin-LR induces reactive oxygen species (ROS). We tried to establish the chemical prevention of microcystin-LR poisoning. We investigated the effect of grapefruit flavanone glycoside naringin on cytotoxicity of microcystin-LR using human hepatocyte uptake transporter OATP1B3-expressing HEK293-OATP1B3 cells. We found cytotoxicity of microcystin-LR was attenuated by naringin in a dose dependent manner. The inhibition magnitude of total cellular serine/threonine protein phosphatase activity induced by microcystin-LR was suppressed by naringin. In addition, uptake of microcystin-LR into HEK293-OATP1B3 cells was inhibited by naringin. Furthermore, microcystin-LR induced phosphorylation of p53 was inhibited by naringin. Regardless of the difference in the exposure pattern of pre-processing and post-processing of naringin, the toxicity of microcystin-LR was comparable. These results suggested that naringin is promising remedy as well as preventive medicine for liver damage with microcystin-LR. In addition, involvement of ROS production after exposure to the sublethal concentrations of microcystin-LR in the onset of cytotoxicity was negligible. Therefore, inhibition of microcystin-LR uptake and the pathway other than ROS production would be involved in the effect of naringin on the attenuation of microcystin-LR toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Mis-Spliced Lr34 Transcript Events in Winter Wheat.

PubMed

Fang, Tilin; Carver, Brett F; Hunger, Robert M; Yan, Liuling

2017-01-01

Lr34 in wheat is a non-race-specific gene that confers resistance against multiple fungal pathogens. The resistant allele Lr34 and the susceptible allele Lr34s can be distinguished by three polymorphisms that cause alternation of deduced amino acid sequences of Lr34 at the protein level. In seedlings of a cultivar carrying the resistant Lr34r allele, only a portion (35%) of its transcripts was correctly spliced and the majority (65%) of its transcripts were incorrectly spliced due to multiple mis-splicing events. Lr34 mis-splicing events were also observed at adult plant age when this gene exerts its function. All of the mis-spliced Lr34r cDNA transcripts observed in this study resulted in a premature stop codon due to a shift of the open reading frame; hence, the mis-spliced Lr34r cDNAs were deduced to encode incomplete proteins. Even if a cultivar has a functional Lr34 gene, its transcripts might not completely splice in a correct pattern. These findings suggested that the partial resistance conferred by a quantitative gene might be due to mis-splicing events in its transcripts; hence, the resistance of the gene could be increased by eliminating or mutating regulators that cause mis-splicing events in wheat.

Auxin distribution is differentially affected by nitrate in roots of two rice cultivars differing in responsiveness to nitrogen

PubMed Central

Song, Wenjing; Sun, Huwei; Li, Jiao; Gong, Xianpo; Huang, Shuangjie; Zhu, Xudong; Zhang, Yali; Xu, Guohua

2013-01-01

Background and Aims Although ammonium (NH4+) is the preferred form of nitrogen over nitrate (NO3−) for rice (Oryza sativa), lateral root (LR) growth in roots is enhanced by partial NO3− nutrition (PNN). The roles of auxin distribution and polar transport in LR formation in response to localized NO3− availability are not known. Methods Time-course studies in a split-root experimental system were used to investigate LR development patterns, auxin distribution, polar auxin transport and expression of auxin transporter genes in LR zones in response to localized PNN in ‘Nanguang’ and ‘Elio’ rice cultivars, which show high and low responsiveness to NO3−, respectively. Patterns of auxin distribution and the effects of polar auxin transport inhibitors were also examined in DR5::GUS transgenic plants. Key Results Initiation of LRs was enhanced by PNN after 7 d cultivation in ‘Nanguang’ but not in ‘Elio’. Auxin concentration in the roots of ‘Nanguang’ increased by approx. 24 % after 5 d cultivation with PNN compared with NH4+ as the sole nitrogen source, but no difference was observed in ‘Elio’. More auxin flux into the LR zone in ‘Nanguang’ roots was observed in response to NO3− compared with NH4+ treatment. A greater number of auxin influx and efflux transporter genes showed increased expression in the LR zone in response to PNN in ‘Nanguang’ than in ‘Elio’. Conclusions The results indicate that higher NO3− responsiveness is associated with greater auxin accumulation in the LR zone and is strongly related to a higher rate of LR initiation in the cultivar ‘Nanguang’. PMID:24095838

Salient features of the ciliated organ of asymmetry

PubMed Central

Amack, Jeffrey D.

2014-01-01

Many internal organs develop distinct left and right sides that are essential for their functions. In several vertebrate embryos, motile cilia generate an asymmetric fluid flow that plays an important role in establishing left-right (LR) signaling cascades. These ‘LR cilia’ are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer’s vesicle in teleost fish. I consider these transient ciliated structures as the ‘organ of asymmetry’ that directs LR patterning of the developing embryo. Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination. Here, I review current models for how LR asymmetry is established in vertebrates, discuss the cellular architecture of the ciliated organ of asymmetry and then propose key features of this organ that are critical for orienting the LR body axis. PMID:24481178

Cell chirality: emergence of asymmetry from cell culture.

PubMed

Wan, Leo Q; Chin, Amanda S; Worley, Kathryn E; Ray, Poulomi

2016-12-19

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left-right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

Cell chirality: emergence of asymmetry from cell culture

PubMed Central

Wan, Leo Q.; Chin, Amanda S.; Worley, Kathryn E.; Ray, Poulomi

2016-01-01

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left–right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821525

The myosin ID pathway and left-right asymmetry in Drosophila.

PubMed

Géminard, Charles; González-Morales, Nicanor; Coutelis, Jean-Baptiste; Noselli, Stéphane

2014-06-01

Drosophila is a classical model to study body patterning, however left-right (L/R) asymmetry had remained unexplored, until recently. The discovery of the conserved myosin ID gene as a major determinant of L/R asymmetry has revealed a novel L/R pathway involving the actin cytoskeleton and the adherens junction. In this process, the HOX gene Abdominal-B plays a major role through the control of myosin ID expression and therefore symmetry breaking. In this review, we present organs and markers showing L/R asymmetry in Drosophila and discuss our current understanding of the underlying molecular genetic mechanisms. Drosophila represents a valuable model system revealing novel strategies to establish L/R asymmetry in invertebrates and providing an evolutionary perspective to the problem of laterality in bilateria. © 2014 Wiley Periodicals, Inc.

Three-Dimensional Biomechanical Analysis of Rearfoot and Forefoot Running.

PubMed

Knorz, Sebastian; Kluge, Felix; Gelse, Kolja; Schulz-Drost, Stefan; Hotfiel, Thilo; Lochmann, Matthias; Eskofier, Björn; Krinner, Sebastian

2017-07-01

In the running community, a forefoot strike (FFS) pattern is increasingly preferred compared with a rearfoot strike (RFS) pattern. However, it has not been fully understood which strike pattern may better reduce adverse joint forces within the different joints of the lower extremity. To analyze the 3-dimensional (3D) stress pattern in the ankle, knee, and hip joint in runners with either a FFS or RFS pattern. Descriptive laboratory study. In 22 runners (11 habitual rearfoot strikers, 11 habitual forefoot strikers), RFS and FFS patterns were compared at 3.0 m/s (6.7 mph) on a treadmill with integrated force plates and a 3D motion capture analysis system. This combined analysis allowed characterization of the 3D biomechanical forces differentiated for the ankle, knee, and hip joint. The maximum peak force (MPF) and maximum loading rate (LR) were determined in their 3 ordinal components: vertical, anterior-posterior (AP), and medial-lateral (ML). For both strike patterns, the vertical components of the MPF and LR were significantly greater than their AP or ML components. In the vertical axis, FFS was generally associated with a greater MPF but significantly lower LR in all 3 joints. The AP components of MPF and LR were significantly lower for FFS in the knee joint but significantly greater in the ankle and hip joints. The ML components of MPF and LR tended to be greater for FFS but mostly did not reach a level of significance. FFS and RFS were associated with different 3D stress patterns in the ankle, knee, and hip joint, although there was no global advantage of one strike pattern over the other. The multimodal individual assessment for the different anatomic regions demonstrated that FFS seems favorable for patients with unstable knee joints in the AP axis and RFS may be recommended for runners with unstable ankle joints. Different strike patterns show different 3D stress in joints of the lower extremity. Due to either rehabilitation after injuries or training in running sports, rearfoot or forefoot running should be preferred to prevent further damage or injuries caused by inadequate biomechanical load. Runners with a history of knee joint injuries may benefit from FFS whereas RFS may be favorable for runners with a history of ankle joint injuries.

Three-Dimensional Biomechanical Analysis of Rearfoot and Forefoot Running

PubMed Central

Knorz, Sebastian; Kluge, Felix; Gelse, Kolja; Schulz-Drost, Stefan; Hotfiel, Thilo; Lochmann, Matthias; Eskofier, Björn; Krinner, Sebastian

2017-01-01

Background: In the running community, a forefoot strike (FFS) pattern is increasingly preferred compared with a rearfoot strike (RFS) pattern. However, it has not been fully understood which strike pattern may better reduce adverse joint forces within the different joints of the lower extremity. Purpose: To analyze the 3-dimensional (3D) stress pattern in the ankle, knee, and hip joint in runners with either a FFS or RFS pattern. Study Design: Descriptive laboratory study. Methods: In 22 runners (11 habitual rearfoot strikers, 11 habitual forefoot strikers), RFS and FFS patterns were compared at 3.0 m/s (6.7 mph) on a treadmill with integrated force plates and a 3D motion capture analysis system. This combined analysis allowed characterization of the 3D biomechanical forces differentiated for the ankle, knee, and hip joint. The maximum peak force (MPF) and maximum loading rate (LR) were determined in their 3 ordinal components: vertical, anterior-posterior (AP), and medial-lateral (ML). Results: For both strike patterns, the vertical components of the MPF and LR were significantly greater than their AP or ML components. In the vertical axis, FFS was generally associated with a greater MPF but significantly lower LR in all 3 joints. The AP components of MPF and LR were significantly lower for FFS in the knee joint but significantly greater in the ankle and hip joints. The ML components of MPF and LR tended to be greater for FFS but mostly did not reach a level of significance. Conclusion: FFS and RFS were associated with different 3D stress patterns in the ankle, knee, and hip joint, although there was no global advantage of one strike pattern over the other. The multimodal individual assessment for the different anatomic regions demonstrated that FFS seems favorable for patients with unstable knee joints in the AP axis and RFS may be recommended for runners with unstable ankle joints. Clinical Relevance: Different strike patterns show different 3D stress in joints of the lower extremity. Due to either rehabilitation after injuries or training in running sports, rearfoot or forefoot running should be preferred to prevent further damage or injuries caused by inadequate biomechanical load. Runners with a history of knee joint injuries may benefit from FFS whereas RFS may be favorable for runners with a history of ankle joint injuries. PMID:28812039

A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus.

PubMed

Friedland-Little, Joshua M; Hoffmann, Andrew D; Ocbina, Polloneal Jymmiel R; Peterson, Mike A; Bosman, Joshua D; Chen, Yan; Cheng, Steven Y; Anderson, Kathryn V; Moskowitz, Ivan P

2011-10-01

The primary cilium is emerging as a crucial regulator of signaling pathways central to vertebrate development and human disease. We identified atrioventricular canal 1 (avc1), a mouse mutation that caused VACTERL association with hydrocephalus, or VACTERL-H. We showed that avc1 is a hypomorphic mutation of intraflagellar transport protein 172 (Ift172), required for ciliogenesis and Hedgehog (Hh) signaling. Phenotypically, avc1 caused VACTERL-H but not abnormalities in left-right (L-R) axis formation. Avc1 resulted in structural cilia defects, including truncated cilia in vivo and in vitro. We observed a dose-dependent requirement for Ift172 in ciliogenesis using an allelic series generated with Ift172(avc1) and Ift172(wim), an Ift172 null allele: cilia were present on 42% of avc1 mouse embryonic fibroblast (MEF) and 28% of avc1/wim MEFs, in contrast to >90% of wild-type MEFs. Furthermore, quantitative cilium length analysis identified two specific cilium populations in mutant MEFS: a normal population with normal IFT and a truncated population, 50% of normal length, with disrupted IFT. Cells from wild-type embryos had predominantly full-length cilia, avc1 embryos, with Hh signaling abnormalities but not L-R abnormalities, had cilia equally divided between full-length and truncated, and avc1/wim embryos, with both Hh signaling and L-R abnormalities, were primarily truncated. Truncated Ift172 mutant cilia showed defects of the distal ciliary axoneme, including disrupted IFT88 localization and Hh-dependent Gli2 localization. We propose a model in which mutation of Ift172 results in a specific class of abnormal cilia, causing disrupted Hh signaling while maintaining L-R axis determination, and resulting in the VACTERL-H phenotype.

Left-right asymmetry in the light of TOR: An update on what we know so far.

PubMed

Casar Tena, Teresa; Burkhalter, Martin D; Philipp, Melanie

2015-09-01

The internal left-right (LR) asymmetry is a characteristic that exists throughout the animal kingdom from roundworms over flies and fish to mammals. Cilia, which are antenna-like structures protruding into the extracellular space, are involved in establishing LR asymmetry during early development. Humans who suffer from dysfunctional cilia often develop conditions such as heterotaxy, where internal organs appear to be placed randomly. As a consequence to this failure in asymmetry development, serious complications such as congenital heart defects (CHD) occur. The mammalian (or mechanistic) target of rapamycin (mTOR) pathway has recently emerged as an important regulator regarding symmetry breaking. The mTOR pathway governs fundamental processes such as protein translation or metabolism. Its activity can be transduced by two complexes, which are called TORC1 and TORC2, respectively. So far, only TORC1 has been implicated with asymmetry development and appears to require very precise regulation. A number of recent papers provided evidence that dysregulated TORC1 results in alterations of motile cilia and asymmetry defects. In here, we give an update on what we know so far of mTORC1 in LR asymmetry development. © 2015 The Authors. Biology of the Cell published by John Wiley & Sons Ltd on behalf of Société Française des Microscopies and Société de Biologie Cellulaire de France.

A proposed role for selective autophagy in regulating auxin-dependent lateral root development under phosphate starvation in Arabidopsis.

PubMed

Sankaranarayanan, Subramanian; Samuel, Marcus A

2015-01-01

Plants respond to limited soil nutrient availability by inducing more lateral roots (LR) to increase the root surface area. At the cellular level, nutrient starvation triggers the process of autophagy through which bulk degradation of cellular materials is achieved to facilitate nutrient mobilization. Whether there is any link between the cellular autophagy and induction of LR had remained unknown. We recently showed that the S-Domain receptor Kinase (ARK2) and U Box/Armadillo Repeat-Containing E3 ligase (PUB9) module is required for lateral root formation under phosphate starvation in Arabidopsis thaliana.(1) We also showed that PUB9 localized to autophagic bodies following either activation by ARK2 or under phosphate starvation and ark2-1/pub9-1 plants displayed lateral root defects with inability to accumulate auxin in the root tips under phosphate starvation.(1) Supplementing exogenous auxin was sufficient to rescue the LR defects in ark2-1/pub9-1 mutant. Blocking of autophagic responses in wild-type Arabidopsis also resulted in inhibition of both lateral roots and auxin accumulation in the root tips indicating the importance of autophagy in mediating auxin accumulation under phosphate starved conditions.(1) Here, we propose a model for ARK2/AtPUB9 module in regulation of lateral root development via selective autophagy.

Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut.

PubMed

Essner, Jeffrey J; Amack, Jeffrey D; Nyholm, Molly K; Harris, Erin B; Yost, H Joseph

2005-03-01

Monocilia have been proposed to establish the left-right (LR) body axis in vertebrate embryos by creating a directional fluid flow that triggers asymmetric gene expression. In zebrafish, dorsal forerunner cells (DFCs) express a conserved ciliary dynein gene (left-right dynein-related1, lrdr1) and form a ciliated epithelium inside a fluid-filled organ called Kupffer's vesicle (KV). Here, videomicroscopy demonstrates that cilia inside KV are motile and create a directional fluid flow just prior to the onset of asymmetric gene expression in lateral cells. Laser ablation of DFCs and surgical disruption of KV provide direct evidence that ciliated KV cells are required during early somitogenesis for subsequent LR patterning in the brain, heart and gut. Antisense morpholinos against lrdr1 disrupt KV fluid flow and perturb LR development. Furthermore, lrdr1 morpholinos targeted to DFC/KV cells demonstrate that Lrdr1 functions in these ciliated cells to control LR patterning. This provides the first direct evidence, in any vertebrate, that impairing cilia function in derivatives of the dorsal organizer, and not in other cells that express ciliogenic genes, alters LR development. Finally, genetic analysis reveals novel roles for the T-box transcription factor no tail and the Nodal signaling pathway as upstream regulators of lrdr1 expression and KV morphogenesis. We propose that KV is a transient embryonic 'organ of asymmetry' that directs LR development by establishing a directional fluid flow. These results suggest that cilia are an essential component of a conserved mechanism that controls the transition from bilateral symmetry to LR asymmetry in vertebrates.

Knockdown of the partner protein OsNAR2.1 for high-affinity nitrate transport represses lateral root formation in a nitrate-dependent manner

PubMed Central

Huang, Shuangjie; Chen, Si; Liang, Zhihao; Zhang, Chenming; Yan, Ming; Chen, Jingguang; Xu, Guohua; Fan, Xiaorong; Zhang, Yali

2015-01-01

The morphological plasticity of root systems is critical for plant survival, and understanding the mechanisms underlying root adaptation to nitrogen (N) fluctuation is critical for sustainable agriculture; however, the molecular mechanism of N-dependent root growth in rice remains unclear. This study aimed to identify the role of the complementary high-affinity NO3− transport protein OsNAR2.1 in NO3−-regulated rice root growth. Comparisons with wild-type (WT) plants showed that knockdown of OsNAR2.1 inhibited lateral root (LR) formation under low NO3− concentrations, but not under low NH4+ concentrations. 15N-labelling NO3− supplies (provided at concentrations of 0–10 mM) demonstrated that (i) defects in LR formation in mutants subjected to low external NO3− concentrations resulted from impaired NO3− uptake, and (ii) the mutants had significantly fewer LRs than the WT plants when root N contents were similar between genotypes. LR formation in osnar2.1 mutants was less sensitive to localised NO3− supply than LR formation in WT plants, suggesting that OsNAR2.1 may be involved in a NO3−-signalling pathway that controls LR formation. Knockdown of OsNAR2.1 inhibited LR formation by decreasing auxin transport from shoots to roots. Thus, OsNAR2.1 probably functions in both NO3− uptake and NO3−-signalling. PMID:26644084

Neural Markers in Pediatric Bipolar Disorder and Familial Risk for Bipolar Disorder.

PubMed

Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Wambach, Caroline G; Reynolds, Richard C; Chen, Gang; Towbin, Kenneth; Pine, Daniel S; Leibenluft, Ellen

2017-01-01

Bipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR). During functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth. We found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction). If replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177. Published by Elsevier Inc.

New methodologies for measuring Brugada ECG patterns cannot differentiate the ECG pattern of Brugada syndrome from Brugada phenocopy.

PubMed

Gottschalk, Byron H; Garcia-Niebla, Javier; Anselm, Daniel D; Jaidka, Atul; De Luna, Antoni Bayés; Baranchuk, Adrian

2016-01-01

Brugada phenocopies (BrP) are clinical entities characterized by ECG patterns that are identical to true Brugada syndrome (BrS), but are elicited by various clinical circumstances. A recent study demonstrated that the patterns of BrP and BrS are indistinguishable under the naked eye, thereby validating the concept that the patterns are identical. The aim of our study was to determine whether recently developed ECG criteria would allow for discrimination between type-2 BrS ECG pattern and type-2 BrP ECG pattern. Ten ECGs from confirmed BrS (aborted sudden death, transformation into type 1 upon sodium channel blocking test and/or ventricular arrhythmias, positive genetics) cases and 9 ECGs from confirmed BrP were included in the study. Surface 12-lead ECGs were scanned, saved in JPEG format for blind measurement of two values: (i) β-angle; and (ii) the base of the triangle. Cut-off values of ≥58° for the β-angle and ≥4mm for the base of the triangle were used to determine the BrS ECG pattern. Mean values for the β-angle in leads V1 and V2 were 66.7±25.5 and 55.4±28.1 for BrS and 54.1±26.5 and 43.1±16.1 for BrP respectively (p=NS). Mean values for the base of the triangle in V1 and V2 were 7.5±3.9 and 5.7±3.9 for BrS and 5.6±3.2 and 4.7±2.7 for BrP respectively (p=NS). The β-angle had a sensitivity of 60%, specificity of 78% (LR+ 2.7, LR- 0.5). The base of the triangle had a sensitivity of 80%, specificity of 40% (LR+ 1.4, LR- 0.5). New ECG criteria presented relatively low sensitivity and specificity, positive and negative predictive values to discriminate between BrS and BrP ECG patterns, providing further evidence that the two patterns are identical. Copyright © 2016 Elsevier Inc. All rights reserved.

SIZ1 Regulation of Phosphate Starvation-Induced Root Architecture Remodeling Involves the Control of Auxin Accumulation1[C][W][OA

PubMed Central

Miura, Kenji; Lee, Jiyoung; Gong, Qingqiu; Ma, Shisong; Jin, Jing Bo; Yoo, Chan Yul; Miura, Tomoko; Sato, Aiko; Bohnert, Hans J.; Hasegawa, Paul M.

2011-01-01

Phosphate (Pi) limitation causes plants to modulate the architecture of their root systems to facilitate the acquisition of Pi. Previously, we reported that the Arabidopsis (Arabidopsis thaliana) SUMO E3 ligase SIZ1 regulates root architecture remodeling in response to Pi limitation; namely, the siz1 mutations cause the inhibition of primary root (PR) elongation and the promotion of lateral root (LR) formation. Here, we present evidence that SIZ1 is involved in the negative regulation of auxin patterning to modulate root system architecture in response to Pi starvation. The siz1 mutations caused greater PR growth inhibition and LR development of seedlings in response to Pi limitation. Similar root phenotypes occurred if Pi-deficient wild-type seedlings were supplemented with auxin. N-1-Naphthylphthalamic acid, an inhibitor of auxin efflux activity, reduced the Pi starvation-induced LR root formation of siz1 seedlings to a level equivalent to that seen in the wild type. Monitoring of the auxin-responsive reporter DR5::uidA indicated that auxin accumulates in PR tips at early stages of the Pi starvation response. Subsequently, DR5::uidA expression was observed in the LR primordia, which was associated with LR elongation. The time-sequential patterning of DR5::uidA expression occurred earlier in the roots of siz1 as compared with the wild type. In addition, microarray analysis revealed that several other auxin-responsive genes, including genes involved in cell wall loosening and biosynthesis, were up-regulated in siz1 relative to wild-type seedlings in response to Pi starvation. Together, these results suggest that SIZ1 negatively regulates Pi starvation-induced root architecture remodeling through the control of auxin patterning. PMID:21156857

It’s never too early to get it Right

PubMed Central

Vandenberg, Laura N; Lemire, Joan M; Levin, Michael

2013-01-01

For centuries, scientists and physicians have been captivated by the consistent left-right (LR) asymmetry of the heart, viscera, and brain. A recent study implicated tubulin proteins in establishing laterality in several experimental models, including asymmetric chemosensory receptor expression in C. elegans neurons, polarization of HL-60 human neutrophil-like cells in culture, and asymmetric organ placement in Xenopus. The same mutations that randomized asymmetry in these diverse systems also affect chirality in Arabidopsis, revealing a remarkable conservation of symmetry-breaking mechanisms among kingdoms. In Xenopus, tubulin mutants only affected LR patterning very early, suggesting that this axis is established shortly after fertilization. This addendum summarizes and extends the knowledge of the cytoskeleton’s role in the patterning of the LR axis. Results from many species suggest a conserved role for the cytoskeleton as the initiator of asymmetry, and indicate that symmetry is first broken during early embryogenesis by an intracellular process. PMID:24505508

Stomach curvature is generated by left-right asymmetric gut morphogenesis

PubMed Central

Davis, Adam; Amin, Nirav M.; Johnson, Caroline; Bagley, Kristen; Ghashghaei, H. Troy

2017-01-01

Left-right (LR) asymmetry is a fundamental feature of internal anatomy, yet the emergence of morphological asymmetry remains one of the least understood phases of organogenesis. Asymmetric rotation of the intestine is directed by forces outside the gut, but the morphogenetic events that generate anatomical asymmetry in other regions of the digestive tract remain unknown. Here, we show in mouse and Xenopus that the mechanisms that drive the curvature of the stomach are intrinsic to the gut tube itself. The left wall of the primitive stomach expands more than the right wall, as the left epithelium becomes more polarized and undergoes radial rearrangement. These asymmetries exist across several species, and are dependent on LR patterning genes, including Foxj1, Nodal and Pitx2. Our findings have implications for how LR patterning manifests distinct types of morphological asymmetries in different contexts. PMID:28242610

Stomach curvature is generated by left-right asymmetric gut morphogenesis.

PubMed

Davis, Adam; Amin, Nirav M; Johnson, Caroline; Bagley, Kristen; Ghashghaei, H Troy; Nascone-Yoder, Nanette

2017-04-15

Left-right (LR) asymmetry is a fundamental feature of internal anatomy, yet the emergence of morphological asymmetry remains one of the least understood phases of organogenesis. Asymmetric rotation of the intestine is directed by forces outside the gut, but the morphogenetic events that generate anatomical asymmetry in other regions of the digestive tract remain unknown. Here, we show in mouse and Xenopus that the mechanisms that drive the curvature of the stomach are intrinsic to the gut tube itself. The left wall of the primitive stomach expands more than the right wall, as the left epithelium becomes more polarized and undergoes radial rearrangement. These asymmetries exist across several species, and are dependent on LR patterning genes, including Foxj1 , Nodal and Pitx2 Our findings have implications for how LR patterning manifests distinct types of morphological asymmetries in different contexts. © 2017. Published by The Company of Biologists Ltd.

Mechanisms of left-right asymmetry and patterning: driver, mediator and responder.

PubMed

Hamada, Hiroshi; Tam, Patrick P L

2014-01-01

The establishment of a left-right (LR) organizer in the form of the ventral node is an absolute prerequisite for patterning the tissues on contralateral sides of the body of the mouse embryo. The experimental findings to date are consistent with a mechanistic paradigm that the laterality information, which is generated in the ventral node, elicits asymmetric molecular activity and cellular behaviour in the perinodal tissues. This information is then relayed to the cells in the lateral plate mesoderm (LPM) when the left-specific signal is processed and translated into LR body asymmetry. Here, we reflect on our current knowledge and speculate on the following: (a) what are the requisite anatomical and functional attributes of an LR organizer, (b) what asymmetric information is emanated from this organizer, and (c) how this information is transferred across the paraxial tissue compartment and elicits a molecular response specifically in the LPM.

Late-onset cone photoreceptor degeneration induced by R172W mutation in Rds and partial rescue by gene supplementation.

PubMed

Conley, Shannon; Nour, May; Fliesler, Steven J; Naash, Muna I

2007-12-01

R172W is a common mutation in the human retinal degeneration slow (RDS) gene, associated with a late-onset dominant macular dystrophy. In this study, the authors characterized a mouse model that closely mimics the human phenotype and tested the feasibility of gene supplementation as a disease treatment strategy. Transgenic mouse lines carrying the R172W mutation were generated. The retinal phenotype associated with this mutation in a low-expresser line (L-R172W) was examined, both structurally (histology with correlative immunohistochemistry) and functionally (electroretinography). By examining animals over time and with various rds genetic backgrounds, the authors evaluated the dominance of the defect. To assess the efficacy of gene transfer therapy as a treatment for this defect, a previously characterized transgenic line expressing the normal mouse peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the R172W mutation (H-R172W). Functional, structural, and biochemical analyses were used to assess rescue of the retinal disease phenotype. In the wild-type (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone degeneration without any apparent effect on rods. The degeneration was slightly accelerated (9 months) in the rds(+/-) background. L-R172W retinas did not form outer segments in the absence of endogenous Rds. With use of the H-R172W line on an rds(+/-) background for proof-of-principle genetic supplementation studies, the NMP transgene product rescued rod and cone functional defects and supported outer segment integrity up to 3 months of age, but the rescue effect did not persist in older (11-month) animals. The R172W mutation leads to dominant cone degeneration in the mouse model, regardless of the expression level of the transgene. In contrast, effects of the mutation on rods are dose dependent, underscoring the usefulness of the L-R172W line as a faithful model of the human phenotype. This model may prove helpful in future studies on the mechanisms of cone degeneration and for elucidating the different roles of Rds in rods and cones. This study provides evidence that Rds genetic supplementation can be used to partially rescue visual function. Although this strategy is capable of rescuing haploinsufficiency, it does not rescue the long-term degeneration associated with a gain-of-function mutation.

Prospective evaluation of IOTA logistic regression models LR1 and LR2 in comparison with subjective pattern recognition for diagnosis of ovarian cancer in an outpatient setting.

PubMed

Nunes, N; Ambler, G; Foo, X; Widschwendter, M; Jurkovic, D

2018-06-01

To determine whether International Ovarian Tumor Analysis (IOTA) logistic regression models LR1 and LR2 developed for the preoperative diagnosis of ovarian cancer could also be used to differentiate between benign and malignant adnexal tumors in the population of women attending gynecology outpatient clinics. This was a single-center prospective observational study of consecutive women attending our gynecological diagnostic outpatient unit, recruited between May 2009 and January 2012. All the women were first examined by a Level-II ultrasound operator. In those diagnosed with adnexal tumors, the IOTA-LR1/2 protocol was used to evaluate the masses. The LR1 and LR2 models were then used to assess the risk of malignancy. Subsequently, the women were also examined by a Level-III examiner, who used pattern recognition to differentiate between benign and malignant tumors. Women with an ultrasound diagnosis of malignancy were offered surgery, while asymptomatic women with presumed benign lesions were offered conservative management with a minimum follow-up of 12 months. The initial diagnosis was compared with two reference standards: histological findings and/or a comparative assessment of tumor morphology on follow-up ultrasound scans. All women for whom the tumor classification on follow-up changed from benign to malignant were offered surgery. In the final analysis, 489 women who had either or both of the reference standards were included. Their mean age was 50 years (range, 16-91 years) and 45% were postmenopausal. Of the included women, 342/489 (69.9%) had surgery and 147/489 (30.1%) were managed conservatively. The malignancy rate was 137/489 (28.0%). Overall, sensitivities of LR1 and LR2 for the diagnosis of malignancy were 97.1% (95% CI, 92.7-99.2%) and 94.9% (95% CI, 89.8-97.9%) and specificities were 77.3% (95% CI, 72.5-81.5%) and 76.7% (95% CI, 71.9-81.0%), respectively (P > 0.05). In comparison with pattern recognition (sensitivity 94.2% (95% CI, 88.8-97.4%), specificity 96.3% (95% CI, 93.8-98.0%)), the specificities of the IOTA models were significantly lower (P < 0.0001). A significantly higher number of women would have been offered surgery for suspected cancer if the women had been assessed using the IOTA models instead of pattern recognition (213/489 (43.6%) vs 142/489 (29.0%); P < 0.001). The IOTA models maintained their high sensitivity when used in an outpatient setting. Specificity was relatively low, which indicates that a significant proportion of the women would have been offered unnecessary surgery for suspected ovarian cancer. These findings show that the IOTA models could be used as a first-stage test to diagnose ovarian cancer in an outpatient setting, but a different second-stage test is required to minimize the number of false-positive findings. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Genetic and Phenotypic Analysis of Lateral Root Development in Arabidopsis thaliana.

PubMed

Napsucialy-Mendivil, Selene; Dubrovsky, Joseph G

2018-01-01

Root system formation to a great extent depends on lateral root (LR) formation. In Arabidopsis thaliana, LRs are initiated within a parent root in pericycle that is an external tissue of the stele. LR initiation takes place in a strictly acropetal pattern, whereas posterior lateral root primordium (LRP) formation is asynchronous. In this chapter, we focus on methods of genetic and phenotypic analysis of LR initiation, LRP morphogenesis, and LR emergence in Arabidopsis. We provide details on how to make cleared root preparations and how to identify the LRP stages. We also pay attention to the categorization of the LRP developmental stages and their variations and to the normalization of the number of LRs and LRPs formed, per length of the primary root, and per number of cells produced within a root. Hormonal misbalances and mutations affect LRP morphogenesis significantly, and the evaluation of LRP abnormalities is addressed as well. Finally, we deal with various molecular markers that can be used for genetic and phenotypic analyses of LR development.

Fresh produce and their soils accumulate cyanotoxins from irrigation water: Implications for public health and food security.

PubMed

Lee, Seungjun; Jiang, Xuewen; Manubolu, Manjunath; Riedl, Ken; Ludsin, Stuart A; Martin, Jay F; Lee, Jiyoung

2017-12-01

Microcystin (MC), a hepatotoxin that can adversely affect human health, has become more prevalent in freshwater ecosystems worldwide, owing to an increase in toxic cyanobacteria blooms. While consumption of water and fish are well-documented exposure pathways of MCs to humans, less is known about the potential transfer to humans through consumption of vegetables that have been irrigated with MC-contaminated water. Likewise, the impact of MC on the performance of food crops is understudied. To help fill these information gaps, we conducted a controlled laboratory experiment in which we exposed lettuce, carrots, and green beans to environmentally relevant concentrations of MC-LR (0, 1, 5, and 10μg/L) via two irrigation methods (drip and spray). We used ELISA and LC-MS/MS to quantify MC-LR concentrations and in different parts of the plant (edible vs. inedible fractions), measured plant performance (e.g., size, mass, edible leaves, color), and calculated human exposure risk based on accumulation patterns. MC-LR accumulation was positively dose-dependent, with it being greater in the plants (2.2-209.2μg/kg) than in soil (0-19.4μg/kg). MC-LR accumulation varied among vegetable types, between plant parts, and between irrigation methods. MC-LR accumulation led to reduced crop growth and quality, with MC-LR persisting in the soil after harvest. Observed toxin accumulation patterns in edible fractions of plants also led to estimates of daily MC-LR intake that exceeded both the chronic reference dose (0.003μg/kg of body weight) and total daily intake guidelines (0.04μg/kg of body weight). Because the use of MC-contaminated water is common in many parts of the world, our collective findings highlight the need for guidelines concerning the use of MC-contaminated water in irrigation, as well as consumption of these crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Micropatterning of cells reveals chiral morphogenesis

PubMed Central

2013-01-01

Invariant left-right (LR) patterning or chirality is critical for embryonic development. The loss or reversal of LR asymmetry is often associated with malformations and disease. Although several theories have been proposed, the exact mechanism of the initiation of the LR symmetry has not yet been fully elucidated. Recently, chirality has been detected within single cells as well as multicellular structures using several in vitro approaches. These studies demonstrated the universality of cell chirality, its dependence on cell phenotype, and the role of physical boundaries. In this review, we discuss the theories for developmental LR asymmetry, compare various in vitro cell chirality model systems, and highlight possible roles of cell chirality in stem cell differentiation. We emphasize that the in vitro cell chirality systems have great promise for helping unveil the nature of chiral morphogenesis in development. PMID:23672821

A Unified Model for Left-Right Asymmetry? Comparison and Synthesis of Molecular Models of Embryonic Laterality

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2013-01-01

Understanding how and when the left-right (LR) axis is first established is a fundamental question in developmental biology. A popular model is that the LR axis is established relatively late in embryogenesis, due to the movement of motile cilia and the resultant directed fluid flow during late gastrulation/early neurulation. Yet, a large body of evidence suggests that biophysical, molecular, and bioelectrical asymmetries exist much earlier in development, some as early as the first cell cleavage after fertilization. Alternative models of LR asymmetry have been proposed that accommodate these data, postulating that asymmetry is established due to a chiral cytoskeleton and/or the asymmetric segregation of chromatids. There are some similarities, and many differences, in how these various models postulate the origin and timing of symmetry breaking and amplification, and these events’ linkage to the well-conserved subsequent asymmetric transcriptional cascades. This review examines experimental data that lend strong support to an early origin of LR asymmetry, yet are also consistent with later roles for cilia in the amplification of LR pathways. In this way, we propose that the various models of asymmetry can be unified: early events are needed to initiate LR asymmetry, and later events could be utilized by some species to maintain LR-biases. We also present an alternative hypothesis, which proposes that individual embryos stochastically choose one of several possible pathways with which to establish their LR axis. These two hypotheses are both tractable in appropriate model species; testing them to resolve open questions in the field of LR patterning will reveal interesting new biology of wide relevance to developmental, cell, and evolutionary biology. PMID:23583583

A unified model for left-right asymmetry? Comparison and synthesis of molecular models of embryonic laterality.

PubMed

Vandenberg, Laura N; Levin, Michael

2013-07-01

Understanding how and when the left-right (LR) axis is first established is a fundamental question in developmental biology. A popular model is that the LR axis is established relatively late in embryogenesis, due to the movement of motile cilia and the resultant directed fluid flow during late gastrulation/early neurulation. Yet, a large body of evidence suggests that biophysical, molecular, and bioelectrical asymmetries exist much earlier in development, some as early as the first cell cleavage after fertilization. Alternative models of LR asymmetry have been proposed that accommodate these data, postulating that asymmetry is established due to a chiral cytoskeleton and/or the asymmetric segregation of chromatids. There are some similarities, and many differences, in how these various models postulate the origin and timing of symmetry breaking and amplification, and these events' linkage to the well-conserved subsequent asymmetric transcriptional cascades. This review examines experimental data that lend strong support to an early origin of LR asymmetry, yet are also consistent with later roles for cilia in the amplification of LR pathways. In this way, we propose that the various models of asymmetry can be unified: early events are needed to initiate LR asymmetry, and later events could be utilized by some species to maintain LR-biases. We also present an alternative hypothesis, which proposes that individual embryos stochastically choose one of several possible pathways with which to establish their LR axis. These two hypotheses are both tractable in appropriate model species; testing them to resolve open questions in the field of LR patterning will reveal interesting new biology of wide relevance to developmental, cell, and evolutionary biology. Copyright © 2013 Elsevier Inc. All rights reserved.

It's never too early to get it Right: A conserved role for the cytoskeleton in left-right asymmetry.

PubMed

Vandenberg, Laura N; Lemire, Joan M; Levin, Michael

2013-11-01

For centuries, scientists and physicians have been captivated by the consistent left-right (LR) asymmetry of the heart, viscera, and brain. A recent study implicated tubulin proteins in establishing laterality in several experimental models, including asymmetric chemosensory receptor expression in C. elegans neurons, polarization of HL-60 human neutrophil-like cells in culture, and asymmetric organ placement in Xenopus. The same mutations that randomized asymmetry in these diverse systems also affect chirality in Arabidopsis, revealing a remarkable conservation of symmetry-breaking mechanisms among kingdoms. In Xenopus, tubulin mutants only affected LR patterning very early, suggesting that this axis is established shortly after fertilization. This addendum summarizes and extends the knowledge of the cytoskeleton's role in the patterning of the LR axis. Results from many species suggest a conserved role for the cytoskeleton as the initiator of asymmetry, and indicate that symmetry is first broken during early embryogenesis by an intracellular process.

Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior

PubMed Central

Melendez-Ferro, Miguel; Perez-Costas, Emma; Glover, Matthew E.; Jackson, Nateka L.; Stringfellow, Sara A.; Pugh, Phyllis C.; Fant, Andrew D.; Clinton, Sarah M.

2016-01-01

Individual differences in human temperament can increase risk for psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of Cytochrome C Oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes. PMID:26979051

Late-Onset Cone Photoreceptor Degeneration Induced by R172W Mutation in Rds and Partial Rescue by Gene Supplementation

PubMed Central

Conley, Shannon; Nour, May; Fliesler, Steven J.; Naash, Muna I.

2008-01-01

Purpose R172W is a common mutation in the human retinal degeneration slow (RDS) gene, associated with a late-onset dominant macular dystrophy. In this study, the authors characterized a mouse model that closely mimics the human phenotype and tested the feasibility of gene supplementation as a disease treatment strategy. Methods Transgenic mouse lines carrying the R172W mutation were generated. The retinal phenotype associated with this mutation in a low-expresser line (L-R172W) was examined, both structurally (histology with correlative immunohistochemistry) and functionally (electroretinography). By examining animals over time and with various rds genetic backgrounds, the authors evaluated the dominance of the defect. To assess the efficacy of gene transfer therapy as a treatment for this defect, a previously characterized transgenic line expressing the normal mouse peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the R172W mutation (H-R172W). Functional, structural, and biochemical analyses were used to assess rescue of the retinal disease phenotype. Results In the wild-type (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone degeneration without any apparent effect on rods. The degeneration was slightly accelerated (9 months) in the rds+/− background. L-R172W retinas did not form outer segments in the absence of endogenous Rds. With use of the H-R172W line on an rds+/− background for proof-of-principle genetic supplementation studies, the NMP transgene product rescued rod and cone functional defects and supported outer segment integrity up to 3 months of age, but the rescue effect did not persist in older (11-month) animals. Conclusions The R172W mutation leads to dominant cone degeneration in the mouse model, regardless of the expression level of the transgene. In contrast, effects of the mutation on rods are dose dependent, underscoring the usefulness of the L-R172W line as a faithful model of the human phenotype. This model may prove helpful in future studies on the mechanisms of cone degeneration and for elucidating the different roles of Rds in rods and cones. This study provides evidence that Rds genetic supplementation can be used to partially rescue visual function. Although this strategy is capable of rescuing haplo-insufficiency, it does not rescue the long-term degeneration associated with a gain-of-function mutation. PMID:18055786

Solar photo-Fenton treatment of microcystin-LR in aqueous environment: Transformation products and toxicity in different water matrices.

PubMed

Karci, Akin; Wurtzler, Elizabeth M; de la Cruz, Armah A; Wendell, David; Dionysiou, Dionysios D

2018-05-05

Transformation products and toxicity patterns of microcystin-LR (MC-LR), a common cyanotoxin in freshwaters, during degradation by solar photo-Fenton process were studied in the absence and presence of two major water components, namely fulvic acid and alkalinity. The transformation products m/z 795, 835, 515/1030 and 532 can be formed through attack of OH on the conjugated carbon double bonds of Adda. Transformation products with m/z 1010, 966 and 513 can be generated through the attack of OH on the methoxy group of Adda. The transformation products m/z 783, 508 and 1012 can be originated from the attack of OH on the cyclic structure of MC-LR. Transformation products (m/z 522, 1028, 1012, 1046 and 514) formed after hydroxylation of the aromatic ring with OH were also identified in this study. The toxicity study revealed that fulvic acid and alkalinity strongly influence the toxicity profiles of solar photo-Fenton treated MC-LR. Fulvic acid enhanced the detoxification whereas low level total alkalinity (1.8 mg L -1 CaCO 3 ) inhibited the detoxification of MC-LR by solar photo-Fenton process as assessed by protein phosphatase-1 (PP-1) inhibition assay. This work provides insights on the utility of solar photo-Fenton destruction of MC-LR in water based on transformation products and toxicity data. Copyright © 2017 Elsevier B.V. All rights reserved.

Male rats that differ in novelty exploration demonstrate distinct patterns of sexual behavior

PubMed Central

Cummings, Jennifer A.; Clinton, Sarah M.; Perry, Adam N.; Akil, Huda; Becker, Jill B.

2014-01-01

High versus low novelty exploration predicts a variety of behavioral differences. For example, rats selectively-bred for high novelty exploration (bred High Responders, bHR) exhibit exaggerated aggression, impulsivity, and proclivity to addictive behaviors compared to low novelty-reactive rats (bred Low Responders, bLRs), which are characterized by a high anxiety/depressive-like phenotype. Since bHR/bLR rats exhibit differences in dopaminergic circuitry and differential response to rewarding stimuli (i.e., psychostimulants, food), the present study examined whether they also differ in another key hedonic behavior – sex. Thus, adult bHR/bLR males were given five 30-min opportunities to engage in sexual activity with a receptive female. Sexual behavior and motivation were examined and compared between the groups. The bHR/bLR phenotype affected both sexual motivation and behavior, with bLR males demonstrating reduced motivation for sex compared with bHR males (i.e., fewer animals copulated, longer latency to engage in sex). The bHR males required more intromissions at a faster pace per ejaculation than did bLR males. Thus, neurobiological differences that affect motivation for drugs of abuse, aggression, and impulsivity in rats also affect sexual motivation and performance. PMID:23398441

The potential synergistic behaviour of inter- and intra-genus probiotic combinations in the pattern and rate of short chain fatty acids formation during fibre fermentation.

PubMed

Fernando, Warnakulasuriya M A D B; Flint, Steve H; Ranaweera, K K D S; Bamunuarachchi, Arthur; Johnson, Stuart K; Brennan, Charles S

2018-03-01

This study compared the rate of short chain fatty acid (SCFA) production by different probiotic combinations of Lactobacillus and Bifidobacterium to determine any synergistic effects. Six different fibre fractions were fermented with nine combinations of Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA), Bifidobacterium longum (BL) and Bifidobacterium breve (BB) for 0, 6, 24 and 48 h. SCFAs were quantified by gas chromatography. Inter-genus combinations of bacteria produced more SCFA, especially BB + BL + LR, compared to intra-genus that yielded the lowest SCFA production. Acetate was the most abundant, while propionate and butyrate were the most utilised. The SCFA formation was as acetate > propionate > butyrate and the total dietary fibre produced most of the SCFA. Most combinations utilised 60-80% of the fibre; BB + BL + LR digested the fibre completely. The quantity, pattern and the time of release of SCFA depends on the genus, but the combination of pre and probiotics is of great importance for the outcome.

Comparing performances of logistic regression and neural networks for predicting melatonin excretion patterns in the rat exposed to ELF magnetic fields.

PubMed

Jahandideh, Samad; Abdolmaleki, Parviz; Movahedi, Mohammad Mehdi

2010-02-01

Various studies have been reported on the bioeffects of magnetic field exposure; however, no consensus or guideline is available for experimental designs relating to exposure conditions as yet. In this study, logistic regression (LR) and artificial neural networks (ANNs) were used in order to analyze and predict the melatonin excretion patterns in the rat exposed to extremely low frequency magnetic fields (ELF-MF). Subsequently, on a database containing 33 experiments, performances of LR and ANNs were compared through resubstitution and jackknife tests. Predictor variables were more effective parameters and included frequency, polarization, exposure duration, and strength of magnetic fields. Also, five performance measures including accuracy, sensitivity, specificity, Matthew's Correlation Coefficient (MCC) and normalized percentage, better than random (S) were used to evaluate the performance of models. The LR as a conventional model obtained poor prediction performance. Nonetheless, LR distinguished the duration of magnetic fields as a statistically significant parameter. Also, horizontal polarization of magnetic fields with the highest logit coefficient (or parameter estimate) with negative sign was found to be the strongest indicator for experimental designs relating to exposure conditions. This means that each experiment with horizontal polarization of magnetic fields has a higher probability to result in "not changed melatonin level" pattern. On the other hand, ANNs, a more powerful model which has not been introduced in predicting melatonin excretion patterns in the rat exposed to ELF-MF, showed high performance measure values and higher reliability, especially obtaining 0.55 value of MCC through jackknife tests. Obtained results showed that such predictor models are promising and may play a useful role in defining guidelines for experimental designs relating to exposure conditions. In conclusion, analysis of the bioelectromagnetic data could result in finding a relationship between electromagnetic fields and different biological processes. (c) 2009 Wiley-Liss, Inc.

Progression of Patterns (POP): A Machine Classifier Algorithm to Identify Glaucoma Progression in Visual Fields

PubMed Central

Goldbaum, Michael H.; Lee, Intae; Jang, Giljin; Balasubramanian, Madhusudhanan; Sample, Pamela A.; Weinreb, Robert N.; Liebmann, Jeffrey M.; Girkin, Christopher A.; Anderson, Douglas R.; Zangwill, Linda M.; Fredette, Marie-Josee; Jung, Tzyy-Ping; Medeiros, Felipe A.; Bowd, Christopher

2012-01-01

Purpose. We evaluated Progression of Patterns (POP) for its ability to identify progression of glaucomatous visual field (VF) defects. Methods. POP uses variational Bayesian independent component mixture model (VIM), a machine learning classifier (MLC) developed previously. VIM separated Swedish Interactive Thresholding Algorithm (SITA) VFs from a set of 2,085 normal and glaucomatous eyes into nine axes (VF patterns): seven glaucomatous. Stable glaucoma was simulated in a second set of 55 patient eyes with five VFs each, collected within four weeks. A third set of 628 eyes with 4,186 VFs (mean ± SD of 6.7 ± 1.7 VFs over 4.0 ± 1.4 years) was tested for progression. Tested eyes were placed into suspect and glaucoma categories at baseline, based on VFs and disk stereoscopic photographs; a subset of eyes had stereophotographic evidence of progressive glaucomatous optic neuropathy (PGON). Each sequence of fields was projected along seven VIM glaucoma axes. Linear regression (LR) slopes generated from projections onto each axis yielded a degree of confidence (DOC) that there was progression. At 95% specificity, progression cutoffs were established for POP, visual field index (VFI), and mean deviation (MD). Guided progression analysis (GPA) was also compared. Results. POP identified a statistically similar number of eyes (P > 0.05) as progressing compared with VFI, MD, and GPA in suspects (3.8%, 2.7%, 5.6%, and 2.9%, respectively), and more eyes than GPA (P = 0.01) in glaucoma (16.0%, 15.3%, 12.0%, and 7.3%, respectively), and more eyes than GPA (P = 0.05) in PGON eyes (26.3%, 23.7%, 27.6%, and 14.5%, respectively). Conclusions. POP, with its display of DOC of progression and its identification of progressing VF defect pattern, adds to the information available to the clinician for detecting VF progression. PMID:22786913

Stochastic Downscaling of Digital Elevation Models

NASA Astrophysics Data System (ADS)

Rasera, Luiz Gustavo; Mariethoz, Gregoire; Lane, Stuart N.

2016-04-01

High-resolution digital elevation models (HR-DEMs) are extremely important for the understanding of small-scale geomorphic processes in Alpine environments. In the last decade, remote sensing techniques have experienced a major technological evolution, enabling fast and precise acquisition of HR-DEMs. However, sensors designed to measure elevation data still feature different spatial resolution and coverage capabilities. Terrestrial altimetry allows the acquisition of HR-DEMs with centimeter to millimeter-level precision, but only within small spatial extents and often with dead ground problems. Conversely, satellite radiometric sensors are able to gather elevation measurements over large areas but with limited spatial resolution. In the present study, we propose an algorithm to downscale low-resolution satellite-based DEMs using topographic patterns extracted from HR-DEMs derived for example from ground-based and airborne altimetry. The method consists of a multiple-point geostatistical simulation technique able to generate high-resolution elevation data from low-resolution digital elevation models (LR-DEMs). Initially, two collocated DEMs with different spatial resolutions serve as an input to construct a database of topographic patterns, which is also used to infer the statistical relationships between the two scales. High-resolution elevation patterns are then retrieved from the database to downscale a LR-DEM through a stochastic simulation process. The output of the simulations are multiple equally probable DEMs with higher spatial resolution that also depict the large-scale geomorphic structures present in the original LR-DEM. As these multiple models reflect the uncertainty related to the downscaling, they can be employed to quantify the uncertainty of phenomena that are dependent on fine topography, such as catchment hydrological processes. The proposed methodology is illustrated for a case study in the Swiss Alps. A swissALTI3D HR-DEM (with 5 m resolution) and a SRTM-derived LR-DEM from the Western Alps are used to downscale a SRTM-based LR-DEM from the eastern part of the Alps. The results show that the method is capable of generating multiple high-resolution synthetic DEMs that reproduce the spatial structure and statistics of the original DEM.

A comparison of data-driven groundwater vulnerability assessment methods

USGS Publications Warehouse

Sorichetta, Alessandro; Ballabio, Cristiano; Masetti, Marco; Robinson, Gilpin R.; Sterlacchini, Simone

2013-01-01

Increasing availability of geo-environmental data has promoted the use of statistical methods to assess groundwater vulnerability. Nitrate is a widespread anthropogenic contaminant in groundwater and its occurrence can be used to identify aquifer settings vulnerable to contamination. In this study, multivariate Weights of Evidence (WofE) and Logistic Regression (LR) methods, where the response variable is binary, were used to evaluate the role and importance of a number of explanatory variables associated with nitrate sources and occurrence in groundwater in the Milan District (central part of the Po Plain, Italy). The results of these models have been used to map the spatial variation of groundwater vulnerability to nitrate in the region, and we compare the similarities and differences of their spatial patterns and associated explanatory variables. We modify the standard WofE method used in previous groundwater vulnerability studies to a form analogous to that used in LR; this provides a framework to compare the results of both models and reduces the effect of sampling bias on the results of the standard WofE model. In addition, a nonlinear Generalized Additive Model has been used to extend the LR analysis. Both approaches improved discrimination of the standard WofE and LR models, as measured by the c-statistic. Groundwater vulnerability probability outputs, based on rank-order classification of the respective model results, were similar in spatial patterns and identified similar strong explanatory variables associated with nitrate source (population density as a proxy for sewage systems and septic sources) and nitrate occurrence (groundwater depth).

Allelopathic effects of microcystin-LR on the germination, growth and metabolism of five charophyte species and a submerged angiosperm.

PubMed

Rojo, Carmen; Segura, Matilde; Cortés, Francisco; Rodrigo, María A

2013-11-15

Microcystins (MCs) are produced by cyanobacteria in aquatic environments and adversely affect macrophytes at very high concentrations. However, the effects of MC on macrophytes at concentrations of environmental relevance are largely unknown. The main objective of this study was to analyze the allelopathic effects of MC-LR at natural concentrations (1, 8 and 16 μg MC-LR/L) on five charophyte species (Chara aspera, C. baltica, C. hispida, C. vulgaris and Nitella hyalina) and the angiosperm Myriophyllum spicatum. Macrophyte specimens were obtained from a restored area located in Albufera de València Natural Park, a protected coastal Mediterranean wetland. Two different experiments were conducted involving (i) the addition of MC-LR to natural sediment to evaluate its effects on seed germination and (ii) the addition of MC-LR to water cultures of macrophytes to evaluate its effects on growth and metabolic functions. In water, the MC-LR concentration decreased by 84% in two weeks; the loss was not significant in sediment. The first seedlings (all C. hispida) emerged from the wetland sediment following a delay of a few days in the presence of MC-LR. The germination rates in 8 and 16 μg MC-LR/L treatments were 44% and 11% of that occurring in the absence of MC, but these differences disappeared over time. The final density was 6-7 germlings/dm(3). Final germling length was unaffected by MC-LR. Rotifers (Lecane spp.) emerging from the natural sediment during the experiment were favored by MC-LR; the opposite pattern was observed in the cladoceran Daphnia magna. The growth rates of C. vulgaris, C. baltica and N. hyalina were unaffected by MC exposure, whereas those of C. hispida and C. aspera were reduced in the MC treatments relative to the control treatment. The concentration of chlorophyll-a and the in vivo net photosynthetic rate were lower in the presence of MC-LR, even at the lowest concentration, for all of the characeans tested. M. spicatum was sensitive to the presence of MC-LR in the culture medium; the growth and chlorophyll-a concentrations were reduced. Therefore, environmentally relevant concentrations of MC might induce important changes in macrophyte meadows and the structure of the associated plankton community. Synchrony or delay in the processes evaluated here in response to environmentally relevant concentrations of cyanobacteria MC exudates can enhance understanding of the turning point to alternative states and the point of no return in eutrophicated shallow lakes. Copyright © 2013 Elsevier B.V. All rights reserved.

Loading rate increases during barefoot running in habitually shod runners: Individual responses to an unfamiliar condition.

PubMed

Tam, Nicholas; Astephen Wilson, Janie L; Coetzee, Devon R; van Pletsen, Leanri; Tucker, Ross

2016-05-01

The purpose of this study was to examine the effect of barefoot running on initial loading rate (LR), lower extremity joint kinematics and kinetics, and neuromuscular control in habitually shod runners with an emphasis on the individual response to this unfamiliar condition. Kinematics and ground reaction force data were collected from 51 habitually shod runners during overground running in a barefoot and shod condition. Joint kinetics and stiffness were calculated with inverse dynamics. Inter-individual initial LR variability was explored by separating individuals by a barefoot/shod ratio to determine acute responders/non-responders. Mean initial LR was 54.1% greater in the barefoot when compared to the shod condition. Differences between acute responders/non-responders were found at peak and initial contact sagittal ankle angle and at initial ground contact. Correlations were found between barefoot sagittal ankle angle at initial ground contact and barefoot initial LR. A large variability in biomechanical responses to an acute exposure to barefoot running was found. A large intra-individual variability was found in initial LR but not ankle plantar-dorsiflexion between footwear conditions. A majority of habitually shod runners do not exhibit previously reported benefits in terms of reduced initial LRs when barefoot. Lastly, runners who increased LR when barefoot reduced LRs when wearing shoes to levels similar seen in habitually barefoot runners who do adopt a forefoot-landing pattern, despite increased dorsiflexion. Copyright © 2016 Elsevier B.V. All rights reserved.

Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.

PubMed

Kabbaj, M; Norton, C S; Kollack-Walker, S; Watson, S J; Robinson, T E; Akil, H

2001-12-01

It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.

Degradation mechanisms of Microcystin-LR during UV-B photolysis and UV/H2O2 processes: Byproducts and pathways.

PubMed

Moon, Bo-Ram; Kim, Tae-Kyoung; Kim, Moon-Kyung; Choi, Jaewon; Zoh, Kyung-Duk

2017-10-01

The removal and degradation pathways of microcystin-LR (MC-LR, [M+H] +  = 995.6) in UV-B photolysis and UV-B/H 2 O 2 processes were examined using liquid chromatography-tandem mass spectrometry. The UV/H 2 O 2 process was more efficient than UV-B photolysis for MC-LR removal. Eight by-products were newly identified in the UV-B photolysis ([M+H] +  = 414.3, 417.3, 709.6, 428.9, 608.6, 847.5, 807.4, and 823.6), and eleven by-products were identified in the UV-B/H 2 O 2 process ([M+H] +  = 707.4, 414.7, 429.3, 445.3, 608.6, 1052.0, 313.4, 823.6, 357.3, 245.2, and 805.7). Most of the MC-LR by-products had lower [M+H] + values than the MC-LR itself during both processes, except for the [M+H] + value of 1052.0 during UV-B photolysis. Based on identified by-products and peak area patterns, we proposed potential degradation pathways during the two processes. Bond cleavage and intramolecular electron rearrangement by electron pair in the nitrogen atom were the major reactions during UV-B photolysis and UV-B/H 2 O 2 processes, and hydroxylation by OH radical and the adduct formation reaction between the produced by-products were identified as additional pathways during the UV-B/H 2 O 2 process. Meanwhile, the degradation by-products identified from MC-LR during UV-B/H 2 O 2 process can be further degraded by increasing H 2 O 2 dose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

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

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no; Department of Oncology, Haukeland University Hospital, Bergen; Engellau, Jacob

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence intervalmore » [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.« less

The Antidepressant Effect of Laser Acupuncture: A Comparison of the Resting Brain's Default Mode Network in Healthy and Depressed Subjects During Functional Magnetic Resonance Imaging

PubMed Central

Quah-Smith, Im; Suo, Chao; Williams, Mark A.

2013-01-01

Abstract Background It has been suggested that the antidepressant effect of laser acupuncture involves modulation of the default mode network (DMN) or resting state network (RSN). In this study, the authors investigated changes in the DMN during laser acupuncture in depressed and nondepressed participants. Objective To aim of this study was to determine if the modulation of the DMN effects by laser acupuncture in depressed participants are different from those of nondepressed participants. Design Randomized stimulation was performed with laser acupuncture on four putative antidepressant acupoints (LR 14, LR 8, CV 14, and HT 7) in a block on–off design, while the blood oxygenation level–dependent (BOLD) fMRI response was recorded from each subject's whole brain on a 3T scanner. DMN patterns of the participants were identified, using an independent component analysis. The identified DMN components from both the nondepressed group and the depressed group were then analytically compared using SPM5. Setting This study took place at a research institute. Subjects Ten nondepressed participants and 10 depressed participants (DS) as confirmed by the Hamilton Depression Rating Scale (HAM-D) participated in this study. Intervention Low Intensity Laser Acupuncture. Main outcome measures Significant DMN patterns in one group were greater than those in the other group. Results The nondepressed participants had significant modulation of DMN in the frontal region at the medial frontal gyrus (verum laser>rest, p<0.001) for three acupoints (LR 14, LR 8, and CV 14). For the depressive participants, the DMN modulation occurred at the inferior parietal cortex and the cerebellum (verum laser>rest, p<0.001). Conclusions Laser acupuncture on LR 8, LR 14, and CV 14 stimulated both the anterior and posterior DMN in both the nondepressed and depressed participants. However, in the nondepressed participants, there was consistently outstanding modulation of the anterior DMN at the medial frontal gyrus across all three acupoints. In the depressed participants, there was wider posterior DMN modulation at the parieto–temporal–limbic cortices. This is part of the antidepressant effect of laser acupuncture. PMID:24761169

Recurrence patterns and factors associated with regular, irregular, and late return to service of female pigs and their lifetime performance on southern European farms.

PubMed

Tani, S; Piñeiro, C; Koketsu, Y

2016-05-01

A return-to-service occurrence increases nonproductive days of female pigs and decreases herd productivity. The objectives of the present study were 1) to characterize 3 return types based on reservice intervals in female pigs on southern European farms, 2) to determine return risks and recurrence patterns for these types of returns, and 3) to assess lifetime performance of females with the 3 types of returns. We analyzed 653,528 service records and lifetime records of 114,906 females on 125 farms between 2008 and 2013. Reservice intervals were categorized into 3 groups: regular returns (RR: 18 to 24 d), irregular returns (IR: 25 to 38 d), and late returns (LR: 39 d or later). Multilevel generalized linear models were applied to the data. There were 64,385 reservice records (9.9%), with mean risks of RR, IR, and LR per service (±SEM) of 3.6% ± 0.06%, 2.5% ± 0.05%, and 3.0% ± 0.06%, respectively. Of the 43,931 first-returned females, 32.7% had a second return in the same or later parity. Also, 18.8%, 10.2%, and 11.6% of females that had RR, IR, and LR first returns, respectively, had a second return of the same return type. Summer servicing was associated with greater RR, IR, and LR risks in gilts. Also, increased gilt age at first mating was associated with RR ( = 0.03) and LR risk ( < 0.01) but not with IR risk ( = 0.53). For sows, factors associated with greater RR, IR, or LR risks were summer servicing, lower parity, farrowing more stillborn piglets, and having a weaning-to-first-mating interval of 7 d or more ( < 0.01). In lifetime, 33.5% of serviced females had 1 or more returns. These returned females had 41.5 more lifetime nonproductive days than nonreturn females but also 1.9 more lifetime pigs born alive ( < 0.01). We recommend that producers closely monitor females in high-risk groups to reduce their return-to-service intervals.

Bioacumulation of cyanotoxins in Hypophthalmichthys molitrix (silver carp) in Paranoá Lake, Brasilia-DF, Brazil.

PubMed

Oliveira, N B; Schwartz, C A; Bloch, C; Paulino, L; Pires, O R

2013-03-01

Three individuals of silver carp (Hypophthalmichthys molitrix) were collected biweekly from Paranoá Lake (DF, Brazil) for analysis of microcystin (MC) concentrations in their muscle and liver tissue. Analysis by high performance liquid chromatography and mass spectrometry revealed MC masses and fragmentation patterns that were identified as MC-LR (995.04 m/z), MC-LA (909.01 m/z) and an unknown MC (987.07 m/z). Concentrations were calculated as MC-LR equivalents using a calibration curve prepared with a standard of MC-LR. May/06 was the month with the highest MC-LR equivalent concentrations in muscle and liver (3.83 ± 2.78, and 12.94 ± 10.51 μg g(-1), respectively). Our results show that during the drought months (April-September), consumption of fish with these MC concentrations would result in exposure to MCs that greatly exceed the World Health Organization's recommended tolerable daily intake limit of 0.04 μg MC kg(-1) body weight.

Occurrence of Toxic Cyanobacterial Blooms in Rio de la Plata Estuary, Argentina: Field Study and Data Analysis

PubMed Central

Giannuzzi, L.; Carvajal, G.; Corradini, M. G.; Araujo Andrade, C.; Echenique, R.; Andrinolo, D.

2012-01-01

Water samples were collected during 3 years (2004–2007) at three sampling sites in the Rio de la Plata estuary. Thirteen biological, physical, and chemical parameters were determined on the water samples. The presence of microcystin-LR in the reservoir samples, and also in domestic water samples, was confirmed and quantified. Microcystin-LR concentration ranged between 0.02 and 8.6 μg.L−1. Principal components analysis was used to identify the factors promoting cyanobacteria growth. The proliferation of cyanobacteria was accompanied by the presence of high total and fecal coliforms bacteria (>1500 MNP/100 mL), temperature ≥25°C, and total phosphorus content ≥1.24 mg·L−1. The observed fluctuating patterns of Microcystis aeruginosa, total coliforms, and Microcystin-LR were also described by probabilistic models based on the log-normal and extreme value distributions. The sampling sites were compared in terms of the distribution parameters and the probability of observing high concentrations for Microcystis aeruginosa, total coliforms, and microcystin-LR concentration. PMID:22523486

Cellular and Nuclear Alignment Analysis for Determining Epithelial Cell Chirality

PubMed Central

Raymond, Michael J.; Ray, Poulomi; Kaur, Gurleen; Singh, Ajay V.; Wan, Leo Q.

2015-01-01

Left-right (LR) asymmetry is a biologically conserved property in living organisms that can be observed in the asymmetrical arrangement of organs and tissues and in tissue morphogenesis, such as the directional looping of the gastrointestinal tract and heart. The expression of LR asymmetry in embryonic tissues can be appreciated in biased cell alignment. Previously an in vitro chirality assay was reported by patterning multiple cells on microscale defined geometries and quantified the cell phenotype–dependent LR asymmetry, or cell chirality. However, morphology and chirality of individual cells on micropatterned surfaces has not been well characterized. Here, a Python-based algorithm was developed to identify and quantify immunofluorescence stained individual epithelial cells on multicellular patterns. This approach not only produces results similar to the image intensity gradient-based method reported previously, but also can capture properties of single cells such as area and aspect ratio. We also found that cell nuclei exhibited biased alignment. Around 35% cells were misaligned and were typically smaller and less elongated. This new imaging analysis approach is an effective tool for measuring single cell chirality inside multicellular structures and can potentially help unveil biophysical mechanisms underlying cellular chiral bias both in vitro and in vivo. PMID:26294010

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules.

PubMed

Terzi, Eleonora; Iavarone, Massimo; Pompili, Maurizio; Veronese, Letizia; Cabibbo, Giuseppe; Fraquelli, Mirella; Riccardi, Laura; De Bonis, Ludovico; Sangiovanni, Angelo; Leoni, Simona; Zocco, Maria Assunta; Rossi, Sandro; Alessi, Nicola; Wilson, Stephanie R; Piscaglia, Fabio

2018-03-01

The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500). The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 [47%]) and the LR-4 202 (HCC 173 [87%]). The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis. This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Sources of Intermodel Spread in the Lapse Rate and Water Vapor Feedbacks

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

Po-Chedley, Stephen; Armour, Kyle C.; Bitz, Cecilia M.

Sources of intermodel differences in the global lapse rate (LR) and water vapor (WV) feedbacks are assessed using CO 2 forcing simulations from 28 general circulation models. Tropical surface warming leads to significant warming and moistening in the tropical and extratropical upper troposphere, signifying a nonlocal, tropical influence on extratropical radiation and feedbacks. Model spread in the locally defined LR and WV feedbacks is pronounced in the Southern Ocean because of large-scale ocean upwelling, which reduces surface warming and decouples the surface from the tropospheric response. The magnitude of local extratropical feedbacks across models and over time is well characterizedmore » using the ratio of tropical to extratropical surface warming. It is shown that model differences in locally defined LR and WV feedbacks, particularly over the southern extratropics, drive model variability in the global feedbacks. The cross-model correlation between the global LR and WV feedbacks therefore does not arise from their covariation in the tropics, but rather from the pattern of warming exerting a common control on extratropical feedback responses. Because local feedbacks over the Southern Hemisphere are an important contributor to the global feedback, the partitioning of surface warming between the tropics and the southern extratropics is a key determinant of the spread in the global LR and WV feedbacks. It is also shown that model Antarctic sea ice climatology influences sea ice area changes and southern extratropical surface warming. In conclusion, as a result, model discrepancies in climatological Antarctic sea ice area have a significant impact on the intermodel spread of the global LR and WV feedbacks.« less

Different uptake of 123I-MIBG in the two main liver lobes: A persistant unsolved mistery.

PubMed

Bonacina, M; Albano, D; Steimberg, N; Bosio, G; Camoni, L; Bertagna, F; Giubbini, R; Mazzoleni, G

2018-05-10

After radiopharmaceutical injection, a heightened 123 I-MIBG concentration is frequently observed in the left hepatic lobe compared to the right one, but the reason of this finding remains unknown. Our aim was to retrospectively analyze the different 123 I-MIBG uptake pattern between the two hepatic lobes and correlate our results with some epidemiological/clinical features. Ninety-four 123 I-MIBG scintigraphies from 71 patients were selected. Regions of interest were drawn in the right and left lobes using transverse tomographic sections and left to right activity ratios (L/R ratio) were calculated at 6 and 24h after radiotracer administration. Twenty-seven examinations were positive for hypermetabolic lesions while the remaining 67 were negative. In all cases mean early and delayed L/R ratios were greater than 1.00; average early L/R ratio was 1.37 and delayed L/R ratio 1.52. The delayed L/R ratio was significantly higher than the early one. There was no difference in the L/R ratios with regard to age, gender, primary disease and result of scintigraphy. 123 I-MIBG uptake was higher in left hepatic lobe compared to right and this ratio did not correlate with any epidemiological or clinical feature. The reason of this metabolic is not yet explained and some biomolecular hypotheses could be tested in 3D dynamic in vitro models. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

Sources of Intermodel Spread in the Lapse Rate and Water Vapor Feedbacks

DOE PAGES

Po-Chedley, Stephen; Armour, Kyle C.; Bitz, Cecilia M.; ...

2018-03-23

Sources of intermodel differences in the global lapse rate (LR) and water vapor (WV) feedbacks are assessed using CO 2 forcing simulations from 28 general circulation models. Tropical surface warming leads to significant warming and moistening in the tropical and extratropical upper troposphere, signifying a nonlocal, tropical influence on extratropical radiation and feedbacks. Model spread in the locally defined LR and WV feedbacks is pronounced in the Southern Ocean because of large-scale ocean upwelling, which reduces surface warming and decouples the surface from the tropospheric response. The magnitude of local extratropical feedbacks across models and over time is well characterizedmore » using the ratio of tropical to extratropical surface warming. It is shown that model differences in locally defined LR and WV feedbacks, particularly over the southern extratropics, drive model variability in the global feedbacks. The cross-model correlation between the global LR and WV feedbacks therefore does not arise from their covariation in the tropics, but rather from the pattern of warming exerting a common control on extratropical feedback responses. Because local feedbacks over the Southern Hemisphere are an important contributor to the global feedback, the partitioning of surface warming between the tropics and the southern extratropics is a key determinant of the spread in the global LR and WV feedbacks. It is also shown that model Antarctic sea ice climatology influences sea ice area changes and southern extratropical surface warming. In conclusion, as a result, model discrepancies in climatological Antarctic sea ice area have a significant impact on the intermodel spread of the global LR and WV feedbacks.« less

Homology and homoplasy of swimming behaviors and neural circuits in the Nudipleura (Mollusca, Gastropoda, Opisthobranchia)

PubMed Central

Newcomb, James M.; Sakurai, Akira; Lillvis, Joshua L.; Gunaratne, Charuni A.; Katz, Paul S.

2012-01-01

How neural circuit evolution relates to behavioral evolution is not well understood. Here the relationship between neural circuits and behavior is explored with respect to the swimming behaviors of the Nudipleura (Mollusca, Gastropoda, Opithobranchia). Nudipleura is a diverse monophyletic clade of sea slugs among which only a small percentage of species can swim. Swimming falls into a limited number of categories, the most prevalent of which are rhythmic left–right body flexions (LR) and rhythmic dorsal–ventral body flexions (DV). The phylogenetic distribution of these behaviors suggests a high degree of homoplasy. The central pattern generator (CPG) underlying DV swimming has been well characterized in Tritonia diomedea and in Pleurobranchaea californica. The CPG for LR swimming has been elucidated in Melibe leonina and Dendronotus iris, which are more closely related. The CPGs for the categorically distinct DV and LR swimming behaviors consist of nonoverlapping sets of homologous identified neurons, whereas the categorically similar behaviors share some homologous identified neurons, although the exact composition of neurons and synapses in the neural circuits differ. The roles played by homologous identified neurons in categorically distinct behaviors differ. However, homologous identified neurons also play different roles even in the swim CPGs of the two LR swimming species. Individual neurons can be multifunctional within a species. Some of those functions are shared across species, whereas others are not. The pattern of use and reuse of homologous neurons in various forms of swimming and other behaviors further demonstrates that the composition of neural circuits influences the evolution of behaviors. PMID:22723353

Left Parietal Functional Connectivity Mediates the Association Between COMT rs4633 and Verbal Intelligence in Healthy Adults

PubMed Central

Xu, Qiang; Fu, Jilian; Liu, Feng; Qin, Wen; Liu, Bing; Jiang, Tianzi; Yu, Chunshui

2018-01-01

In Chinese Han population, Catechol-O-methyltransferase gene (COMT) rs4633 is found to be associated with impaired cognitive process. We aimed to investigate the association between COMT rs4633 and verbal intelligence and the underlying neural mechanisms in Chinese Han healthy young adults. In 256 Chinese Han healthy young adults, we explored the modulatory effects of COMT rs4633 on verbal intelligence quotient (VIQ) and functional connectivity density (FCD) of the brain and the mediation effect of FCD on the association between COMT and VIQ. We further investigated the association between the expression patterns of dopamine receptor genes and the effect of COMT on FCD in the human brain. COMT rs4633 TT homozygotes exhibited lower VIQ than CC homozygotes and TC heterozygotes, higher long-range FCD (lrFCD) than CC homozygotes and TC heterozygotes in the left superior frontal gyrus. TT homozygotes and TC heterozygotes showed higher lrFCD than CC homozygotes in the left inferior parietal lobule. The lrFCD differences across genotypic subgroups were negatively associated with the expression of DRD2 and DRD3 genes. The left parietal lrFCD mediated the association between COMT rs4633 and VIQ. These findings provide a biological pathway that COMT rs4633 affects verbal intelligence via modulating the lrFCD of the left inferior parietal lobule. PMID:29692704

Adaptive Behaviour and Cognitive Skills: Stability and Change from 7 Months to 7 Years in Siblings at High Familial Risk of Autism Spectrum Disorder.

PubMed

Salomone, Erica; Shephard, Elizabeth; Milosavljevic, Bosiljka; Johnson, Mark H; Charman, Tony

2018-04-03

Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms.

Verification of STS markers for leaf rust resistance genes of wheat by seven European laboratories.

PubMed

Błaszczyk, Lidia; Chełkowski, Jerzy; Korzun, Victor; Kraic, Jan; Ordon, Frank; Ovesná, Jaroslava; Purnhauser, Laszlo; Tar, Melinda; Vida, Gyula

2004-01-01

A set of Thatcher near-isogenic lines and two breeding lines were used to examine sequence tagged site (STS) markers linked to leaf rust resistance genes Lr9, Lr10, Lr19, Lr24, Lr28, Lr29, Lr35, and a simple sequenced repeat (SSR) marker for Lr39. The selected STS markers for resistance genes Lr9, Lr10, Lr19, Lr24 and Lr28 were identified in seven accessions by seven European laboratories. Near-isogenic lines of the spring wheat Thatcher were used as positive controls. Markers for resistance genes Lr9, Lr10, Lr19, Lr24 were identified in all seven laboratories as amplification products of 1100 bp, 310 bp, 130 bp and 310 bp, respectively. The STS markers linked to resistance genes Lr9, Lr10, Lr19, Lr24, Lr29, Lr35 and the SSR marker for Lr39 were robust and highly specific for these genes and will be useful in marker-assisted selection in wheat. However, the amplification product of 378 bp that corresponded with resistance gene Lr28 was detected in all accessions including genotypes lacking this gene in all seven laboratories. This marker needs to be improved.

Spatial Modeling and Uncertainty Assessment of Fine Scale Surface Processes Based on Coarse Terrain Elevation Data

NASA Astrophysics Data System (ADS)

Rasera, L. G.; Mariethoz, G.; Lane, S. N.

2017-12-01

Frequent acquisition of high-resolution digital elevation models (HR-DEMs) over large areas is expensive and difficult. Satellite-derived low-resolution digital elevation models (LR-DEMs) provide extensive coverage of Earth's surface but at coarser spatial and temporal resolutions. Although useful for large scale problems, LR-DEMs are not suitable for modeling hydrologic and geomorphic processes at scales smaller than their spatial resolution. In this work, we present a multiple-point geostatistical approach for downscaling a target LR-DEM based on available high-resolution training data and recurrent high-resolution remote sensing images. The method aims at generating several equiprobable HR-DEMs conditioned to a given target LR-DEM by borrowing small scale topographic patterns from an analogue containing data at both coarse and fine scales. An application of the methodology is demonstrated by using an ensemble of simulated HR-DEMs as input to a flow-routing algorithm. The proposed framework enables a probabilistic assessment of the spatial structures generated by natural phenomena operating at scales finer than the available terrain elevation measurements. A case study in the Swiss Alps is provided to illustrate the methodology.

Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos.

PubMed

Kawasumi, Aiko; Nakamura, Tetsuya; Iwai, Naomi; Yashiro, Kenta; Saijoh, Yukio; Belo, Jose Antonio; Shiratori, Hidetaka; Hamada, Hiroshi

2011-05-15

Left-right (L-R) asymmetry in the mouse embryo is generated in the node and is dependent on cilia-driven fluid flow, but how the initial asymmetry is transmitted from the node to the lateral plate has remained unknown. We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryo. Dissection of ANE revealed that it is activated in the perinodal cells on the left side by Nodal signaling, suggesting that Nodal activity in the node is asymmetric at a time when Nodal expression is symmetric. Phosphorylated Smad2/3 (pSmad2) indeed manifested an L-R asymmetric distribution at the node, being detected in perinodal cells preferentially on the left side. This asymmetry in pSmad2 distribution was found to be generated not by unidirectional transport of Nodal but rather as a result of LR distribution of active Nodal in the node is translated into the asymmetry in LPM. Copyright © 2011 Elsevier Inc. All rights reserved.

Modified CC-LR algorithm with three diverse feature sets for motor imagery tasks classification in EEG based brain-computer interface.

PubMed

Siuly; Li, Yan; Paul Wen, Peng

2014-03-01

Motor imagery (MI) tasks classification provides an important basis for designing brain-computer interface (BCI) systems. If the MI tasks are reliably distinguished through identifying typical patterns in electroencephalography (EEG) data, a motor disabled people could communicate with a device by composing sequences of these mental states. In our earlier study, we developed a cross-correlation based logistic regression (CC-LR) algorithm for the classification of MI tasks for BCI applications, but its performance was not satisfactory. This study develops a modified version of the CC-LR algorithm exploring a suitable feature set that can improve the performance. The modified CC-LR algorithm uses the C3 electrode channel (in the international 10-20 system) as a reference channel for the cross-correlation (CC) technique and applies three diverse feature sets separately, as the input to the logistic regression (LR) classifier. The present algorithm investigates which feature set is the best to characterize the distribution of MI tasks based EEG data. This study also provides an insight into how to select a reference channel for the CC technique with EEG signals considering the anatomical structure of the human brain. The proposed algorithm is compared with eight of the most recently reported well-known methods including the BCI III Winner algorithm. The findings of this study indicate that the modified CC-LR algorithm has potential to improve the identification performance of MI tasks in BCI systems. The results demonstrate that the proposed technique provides a classification improvement over the existing methods tested. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Likelihood ratios for the prediction of preterm delivery with biomarkers.

PubMed

Hee, Lene

2011-11-01

To conduct a literature search for selected biomarkers on preterm delivery and estimate their likelihood ratios (LR). Structured review. Low and high-risk populations and women with symptoms of preterm delivery. METHODS. Publications were identified in PubMed. LR on selected biomarkers for preterm delivery. In asymptomatic women with low risk of preterm delivery, the following biomarkers gave major shifts in probability (LR above 5): twins (LR+ 10), Ureaplasma urealyticum in amniotic fluid (LR+ of 10), cervical length <25mm (LR+ 6), salival estriol (LR+ 5) and various combined tests. In asymptomatic women with high risk of preterm delivery, short cervical length (LR+ 11, LR- 0.7), high serum tumor necrosis factor-alpha (LR+ 10, LR- 0.6) gave major shifts in probability. In women with symptoms of preterm delivery, major shifts in probability can be obtained from the following amniotic fluid biomarkers: high matrix metalloproteinase-8 (LR+ 23, LR- 0.6), Ureaplasma urealyticum (LR+ 19, LR- 0.8), high interleukin (IL)-6 (LR+ 9, LR- 0.2), IL-8 (LR+10, LR- 0.2) and tumor necrosis factor-alpha (LR+ 8, LR- 0.4). In serum IL-6 (LR+ 12, LR- 0.2), Cluster of Differentiation 163 (LR+9, LR-0.8) and various combined tests. Vaginal fetal fibronectin (LR+ 3 and LR- 0.5) and short cervical length (LR+ 2, LR- 0.3) gave LRs of some importance (LR below 5). Several biomarkers have been identified for assessment of risk of preterm delivery. Their clinical relevance depends on the efficacy of the interventions which can be offered to these patients. © 2011 The Author Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo.

PubMed

Katsu, Kenjiro; Tokumori, Daisuke; Tatsumi, Norifumi; Suzuki, Atsushi; Yokouchi, Yuji

2012-03-01

During left-right (L-R) axis formation, Nodal is expressed in the node and has a central role in the transfer of L-R information in the vertebrate embryo. Bone morphogenetic protein (BMP) signaling also has an important role for maintenance of gene expression around the node. Several members of the Cerberus/Dan family act on L-R patterning by regulating activity of the transforming growth factor-β (TGF-β) family. We demonstrate here that chicken Dan plays a critical role in L-R axis formation. Chicken Dan is expressed in the left side of the node shortly after left-handed Shh expression and before the appearance of asymmetrically expressed genes in the lateral plate mesoderm (LPM). In vitro experiments revealed that DAN inhibited BMP signaling but not NODAL signaling. SHH had a positive regulatory effect on Dan expression while BMP4 had a negative effect. Using overexpression and RNA interference-mediated knockdown strategies, we demonstrate that Dan is indispensable for Nodal expression in the LPM and for Lefty-1 expression in the notochord. In the perinodal region, expression of Dan and Nodal was independent of each other. Nodal up-regulation by DAN required NODAL signaling, suggesting that DAN might act synergistically with NODAL. Our data indicate that Dan plays an essential role in the establishment of the L-R axis by inhibiting BMP signaling around the node. Copyright © 2012. Published by Elsevier Inc.

Inheritance patterns of morphological laterality in mouth opening of zebrafish, Danio rerio.

PubMed

Hata, Hiroki; Hori, Michio

2012-01-01

The inheritance patterns of asymmetry in mouth opening in zebrafish were investigated using crossing experiments. Zebrafish exhibit asymmetric laterality in mouth opening, with each individual having either a leftward (righty) or rightward (lefty) bias. All righty incrosses produced only righty F(1), whereas all lefty incrosses resulted in an F(1) L:R ratio of 2:1. All test crosses between lefty and righty individuals resulted in an F(1) L:R=1:1. These results were consistent with the hereditary pattern for Japanese medaka, three Tanganyikan cichlids, and a Japanese riverine goby. The pattern suggests a one-locus two-allele Mendelian model of inheritance, with the lefty allele being dominant over righty and the dominant homozygote being lethal. To determine the reason for the absence of lefty homozygotes, the survival rates of the offspring were examined according to developmental stage. Survival did not differ among combinations of parent laterality. Thus the mechanism underlying the lethality of the dominant homozygote remains unclear. This study showed that the mouth-opening laterality of zebrafish is genetically determined and that the direction follows a Mendelian inheritance pattern that is shared among cypriniform zebrafish, beloniform medaka, perciform cichlids, and a goby, suggesting a common genetic background in mouth-opening laterality among these species.

Phylogenetic correspondence of the body axes in bilaterians is revealed by the right-sided expression of Pitx genes in echinoderm larvae.

PubMed

Hibino, Taku; Nishino, Atsuo; Amemiya, Shonan

2006-12-01

Chordates and echinoderms are two of the three major deuterostome phyla and show conspicuous left-right (LR) asymmetry. The establishment of LR asymmetry has been explored in vertebrates, but is largely unknown in echinoderms. Here, we report the expression pattern of genes that are orthologous to the chordate left-side specific gene Pitx, cloned from the sea urchin Hemicentrotus pulcherrimus (HpPitx) and the starfish Asterina pectinifera (ApPitx). HpPitx transcripts were first detected bilaterally in one cell of the ventrolateral primary mesenchyme-cell aggregate of early prism larvae. New expression was detected asymmetrically in the right counterpart of a bilateral pair of mesodermal coelomic pouches and in the right ectoderm. In starfish bipinnaria larvae, the ApPitx signal was detected in the right coelomic pouch and in the right half of the ectoderm along the ciliary bands. These results suggest that the function of Pitx in establishing LR asymmetry was introduced in the last common ancestor of echinoderms and chordates. However, the right-side specific expression in echinoderm larvae is inverted compared to chordate embryos. This indicates that the LR axis is inversely represented between echinoderms and chordates, which supports the scenario that dorsoventral axis inversion was introduced into the chordate lineage by turning upside down.

Neural signatures of co-occurring reading and mathematical difficulties.

PubMed

Skeide, Michael A; Evans, Tanya M; Mei, Edward Z; Abrams, Daniel A; Menon, Vinod

2018-06-19

Impaired abilities in multiple domains is common in children with learning difficulties. Co-occurrence of low reading and mathematical abilities (LRLM) appears in almost every second child with learning difficulties. However, little is known regarding the neural bases of this combination. Leveraging a unique and tightly controlled sample including children with LRLM, isolated low reading ability (LR), and isolated low mathematical ability (LM), we uncover a distinct neural signature in children with co-occurring low reading and mathematical abilities differentiable from LR and LM. Specifically, we show that LRLM is neuroanatomically distinct from both LR and LM based on reduced cortical folding of the right parahippocampal gyrus, a medial temporal lobe region implicated in visual associative learning. LRLM children were further distinguished from LR and LM by patterns of intrinsic functional connectivity between parahippocampal gyrus and brain circuitry underlying reading and numerical quantity processing. Our results critically inform cognitive and neural models of LRLM by implicating aberrations in both domain-specific and domain-general brain regions involved in reading and mathematics. More generally, our results provide the first evidence for distinct multimodal neural signatures associated with LRLM, and suggest that this population displays an independent phenotype of learning difficulty that cannot be explained simply as a combination of isolated low reading and mathematical abilities. © 2018 John Wiley & Sons Ltd.

Lettuce (Lactuca sativa L.) leaf-proteome profiles after exposure to cylindrospermopsin and a microcystin-LR/cylindrospermopsin mixture: a concentration-dependent response.

PubMed

Freitas, Marisa; Campos, Alexandre; Azevedo, Joana; Barreiro, Aldo; Planchon, Sébastien; Renaut, Jenny; Vasconcelos, Vitor

2015-02-01

The intensification of agricultural productivity is an important challenge worldwide. However, environmental stressors can provide challenges to this intensification. The progressive occurrence of the cyanotoxins cylindrospermopsin (CYN) and microcystin-LR (MC-LR) as a potential consequence of eutrophication and climate change is of increasing concern in the agricultural sector because it has been reported that these cyanotoxins exert harmful effects in crop plants. A proteomic-based approach has been shown to be a suitable tool for the detection and identification of the primary responses of organisms exposed to cyanotoxins. The aim of this study was to compare the leaf-proteome profiles of lettuce plants exposed to environmentally relevant concentrations of CYN and a MC-LR/CYN mixture. Lettuce plants were exposed to 1, 10, and 100 μg/l CYN and a MC-LR/CYN mixture for five days. The proteins of lettuce leaves were separated by two-dimensional electrophoresis (2-DE), and those that were differentially abundant were then identified by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF/TOF MS). The biological functions of the proteins that were most represented in both experiments were photosynthesis and carbon metabolism and stress/defense response. Proteins involved in protein synthesis and signal transduction were also highly observed in the MC-LR/CYN experiment. Although distinct protein abundance patterns were observed in both experiments, the effects appear to be concentration-dependent, and the effects of the mixture were clearly stronger than those of CYN alone. The obtained results highlight the putative tolerance of lettuce to CYN at concentrations up to 100 μg/l. Furthermore, the combination of CYN with MC-LR at low concentrations (1 μg/l) stimulated a significant increase in the fresh weight (fr. wt) of lettuce leaves and at the proteomic level resulted in the increase in abundance of a high number of proteins. In contrast, many proteins exhibited a decrease in abundance or were absent in the gels of the simultaneous exposure to 10 and 100 μg/l MC-LR/CYN. In the latter, also a significant decrease in the fr. wt of lettuce leaves was obtained. These findings provide important insights into the molecular mechanisms of the lettuce response to CYN and MC-LR/CYN and may contribute to the identification of potential protein markers of exposure and proteins that may confer tolerance to CYN and MC-LR/CYN. Furthermore, because lettuce is an important crop worldwide, this study may improve our understanding of the potential impact of these cyanotoxins on its quality traits (e.g., presence of allergenic proteins). Copyright © 2014 Elsevier Ltd. All rights reserved.

Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI.

PubMed

Freitag, Martin T; Radtke, Jan P; Afshar-Oromieh, Ali; Roethke, Matthias C; Hadaschik, Boris A; Gleave, Martin; Bonekamp, David; Kopka, Klaus; Eder, Matthias; Heusser, Thorsten; Kachelriess, Marc; Wieczorek, Kathrin; Sachpekidis, Christos; Flechsig, Paul; Giesel, Frederik; Hohenfellner, Markus; Haberkorn, Uwe; Schlemmer, Heinz-Peter; Dimitrakopoulou-Strauss, A

2017-05-01

The positron emission tomography (PET) tracer 68 Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the 68 Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR. One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid 68 Ga-PSMA-11-PET/CT low-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in 68 Ga-PSMA-11-PET. Standardized-uptake-value (SUV mean ) quantification of LR was performed. There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUV mean in nine men was 8.7 ± 3.7 (PET/CT) and 7.0 ± 4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder). The present study demonstrates additional value of hybrid 68 Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to the 68 Ga-PSMA-11-PET/CT low-dose for patients with LR of PC.

Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction.

PubMed

Piccolo, Brian D; Keim, Nancy L; Fiehn, Oliver; Adams, Sean H; Van Loan, Marta D; Newman, John W

2015-04-01

Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation. This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity. Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders. Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P = 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01]. Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312. © 2015 American Society for Nutrition.

An investigation into resting behavior in Asian elephants in UK zoos.

PubMed

Williams, Ellen; Bremner-Harrison, Samantha; Harvey, Naomi; Evison, Emma; Yon, Lisa

2015-01-01

Maintaining adequate welfare in captive elephants is challenging. Few studies have investigated overnight rest behavior in zoo elephants, yet time spent resting has been identified as a welfare indicator in some species. We investigated resting behavior in Asian elephants (Elephas maximus) in UK zoos, with the aim of identifying patterns or preferences in lying rest. Details of standing (SR) and lying (LR) rest behavior were identified by observing video footage of inside enclosures collected for 14 elephants (2 male, 12 female) housed at three UK zoos (Zoo A: 18 nights; Zoo B: 27 nights; Zoo C: 46 nights) from 16:00 to 08:30 (approximately). Elephants engaged in a mean of 58-337 min rest per night. Time of night affected mean duration of LR bouts (P < 0.001); longest bouts were observed between 22:01 and 06:00. Elephants showed a substrate preference when lying to rest; LR was not observed on concrete or tiled flooring. Where sand was available (to 11/14 elephants), all elephants engaged in LR on sand flooring. Only two elephants engaged in LR on rubber flooring (available to 7/14 elephants). Mean duration of rest bouts was greater when a conspecific was within two body lengths than when conspecifics were not (P < 0.01). Our study indicated that elephants show substrate preferences when choosing an area for rest and engage in more rest when conspecifics are in close proximity. The results of this study could be used as a basis for future studies investigating the link between rest and welfare in captive elephants. © 2015 Wiley Periodicals, Inc.

Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala

PubMed Central

McCoy, Chelsea R.; Jackson, Nateka L.; Day, Jeremy; Clinton, Sarah M.

2016-01-01

Understanding biological mechanisms that shape vulnerability to emotional dysfunction is critical for elucidating the neurobiology of psychiatric illnesses like anxiety and depression. To elucidate molecular and epigenetic alterations in the brain that contribute to individual differences in emotionality, our laboratory utilized a rodent model of temperamental differences. Rats bred for low response to novelty (Low Responders, LRs) are inhibited in novel situations and display high anxiety, helplessness, and diminished sociability compared to High Novelty Responder (HR) rats. Our current transcriptome profiling experiment identified widespread gene expression differences in the amygdala of adult HR/LR rats; we hypothesize that HR/LR gene expression and downstream behavioral differences stem from distinct epigenetic (specifically DNA methylation) patterning in the HR/LR brain. Although we found similar levels of DNA methyltransferase proteins in the adult HR/LR amygdala, next-generation sequencing analysis of the methylome revealed 793 differentially methylated genomic sites between the groups. Most of the differentially methylated sites were hypermethylated in HR versus LR, so we next tested the hypothesis that enhancing DNA methylation in LRs would improve their anxiety/depression-like phenotype. We found that increasing DNA methylation in LRs (via increased dietary methyl donor content) improved their anxiety-like behavior and decreased their typically high levels of Forced Swim Test (FST) immobility; however, dietary methyl donor depletion exacerbated LRs’ high FST immobility. These data are generally consistent with findings in depressed patients showing that treatment with DNA methylation-promoting agents improves depressive symptoms, and highlight epigenetic mechanisms that may contribute to individual differences in risk for emotional dysfunction. PMID:27965039

Registration of spring wheat sources of the resistance genes Lr53, Lr56, Lr59 and Lr62

USDA-ARS?s Scientific Manuscript database

Spring wheat (Triticum aestivum L.) germplasm with the alien derived leaf rust (caused by Puccinia triticina Erikss) resistance genes, Lr53, Lr56, Lr59, and Lr62 has been developed with infrastructure and financial support provided consecutively by the University of Stellenbosch (South Africa), the ...

Experimental investigation of the mechanical properties of brain simulants used for cranial gunshot simulation.

PubMed

Lazarjan, Milad Soltanipour; Geoghegan, Patrick Henry; Jermy, Mark Christopher; Taylor, Michael

2014-06-01

The mechanical properties of the human brain at high strain rate were investigated to analyse the mechanisms that cause backspatter when a cranial gunshot wound occurs. Different concentrations of gelatine and a new material (M1) developed in this work were tested and compared to bovine brain samples. Kinetic energy absorption and expansion rate of the samples caused by the impact of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22 long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high speed camera (24,000fps). The AR projectile had, in the region of interest, an average kinetic energy (Ek) of 42±1.3J. On average, the bovine brain absorbed 50±5% of Ek, and the simulants 46-58±5%. The Ek of the .22 LR was 141±3.7J. The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The expansion of the sample, after penetration, was measured. The bovine brain experienced significant plastic deformation whereas the gelatine solution exhibited a principally elastic response. The permanent damage patterns in the M1 material were much closer to those in brain tissue, than were the damage patterns in the gelatine. The results provide a first step to developing a realistic experimental simulant for the human brain which can produce the same blood backspatter patterns as a human brain during a cranial gunshot. These results can also be used to improve the 3D models of human heads used in car crash and blast trauma injury research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

YUCCA9-Mediated Auxin Biosynthesis and Polar Auxin Transport Synergistically Regulate Regeneration of Root Systems Following Root Cutting

PubMed Central

Xu, Dongyang; Miao, Jiahang; Yumoto, Emi; Yokota, Takao; Asahina, Masashi; Watahiki, Masaaki

2017-01-01

Abstract Recovery of the root system following physical damage is an essential issue for plant survival. An injured root system is able to regenerate by increases in lateral root (LR) number and acceleration of root growth. The horticultural technique of root pruning (root cutting) is an application of this response and is a common garden technique for controlling plant growth. Although root pruning is widely used, the molecular mechanisms underlying the subsequent changes in the root system are poorly understood. In this study, root pruning was employed as a model system to study the molecular mechanisms of root system regeneration. Notably, LR defects in wild-type plants treated with inhibitors of polar auxin transport (PAT) or in the auxin signaling mutant auxin/indole-3-acetic acid19/massugu2 were recovered by root pruning. Induction of IAA19 following root pruning indicates an enhancement of auxin signaling by root pruning. Endogenous levels of IAA increased after root pruning, and YUCCA9 was identified as the primary gene responsible. PAT-related genes were induced after root pruning, and the YUCCA inhibitor yucasin suppressed root regeneration in PAT-related mutants. Therefore, we demonstrate the crucial role of YUCCA9, along with other redundant YUCCA family genes, in the enhancement of auxin biosynthesis following root pruning. This further enhances auxin transport and activates downstream auxin signaling genes, and thus increases LR number. PMID:29016906

The wheat resistance gene Lr34 results in the constitutive induction of multiple defense pathways in transgenic barley.

PubMed

Chauhan, Harsh; Boni, Rainer; Bucher, Rahel; Kuhn, Benjamin; Buchmann, Gabriele; Sucher, Justine; Selter, Liselotte L; Hensel, Goetz; Kumlehn, Jochen; Bigler, Laurent; Glauser, Gaëtan; Wicker, Thomas; Krattinger, Simon G; Keller, Beat

2015-10-01

The wheat gene Lr34 encodes an ABCG-type transporter which provides durable resistance against multiple pathogens. Lr34 is functional as a transgene in barley, but its mode of action has remained largely unknown both in wheat and barley. Here we studied gene expression in uninfected barley lines transgenic for Lr34. Genes from multiple defense pathways contributing to basal and inducible disease resistance were constitutively active in seedlings and mature leaves. In addition, the hormones jasmonic acid and salicylic acid were induced to high levels, and increased levels of lignin as well as hordatines were observed. These results demonstrate a strong, constitutive re-programming of metabolism by Lr34. The resistant Lr34 allele (Lr34res) encodes a protein that differs by two amino acid polymorphisms from the susceptible Lr34sus allele. The deletion of a single phenylalanine residue in Lr34sus was sufficient to induce the characteristic Lr34-based responses. Combination of Lr34res and Lr34sus in the same plant resulted in a reduction of Lr34res expression by 8- to 20-fold when the low-expressing Lr34res line BG8 was used as a parent. Crosses with the high-expressing Lr34res line BG9 resulted in an increase of Lr34sus expression by 13- to 16-fold in progenies that inherited both alleles. These results indicate an interaction of the two Lr34 alleles on the transcriptional level. Reduction of Lr34res expression in BG8 crosses reduced the negative pleiotropic effects of Lr34res on barley growth and vigor without compromising disease resistance, suggesting that transgenic combination of Lr34res and Lr34sus can result in agronomically useful resistance. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Pattern centric design based sensitive patterns and process monitor in manufacturing

NASA Astrophysics Data System (ADS)

Hsiang, Chingyun; Cheng, Guojie; Wu, Kechih

2017-03-01

When design rule is mitigating to smaller dimension, process variation requirement is tighter than ever and challenges the limits of device yield. Masks, lithography, etching and other processes have to meet very tight specifications in order to keep defect and CD within the margins of the process window. Conventionally, Inspection and metrology equipments are utilized to monitor and control wafer quality in-line. In high throughput optical inspection, nuisance and review-classification become a tedious labor intensive job in manufacturing. Certain high-resolution SEM images are taken to validate defects after optical inspection. These high resolution SEM images catch not only optical inspection highlighted point, also its surrounding patterns. However, this pattern information is not well utilized in conventional quality control method. Using this complementary design based pattern monitor not only monitors and analyzes the variation of patterns sensitivity but also reduce nuisance and highlight defective patterns or killer defects. After grouping in either single or multiple layers, systematic defects can be identified quickly in this flow. In this paper, we applied design based pattern monitor in different layers to monitor process variation impacts on all kinds of patterns. First, the contour of high resolutions SEM image is extracted and aligned to design with offset adjustment and fine alignment [1]. Second, specified pattern rules can be applied on design clip area, the same size as SEM image, and form POI (pattern of interest) areas. Third, the discrepancy of contour and design measurement at different pattern types in measurement blocks. Fourth, defective patterns are reported by discrepancy detection criteria and pattern grouping [4]. Meanwhile, reported pattern defects are ranked by number and severity by discrepancy. In this step, process sensitive high repeatable systematic defects can be identified quickly Through this design based process pattern monitor method, most of optical inspection nuisances can be filtered out at contour to design discrepancy measurement. Daily analysis results are stored at database as reference to compare with incoming data. Defective pattern library contains existing and known systematic defect patterns which help to catch and identify new pattern defects or process impacts. On the other hand, this defect pattern library provides extra valuable information for mask, pattern and defects verification, inspection care area generation, further OPC fix and process enhancement and investigation.

Intestinal fatty acid-binding protein and gut permeability responses to exercise.

PubMed

March, Daniel S; Marchbank, Tania; Playford, Raymond J; Jones, Arwel W; Thatcher, Rhys; Davison, Glen

2017-05-01

Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Two-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P < 0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P < 0.001) and Col (148% of pre, P < 0.001) with post-exercise values significantly lower with Col (P < 0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each. These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

Effects of alien and intraspecies cytoplasms on manifestation of nuclear genes for wheat resistance to brown rust: II. Specificity of cytoplasm influence on different Lr genes

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

Voluevich, E.A.; Buloichik, A.A.; Palilova, A.N.

Specificity of expression of the major nuclear genes Lr to two brown rust clones in hybrids with the same maternal cytoplasm was analyzed. It was evaluated by a resistant: susceptible ratio in the F{sub 2}. Reciprocal hybrids were obtained from the cross between the progeny of homozygous susceptible plants of the cultivar Penjamo 62 and its alloplasmatic lines carrying cytoplasms of Triticum dicoccoides var. fulvovillosum, Aegilops squarrosa var. typical, Agropyron trichophorum, and isogenic lines of the cultivar Thatcher (Th) with the Lr1, Lr9, Lr15, and Lr19 genes. It was shown that the effect of the Lr1 gene in the cytoplasmmore » of cultivar Thatcher and in eu-, and alloplasmatic forms of Penjamo 62 was less expressed than that of other Lr genes. Cytoplasm of the alloplasmatic line (dicoccoides)-Penjamo 62 was the only exception: in the F{sub 2}, hybrids with Th (Lr1) had a higher yield of resistant forms than those with Th (Lr15). In the hybrid combinations studied, expression and/or transmission of the Lr19 gene was more significant than that of other genes. This gene had no advantages over Lr15 and Lr19 only in cytoplasm of the alloplasmatic line (squarrosa)-Penjamo 62. In certain hybrid cytoplasms, the display of the Lr1, Lr15, and Lr19 genes, in contrast to Lr9, varied with the virulence of the pathogen clones. 15 refs., 5 tabs.« less

Applications of Parsing Theory to Computer-Assisted Instruction.

ERIC Educational Resources Information Center

Markosian, Lawrence Z.; Ager, Tryg A.

1983-01-01

Applications of an LR-1 parsing algorithm to intelligent programs for computer assisted instruction in symbolic logic and foreign languages are discussed. The system has been adequately used for diverse instructional applications, including analysis of student input, generation of pattern drills, and modeling the student's understanding of the…

Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

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

Varlotto, John M., E-mail: john.varlotto@umassmemorial.org; Yao, Aaron N.; DeCamp, Malcolm M.

Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy.more » Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.« less

Oncologic outcome after local recurrence of chondrosarcoma: Analysis of prognostic factors.

PubMed

Kim, Han-Soo; Bindiganavile, Srimanth S; Han, Ilkyu

2015-06-01

Literature on outcome after local recurrence (LR) in chondrosarcoma is scarce and better appreciation of prognostic factors is needed. (1) To evaluate post-LR oncologic outcomes of disease-specific survival and subsequent LR and (2) to identify prognostic factors for post-LR oncologic outcomes. Review of 28 patients with locally recurrent chondrosarcoma from the original cohort of 150 patients, who were treated surgically with or without adjuvants between 1982 and 2011, was performed. Mean age was 46 years (range, 21-73) which included 20 males and 8 females with mean follow up of 8.4 ± 7.5 years (range, 1.2-31.0). Post-LR survival at 5 years was 58.6 ± 10.3%. Age greater than 50 years (P = 0.011) and LR occurring within 1 year of primary surgery (P = 0.011) independently predicted poor survival. Seven patients suffered subsequent LR, which was significantly affected by surgical margin for LR (P = 0.038). Long-term survival of locally recurrent chondrosarcoma is achievable in a substantial number of patients. Older age at onset of LR and shorter interval from primary surgery to LR identifies high risk patients for poor post-LR survival while, wide surgical margins at LR surgery reduces the risk of subsequent LR. © 2015 Wiley Periodicals, Inc.

An experimental method for the assessment of color simulation tools.

PubMed

Lillo, Julio; Alvaro, Leticia; Moreira, Humberto

2014-07-22

The Simulcheck method for evaluating the accuracy of color simulation tools in relation to dichromats is described and used to test three color simulation tools: Variantor, Coblis, and Vischeck. A total of 10 dichromats (five protanopes, five deuteranopes) and 10 normal trichromats participated in the current study. Simulcheck includes two psychophysical tasks: the Pseudoachromatic Stimuli Identification task and the Minimum Achromatic Contrast task. The Pseudoachromatic Stimuli Identification task allows determination of the two chromatic angles (h(uv) values) that generate a minimum response in the yellow–blue opponent mechanism and, consequently, pseudoachromatic stimuli (greens or reds). The Minimum Achromatic Contrast task requires the selection of the gray background that produces minimum contrast (near zero change in the achromatic mechanism) for each pseudoachromatic stimulus selected in the previous task (L(R) values). Results showed important differences in the colorimetric transformations performed by the three evaluated simulation tools and their accuracy levels. Vischeck simulation accurately implemented the algorithm of Brettel, Viénot, and Mollon (1997). Only Vischeck appeared accurate (similarity in huv and L(R) values between real and simulated dichromats) and, consequently, could render reliable color selections. It is concluded that Simulcheck is a consistent method because it provided an equivalent pattern of results for huv and L(R) values irrespective of the stimulus set used to evaluate a simulation tool. Simulcheck was also considered valid because real dichromats provided expected huv and LR values when performing the two psychophysical tasks included in this method. © 2014 ARVO.

Microcystin production and ecological physiology of Caribbean black band disease cyanobacteria.

PubMed

Stanić, Dina; Oehrle, Stuart; Gantar, Miroslav; Richardson, Laurie L

2011-04-01

Molecular studies of black band disease (BBD), a coral disease found on tropical and subtropical reefs worldwide, have shown that one 16S rRNA gene sequence is ubiquitous. This sequence has been reported to be a member of the cyanobacterial genus Oscillatoria. In this study, extracts of two cultured laboratory strains of BBD Oscillatoria, and for comparison two strains of BBD Geitlerinema, all isolated from reefs of the wider Caribbean, were analysed using Ultra-Performance Liquid Chromatography-Tandem Quad Mass Spectrometry (UPLC-MS/MS). The cyanotoxin microcystin-LR (MC-LR) was found in all strains, and one Geitlerinema strain additionally produced MC-YR. Growth experiments that monitored toxin production using enzyme-linked immunosorbent assay (ELISA) showed that BBD Oscillatoria produced yields of MC-LR equivalent (0.02-0.04 mg g(-1)) independent of biomass and culture conditions (varying temperature, pH, light and organic carbon). This pattern is different from BBD Geitlerinema, which increased production of MC-LR equivalent in the presence of organic carbon in the light and dark and at a relatively lower temperature. These results indicate that different species and strains of BBD cyanobacteria, which can occur in the same BBD infection, may contribute to BBD pathobiology by producing different toxins and different amounts of toxin at different stages in the disease process. This is the first detailed study of laboratory cultures of the ubiquitous BBD cyanobacterium Oscillatoria sp. isolated from Caribbean reefs. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Diagnostic accuracy of history and physical examination in bacterial acute rhinosinusitis.

PubMed

Autio, Timo J; Koskenkorva, Timo; Närkiö, Mervi; Leino, Tuomo K; Koivunen, Petri; Alho, Olli-Pekka

2015-07-01

To evaluate the diagnostic accuracy of symptoms, the symptom progression pattern, and clinical signs in identifying bacterial acute rhinosinusitis (ARS). We conducted an inception cohort study among 50 military recruits with ARS. We collected symptoms daily from the onset of symptoms to approximately 10 days. At 9 to 10 days, standardized data on symptoms and physical findings were gathered. A positive culture of maxillary sinus aspirate was considered to be the reference standard for bacterial ARS. At 9 to 10 days, the presence or deterioration after 5 days of any of the symptoms could not be used to diagnose bacterial ARS. Toothache had an adequate positive likelihood ratio (positive likelihood ratio [LR+] 4.4) but was too rare to be used for screening. In contrast, several physical findings at 9 to 10 days were of more diagnostic use and frequent enough for screening. Moderate or profuse (vs. none/minimal) amount of secretion in nasal passage seen in anterior rhinoscopy satisfactorily either ruled in, if present (LR+ 3.2), or ruled out, if absent (negative likelihood ratio 0.2), bacterial ARS. If any secretion was seen in the posterior pharynx or middle meatus, the probability of bacterial ARS increased markedly (LR+ 5.3 and LR+ 11.0, respectively). We found symptoms or their change to be of little use in identifying bacterial ARS. In contrast, we observed several clinical findings after 9 to 10 days of symptoms to predict bacterial ARS quite accurately. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Back-irradiation photonic sintering for defect-free high-conductivity metal patterns on transparent plastic

NASA Astrophysics Data System (ADS)

Kwak, Ji Hye; Chun, Su Jin; Shon, Chae-Hwa; Jung, Sunshin

2018-04-01

Photonic sintering has attracted considerable attention for printed electronics. It irradiates high-intensity light onto the front surface of metal nanoparticle patterns, which often causes defects such as delamination, cavities, and cracks in the patterns. Here, a back-irradiation photonic sintering method is developed for obtaining defect-free high-conductivity metal patterns on a transparent plastic substrate, through which high-intensity light is irradiated onto the back surface of the patterns for a few milliseconds. Ag patterns back-irradiated with ˜10.0 J cm-2 are defect-free in contrast to front-irradiated patterns and exhibited an electrical conductivity of ˜2.3 × 107 S m-1. Furthermore, real-time high-speed observation reveals that the mechanisms that generate defects in the front-irradiated patterns and prevent defects in the back-irradiated patterns are closely related to vapor trapping. In contrast to the latter, in the former, vapor is trapped and delaminates the patterns from the substrate because the front of the patterns acts as a barrier to vapor venting.

Detecting Submicron Pattern Defects On Optical Photomasks Using An Enhanced El-3 Electron-Beam Lithography Tool

NASA Astrophysics Data System (ADS)

Simpson, R. A.; Davis, D. E.

1982-09-01

This paper describes techniques to detect submicron pattern defects on optical photomasks with an enhanced direct-write, electron-beam lithographic tool. EL-3 is a third generation, shaped spot, electron-beam lithography tool developed by IBM to fabricate semiconductor devices and masks. This tool is being upgraded to provide 100% inspection of optical photomasks for submicron pattern defects, which are subsequently repaired. Fixed-size overlapped spots are stepped over the mask patterns while a signal derived from the back-scattered electrons is monitored to detect pattern defects. Inspection does not require pattern recognition because the inspection scan patterns are derived from the original design data. The inspection spot is square and larger than the minimum defect to be detected, to improve throughput. A new registration technique provides the beam-to-pattern overlay required to locate submicron defects. The 'guard banding" of inspection shapes prevents mask and system tolerances from producing false alarms that would occur should the spots be mispositioned such that they only partially covered a shape being inspected. A rescanning technique eliminates noise-related false alarms and significantly improves throughput. Data is accumulated during inspection and processed offline, as required for defect repair. EL-3 will detect 0.5 um pattern defects at throughputs compatible with mask manufacturing.

Driving down defect density in composite EUV patterning film stacks

NASA Astrophysics Data System (ADS)

Meli, Luciana; Petrillo, Karen; De Silva, Anuja; Arnold, John; Felix, Nelson; Johnson, Richard; Murray, Cody; Hubbard, Alex; Durrant, Danielle; Hontake, Koichi; Huli, Lior; Lemley, Corey; Hetzer, Dave; Kawakami, Shinichiro; Matsunaga, Koichi

2017-03-01

Extreme ultraviolet lithography (EUVL) technology is one of the leading candidates for enabling the next generation devices, for 7nm node and beyond. As the technology matures, further improvement is required in the area of blanket film defectivity, pattern defectivity, CD uniformity, and LWR/LER. As EUV pitch scaling approaches sub 20 nm, new techniques and methods must be developed to reduce the overall defectivity, mitigate pattern collapse and eliminate film related defect. IBM Corporation and Tokyo Electron Limited (TELTM) are continuously collaborating to develop manufacturing quality processes for EUVL. In this paper, we review key defectivity learning required to enable 7nm node and beyond technology. We will describe ongoing progress in addressing these challenges through track-based processes (coating, developer, baking), highlighting the limitations of common defect detection strategies and outlining methodologies necessary for accurate characterization and mitigation of blanket defectivity in EUV patterning stacks. We will further discuss defects related to pattern collapse and thinning of underlayer films.

Shorter spontaneous fixation durations in infants with later emerging autism.

PubMed

Wass, Sam V; Jones, Emily J H; Gliga, Teodora; Smith, Tim J; Charman, Tony; Johnson, Mark H

2015-02-06

Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined.

Substrate Stiffness Regulates the Development of Left-Right Asymmetry in Cell Orientation.

PubMed

Bao, Yuanye; Huang, Yaozhun; Lam, Miu Ling; Xu, Ting; Zhu, Ninghao; Guo, Zhaobin; Cui, Xin; Lam, Raymond H W; Chen, Ting-Hsuan

2016-07-20

Left-right (LR) asymmetry of tissue/organ structure is a morphological feature essential for many tissue functions. The ability to incorporate the LR formation in constructing tissue/organ replacement is important for recapturing the inherent tissue structure and functions. However, how LR asymmetry is formed remains largely underdetermined, which creates significant hurdles to reproduce and regulate the formation of LR asymmetry in an engineering context. Here, we report substrate rigidity functioning as an effective switch that turns on the development of LR asymmetry. Using micropatterned cell-adherent stripes on rigid substrates, we found that cells collectively oriented at a LR-biased angle relative to the stripe boundary. This LR asymmetry was initiated by a LR-biased migration of cells at stripe boundary, which later generated a velocity gradient propagating from stripe boundary to the center. After a series of cell translocations and rotations, ultimately, an LR-biased cell orientation within the micropatterned stripe was formed. Importantly, this initiation and propagation of LR asymmetry was observed only on rigid but not on soft substrates, suggesting that the LR asymmetry was regulated by rigid substrate probably through the organization of actin cytoskeleton. Together, we demonstrated substrate rigidity as a determinant factor that mediates the self-organizing LR asymmetry being unfolded from single cells to multicellular organization. More broadly, we anticipate that our findings would pave the way for rebuilding artificial tissue constructs with inherent LR asymmetry in the future.

Brief Report: Atypical expression of distress during the separation phase of the strange situation procedure in infant siblings at high risk for ASD.

PubMed

Esposito, Gianluca; Del Carmen Rostagno, Maria; Venuti, Paola; Haltigan, John D; Messinger, Daniel S

2014-04-01

Previous studies have provided preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism early in life. We examined the acoustic characteristics of cries extracted from the separation phase of the strange situation procedure in a sample of toddler of younger siblings of a child with autism spectrum disorder-autism spectrum disorders (ASD) (high risk, HR) and a low risk (LR) group. Cry samples derived from vocal recordings of 15-month-old HR (n = 13) and LR infants (n = 14) were subjected to acoustic analyses. HR toddlers, compared to those with LR, produced cries that were shorter and had a higher fundamental frequency (F0). Three HR toddlers later classified with an ASD at 36 months (autistic disorder in all cases) produced cries that had among the highest F0 and shortest durations. Taken together these results indicate that toddlers at high risk for ASD (and those with an ASD) express atypical patterns of distress in response a social stressor. Implications for early diagnosis and parenting are discussed.

Immunohistochemical myofiber typing and high-resolution myofibrillar lesion detection in LR white embedded muscle

NASA Technical Reports Server (NTRS)

Thompson, J. L.; Vijayan, K.; Riley, D. A.

2000-01-01

We have developed a method of fixing, embedding, sectioning, and staining that allows high-resolution detection of myofibrillar structure and myosin immunocytochemical muscle fiber typing in serial semithin sections of LR White plastic embedded muscle at the light microscopic level. Traditional approaches, such as cryostat sections, permit fiber typing, but small myofibrillar lesions (1-3 sarcomeres) are difficult to detect because of section thickness. Semithin sections of hydrophobic resins do not stain well either histochemically or immunocytochemically. Electron microscopy can resolve lesions and discriminate fiber types based on morphology, but the sampling area is small. Our goal was to develop a rapid method for defining both fiber type and high-resolution primary myofibrillar lesion damage. Mild fixation (1-4% paraformaldehyde, 0. 05-0.1% glutaraldehyde) and embedment in a hydrophilic resin (LR White) were used. Myofibrillar structure was extremely well preserved at the light microscopic (LM) level, and lesions could be readily resolved in Toluidine blue stained 500-nm sections. Fiber type was defined by LM immunomyosin staining of serial plastic semithin sections, which demonstrated reciprocal staining patterns for "fast (Sigma M4276) and "total" (skeletal muscle) myosins (Sigma M7523). Copyright 2000 Wiley-Liss, Inc.

Does the patient with chest pain have a coronary heart disease? Diagnostic value of single symptoms and signs--a meta-analysis.

PubMed

Haasenritter, Jorg; Stanze, Damaris; Widera, Grit; Wilimzig, Christian; Abu Hani, Maren; Sonnichsen, Andreas C; Bosner, Stefan; Rochon, Justine; Donner-Banzhoff, Norbert

2012-10-01

To determine the diagnostic value of single symptoms and signs for coronary heart disease (CHD) in patients with chest pain. Searches of two electronic databases (EMBASE 1980 to March 2008, PubMed 1966 to May 2009) and hand searching in seven journals were conducted. Eligible studies recruited patients presenting with acute or chronic chest pain. The target disease was CHD, with no restrictions regarding case definitions, eg, stable CHD, acute coronary syndrome (ACS), acute myocardial infarction (MI), or major cardiac event (MCE). Diagnostic tests of interest were items of medical history and physical examination. Bivariate random effects model was used to derive summary estimates of positive (pLR) and negative likelihood ratios (nLR). We included 172 studies providing data on the diagnostic value of 42 symptoms and signs. With respect to case definition of CHD, diagnostically most useful tests were history of CHD (pLR=3.59), known MI (pLR=3.21), typical angina (pLR=2.35), history of diabetes mellitus (pLR=2.16), exertional pain (pLR=2.13), history of angina pectoris (nLR=0.42), and male sex (nLR=0.49) for diagnosing stable CHD; pain radiation to right arm/shoulder (pLR=4.43) and palpitation (pLR=0.47) for diagnosing MI; visceral pain (pLR=2.05) for diagnosing ACS; and typical angina (pLR=2.60) and pain reproducible by palpation (pLR=0.13) for predicting MCE. We comprehensively reported the accuracy of a broad spectrum of single symptoms and signs for diagnosing myocardial ischemia. Our results suggested that the accuracy of several symptoms and signs varied in the published studies according to the case definition of CHD.

Molecular and analysis of a phenylalanine ammonia-lyase gene (LrPAL2) from Lycoris radiata.

PubMed

Jiang, Yumei; Xia, Bing; Liang, Lijian; Li, Xiaodan; Xu, Sheng; Peng, Feng; Wang, Ren

2013-03-01

Phenylalanine ammonia-lyase (PAL), the first enzyme of phenylpropanoid biosynthesis, participates in the biosynthesis of flavonoids, lignins, stilbenes and many other compounds. In this study, we cloned a 2,326 bp full-length PAL2 gene from Lycoris radiata by using degenerate oligonucleotide primer PCR (DOP-PCR) and the rapid amplification of cDNA ends method. The cDNA contains a 2,124 bp coding region encoding 707 amino acids. The LrPAL2 shares about 77.0 % nucleic acid identity and 83 % amino acid identity with LrPAL1. Furthermore, genome sequence analysis demonstrated that LrPAL2 gene contains one intron and two exons. The 5' flanking sequence of LrPAL2 was also cloned by self-formed adaptor PCR (SEFA-PCR), and a group of putative cis-acting elements such as TATA box, CAAT box, G box, TC-rich repeats, CGTCA motif and TCA-element were identified. The LrPAL2 was detected in all tissues examined, with high abundance in bulbs at leaf sprouting stage and in petals at blooming stage. Besides, LrPAL2 drastically responded to MJ, SNP and UV, moderately responded to GA and SA, and a little increased under wounding. Comparison of LrPAL2 expression and LrPAL1 expression demonstrated that LrPAL2 can be more significantly induced than LrPAL1 under the above treatments, and LrPAL2 transcripts accumulated prominently at blooming stage, especially in petals, while LrPAL1 transcripts did not accumulated significantly at blooming stage. All these results suggested that LrPAL2 might play distinct roles in different branches of the phenylpropanoid pathway.

Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study.

PubMed

Weiss, Scott L; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Rachael; Fitzgerald, Julie C; Gerber, Jeffrey S

2017-03-01

To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids. Copyright © 2016 Elsevier Inc. All rights reserved.

Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study

PubMed Central

Weiss, Scott L.; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Rachael; Fitzgerald, Julie C.; Gerber, Jeffrey S.

2017-01-01

Objective To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. Study design We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. Results The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. Conclusions Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids. PMID:28063688

Functional analysis of a pathogenesis-related thaumatin-like protein gene TaLr35PR5 from wheat induced by leaf rust fungus.

PubMed

Zhang, Jiarui; Wang, Fei; Liang, Fang; Zhang, Yanjun; Ma, Lisong; Wang, Haiyan; Liu, Daqun

2018-05-04

Plants have evolved multifaceted defence mechanisms to resist pathogen infection. Production of the pathogenesis-related (PR) proteins in response to pathogen attack has been implicated in plant disease resistance specialized in systemic-acquired resistance (SAR). Our earlier studies have reported that a full length TaLr35PR5 gene, encoding a protein exhibiting amino acid and structural similarity to a sweet protein thaumatin, was isolated from wheat near-isogenic line TcLr35. The present study aims to understand the function of TaLr35PR5 gene in Lr35-mediated adult resistance to Puccinia triticina. We determined that the TaLr35PR5 protein contained a functional secretion peptide by utilizing the yeast signal sequence trap system. Using a heterologous expression assay on onion epidermal cells we found that TaLr35PR5 protein was secreted into the apoplast of onion cell. Expression of TaLr35PR5 was significantly reduced in BSMV-induced gene silenced wheat plants, and pathology test on these silenced plants revealed that Lr35-mediated resistance phenotype was obviously altered, indicating that Lr35-mediated resistance was compromised. All these findings strongly suggest that TaLr35PR5 is involved in Lr35-mediated adult wheat defense in response to leaf rust attack.

Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents.

PubMed

Labine, Meaghan; Gong, Yuewen; Minuk, Gerald Y

Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis.

Photocatalytic Removal of Microcystin-LR by Advanced WO3-Based Nanoparticles under Simulated Solar Light

PubMed Central

Zhao, Chao; Li, Dawei; Feng, Chuanping; Zhang, Zhenya; Sugiura, Norio; Yang, Yingnan

2015-01-01

A series of advanced WO3-based photocatalysts including CuO/WO3, Pd/WO3, and Pt/WO3 were synthesized for the photocatalytic removal of microcystin-LR (MC-LR) under simulated solar light. In the present study, Pt/WO3 exhibited the best performance for the photocatalytic degradation of MC-LR. The MC-LR degradation can be described by pseudo-first-order kinetic model. Chloride ion (Cl−) with proper concentration could enhance the MC-LR degradation. The presence of metal cations (Cu2+ and Fe3+) improved the photocatalytic degradation of MC-LR. This study suggests that Pt/WO3 photocatalytic oxidation under solar light is a promising option for the purification of water containing MC-LR. PMID:25884038

Defect inspection of periodic patterns with low-order distortions

NASA Astrophysics Data System (ADS)

Khalaj, Babak H.; Aghajan, Hamid K.; Paulraj, Arogyaswami; Kailath, Thomas

1994-03-01

A self-reliance technique is developed for detecting defects in repeated pattern wafers and masks with low-order distortions. If the patterns are located on a perfect rectangular grid, it is possible to estimate the period of repeated patterns in both directions, and then produce a defect-free reference image for making comparison with the actual image. But in some applications, the repeated patterns are somehow shifted from their desired position on a rectangular grid, and the aforementioned algorithm cannot be directly applied. In these situations, to produce a defect-free reference image and locate the defected cells, it is necessary to estimate the amount of misalignment of each cell beforehand. The proposed technique first estimates the misalignment of repeated patterns in each row and column. After estimating the location of all cells in the image, a defect-free reference image is generated by averaging over all the cells and is compared with the input image to localize the possible defects.

A new leaf rust resistance gene Lr79 mapped in chromosome 3BL from the durum wheat landrace Aus26582.

PubMed

Qureshi, Naeela; Bariana, Harbans; Kumran, Vikas Venu; Muruga, Sivasamy; Forrest, Kerrie L; Hayden, Mathew J; Bansal, Urmil

2018-05-01

A new leaf rust resistance gene Lr79 has been mapped in the long arm of chromosome 3B and a linked marker was identified for marker-assisted selection. Aus26582, a durum wheat landrace from the A. E. Watkins Collection, showed seedling resistance against durum-specific and common wheat-specific Puccinia triticina (Pt) pathotypes. Genetic analysis using a recombinant inbred line (RIL) population developed from a cross between Aus26582 and the susceptible parent Bansi with Australian Pt pathotype showed digenic inheritance and the underlying loci were temporarily named LrAW2 and LrAW3. LrAW2 was located in chromosome 6BS and this study focused on characterisation of LrAW3 using RILs lacking LrAW2. LrAW3 was incorporated into the DArTseq map of Aus26582/Bansi and was located in chromosome 3BL. Markers linked with LrAW3 were developed from the chromosome survey sequence contig 3B_10474240 in which closely-linked DArTseq markers 1128708 and 3948563 were located. Although bulk segregant analysis (BSA) with the 90 K Infinium array identified 51 SNPs associated with LrAW3, only one SNP-derived KASP marker mapped close to the locus. Deletion bin mapping of LrAW3-linked markers located LrAW3 between bins 3BL11-0.85-0.90 and 3BL7-0.63. Since no other all stage leaf rust resistance gene is located in chromosome 3BL, LrAW3 represented a new locus and was designated Lr79. Marker sun786 mapped 1.8 cM distal to Lr79 and Aus26582 was null for this locus. However, the marker can be reliably scored as it also amplifies a monomorphic fragment that serves as an internal control to differentiate the null status of Aus26582 from reaction failure. This marker was validated among a set of durum and common wheat cultivars and was shown to be useful for marker-assisted selection of Lr79 at both ploidy levels.

The Atypical Cadherin Dachsous Controls Left-Right Asymmetry in Drosophila.

PubMed

González-Morales, Nicanor; Géminard, Charles; Lebreton, Gaëlle; Cerezo, Delphine; Coutelis, Jean-Baptiste; Noselli, Stéphane

2015-06-22

Left-right (LR) asymmetry is essential for organ development and function in metazoans, but how initial LR cue is relayed to tissues still remains unclear. Here, we propose a mechanism by which the Drosophila LR determinant Myosin ID (MyoID) transfers LR information to neighboring cells through the planar cell polarity (PCP) atypical cadherin Dachsous (Ds). Molecular interaction between MyoID and Ds in a specific LR organizer controls dextral cell polarity of adjoining hindgut progenitors and is required for organ looping in adults. Loss of Ds blocks hindgut tissue polarization and looping, indicating that Ds is a crucial factor for both LR cue transmission and asymmetric morphogenesis. We further show that the Ds/Fat and Frizzled PCP pathways are required for the spreading of LR asymmetry throughout the hindgut progenitor tissue. These results identify a direct functional coupling between the LR determinant MyoID and PCP, essential for non-autonomous propagation of early LR asymmetry. Copyright © 2015 Elsevier Inc. All rights reserved.

The occasional role of low-risk human papillomaviruses 6, 11, 42, 44, and 70 in anogenital carcinoma defined by laser capture microdissection/PCR methodology: results from a global study.

PubMed

Guimerà, Núria; Lloveras, Belén; Lindeman, Jan; Alemany, Laia; van de Sandt, Miekel; Alejo, Maria; Hernandez-Suarez, Gustavo; Bravo, Ignacio G; Molijn, Anco; Jenkins, David; Cubilla, Antonio; Muñoz, Nubia; de Sanjose, Silvia; Bosch, Francesc Xavier; Quint, Wim

2013-09-01

Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.

Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

PubMed Central

Yusof, Mozow; Kamada, Kazuhiro; Kalogeris, Theodore; Gaskin, F. Spencer; Korthuis, Ronald J.

2009-01-01

Hydrogen sulfide (H2S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H2S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H2S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS−/−) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS−/− mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR. PMID:19168723

Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs.

PubMed

Ji, Yongchang; Buel, Sharleen M; Amack, Jeffrey D

2016-08-01

Pitx2 is a conserved homeodomain transcription factor that has multiple functions during embryonic development. Mutations in human PITX2 cause autosomal dominant Axenfeld-Rieger syndrome (ARS), characterized by congenital eye and tooth malformations. Pitx2(-/-) knockout mouse models recapitulate aspects of ARS, but are embryonic lethal. To date, ARS treatments remain limited to managing individual symptoms due to an incomplete understanding of PITX2 function. In addition to regulating eye and tooth development, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates left-right (LR) asymmetry of visceral organs. Based on its highly conserved asymmetric expression domain, the Nodal-Pitx2 axis has long been considered a common denominator of LR development in vertebrate embryos. However, functions of Pitx2 during asymmetric organ morphogenesis are not well understood. To gain new insight into Pitx2 function we used genome editing to create mutations in the zebrafish pitx2 gene. Mutations in the pitx2 homeodomain caused phenotypes reminiscent of ARS, including aberrant development of the cornea and anterior chamber of the eye and reduced or absent teeth. Intriguingly, LR asymmetric looping of the heart and gut was normal in pitx2 mutants. These results suggest conserved roles for Pitx2 in eye and tooth development and indicate Pitx2 is not required for asymmetric looping of zebrafish visceral organs. This work establishes zebrafish pitx2 mutants as a new animal model for investigating mechanisms underlying congenital malformations in ARS and high-throughput drug screening for ARS therapeutics. Additionally, pitx2 mutants present a unique opportunity to identify new genes involved in vertebrate LR patterning. We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Ecological risk assessment of microcystin-LR in the upstream section of the Haihe River based on a species sensitivity distribution model.

PubMed

Niu, Zhiguang; Du, Lei; Li, Jiafu; Zhang, Ying; Lv, Zhiwei

2018-02-01

The eutrophication of surface water has been the main problem of water quality management in recent decades, and the ecological risk of microcystin-LR (MC-LR), which is the by-product of eutrophication, has drawn more attention worldwide. The aims of our study were to determine the predicted no effect concentration (PNEC) of MC-LR and to assess the ecological risk of MC-LR in the upstream section of the Haihe River. HC 5 (hazardous concentration for 5% of biological species) and PNEC were obtained from a species sensitivity distribution (SSD) model, which was constructed with the acute toxicity data of MC-LR on aquatic organisms. The concentrations of MC-LR in the upstream section of the Haihe River from April to August of 2015 were analysed, and the ecological risk characteristics of MC-LR were evaluated based on the SSD model. The results showed that the HC 5 of MC-LR in freshwater was 17.18 μg/L and PNEC was 5.73 μg/L. The concentrations of MC-LR ranged from 0.68 μg/L to 32.21 μg/L and were obviously higher in summer than in spring. The values of the risk quotient (RQ) ranged from 0.12 to 5.62, suggesting that the risk of MC-LR for aquatic organisms in the river was at a medium or high level during the study period. Compared with other waterbodies in the world, the pollution level of MC-LR in the Haihe River was at a moderate level. This research could promote the study of the ecological risk of MC-LR at the ecosystem level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microcystin-LR-induced phytotoxicity in rice crown root is associated with the cross-talk between auxin and nitric oxide.

PubMed

Chen, Jian; Zhang, Hai-Qiang; Hu, Liang-Bin; Shi, Zhi-Qi

2013-09-01

Irrigation with cyanobacterial-blooming water containing microcystin-LR (MC-LR) poses threat to the growth of agricultural plants. Large amounts of rice (Oryza sativa) field in the middle part of China has been irrigating with cyanobacterial-blooming water. Nevertheless, the mechanism of MC-LR-induced phytotoxicity in the root of monocot rice remains unclear. In the present study, we demonstrate that MC-LR stress significantly inhibits the growth of rice root by impacting the morphogenesis rice crown root. MC-LR treatment results in the decrease in IAA (indole-3-acetic acid) concentration as well as the expression of CRL1 and WOX11 in rice roots. The application of NAA (1-naphthylacetic acid), an IAA homologue, is able to attenuate the inhibitory effect of MC-LR on rice root development. MC-LR treatment significantly inhibits OsNia1-dependent NO generation in rice roots. The application of NO donor SNP (sodium nitroprusside) is able to partially reverse the inhibitory effects of MC-LR on the growth of rice root and the expression of CRL1 and WOX11 by enhancing endogenous NO level in rice roots. The application of NO scavenger cPTIO [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide] eliminates the effects of SNP. Treatment with NAA stimulates the generation of endogenous NO in MC-LR-treated rice roots. Treatment with NO scavenger cPTIO abolishes the ameliorated effect of NAA on MC-LR-induced growth inhibition of rice root. Treatment with SNP enhanced IAA concentration in MC-LR-treated rice roots. Altogether, our data suggest that NO acts both downstream and upstream of auxin in regulating rice root morphogenesis under MC-LR stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer’s Disease (AD): Relevance to AD Prevention

PubMed Central

Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J.; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D.; Tuck, Michael L.; Frautschy, Sally A.; Cole, Greg M.

2008-01-01

Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer’s disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate β-amyloid (Aβ). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential ω-3 fatty acid related to reduced AD risk and reduced Aβ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Aβ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD. PMID:18160637

Effects of microcystin-LR, cylindrospermopsin and a microcystin-LR/cylindrospermopsin mixture on growth, oxidative stress and mineral content in lettuce plants (Lactuca sativa L.).

PubMed

Freitas, Marisa; Azevedo, Joana; Pinto, Edgar; Neves, Joana; Campos, Alexandre; Vasconcelos, Vitor

2015-06-01

Toxic cyanobacterial blooms are documented worldwide as an emerging environmental concern. Recent studies support the hypothesis that microcystin-LR (MC-LR) and cylindrospermopsin (CYN) produce toxic effects in crop plants. Lettuce (Lactuca sativa L.) is an important commercial leafy vegetable that supplies essential elements for human nutrition; thus, the study of its sensitivity to MC-LR, CYN and a MC-LR/CYN mixture is of major relevance. This study aimed to assess the effects of environmentally relevant concentrations (1, 10 and 100 µg/L) of MC-LR, CYN and a MC-LR/CYN mixture on growth, antioxidant defense system and mineral content in lettuce plants. In almost all treatments, an increase in root fresh weight was obtained; however, the fresh weight of leaves was significantly decreased in plants exposed to 100 µg/L concentrations of each toxin and the toxin mixture. Overall, GST activity was significantly increased in roots, contrary to GPx activity, which decreased in roots and leaves. The mineral content in lettuce leaves changed due to its exposure to cyanotoxins; in general, the mineral content decreased with MC-LR and increased with CYN, and apparently these effects are time and concentration-dependent. The effects of the MC-LR/CYN mixture were almost always similar to the single cyanotoxins, although MC-LR seems to be more toxic than CYN. Our results suggest that lettuce plants in non-early stages of development are able to cope with lower concentrations of MC-LR, CYN and the MC-LR/CYN mixture; however, higher concentrations (100 µg/L) can affect both lettuce yield and nutritional quality. Copyright © 2015 Elsevier Inc. All rights reserved.

Residue Phe112 of the Human-Type Corrinoid Adenosyltransferase (PduO) Enzyme of Lactobacillus reuteri Is Critical to the Formation of the Four-Coordinate Co(II) Corrinoid Substrate and to the Activity of the Enzyme

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

Mera, Paola E.; St. Maurice, Martin; Rayment, Ivan

2009-06-08

ATP:Corrinoid adenosyltransferases (ACAs) catalyze the transfer of the adenosyl moiety from ATP to cob(I)alamin via a four-coordinate cob(II)alamin intermediate. At present, it is unknown how ACAs promote the formation of the four-coordinate corrinoid species needed for activity. The published high-resolution crystal structure of the ACA from Lactobacillus reuteri (LrPduO) in complex with ATP and cob(II)alamin shows that the environment around the alpha face of the corrin ring consists of bulky hydrophobic residues. To understand how these residues promote the generation of the four-coordinate cob(II)alamin, variants of the human-type ACA enzyme from L. reuteri (LrPduO) were kinetically and structurally characterized. Thesemore » studies revealed that residue Phe112 is critical in the displacement of 5,6-dimethylbenzimidazole (DMB) from its coordination bond with the Co ion of the ring, resulting in the formation of the four-coordinate species. An F112A substitution resulted in a 80% drop in the catalytic efficiency of the enzyme. The explanation for this loss of activity was obtained from the crystal structure of the mutant protein, which showed cob(II)alamin bound in the active site with DMB coordinated to the cobalt ion. The crystal structure of an LrPduO(F112H) variant showed a DMB-off/His-on interaction between the corrinoid and the enzyme, whose catalytic efficiency was 4 orders of magnitude lower than that of the wild-type protein. The analysis of the kinetic parameters of LrPduO(F112H) suggests that the F112H substitution negatively impacts product release. Substitutions of other hydrophobic residues in the Cbl binding pocket did not result in significant defects in catalytic efficiency in vitro; however, none of the variant enzymes analyzed in this work supported AdoCbl biosynthesis in vivo.« less

Aberrant patterns of local and long-range functional connectivity densities in schizophrenia

PubMed Central

Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun

2017-01-01

Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions. PMID:28654893

Aberrant patterns of local and long-range functional connectivity densities in schizophrenia.

PubMed

Liu, Chuanxin; Zhang, Wei; Chen, Guangdong; Tian, Hongjun; Li, Jie; Qu, Hongru; Cheng, Langlang; Zhu, Jingjing; Zhuo, Chuanjun

2017-07-18

Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.

Analysis of river planforms in the New Madrid region and possible relations to tectonic warping across the loess bluffs and within the meander belt of the Mississippi River

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

Johnson, K.A.; Mayer, L.

1993-03-01

Stream channel planforms measured from such streams as the Hatchie (H), L'Anguille (LA), St. Francis, White (W) and Little Red (LR) rivers provide a way to study influences of topographic warping between the loess bluffs that bound the Mississippi river valley. Planforms are analyzed using sinuosity, Richardson analysis, and pattern. Pattern changes include transitions from braided to meandering and meandering to straight. Sinuosities of the W and LR rivers show a transition from low sinuosity, [1.3, 1.4] to higher sinuosity [2.6, 2.8], over a short distance, as they cross the bluffs from the uplands to the Western Lowlands. On themore » east, the Hatchie changes from a braided to meandering pattern upon crossing the bluffs. Its sinuosity varies from a low of about 1.4 to a high of 2.2, coincident with a marsh area. The LA river flows on the west side of Crowley's Ridge and is paralleled by the St. Francis river on the east. These rivers, with very different drainage areas and sinuosities, show matching meander bends at similar wavelengths along Crowley's Ridge. The bends are about 10 km in 1/2 wavelength suggesting some extraordinary influence on pattern perpendicular to the ridge. Richardson analysis indicates that features with a 1/2 wavelength of 2 km may control several rivers' bending patterns. These features are analyzed to determine their spatial relations with one another.« less

1,3-Propanediol dehydrogenases in Lactobacillus reuteri: impact on central metabolism and 3-hydroxypropionaldehyde production.

PubMed

Stevens, Marc J A; Vollenweider, Sabine; Meile, Leo; Lacroix, Christophe

2011-08-03

Lactobacillus reuteri metabolizes glycerol to 3-hydroxypropionaldehyde (3-HPA) and further to 1,3-propanediol (1,3-PDO), the latter step catalysed by a propanediol dehydrogenase (PDH). The last step in this pathway regenerates NAD+ and enables therefore the energetically more favourable production of acetate over ethanol during growth on glucose. A search throughout the genome of L. reuteri DSM 20016 revealed two putative PDHs encoded by ORFs lr_0030 and lr_1734. ORF lr_1734 is situated in the pdu operon encoding the glycerol conversion machinery and therefore likely involved in 1,3-PDO formation. ORF lr_0030 has not been associated with PDH-activity so far. To elucidate the role of these two PDHs, gene deletion mutant strains were constructed. Growth behaviour on glucose was comparable between the wild type and both mutant strains. However, on glucose + glycerol, the exponential growth rate of Δlr_0030 was lower compared to the wild type and the lr_1734 mutant. Furthermore, glycerol addition resulted in decreased ethanol production in the wild type and Δlr_1734, but not in Δlr_0030. PDH activity measurements using 3-HPA as a substrate revealed lower activity of Δlr_0030 extracts from exponential growing cells compared to wild type and Δlr_1734 extracts.During biotechnological 3-HPA production using non-growing cells, the ratio 3-HPA to 1,3-PDO was approximately 7 in the wild type and Δlr_0030, whereas this ratio was 12.5 in the mutant Δlr_1734. The enzyme encoded by lr_0030 plays a pivotal role in 3-HPA conversion in exponential growing L. reuteri cells. The enzyme encoded by lr_1734 is active during 3-HPA production by non-growing cells and this enzyme is a useful target to enhance 3-HPA production and minimize formation of the by-product 1,3-PDO.

Cytogenetic analysis and mapping of leaf rust resistance in Aegilops speltoides Tausch derived bread wheat line Selection2427 carrying putative gametocidal gene(s).

PubMed

Niranjana, M; Vinod; Sharma, J B; Mallick, Niharika; Tomar, S M S; Jha, S K

2017-12-01

Leaf rust (Puccinia triticina) is a major biotic stress affecting wheat yields worldwide. Host-plant resistance is the best method for controlling leaf rust. Aegilops speltoides is a good source of resistance against wheat rusts. To date, five Lr genes, Lr28, Lr35, Lr36, Lr47, and Lr51, have been transferred from Ae. speltoides to bread wheat. In Selection2427, a bread wheat introgresed line with Ae. speltoides as the donor parent, a dominant gene for leaf rust resistance was mapped to the long arm of chromosome 3B (LrS2427). None of the Lr genes introgressed from Ae. speltoides have been mapped to chromosome 3B. Since none of the designated seedling leaf rust resistance genes have been located on chromosome 3B, LrS2427 seems to be a novel gene. Selection2427 showed a unique property typical of gametocidal genes, that when crossed to other bread wheat cultivars, the F 1 showed partial pollen sterility and poor seed setting, whilst Selection2427 showed reasonable male and female fertility. Accidental co-transfer of gametocidal genes with LrS2427 may have occurred in Selection2427. Though LrS2427 did not show any segregation distortion and assorted independently of putative gametocidal gene(s), its utilization will be difficult due to the selfish behavior of gametocidal genes.

Removal of microcystin-LR from spiked water using either activated carbon or anthracite as filter material.

PubMed

Drogui, Patrick; Daghrir, Rimeh; Simard, Marie-Christine; Sauvageau, Christine; Blais, Jean François

2012-01-01

The occurrence of cyanobacterial toxins (blue-green algae) in drinking water sources is a big concern for human health. Removal of microcystin-LR (MC-LR) from drinking water was evaluated at the laboratory pilot scale using either granular activated carbon (GAC) or powdered activated carbon (PAC) and compared with the treatment using anthracite as filter material. Virgin GAC was more effective at removing MC-LR (initial concentration ranging from 9 to 47 microg L(-1)) to reach the World Health Organization recommended level (1.0 microg L(-1)). When the GAC filter was colonized by bacteria, the filter became less effective at removing MC-LR owing to competitive reactions occurring between protein adsorption (released by bacteria) and MC-LR adsorption. Using PAC, the concentration of MC-LR decreased from 22 to 3 microg L(-1) (removal of 86% of MC-LR) by the addition of 100 mg PAC L(-1).

IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease.

PubMed

Tateosian, Nancy Liliana; Pellegrini, Joaquín Miguel; Amiano, Nicolás Oscar; Rolandelli, Agustín; Casco, Nicolás; Palmero, Domingo Juan; Colombo, María Isabel; García, Verónica Edith

2017-07-03

During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.

Diagnostic capability of scanning laser polarimetry with variable cornea compensator in Indian patients with early primary open-angle glaucoma.

PubMed

Parikh, Rajul S; Parikh, Shefali R; Kumar, Rajesh S; Prabakaran, S; Babu, J Gansesh; Thomas, Ravi

2008-07-01

To evaluate the diagnostic ability of scanning laser polarimetry (GDx variable corneal compensator [VCC]) for early glaucoma in Asian Indian eyes. Cross-sectional observational study. Two groups of patients (early glaucoma and normal) who satisfied the inclusion and exclusion criteria were included. Early glaucoma was diagnosed in presence of open angles, characteristic glaucomatous optic disc changes correlating with the visual field (VF) on automated perimetry (VF defect fulfilling at least 2 of 3 Anderson and Patella's criteria with mean deviation >or= -6 decibels). Normal subjects had visual acuity >or= 20/30 and intraocular pressure < 22 mmHg, with a normal optic disc and fields and no ocular abnormality. All patients underwent complete ophthalmic evaluation, including VF examination (24-2/30-2 Swedish interactive threshold algorithm standard program) and imaging with GDx VCC. Sensitivity, specificity, positive predictive value and negative predictive value, area under the receiving operating characteristic curve, and likelihood ratios (LRs) were calculated for various GDx VCC parameters. Seventy-four eyes (74 patients) with early glaucoma and 104 eyes (104 normal subjects) were enrolled. TSNIT Std Dev (temporal-superior-nasal-inferior-temporal standard deviation) had the best combination of sensitivity and specificity-61.3 and 95.2, respectively-followed by nerve fiber index score > 50 (sensitivity, 52.7%; specificity, 99%). Nerve fiber index score > 50 had positive and negative predictive values of 74.3% and 97.6%, respectively, for an assumed glaucoma prevalence of 5%. Nerve fiber index score > 50 had a positive LR (+LR) of 54.8 for early glaucoma. GDx VCC has moderate sensitivity, with high specificity, in the diagnosis of early glaucoma. The high +LR for the nerve fiber index score can provide valuable diagnostic information for individual patients.

An aptamer-based immunoassay in microchannels of a portable analyzer for detection of microcystin-leucine-arginine.

PubMed

Xiang, An; Lei, Xiaoying; Ren, Fengling; Zang, Liuqin; Wang, Qin; Zhang, Ju; Lu, Zifan; Guo, Yanhai

2014-12-01

The rapid detection of microcystin-leucine-arginine (MC-LR), the most highly toxic among MCs, is significantly important to environmental and human health protection and prevention of MC-LR from being used as a bioweapon. Although aptamers offer higher affinity, specificity, and stability with MC-LR than antibodies in the immunodetection of MC-LR due to steric hindrance between two antibodies and limited epitopes of MC-LR for use in a sandwich immunoassay, no sandwich immunoassay using an aptmer has been developed for MC-LR detection. This study is aimed at developing an aptamer-antibody immunoassay (AAIA) to detect MC-LR using a portable analyzer. The aptamers were immobilized onto the glass surface of a microchamber to capture MC-LR. MC-LR and horseradish peroxidase (HRP)-labeled antibody were pulled into the microchamber to react with the immobilized aptamer. The chemiluminescence (CL) catalyzed by HRP was tested by a photodiode-based portable analyzer. MC-LR at 0.5-4.0 μg/L was detected quantitatively by the AAIA, with a CL signal sensitivity of 0.3 μg/L. The assay took less than 35 min for a single sample and demonstrated a high specificity, detecting only MC-LR, but not MC-LA, MC-YR, or nodularin-R. The recovery of two spiked real environmental samples calculated as 94.5-112.7%. Therefore, this AAIA was proved to be a rapid and simple method to detect MC-LR in the field by a single analyst. Copyright © 2014 Elsevier B.V. All rights reserved.

Shorter spontaneous fixation durations in infants with later emerging autism

PubMed Central

Wass, Sam V.; Jones, Emily J. H.; Gliga, Teodora; Smith, Tim J.; Charman, Tony; Johnson, Mark H.; Baron-Cohen, Simon; Bedford, Rachael; Bolton, Patrick; Chandler, Susie; Davies, Kim; Fernandes, Janice; Garwood, Holly; Hudry, Kristelle; Maris, Helen; Pasco, Greg; Pickles, Andrew; Ribiero, Helena; Tucker, Leslie; Volein, Agnes

2015-01-01

Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined. PMID:25655672

Further development of image processing algorithms to improve detectability of defects in Sonic IR NDE

NASA Astrophysics Data System (ADS)

Obeidat, Omar; Yu, Qiuye; Han, Xiaoyan

2017-02-01

Sonic Infrared imaging (SIR) technology is a relatively new NDE technique that has received significant acceptance in the NDE community. SIR NDE is a super-fast, wide range NDE method. The technology uses short pulses of ultrasonic excitation together with infrared imaging to detect defects in the structures under inspection. Defects become visible to the IR camera when the temperature in the crack vicinity increases due to various heating mechanisms in the specimen. Defect detection is highly affected by noise levels as well as mode patterns in the image. Mode patterns result from the superposition of sonic waves interfering within the specimen during the application of sound pulse. Mode patterns can be a serious concern, especially in composite structures. Mode patterns can either mimic real defects in the specimen, or alternatively, hide defects if they overlap. In last year's QNDE, we have presented algorithms to improve defects detectability in severe noise. In this paper, we will present our development of algorithms on defect extraction targeting specifically to mode patterns in SIR images.

Assessment of local variability by high-throughput e-beam metrology for prediction of patterning defect probabilities

NASA Astrophysics Data System (ADS)

Wang, Fuming; Hunsche, Stefan; Anunciado, Roy; Corradi, Antonio; Tien, Hung Yu; Tang, Peng; Wei, Junwei; Wang, Yongjun; Fang, Wei; Wong, Patrick; van Oosten, Anton; van Ingen Schenau, Koen; Slachter, Bram

2018-03-01

We present an experimental study of pattern variability and defectivity, based on a large data set with more than 112 million SEM measurements from an HMI high-throughput e-beam tool. The test case is a 10nm node SRAM via array patterned with a DUV immersion LELE process, where we see a variation in mean size and litho sensitivities between different unique via patterns that leads to a seemingly qualitative differences in defectivity. The large available data volume enables further analysis to reliably distinguish global and local CDU variations, including a breakdown into local systematics and stochastics. A closer inspection of the tail end of the distributions and estimation of defect probabilities concludes that there is a common defect mechanism and defect threshold despite the observed differences of specific pattern characteristics. We expect that the analysis methodology can be applied for defect probability modeling as well as general process qualification in the future.

Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder.

PubMed

Shephard, Elizabeth; Milosavljevic, Bosiljka; Pasco, Greg; Jones, Emily J H; Gliga, Teodora; Happé, Francesca; Johnson, Mark H; Charman, Tony

2017-03-01

Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk infants are less clear. We examined symptoms of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children prospectively studied since the first year of life. Clinical outcomes were compared between high-risk children who met diagnostic criteria for ASD at age 7 (HR-ASD-7 group, n = 15), high-risk children without ASD (HR-Non-ASD-7 group, n = 24), and low-risk control children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was moderate, with five children who did not meet diagnostic criteria for ASD at age 3 years being assigned the diagnosis at age 7, and three children showing the opposite pattern. The HR-ASD-7 group showed elevated ADHD and anxiety symptoms and had lower adaptive behaviour scores than LR controls. The HR-Non-ASD-7 group had higher repetitive behaviour, lower adaptive functioning and elevated scores on one anxiety subscale (Separation Anxiety) compared to LR controls, but evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was limited in the group as a whole, although we identified a subgroup with elevated ASD traits. The difficulties experienced by high-risk siblings at school-age extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR-ASD-7 group may inform our understanding of developmental trajectories of co-occurring psychopathology in ASD. Autism Res 2017, 10: 546-557. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions.

PubMed

Zubillaga-Guerrero, M I; Illades-Aguiar, B; Leyva-Vazquez, M A; Flores-Alfaro, E; Castañeda-Saucedo, E; Muñoz-Valle, J F; Alarcón-Romero, L C

2013-01-01

Cyclin-A and cyclin-E are regulators of G1-S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer. To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL). 115 cytological specimens in liquid base (liquid-PREP(™)) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide. In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated. The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV.

Precise design-based defect characterization and root cause analysis

NASA Astrophysics Data System (ADS)

Xie, Qian; Venkatachalam, Panneerselvam; Lee, Julie; Chen, Zhijin; Zafar, Khurram

2017-03-01

As semiconductor manufacturing continues its march towards more advanced technology nodes, it becomes increasingly important to identify and characterize design weak points, which is typically done using a combination of inline inspection data and the physical layout (or design). However, the employed methodologies have been somewhat imprecise, relying greatly on statistical techniques to signal excursions. For example, defect location error that is inherent to inspection tools prevents them from reporting the true locations of defects. Therefore, common operations such as background-based binning that are designed to identify frequently failing patterns cannot reliably identify specific weak patterns. They can only identify an approximate set of possible weak patterns, but within these sets there are many perfectly good patterns. Additionally, characterizing the failure rate of a known weak pattern based on inline inspection data also has a lot of fuzziness due to coordinate uncertainty. SEM (Scanning Electron Microscope) Review attempts to come to the rescue by capturing high resolution images of the regions surrounding the reported defect locations, but SEM images are reviewed by human operators and the weak patterns revealed in those images must be manually identified and classified. Compounding the problem is the fact that a single Review SEM image may contain multiple defective patterns and several of those patterns might not appear defective to the human eye. In this paper we describe a significantly improved methodology that brings advanced computer image processing and design-overlay techniques to better address the challenges posed by today's leading technology nodes. Specifically, new software techniques allow the computer to analyze Review SEM images in detail, to overlay those images with reference design to detect every defect that might be present in all regions of interest within the overlaid reference design (including several classes of defects that human operators will typically miss), to obtain the exact defect location on design, to compare all defective patterns thus detected against a library of known patterns, and to classify all defective patterns as either new or known. By applying the computer to these tasks, we automate the entire process from defective pattern identification to pattern classification with high precision, and we perform this operation en masse during R & D, ramp, and volume production. By adopting the methodology, whenever a specific weak pattern is identified, we are able to run a series of characterization operations to ultimately arrive at the root cause. These characterization operations can include (a) searching all pre-existing Review SEM images for the presence of the specific weak pattern to determine whether there is any spatial (within die or within wafer) or temporal (within any particular date range, before or after a mask revision, etc.) correlation and (b) understanding the failure rate of the specific weak pattern to prioritize the urgency of the problem, (c) comparing the weak pattern against an OPC (Optical Procimity Correction) Verification report or a PWQ (Process Window Qualification)/FEM (Focus Exposure Matrix) result to assess the likelihood of it being a litho-sensitive pattern, etc. After resolving the specific weak pattern, we will categorize it as known pattern, and the engineer will move forward with discovering new weak patterns.

A simple highly sensitive and selective aptamer-based colorimetric sensor for environmental toxins microcystin-LR in water samples.

PubMed

Li, Xiuyan; Cheng, Ruojie; Shi, Huijie; Tang, Bo; Xiao, Hanshuang; Zhao, Guohua

2016-03-05

A simple and highly sensitive aptamer-based colorimetric sensor was developed for selective detection of Microcystin-LR (MC-LR). The aptamer (ABA) was employed as recognition element which could bind MC-LR with high-affinity, while gold nanoparticles (AuNPs) worked as sensing materials whose plasma resonance absorption peaks red shifted upon binding of the targets at a high concentration of sodium chloride. With the addition of MC-LR, the random coil aptamer adsorbed on Au NPs altered into regulated structure to form MC-LR-aptamer complexes and broke away from the surface of Au NPs, leading to the aggregation of AuNPs, and the color converted from red to blue due to the interparticle plasmon coupling. Results showed that our aptamer-based colorimetric sensor exhibited rapid and sensitive detection performance for MC-LR with linear range from 0.5 nM to 7.5 μM and the detection limit reached 0.37 nM. Meanwhile, the pollutants usually coexisting with MC-LR in pollutant water samples had not demonstrated disturbance for detecting of MC-LR. The mechanism was also proposed suggesting that high affinity interaction between aptamer and MC-LR significantly enhanced the sensitivity and selectivity for MC-LR detection. Besides, the established method was utilized in analyzing real water samples and splendid sensitivity and selectivity were obtained as well. Copyright © 2015 Elsevier B.V. All rights reserved.

The Laser Ranging Experiment of the Lunar Reconnaissance Orbiter: Five Years of Operations and Data Analysis

NASA Technical Reports Server (NTRS)

Mao, Dandan; McGarry, Jan F.; Mazarico, Erwan; Neumann, Gregory A.; Sun, Xiaoli; Torrence, Mark H.; Zagwodzki, Thomas W.; Rowlands, David D.; Hoffman, Evan D.; Horvath, Julie E.;

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

PubMed

Ida, K K; Chisholm, K I; Malbouisson, L M S; Papkovsky, D B; Dyson, A; Singer, M; Duchen, M R; Smith, K J

2018-06-01

During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Lithospermi radix extract inhibits histamine release and production of inflammatory cytokine in mast cells.

PubMed

Kim, Eun Kyoung; Kim, Eun-Young; Moon, Phil-Dong; Um, Jae-Young; Kim, Hyung-Min; Lee, Hyun-Sam; Sohn, Youngjoo; Park, Seong Kyu; Jung, Hyuk-Sang; Sohn, Nak-Won

2007-12-01

Lithospermi radix (LR, Borraginaceae, the root of Lithospermum erythrorhizon Siebold. et Zuccarinii) is used in herbal medicine to treat such conditions as eczema, skin burns and frostbite. This study investigates the effects of LR on the anti-allergy mechanism. LR inhibited the release of histamine from rat peritoneal mast cells by compound 48/80 in a dose-dependent manner. LR orally administered at 6.59 mg/100 g also inhibited the anti-DNP IgE-induced passive cutaneous anaphylaxis reaction. LR inhibited the PMA plus A23187-induced increase in IL-6, IL-8, and TNF-alpha expression in HMC-1 cells. In addition, LR also inhibited nuclear factor-kappa B (NF-kappaB) activation and I kappaB-alpha degradation. These results show that LR had an inhibitory effect on the atopic allergic reaction. Furthermore, the in vivo and in vitro anti-allergic effect of LR suggests possible therapeutic applications of this agent for inflammatory allergic diseases.

[Survey on the contamination of microcystin-LR in water supply of Shanghai city].

PubMed

Wu, He-yan; Zheng, Li-xing; Su, Jin; Shi, Wei

2005-03-01

To study the pollution level of microcystin-LR in water supply of Shanghai city and the removal efficacy for microcystin-LR through routine water treatment technique. High performance liquid chromatogram (HPLC) was applied to determine the concentration of microcystin-LR in source water, water samples after various water treatment procedures and tap water. The concentration of microcystin-LR varied with sampling seasons and sites and reached peak during summer and fall. The maximum of microcystin-LR was 2.38 microg/L in source water. Coagulation plus chlorine disinfection were found to be effective for the removal of microcystin-LR, while the remove rate through filtration was not significant. And it could also be detected in tap water as high as 1.27 microg/L. The source waters of Shanghai city were polluted by cyanobacteria toxins represented by microcystin-LR. The source water in suburb was more polluted. Routine water treatment techniques can not remove the toxins effectively.

Analysis of WRKY transcription factors and characterization of two Botrytis cinerea-responsive LrWRKY genes from Lilium regale.

PubMed

Cui, Qi; Yan, Xiao; Gao, Xue; Zhang, Dong-Mei; He, Heng-Bin; Jia, Gui-Xia

2018-06-01

A major constraint in producing lilies is gray mold caused by Botrytis elliptica and B. cinerea. WRKY transcription factors play important roles in plant immune responses. However, limited information is available about the WRKY gene family in lily plants. In this study, 23 LrWRKY genes with complete WRKY domains were identified from the Botrytis-resistant species Lilium regale. The putative WRKY genes were divided into seven subgroups (Group I, IIa-e, and III) according to their structural features. Sequence alignment revealed that LrWRKY proteins have a highly conserved WRKYGQK domain and a variant, the WRKYGKK domain, and these proteins generally contained similar motif compositions throughout the same subgroup. Functional annotation predicted they might be involved in biological processes related to abiotic and biotic stresses. A qRT-PCR analysis confirmed that expression of six LrWRKY genes in L. regale or the susceptible Asian hybrid 'Yale' was induced by B. cinerea infection. Among these genes, LrWRKY4, LrWRKY8 and LrWRKY10 were expressed at a higher level in L. regale than 'Yale', while the expression of LrWRKY6 and LrWRKY12 was lower in L. regale. Furthermore, LrWRKY4 and LrWRKY12 genes, which also respond to salicylic acid (SA) and methyl jasmonate (MeJA) treatments, were isolated from L. regale. Subcellular localization analysis determined that they were targeted to the nucleus. Constitutive expression of LrWRKY4 and LrWRKY12 in Arabidopsis resulted in plants that were more resistant to B. cinerea than wild-type plants. This resistance was coupled with the transcriptional changes of SA and JA-responsive genes. Overall, our study provides valuable information about the structural and functional characterization of LrWRKY genes that will not only deepen our understanding of the molecular mechanisms underlying the defense of lily against B. cinerea but also offer potential targets for cultivar improvement via biotechnology. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Identification of Patients at Very Low Risk of Local Recurrence After Breast-Conserving Surgery

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

Smith, Sally L., E-mail: ssmith11@bccancer.bc.ca; Truong, Pauline T.; Lu, Linghong

2014-07-01

Purpose: To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials: Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated withmore » a 5-year LR risk ≤1.5%. Results: The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions: Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.« less

Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

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

Zhou, Yuan; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093; Wang, Hui

2015-08-15

Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through themore » regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.« less

Effects of cyanobacterial biomass and purified microcystins on malformations in Xenopus laevis: teratogenesis assay (FETAX).

PubMed

Dvoráková, Dagmar; Dvoráková, Katerina; Bláha, Ludek; Marsálek, Blahoslav; Knotková, Zora

2002-12-01

Xenopus laevis (African clawed frog) embryos in a 96-h teratogenesis assay (FETAX) were exposed to 0-250 microg/L and 500 microg/L of purified microcystin-LR (MCYST-LR) for the estimation of lethality, as well as to equivalent concentrations of biomass containing MCYST-LR (natural water bloom dominated by Microcystis aeruginosa) and biomass without MCYST-LR (bloom dominated by Microcystis wesenbergii). The highest tested concentrations of purified MCYST-LR caused up to 30% lethality after a 96-h exposure, corresponding to a LC(25) of 380 microg/L. Cyanobacterial biomass containing MCYST-LR caused significant lethality up to 50% at the highest tested concentrations (300 mg/L, i.e., 250 microg/L of MCYST-LR). The estimated 96-h LC(25) values varied from 125 mg/L (biomass containing MCYST-LR) up to 232 mg/L (biomass without MCYST-LR). A statistically significant increase in the number of malformed embryos was observed after exposure to cyanobacterial samples. Purified MCYST-LR at and above 25 microg/L significantly increased the number of malformations, with 53% of surviving embryos malformed in the highest tested concentration, 250 microg/L (EC(25) = 27 microg/L). Exposure to the highest concentration of MCYST-LR containing biomass resulted in more than 60% of the embryos being malformed and an EC(25) of 52 mg/L (i.e., 43 microg of MCYST-LR/L). Cyanobacterial biomass with no natural microcystin also induced substantial malformations-about 50% aberrant embryos at the highest concentration, 300 mg/L (EC(25) = 75 mg/L). External additions of purified MCYST-LR to the biomass that was originally without microcystins resulted in a slight additional increase in the rate of malformations (80% at the highest concentration, 300 mg of biomass plus 250 microg of MCYST-LR per liter). A comparison of lethality and effects on malformations (teratogenic index, TI = LC(25)/EC(25)) showed that all samples had significant teratogenic potential in the FETAX assay (TI(MCYST-LR) = 14; TI for biomass with and without microcystin ranged between 2.4 and 3.1, respectively). We conclude that cyanobacterial water blooms can significantly alter the normal development of amphibian embryos. Copyright 2002 Wiley Periodicals, Inc.

Item Discrimination and Type I Error in the Detection of Differential Item Functioning

ERIC Educational Resources Information Center

Li, Yanju; Brooks, Gordon P.; Johanson, George A.

2012-01-01

In 2009, DeMars stated that when impact exists there will be Type I error inflation, especially with larger sample sizes and larger discrimination parameters for items. One purpose of this study is to present the patterns of Type I error rates using Mantel-Haenszel (MH) and logistic regression (LR) procedures when the mean ability between the…

Cell Wall Structure of Coccoid Green Algae as an Important Trade-Off Between Biotic Interference Mechanisms and Multidimensional Cell Growth.

PubMed

Dunker, Susanne; Wilhelm, Christian

2018-01-01

Coccoid green algae can be divided in two groups based on their cell wall structure. One group has a highly chemical resistant cell wall (HR-cell wall) containing algaenan. The other group is more susceptible to chemicals (LR-cell wall - Low resistant cell wall). Algaenan is considered as important molecule to explain cell wall resistance. Interestingly, cell wall types (LR- and HR-cell wall) are not in accordance with the taxonomic classes Chlorophyceae and Trebouxiophyceae, which makes it even more interesting to consider the ecological function. It was already shown that algaenan helps to protect against virus, bacterial and fungal attack, but in this study we show for the first time that green algae with different cell wall properties show different sensitivity against interference competition with the cyanobacterium Microcystis aeruginosa . Based on previous work with co-cultures of M. aeruginosa and two green algae ( Acutodesmus obliquus and Oocystis marssonii ) differing in their cell wall structure, it was shown that M. aeruginosa could impair only the growth of the green algae if they belong to the LR-cell wall type. In this study it was shown that the sensitivity to biotic interference mechanism shows a more general pattern within coccoid green algae species depending on cell wall structure.

Pre-operative prediction of surgical morbidity in children: comparison of five statistical models.

PubMed

Cooper, Jennifer N; Wei, Lai; Fernandez, Soledad A; Minneci, Peter C; Deans, Katherine J

2015-02-01

The accurate prediction of surgical risk is important to patients and physicians. Logistic regression (LR) models are typically used to estimate these risks. However, in the fields of data mining and machine-learning, many alternative classification and prediction algorithms have been developed. This study aimed to compare the performance of LR to several data mining algorithms for predicting 30-day surgical morbidity in children. We used the 2012 National Surgical Quality Improvement Program-Pediatric dataset to compare the performance of (1) a LR model that assumed linearity and additivity (simple LR model) (2) a LR model incorporating restricted cubic splines and interactions (flexible LR model) (3) a support vector machine, (4) a random forest and (5) boosted classification trees for predicting surgical morbidity. The ensemble-based methods showed significantly higher accuracy, sensitivity, specificity, PPV, and NPV than the simple LR model. However, none of the models performed better than the flexible LR model in terms of the aforementioned measures or in model calibration or discrimination. Support vector machines, random forests, and boosted classification trees do not show better performance than LR for predicting pediatric surgical morbidity. After further validation, the flexible LR model derived in this study could be used to assist with clinical decision-making based on patient-specific surgical risks. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resveratrol Ameliorates Microcystin-LR-Induced Testis Germ Cell Apoptosis in Rats via SIRT1 Signaling Pathway Activation.

PubMed

Liu, Haohao; Zhang, Shenshen; Liu, Chuanrui; Wu, Jinxia; Wang, Yueqin; Yuan, Le; Du, Xingde; Wang, Rui; Marwa, Phelisters Wegesa; Zhuang, Donggang; Cheng, Xuemin; Zhang, Huizhen

2018-06-09

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli⁻germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli⁻germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli⁻germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.

Role of Surgical Margin on Local Recurrence in High Risk Extremity Osteosarcoma: A Case-Controlled Study

PubMed Central

Song, Won Seok; Kong, Chang-Bae; Cho, Wan Hyeong; Cho, Sang Hyun; Lee, Jeong Dong; Lee, Soo-Yong

2013-01-01

Background The relationship between surgical margin and local recurrence (LR) in osteosarcoma patients with poor responses to chemotherapy is unclear. Moreover, the incidences of LR according to three different resection planes (bone, soft tissue, and perineurovascular) are not commonly known. Methods We evaluated the incidence of LR in three areas. To assess whether there is a role of surgical margin on LR in patients resistant to preoperative chemotherapy, we designed a case (35 patients with LR) and control (70 patients without LR) study. Controls were matched for age, location, initial tumor volume, and tumor volume change during preoperative chemotherapy. Results LR occurred at the soft tissues in 18 cases (51.4%), at the perineurovascular tissues in 11 cases (31.4%), and at the bones in six cases (17.2%). The proportion of inadequate perineurovascular margin was higher in the case group than in the control group (p = 0.01). Within case-control group (105 patients), a correlation between each margin status and LR at corresponding area was found in the bone (p < 0.001) and perineurovascular area (p = 0.001). Conclusions LR is most common in soft tissues. In patients showing similar unfavorable responses to chemotherapy, the losses of perineurovascular fat plane on preoperative magnetic resonance imaging may be a valuable finding in predicting LR. PMID:24009908

Inspection of imprint lithography patterns for semiconductor and patterned media

NASA Astrophysics Data System (ADS)

Resnick, Douglas J.; Haase, Gaddi; Singh, Lovejeet; Curran, David; Schmid, Gerard M.; Luo, Kang; Brooks, Cindy; Selinidis, Kosta; Fretwell, John; Sreenivasan, S. V.

2010-03-01

Imprint lithography has been shown to be an effective technique for replication of nano-scale features. Acceptance of imprint lithography for manufacturing will require demonstration that it can attain defect levels commensurate with the requirements of cost-effective device production. This work summarizes the results of defect inspections of semiconductor masks, wafers and hard disks patterned using Jet and Flash Imprint Lithography (J-FILTM). Inspections were performed with optical and e-beam based automated inspection tools. For the semiconductor market, a test mask was designed which included dense features (with half pitches ranging between 32 nm and 48 nm) containing an extensive array of programmed defects. For this work, both e-beam inspection and optical inspection were used to detect both random defects and the programmed defects. Analytical SEMs were then used to review the defects detected by the inspection. Defect trends over the course of many wafers were observed with another test mask using a KLA-T 2132 optical inspection tool. The primary source of defects over 2000 imprints were particle related. For the hard drive market, it is important to understand the defectivity of both the template and the imprinted disk. This work presents a methodology for automated pattern inspection and defect classification for imprint-patterned media. Candela CS20 and 6120 tools from KLA-Tencor map the optical properties of the disk surface, producing highresolution grayscale images of surface reflectivity, scattered light, phase shift, etc. Defects that have been identified in this manner are further characterized according to the morphology

Solving LR Conflicts Through Context Aware Scanning

NASA Astrophysics Data System (ADS)

Leon, C. Rodriguez; Forte, L. Garcia

2011-09-01

This paper presents a new algorithm to compute the exact list of tokens expected by any LR syntax analyzer at any point of the scanning process. The lexer can, at any time, compute the exact list of valid tokens to return only tokens in this set. In the case than more than one matching token is in the valid set, the lexer can resort to a nested LR parser to disambiguate. Allowing nested LR parsing requires some slight modifications when building the LR parsing tables. We also show how LR parsers can parse conflictive and inherently ambiguous languages using a combination of nested parsing and context aware scanning. These expanded lexical analyzers can be generated from high level specifications.

LC/MS/MS structure elucidation of reaction intermediates formed during the TiO2 photocatalysis of microcystin-LR

EPA Science Inventory

Microcystin-LR (MC-LR), a cyanotoxin and emerging drinking water contaminant, was treated with TiO(2) photocatalysts immobilized on stainless steel plates as an alternative to nanoparticles in slurry. The reaction intermediates of MC-LR were identified with mass spectrometry (MS)...

Kinetic and mechanistic study of microcystin-LR degradation by nitrous acid under ultraviolet irradiation.

PubMed

Ma, Qingwei; Ren, Jing; Huang, Honghui; Wang, Shoubing; Wang, Xiangrong; Fan, Zhengqiu

2012-05-15

Degradation of microcystin-LR (MC-LR) in the presence of nitrous acid (HNO(2)) under irradiation of 365nm ultraviolet (UV) was studied for the first time. The influence of initial conditions including pH value, NaNO(2) concentration, MC-LR concentration and UV intensity were studied. MC-LR was degraded in the presence of HNO(2); enhanced degradation of MC-LR was observed with 365nm UV irradiation, caused by the generation of hydroxyl radicals through the photolysis of HNO(2). The degradation processes of MC-LR could well fit the pseudo-first-order kinetics. Mass spectrometry was applied for identification of the byproducts and the analysis of degradation mechanisms. Major degradation pathways were proposed according to the results of LC-MS analysis. The degradation of MC-LR was initiated via three major pathways: attack of hydroxyl radicals on the conjugated carbon double bonds of Adda, attack of hydroxyl radicals on the benzene ring of Adda, and attack of nitrosonium ion on the benzene ring of Adda. Copyright © 2012 Elsevier B.V. All rights reserved.

The wheat Lr34 multipathogen resistance gene confers resistance to anthracnose and rust in sorghum.

PubMed

Schnippenkoetter, Wendelin; Lo, Clive; Liu, Guoquan; Dibley, Katherine; Chan, Wai Lung; White, Jodie; Milne, Ricky; Zwart, Alexander; Kwong, Eunjung; Keller, Beat; Godwin, Ian; Krattinger, Simon G; Lagudah, Evans

2017-11-01

The ability of the wheat Lr34 multipathogen resistance gene (Lr34res) to function across a wide taxonomic boundary was investigated in transgenic Sorghum bicolor. Increased resistance to sorghum rust and anthracnose disease symptoms following infection with the biotrophic pathogen Puccinia purpurea and the hemibiotroph Colletotrichum sublineolum, respectively, occurred in transgenic plants expressing the Lr34res ABC transporter. Transgenic sorghum lines that highly expressed the wheat Lr34res gene exhibited immunity to sorghum rust compared to the low-expressing single copy Lr34res genotype that conferred partial resistance. Pathogen-induced pigmentation mediated by flavonoid phytoalexins was evident on transgenic sorghum leaves following P. purpurea infection within 24-72 h, which paralleled Lr34res gene expression. Elevated expression of flavone synthase II, flavanone 4-reductase and dihydroflavonol reductase genes which control the biosynthesis of flavonoid phytoalexins characterized the highly expressing Lr34res transgenic lines 24-h post-inoculation with P. purpurea. Metabolite analysis of mesocotyls infected with C. sublineolum showed increased levels of 3-deoxyanthocyanidin metabolites were associated with Lr34res expression, concomitant with reduced symptoms of anthracnose. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

High-speed autoverifying technology for printed wiring boards

NASA Astrophysics Data System (ADS)

Ando, Moritoshi; Oka, Hiroshi; Okada, Hideo; Sakashita, Yorihiro; Shibutani, Nobumi

1996-10-01

We have developed an automated pattern verification technique. The output of an automated optical inspection system contains many false alarms. Verification is needed to distinguish between minor irregularities and serious defects. In the past, this verification was usually done manually, which led to unsatisfactory product quality. The goal of our new automated verification system is to detect pattern features on surface mount technology boards. In our system, we employ a new illumination method, which uses multiple colors and multiple direction illumination. Images are captured with a CCD camera. We have developed a new algorithm that uses CAD data for both pattern matching and pattern structure determination. This helps to search for patterns around a defect and to examine defect definition rules. These are processed with a high speed workstation and a hard-wired circuits. The system can verify a defect within 1.5 seconds. The verification system was tested in a factory. It verified 1,500 defective samples and detected all significant defects with only a 0.1 percent of error rate (false alarm).

Toxic threshold of dietary microcystin (-LR) for quart medaka.

PubMed

Deng, Dong-Fang; Zheng, Keke; Teh, Foo-Ching; Lehman, Peggy W; Teh, Swee J

2010-04-01

This study was designed to estimate the toxic threshold of male and female fish to microcystins based on different biomarkers. Japanese medaka (Oryzias latipes) were fed dietary Microcystin-LR (0, 0.46, 0.85, 2.01 and 3.93 microg MC-LR/g dry diet for 8 weeks at 25 degrees C. The results revealed that dietary MC-LR inhibited growth at the end of 8 weeks. The survival of embryos and the RNA/DNA ratio of whole fish decreased significantly (P < 0.05) in fish fed 3.93 microg MC-LR/g dry diet. Heat shock protein (Hsp60) expression was induced in the liver of female and male fish fed diets containing > or =0.85 and 0.46 microg MC-LR/g diet, respectively. The activity of liver caspase 3/7 was significantly higher in female fish fed 3.93 microg MC-LR/g diet and in males fed 2.01 MC-LR microg/g dry diet than fish fed the control diet. The threshold for inhibition of liver protein phosphatase expression was lower in female (2.01 microg/g diet) than that in male fish (3.93 microg/g diet). Histopathological examination showed significant single-cell necrosis in female and male medaka fed diets containing 0.85 and 3.93 microg MC-LR/g diet, respectively. Based on different biomarkers, this study demonstrated that dietary MC-LR is toxic to Medaka and the effects are gender dependent. Published by Elsevier Ltd.

Process optimization for microcystin-LR degradation by Response Surface Methodology and mechanism analysis in gas-liquid hybrid discharge system.

PubMed

Zhang, Yi; Wei, Hanyu; Xin, Qing; Wang, Mingang; Wang, Qi; Wang, Qiang; Cong, Yanqing

2016-12-01

A gas-liquid hybrid discharge system was applied to microcystin-LR (MC-LR) degradation. MC-LR degradation was completed after 1 min under a pulsed high voltage of 16 kV, gas-liquid interface gap of 10 mm and oxygen flow rate of 160 L/h. The Box-Behnken Design was proposed in Response Surface Methodology to evaluate the influence of pulsed high voltage, electrode distance and oxygen flow rate on MC-LR removal efficiency. Multiple regression analysis, focused on multivariable factors, was employed and a reduced cubic model was developed. The ANOVA analysis shows that the model is significant and the model prediction on MC-LR removal was also validated with experimental data. The optimum conditions for the process are obtained at pulsed voltage of 16 kV, gas-liquid interface gap of 10 mm and oxygen flow rate of 120 L/h with ta removal efficiency of MC-LR of 96.6%. The addition of catalysts (TiO 2 or Fe 2+ ) in the gas-liquid hybrid discharge system was found to enhance the removal of MC-LR. The intermediates of MC-LR degradation were analyzed by liquid chromatography/mass spectrometry. The degradation pathway proposed envisaged the oxidation of hydroxyl radicals and ozone, and attack of high-energy electrons on the unsaturated double bonds of Adda and Mdha, with MC-LR finally decomposing into small molecular products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microbe-independent entry of oomycete RxLR effectors and fungal RxLR-like effectors into plant and animal cells is specific and reproducible.

PubMed

Tyler, Brett M; Kale, Shiv D; Wang, Qunqing; Tao, Kai; Clark, Helen R; Drews, Kelly; Antignani, Vincenzo; Rumore, Amanda; Hayes, Tristan; Plett, Jonathan M; Fudal, Isabelle; Gu, Biao; Chen, Qinghe; Affeldt, Katharyn J; Berthier, Erwin; Fischer, Gregory J; Dou, Daolong; Shan, Weixing; Keller, Nancy P; Martin, Francis; Rouxel, Thierry; Lawrence, Christopher B

2013-06-01

A wide diversity of pathogens and mutualists of plant and animal hosts, including oomycetes and fungi, produce effector proteins that enter the cytoplasm of host cells. A major question has been whether or not entry by these effectors can occur independently of the microbe or requires machinery provided by the microbe. Numerous publications have documented that oomycete RxLR effectors and fungal RxLR-like effectors can enter plant and animal cells independent of the microbe. A recent reexamination of whether the RxLR domain of oomycete RxLR effectors is sufficient for microbe-independent entry into host cells concluded that the RxLR domains of Phytophthora infestans Avr3a and of P. sojae Avr1b alone are NOT sufficient to enable microbe-independent entry of proteins into host and nonhost plant and animal cells. Here, we present new, more detailed data that unambiguously demonstrate that the RxLR domain of Avr1b does show efficient and specific entry into soybean root cells and also into wheat leaf cells, at levels well above background nonspecific entry. We also summarize host cell entry experiments with a wide diversity of oomycete and fungal effectors with RxLR or RxLR-like motifs that have been independently carried out by the seven different labs that coauthored this letter. Finally we discuss possible technical reasons why specific cell entry may have been not detected by Wawra et al. (2013).

A single-nucleotide polymorphism that accounts for allelic variation in the Lr34 gene and leaf rust reaction in hard winter wheat.

PubMed

Cao, Shuanghe; Carver, Brett F; Zhu, Xinkai; Fang, Tilin; Chen, Yihua; Hunger, Robert M; Yan, Liuling

2010-07-01

Leaf rust, caused by Puccinia triticina Eriks, is one of the most common and persistent wheat diseases in the US Great Plains. We report that the Lr34 gene was mapped in the center of a QTL for leaf rust reaction and explained 18-35% of the total phenotypic variation in disease severity of adult plants in a Jagger x 2174 population of recombinant inbred lines (RILs) field-tested for 3 years. The sequence of the complete Lr34 gene was determined for the susceptible Jagger allele and for the resistant 2174 allele. The two alleles had exactly the same sequence as the resistant allele reported previously in Chinese Spring at three polymorphic sites in intron 4, exon 11, and exon 12. A G/T polymorphism was found in exon 22, where a premature stop codon was found in the susceptible Jagger allele (Lr34E22s), confirming a previous report, due to a point mutation compared with the resistant 2174 allele (Lr34E22r). We have experimentally demonstrated a tight association between the point mutation at exon 22 of Lr34 and leaf rust susceptibility in a segregating biparental population. A PCR marker was developed to distinguish between the Lr34E22r and Lr34E22s alleles. A survey of 33 local hard winter wheat cultivars indicated that 7 cultivars carry the Lr34E22s allele and 26 cultivars carry the Lr34E22r allele. This study significantly improves our genetic understanding of allelic variation in the Lr34 gene and provides a functional molecular tool to improve leaf rust resistance in a major US wheat gene pool.

[Influences of arbuscular mycorrhizal fungus and phosphorus level on the lateral root formation of tomato seedlings].

PubMed

Jiang, Xia; Chen, Wei-li; Xu, Chun-xiang; Zhu, Hong-hui; Yao, Qing

2015-04-01

To explore the influences of arbuscular mycorrhizal fungi (AMF) and P level on plant root system architecture, tomato seedlings were inoculated with AMF strain Rhizophagus irregularis BGC JX04B under two P levels, and the influences of AMF and P level on lateral root (LR) formation of tomato seedlings were studied. Results indicated that the promoting effect of AMF on plant biomass was not evident, but significantly decreased the root to shoot ratio of plants. AMF significantly increased the primary root length but decreased the 1st order LR length and interacted with the mycorrhizal colonization period. AMF significantly lowered the 2nd-3rd order LR number and the ratio of 2nd order LR number to 1st order LR number, but did not significantly affect the 1st-2nd order LR density. High P level (50 mg x kg(-1) P) significantly promoted the plant growth and decreased the root to shoot ratio of plants. It had no significant effect on the primary root length and the 1st order root length, but significantly enhanced the 1st-3rd order LR number and the ratio of 2nd order LR number to P order LR number, increased the 1st-2nd order LR density. It suggested that AMF and P level did not share a common mechanism to influence the LR formation of tomato plants. The influence of high P level may depend on its promoting effects on nutrient uptake and plant growth, while the influence of AMF is more complex. Furthermore, the interaction between AMF and mycorrhizal colonization period implies the possible involvement of carbohydrate distribution (sugar signaling) in the regulation of root system architecture by AMF.

Task Context Influences Brain Activation during Music Listening

PubMed Central

Markovic, Andjela; Kühnis, Jürg; Jäncke, Lutz

2017-01-01

In this paper, we examined brain activation in subjects during two music listening conditions: listening while simultaneously rating the musical piece being played [Listening and Rating (LR)] and listening to the musical pieces unconstrained [Listening (L)]. Using these two conditions, we tested whether the sequence in which the two conditions were fulfilled influenced the brain activation observable during the L condition (LR → L or L → LR). We recorded high-density EEG during the playing of four well-known positively experienced soundtracks in two subject groups. One group started with the L condition and continued with the LR condition (L → LR); the second group performed this experiment in reversed order (LR → L). We computed from the recorded EEG the power for different frequency bands (theta, lower alpha, upper alpha, lower beta, and upper beta). Statistical analysis revealed that the power in all examined frequency bands increased during the L condition but only when the subjects had not had previous experience with the LR condition (i.e., L → LR). For the subjects who began with the LR condition, there were no power increases during the L condition. Thus, the previous experience with the LR condition prevented subjects from developing the particular mental state associated with the typical power increase in all frequency bands. The subjects without previous experience of the LR condition listened to the musical pieces in an unconstrained and undisturbed manner and showed a general power increase in all frequency bands. We interpret the fact that unconstrained music listening was associated with increased power in all examined frequency bands as a neural indicator of a mental state that can best be described as a mind-wandering state during which the subjects are “drawn into” the music. PMID:28706480

The relationship of leaf rust resistance gene Lr13 and hybrid necrosis gene Ne2m on wheat chromosome 2BS.

PubMed

Zhang, Peng; Hiebert, Colin W; McIntosh, Robert A; McCallum, Brent D; Thomas, Julian B; Hoxha, Sami; Singh, Davinder; Bansal, Urmil

2016-03-01

Genetic and mutational analyses of wheat leaf rust resistance gene Lr13 and hybrid necrosis gene Ne2 m indicated that they are the same gene. Hybrid necrosis in wheat characterized by chlorosis and eventual necrosis of plant tissues in certain wheat hybrids is controlled by the interaction of complementary dominant genes Ne1 and Ne2 located on chromosome arms 5BL and 2BS, respectively. Multiple alleles at each locus can be identified by differences in necrotic phenotypes when varieties are crossed with a fixed accession of the other genotype. Some of at least five Ne2 alleles were described as s (strong), m (medium) and w (weak); alleles of Ne1 were similarly described. Ne2m causes moderate necrosis in hybrids with genotypes having Ne1s. Ne2 is located on chromosome arm 2BS in close proximity to Lr13. Most wheat lines with Ne2m carry Lr13, and all wheat lines with Lr13 appear to carry Ne2m. To further dissect the relationship between Lr13 and Ne2m, more than 350 crosses were made between cv. Spica (Triticum aestivum) or Kubanka (T. durum) carrying Ne1s and recombinant inbred lines or doubled haploid lines from three crosses segregating for Lr13. F1 plants from lines carrying Lr13 crossed with Spica (Ne1s) always showed progressive necrosis; those lacking Lr13 did not. Four wheat cultivars/lines carrying Lr13 were treated with the mutagen EMS. Thirty-five susceptible mutants were identified; eight were distinctly less glaucous and late maturing indicative of chromosome 2B or sub-chromosome loss. Hybrids of phenotypically normal Lr13 mutant plants crossed with Spica did not produce symptoms of hybrid necrosis. Thus, Lr13 and one particular Ne2m allele may be the same gene.

Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells

PubMed Central

Zacchi, Paola; Stenmark, Harald; Parton, Robert G.; Orioli, Donata; Lim, Filip; Giner, Angelika; Mellman, Ira; Zerial, Marino; Murphy, Carol

1998-01-01

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells. PMID:9490718

Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain.

PubMed

Hwang, Kyung-A; Kwon, Jeong Eun; Noh, YooHun; Park, BongKyun; Jeong, Yong Joon; Lee, Sun-Mee; Kim, Se-Young; Kim, InHye; Kang, Se Chan

2018-06-05

Degenerative arthritis, also known as osteoarthritis (OA), is the most common type of arthritis, which is caused by degenerative damage of the cartilage, which primarily protects the joints, leading to inflammation and pain. The objective of this study was to investigate the in vivo and in vitro effects of treatment with ZPE-LR (90% EtOH extract of Zanthoxylum piperitum) on pain severity and inflammation. When using an in vivo OA model MIA (monosodiumidoacetate-induced arthritis) rats, ZPE-LR (100 mg/kg) oral-administratio significantly inhibited MIA-induced change in loaded weight ratio on the left foot, and articular cartilage thickness. To confirm the positive effects on pain relief, acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. Pain related KCNJ6 mRNA expression as well as K + current was increased after ZPE-LR treatment in BV-2 cells. To confirm the positive effects on inflammation, TPA (12-O-tetradecanoylphorbol-13-acetate) induced inflammation measured by mouse ear thickness and biopsy punch weight and TPA-induced iNOS, COX-2 mRNA and protein expression were remarkably suppressed by 50 and 100 mg/kg ZPE-LR oral-administration. In addition, TPA-induced iNOS, COX-2 mRNA level and protein expression were reduced. Acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. We examined in vitro ZPE-LR effects in LPS-induced RAW 264.7 cells. LPS-induced p65 translocation to the nucleus was prohibited by ZPE-LR 100 μg/ml oral administration. Moreover, ROS generation by LPS was significantly inhibited by ZPE-LR 50 and 100 μg/ml treatment. To investigate new ZPE-LR activating mechanisms, the gene fishing method (not a typical term, should probably use PCR based genetic screening) was used. LPS-induced HPRT1 (hypoxanthine phosphoribosyltransferase 1) was decreased by ZPE-LR. However, RPL8 (Ribosomal protein L8) which showed no change in mRNA expression due to LPS, did show increased mRNA levels after ZPE-LR treatment. Our data elucidate mechanisms underlying ZPE-LR and suggest ZPE-LR may be a potential therapeutic agent to modulate osteoarthritis inflammation and pain. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

PubMed

de los Santos, M J; García-Laez, V; Beltrán, D; Labarta, E; Zuzuarregui, Jose Luis; Alamá, P; Gámiz, P; Crespo, J; Bosch, E; Pellicer, A

2013-01-01

What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E₂), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle. The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

Synthesis of visible light sensitized S, N and C co-doped polymorphic TiO2 for Microcystin-LR MC-LR removal

EPA Science Inventory

Microcystin-LR (MC-LR) is considered as one of the most widespread and toxic cyanotoxins, which had been discovered to be hepatotoxic, cytotoxic and neurotoxic. It is the only cyanotoxin that has been proposed by Word Health Organization (WHO) for a provisional guideline (1 ppb) ...

76 FR 60937 - Draft License Renewal Interim Staff Guidance LR-ISG-2011-02; Aging Management Program for Steam...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

...-2011-02; Aging Management Program for Steam Generators AGENCY: Nuclear Regulatory Commission. ACTION... License Renewal Interim Staff Guidance (LR-ISG), LR-ISG-2011-02, ``Aging Management Program for Steam... using Revision 3 of NEI 97-06 to manage steam generator aging. The Draft LR-ISG revises the NRC staff's...

Separating climate change signals into thermodynamic, lapse-rate and circulation effects: theory and application to the European summer climate

NASA Astrophysics Data System (ADS)

Kröner, Nico; Kotlarski, Sven; Fischer, Erich; Lüthi, Daniel; Zubler, Elias; Schär, Christoph

2017-05-01

Climate models robustly project a strong overall summer warming across Europe showing a characteristic north-south gradient with enhanced warming and drying in southern Europe. However, the processes that are responsible for this pattern are not fully understood. We here employ an extended surrogate or pseudo-warming approach to disentangle the contribution of different mechanisms to this response pattern. The basic idea of the surrogate technique is to use a regional climate model and apply a large-scale warming to the lateral boundary conditions of a present-day reference simulation, while maintaining the relative humidity (and thus implicitly increasing the specific moisture content). In comparison to previous studies, our approach includes two important extensions: first, different vertical warming profiles are applied in order to separate the effects of a mean warming from lapse-rate effects. Second, a twin-design is used, in which the climate change signals are not only added to present-day conditions, but also subtracted from a scenario experiment. We demonstrate that these extensions provide an elegant way to separate the full climate change signal into contributions from large-scale thermodynamic (TD), lapse-rate (LR), and circulation and other remaining effects (CO). The latter in particular include changes in land-ocean contrast and spatial variations of the SST warming patterns. We find that the TD effect yields a large-scale warming across Europe with no distinct latitudinal gradient. The LR effect, which is quantified for the first time in our study, leads to a stronger warming and some drying in southern Europe. It explains about 50 % of the warming amplification over the Iberian Peninsula, thus demonstrating the important role of lapse-rate changes. The effect is linked to an extending Hadley circulation. The CO effect as inherited from the driving GCM is shown to further amplify the north-south temperature change gradient. In terms of mean summer precipitation the TD effect leads to a significant overall increase in precipitation all across Europe, which is compensated and regionally reversed by the LR and CO effects in particular in southern Europe.

EUV multilayer defect compensation (MDC) by absorber pattern modification: from theory to wafer validation

NASA Astrophysics Data System (ADS)

Pang, Linyong; Hu, Peter; Satake, Masaki; Tolani, Vikram; Peng, Danping; Li, Ying; Chen, Dongxue

2011-11-01

According to the ITRS roadmap, mask defects are among the top technical challenges to introduce extreme ultraviolet (EUV) lithography into production. Making a multilayer defect-free extreme ultraviolet (EUV) blank is not possible today, and is unlikely to happen in the next few years. This means that EUV must work with multilayer defects present on the mask. The method proposed by Luminescent is to compensate effects of multilayer defects on images by modifying the absorber patterns. The effect of a multilayer defect is to distort the images of adjacent absorber patterns. Although the defect cannot be repaired, the images may be restored to their desired targets by changing the absorber patterns. This method was first introduced in our paper at BACUS 2010, which described a simple pixel-based compensation algorithm using a fast multilayer model. The fast model made it possible to complete the compensation calculations in seconds, instead of days or weeks required for rigorous Finite Domain Time Difference (FDTD) simulations. Our SPIE 2011 paper introduced an advanced compensation algorithm using the Level Set Method for 2D absorber patterns. In this paper the method is extended to consider process window, and allow repair tool constraints, such as permitting etching but not deposition. The multilayer defect growth model is also enhanced so that the multilayer defect can be "inverted", or recovered from the top layer profile using a calibrated model.

SLC7 family transporters control the establishment of left-right asymmetry during organogenesis in medaka by activating mTOR signaling.

PubMed

Asaoka, Yoichi; Nagai, Yoko; Namae, Misako; Furutani-Seiki, Makoto; Nishina, Hiroshi

2016-05-20

The precise government of the left-right (LR) specification of an organ is an essential aspect of its morphogenesis. Multiple signaling cascades have been implicated in the establishment of vertebrate LR asymmetry. Recently, mTOR signaling was found to critically regulate the development of LR asymmetry in zebrafish. However, the upstream factor(s) that activate mTOR signaling in the context of LR specification are as yet unknown. In this study, we identify the SLC7 amino acid transporters Slc7a7 and Slc7a8 as novel regulators of LR asymmetry development in the small fish medaka. Knockdown of Slc7a7 and/or Slc7a8 in medaka embryos disrupted LR organ asymmetries. Depletion of Slc7a7 hindered left-sided expression of the southpaw (spaw) gene, which is responsible for LR axis determination. Work at the cellular level revealed that Slc7a7 coordinates ciliogenesis in the epithelium of Kupffer's vesicle and thereby the generation of the nodal fluid flow required for LR asymmetry. Interestingly, knockdown of Slc7a7 depressed mTOR signaling activity in medaka embryos. Treatment with rapamycin, an inhibitor of mTOR signaling, together with Slc7a7 knockdown synergistically perturbed spaw expression, indicating an interaction between Slc7a7 and mTOR signaling affecting gene expression required for LR specification. Taken together, our results demonstrate that Slc7a7 governs the regulation of LR asymmetry development via the activation of mTOR signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

A conserved RxLR effector interacts with host RABA-type GTPases to inhibit vesicle-mediated secretion of antimicrobial proteins.

PubMed

Tomczynska, Iga; Stumpe, Michael; Mauch, Felix

2018-04-19

Plant pathogens of the oomycete genus Phytophthora produce virulence factors, known as RxLR effector proteins that are transferred into host cells to suppress disease resistance. Here, we analyse the function of the highly conserved RxLR24 effector of Phytophthora brassicae. RxLR24 was expressed early in the interaction with Arabidopsis plants and ectopic expression in the host enhanced leaf colonization and zoosporangia formation. Co-immunoprecipitation (Co-IP) experiments followed by mass spectrometry identified different members of the RABA GTPase family as putative RxLR24 targets. Physical interaction of RxLR24 or its homologue from the potato pathogen Phytophthora infestans with different RABA GTPases of Arabidopsis or potato, respectively, was confirmed by reciprocal Co-IP. In line with the function of RABA GTPases in vesicular secretion, RxLR24 co-localized with RABA1a to vesicles and the plasma membrane. The effect of RxLR24 on the secretory process was analysed with fusion constructs of secreted antimicrobial proteins with a pH-sensitive GFP tag. PATHOGENESIS RELATED PROTEIN 1 (PR-1) and DEFENSIN (PDF1.2) were efficiently exported in control tissue, whereas in the presence of RxLR24 they both accumulated in the endoplasmic reticulum. Together our results imply a virulence function of RxLR24 effectors as inhibitors of RABA GTPase-mediated vesicular secretion of antimicrobial PR-1, PDF1.2 and possibly other defence-related compounds. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

PubMed Central

Chetty, Carryn; Khumalo, Thandokuhle; Da Costa Dias, Bianca; Reusch, Uwe; Knackmuss, Stefan; Little, Melvyn; Weiss, Stefan F. T.

2014-01-01

Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction. PMID:24798101

Defect reduction of high-density full-field patterns in jet and flash imprint lithography

NASA Astrophysics Data System (ADS)

Singh, Lovejeet; Luo, Kang; Ye, Zhengmao; Xu, Frank; Haase, Gaddi; Curran, David; LaBrake, Dwayne; Resnick, Douglas; Sreenivasan, S. V.

2011-04-01

Imprint lithography has been shown to be an effective technique for replication of nano-scale features. Jet and Flash Imprint Lithography (J-FIL) involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed leaving a patterned resist on the substrate. Acceptance of imprint lithography for manufacturing will require demonstration that it can attain defect levels commensurate with the defect specifications of high end memory devices. Typical defectivity targets are on the order of 0.10/cm2. This work summarizes the results of defect inspections focusing on two key defect types; random non-fill defects occurring during the resist filling process and repeater defects caused by interactions with particles on the substrate. Non-fill defectivity must always be considered within the context of process throughput. The key limiting throughput step in an imprint process is resist filling time. As a result, it is critical to characterize the filling process by measuring non-fill defectivity as a function of fill time. Repeater defects typically have two main sources; mask defects and particle related defects. Previous studies have indicated that soft particles tend to cause non-repeating defects. Hard particles, on the other hand, can cause either resist plugging or mask damage. In this work, an Imprio 500 twenty wafer per hour (wph) development tool was used to study both defect types. By carefully controlling the volume of inkjetted resist, optimizing the drop pattern and controlling the resist fluid front during spreading, fill times of 1.5 seconds were achieved with non-fill defect levels of approximately 1.2/cm2. Longevity runs were used to study repeater defects and a nickel contamination was identified as the key source of particle induced repeater defects.

75 FR 7929 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 190-100 LR...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 190-100 LR, -100 IGW, -100 STD, -200 STD, -200 LR, and -200 IGW Airplanes AGENCY: Federal Aviation Administration (FAA), Department of... applies to Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 190-100 LR, -100 IGW, -100 STD, -200...

Reducible dictionaries for single image super-resolution based on patch matching and mean shifting

NASA Astrophysics Data System (ADS)

Rasti, Pejman; Nasrollahi, Kamal; Orlova, Olga; Tamberg, Gert; Moeslund, Thomas B.; Anbarjafari, Gholamreza

2017-03-01

A single-image super-resolution (SR) method is proposed. The proposed method uses a generated dictionary from pairs of high resolution (HR) images and their corresponding low resolution (LR) representations. First, HR images and the corresponding LR ones are divided into patches of HR and LR, respectively, and then they are collected into separate dictionaries. Afterward, when performing SR, the distance between every patch of the input LR image and those of available LR patches in the LR dictionary is calculated. The minimum distance between the input LR patch and those in the LR dictionary is taken, and its counterpart from the HR dictionary is passed through an illumination enhancement process. By this technique, the noticeable change of illumination between neighbor patches in the super-resolved image is significantly reduced. The enhanced HR patch represents the HR patch of the super-resolved image. Finally, to remove the blocking effect caused by merging the patches, an average of the obtained HR image and the interpolated image obtained using bicubic interpolation is calculated. The quantitative and qualitative analyses show the superiority of the proposed technique over the conventional and state-of-art methods.

Effect of Lithospermi Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice

PubMed Central

Kim, Han-Na; Kim, Mi-Young; Choi, Chan-Hun; Kim, Byung-Joo; Kim, Kyung-Yoon; Kim, Gye-Yeop; Jeong, Hyun-Woo; Kim, Hyung-Woo

2012-01-01

Objective: The root of Lithospermum erythrorhizon Sieb. et Zucc. (Lithospermi Radix, LR) is a kind of heat clearing and blood cooling medicinal herbs. It can clear away heat and cool the blood, reduce toxins and disperse maculae. LR has long been used as efficacious therapy for inflammation, burns, frostbite and skin diseases such as eczema and psoriasis. Methods: In the present study, we investigate anti-allergic and anti-inflammatory effects of LR by using the 1-fluoro-2, 4- dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model. Results: Topical application of 10 mg/mL of LR effectively inhibited skin lesions induced by repeated paintings with DNFB. Topical application of LR also inhibited hyperplasia, edema, spongiosis and infiltrations of mononuclear cells. In addition, production levels of total immunoglobulin and IgG1 in serum were decreased by using LR in vivo. Conclusion: These data suggest that LR acts as an antiinflammatory agent, improving skin lesions in CD mice. PMID:25780635

Automated Defect and Correlation Length Analysis of Block Copolymer Thin Film Nanopatterns

PubMed Central

Murphy, Jeffrey N.; Harris, Kenneth D.; Buriak, Jillian M.

2015-01-01

Line patterns produced by lamellae- and cylinder-forming block copolymer (BCP) thin films are of widespread interest for their potential to enable nanoscale patterning over large areas. In order for such patterning methods to effectively integrate with current technologies, the resulting patterns need to have low defect densities, and be produced in a short timescale. To understand whether a given polymer or annealing method might potentially meet such challenges, it is necessary to examine the evolution of defects. Unfortunately, few tools are readily available to researchers, particularly those engaged in the synthesis and design of new polymeric systems with the potential for patterning, to measure defects in such line patterns. To this end, we present an image analysis tool, which we have developed and made available, to measure the characteristics of such patterns in an automated fashion. Additionally we apply the tool to six cylinder-forming polystyrene-block-poly(2-vinylpyridine) polymers thermally annealed to explore the relationship between the size of each polymer and measured characteristics including line period, line-width, defect density, line-edge roughness (LER), line-width roughness (LWR), and correlation length. Finally, we explore the line-edge roughness, line-width roughness, defect density, and correlation length as a function of the image area sampled to determine each in a more rigorous fashion. PMID:26207990

Defect reduction for semiconductor memory applications using jet and flash imprint lithography

NASA Astrophysics Data System (ADS)

Ye, Zhengmao; Luo, Kang; Irving, J. W.; Lu, Xiaoming; Zhang, Wei; Fletcher, Brian; Liu, Weijun; Xu, Frank; LaBrake, Dwayne; Resnick, Douglas; Sreenivasan, S. V.

2013-03-01

Imprint lithography has been shown to be an effective technique for replication of nano-scale features. Jet and Flash Imprint Lithography (J-FIL) involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed leaving a patterned resist on the substrate. Acceptance of imprint lithography for manufacturing will require demonstration that it can attain defect levels commensurate with the defect specifications of high end memory devices. Typical defectivity targets are on the order of 0.10/cm2. In previous studies, we have focused on defects such as random non-fill defects occurring during the resist filling process and repeater defects caused by interactions with particles on the substrate. In this work, we attempted to identify the critical imprint defect types using a mask with NAND Flash-like patterns at dimensions as small as 26nm. The two key defect types identified were line break defects induced by small particulates and airborne contaminants which result in local adhesion failure. After identification, the root cause of the defect was determined, and corrective measures were taken to either eliminate or reduce the defect source. As a result, we have been able to reduce defectivity levels by more than three orders of magnitude in only 12 months and are now achieving defectivity adders as small as 2 adders per lot of wafers.

Rapid Coarsening of Ion Beam Ripple Patterns by Defect Annihilation

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

Hansen, Henri; Messlinger, Sebastian; Stoian, Georgiana

Ripple patterns formed on Pt(111) through grazing incidence ion beam erosion coarsen rapidly. At and below 450 K coarsening of the patterns is athermal and kinetic, unrelated to diffusion and surface free energy. Similar to the situation for sand dunes, coarsening takes place through annihilation reactions of mobile defects in the pattern. The defect velocity derived on the basis of a simple model agrees quantitatively with the velocity of monatomic steps illuminated by the ion beam.

Mapping of leaf rust resistance genes and molecular characterization of the 2NS/2AS translocation in the wheat cultivar Jagger

USDA-ARS?s Scientific Manuscript database

Winter wheat cultivar 'Jagger' was recently found to have an alien chromosomal segment 'VPM1' that should carry Lr37, a gene conferring resistance against leaf rust caused by Puccinia triticina, and this cultivar was also reported to have the wheat gene Lr17 against leaf rust. Both Lr17 and Lr37 wer...

Automated online optical biosensing system for continuous real-time determination of microcystin-LR with high sensitivity and specificity: early warning for cyanotoxin risk in drinking water sources.

PubMed

Shi, Han-Chang; Song, Bao-Dong; Long, Feng; Zhou, Xiao-Hong; He, Miao; Lv, Qing; Yang, Hai-Yang

2013-05-07

The accelerated eutrophication of surface water sources and climate change have led to an annual occurrence of cyanobacterial blooms in many drinking water resources. To minimize the health risks to the public, cyanotoxin detection methods that are rapid, sensitive, real time, and high frequency must be established. In this study, an innovative automated online optical biosensing system (AOBS) was developed for the rapid detection and early warning of microcystin-LR (MC-LR), one of the most toxic cyanotoxins and most frequently detected in environmental water. In this system, the capturing molecular MC-LR-ovalbumin (MC-LR-OVA) was covalently immobilized onto a biochip surface. By an indirect competitive detection mode, samples containing different concentrations of MC-LR were premixed with a certain concentration of fluorescence-labeled anti-MC-LR-mAb, which binds to MC-LR with high specificity. Then, the sample mixture was pumped onto the biochip surface, and a higher concentration of MC-LR led to less fluorescence-labeled antibody bound onto the biochip surface and thus to lower fluorescence signal. The quantification of MC-LR ranges from 0.2 to 4 μg/L, with a detection limit determined as 0.09 μg/L. The high specificity and selectivity of the sensor were evaluated in terms of its response to a number of potentially interfering cyanotoxins. Potential interference of the environmental sample matrix was assessed by spiked samples, and the recovery of MC-LR ranged from 90 to 120% with relative standard deviation values <8%. The immunoassay performance of the AOBS was validated with respect to that of conventional high-performance liquid chromatography, and the correlation between methods agreed well (R(2) = 0.9762). This system has successfully been applied to long-term, continuous determination and early warning for MC-LR in Lake Tai from June 2011 to May 2012. Thus, the AOBS paves the way for a vital routine online analysis that satisfies the high demand for ensuring the safety of drinking water sources. The AOBS can also serve as early warning system for accidental or intentional water pollution.

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

PubMed

Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M

2015-01-01

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.

Progression of Treated versus Untreated Liver Imaging Reporting and Data System Category 4 Masses after Transcatheter Arterial Embolization Therapy.

PubMed

Ronald, James; Gupta, Rajan T; Marin, Daniele; Wang, Qi; Durocher, Nicholas S; Suhocki, Paul V; Kim, Charles Y

2018-05-01

To compare outcomes of treated vs untreated Liver Imaging Reporting and Data System category 4 (LR-4) masses after transcatheter arterial embolization. In 167 patients undergoing embolization for HCC from January 2005 to December 2012, LR-4 masses were retrospectively identified on CT and MR imaging examinations performed before embolization. In 149 patients undergoing embolization from January 2013 to December 2016, masses prospectively classified as LR-4 were identified. In total, there were 81 LR-4 masses in 62 patients (16 women; mean age 62 y; range 29-83 y). Procedures were reviewed to determine whether LR-4 masses were within or outside the liver volume that received embolization during treatment of dominant masses. Time to progression to LR-5 and by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was estimated for treated vs untreated LR-4 masses using the Kaplan-Meier method and compared using the log rank test. LR-4 masses averaged 1.8 cm; 88%, 60%, 14%, and 14% demonstrated arterial phase hyperenhancement, washout, a capsule, and growth. Of LR-4 masses, 62 were within the liver volume that received embolization and considered treated, and 19 were outside and considered untreated. Response rates according to mRECIST were 37% vs 21% for treated vs untreated masses (P = .27). The 6- and 12-month rates of progression to LR-5 were 7% and 26% for treated masses vs 27% and 75% for untreated masses (P = .001). According to mRECIST, 7% and 27% of treated masses progressed vs 30% and 65% of untreated masses (P = .001). LR-4 masses that receive embolization in the setting of dominant masses elsewhere show lower rates of progression compared with untreated masses. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

PubMed

Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

2016-01-01

Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Homogeneous time-resolved fluoroimmunoassay of microcystin-LR using layered WS2 nanosheets as a transducer

NASA Astrophysics Data System (ADS)

Qin, Xiaodan; Wang, Yuanxiu; Song, Bo; Wang, Xin; Ma, Hua; Yuan, Jingli

2017-06-01

A homogeneous time-resolved fluoroimmunoassay method for rapid and sensitive detection of microcystin-LR (MC-LR) in water samples was developed based on the interaction between water-soluble WS2 nanosheets and the conjugate of MC-LR with a luminescent Eu3+ complex BHHBCB-Eu3+ (BHHBCB: 1,2-bis[4‧-(1″,1″,1″,2″,2″,3″,3″-heptafluoro-4″,6″-hexanedion-6″-yl)- benzyl]-4-chlorosulfobenzene). The large lateral dimensions and high surface areas of two-dimensional layered WS2 nanosheets enable easy adsorption of the MC-LR-BHHBCB-Eu3+ conjugate, that lead to efficient quenching of the luminescence of Eu3+ complex via energy transfer or electron transfer process. However, the addition of monoclonal anti-MC-LR antibody can induce the formation of MC-LR-BHHBCB-Eu3+/antibody immune complex, which prevents the interaction between WS2 nanosheets and MC-LR-BHHBCB-Eu3+ to result in the restoration of Eu3+ luminescence. This signal transduction mechanism made it possible for analysis of the target MC-LR in a homogeneous system. The present method has advantages of rapidity and simplicity since the B/F (bound reagent/free reagent) separation steps, the solid-phase carrier and antibody labeling or modification process are not necessary. The proposed immunosensing system displayed a wide linear range, good precision and accuracy, and comparable sensitivity with a detection limit of 0.3 μg l-1, which satisfied the World Health Organization (WHO) provisional guideline limit of 1.0 μg l-1 for MC-LR in drinking water.

Redox signaling via lipid raft clustering in homocysteine-induced injury of podocytes.

PubMed

Zhang, Chun; Hu, Jun-Jun; Xia, Min; Boini, Krishna M; Brimson, Christopher; Li, Pin-Lan

2010-04-01

Our recent studies have indicated that hyperhomocysteinemia (hHcys) may induce podocyte damage, resulting in glomerulosclerosis. However, the molecular mechanisms mediating hHcys-induced podocyte injury are still poorly understood. In the present study, we first demonstrated that an intact NADPH oxidase system is present in podocytes as shown by detection of its membrane subunit (gp91(phox)) and cytosolic subunit (p47(phox)). Then, confocal microscopy showed that gp91(phox) and p47(phox) could be aggregated in lipid raft (LR) clusters in podocytes treated with homocysteine (Hcys), which were illustrated by their colocalization with cholera toxin B, a common LR marker. Different mechanistic LR disruptors, either methyl-beta-cyclodextrin (MCD) or filipin abolished such Hcys-induced formation of LR-gp91(phox) or LR-p47(phox) transmembrane signaling complexes. By flotation of detergent-resistant membrane fractions we found that gp91(phox) and p47(phox) were enriched in LR fractions upon Hcys stimulation, and such enrichment of NADPH oxidase subunits and increase in its enzyme activity were blocked by MCD or filipin. Functionally, disruption of LR clustering significantly attenuated Hcys-induced podocyte injury, as shown by their inhibitory effects on Hcys-decreased expression of slit diaphragm molecules such as nephrin and podocin. Similarly, Hcys-increased expression of desmin was also reduced by disruption of LR clustering. In addition, inhibition of such LR-associated redox signaling prevented cytoskeleton disarrangement and apoptosis induced by Hcys. It is concluded that NADPH oxidase subunits aggregation and consequent activation of this enzyme through LR clustering is an important molecular mechanism triggering oxidative injury of podocytes induced by Hcys. 2009 Elsevier B.V. All rights reserved.

Redox signaling via lipid raft clustering in homocysteine-induced injury of podocytes

PubMed Central

Zhang, Chun; Hu, Jun-Jun; Xia, Min; Boini, Krishna M.; Brimson, Christopher; Li, Pin-Lan

2010-01-01

Our recent studies have indicated that hyperhomocysteinemia (hHcys) may induce podocyte damage, resulting in glomerulosclerosis. However, the molecular mechanisms mediating hHcys-induced podocyte injury are still poorly understood. In the present study, we first demonstrated that an intact NADPH oxidase system is present in podocytes as shown by detection of its membrane subunit (gp91phox) and cytosolic subunit (p47phox). Then, confocal microscopy showed that gp91phox and p47phox could be aggregated in lipid raft (LR) clusters in podocytes treated with homocysteine (Hcys), which were illustrated by their co-localization with cholera toxin B, a common LR marker. Different mechanistic LR disruptors, either methyl-β-cyclodextrin (MCD) or filipin abolished such Hcys-induced formation of LR-gp91phox or LR-p47phox transmembrane signaling complexes. By flotation of detergent-resistant membrane fractions we found that gp91phox and p47phox were enriched in LR fractions upon Hcys stimulation, and such enrichment of NADPH oxidase subunits and increase in its enzyme activity were blocked by MCD or filipin. Functionally, disruption of LR clustering significantly attenuated Hcys-induced podocyte injury, as shown by their inhibitory effects on Hcys-decreased expression of slit diaphragm molecules such as nephrin and podocin. Similarly, Hcys-increased expression of desmin was also reduced by disruption of LR clustering. In addition, inhibition of such LR-associated redox signaling prevented cytoskeleton disarrangement and apoptosis induced by Hcys. It is concluded that NADPH oxidase subunits aggregation and consequent activation of this enzyme through LR clustering is an important molecular mechanism triggering oxidative injury of podocytes induced by Hcys. PMID:20036696

The interactive effects of microcystin-LR and cylindrospermopsin on the growth rate of the freshwater algae Chlorella vulgaris.

PubMed

Pinheiro, Carlos; Azevedo, Joana; Campos, Alexandre; Vasconcelos, Vítor; Loureiro, Susana

2016-05-01

Microcystin-LR (MC-LR) and cylindrospermopsin (CYN) are the most representative cyanobacterial cyanotoxins. They have been simultaneously detected in aquatic systems, but their combined ecotoxicological effects to aquatic organisms, especially microalgae, is unknown. In this study, we examined the effects of these cyanotoxins individually and as a binary mixture on the growth rate of the freshwater algae Chlorella vulgaris. Using the MIXTOX tool, the reference model concentration addition (CA) was selected to evaluate the combined effects of MC-LR and CYN on the growth of the freshwater green algae due to its conservative prediction of mixture effect for putative similar or dissimilar acting chemicals. Deviations from the CA model such as synergism/antagonism, dose-ratio and dose-level dependency were also assessed. In single exposures, our results demonstrated that MC-LR and CYN had different impacts on the growth rates of C. vulgaris at the highest tested concentrations, being CYN the most toxic. In the mixture exposure trial, MC-LR and CYN showed a synergistic deviation from the conceptual model CA as the best descriptive model. MC-LR individually was not toxic even at high concentrations (37 mg L(-1)); however, the presence of MC-LR at much lower concentrations (0.4-16.7 mg L(-1)) increased the CYN toxicity. From these results, the combined exposure of MC-LR and CYN should be considered for risk assessment of mixtures as the toxicity may be underestimated when looking only at the single cyanotoxins and not their combination. This study also represents an important step to understand the interactions among MC-LR and CYN detected previously in aquatic systems.

Anomalous finite-size effect due to quasidegenerate phases in triangular antiferromagnets with long-range interactions and mapping to the generalized six-state clock model

NASA Astrophysics Data System (ADS)

Nishino, Masamichi; Miyashita, Seiji

2016-11-01

The effect of long-range (LR) interactions on frustrated-spin models is an interesting problem, which provides rich ordering processes. We study the effect of LR interactions on triangular Ising antiferromagnets with the next-nearest-neighbor ferromagnetic interaction (TIAFF). In the thermodynamic limit, the LRTIAFF model should reproduce the corresponding mean-field results, in which successive phase transitions occur among various phases, i.e., the disordered paramagnetic phase, so-called partially disordered phase, three-sublattice ferrimagnetic phase, and two-sublattice ferrimagnetic phase. In the present paper we focus on the magnetic susceptibility at the transition point between the two-sublattice ferrimagnetic and the disordered paramagnetic phases at relatively large ferromagnetic interactions. In the mean-field analysis, the magnetic susceptibility shows no divergence at the transition point. In contrast, a divergencelike enhancement of the susceptibility is observed in Monte Carlo simulations in finite-size systems. We investigate the origin of this difference and find that it is attributed to a virtual degeneracy of the free energies of the partially disordered and 2-FR phases. We also exploit a generalized six-state clock model with an LR interaction, which is a more general system with Z6 symmetry. We discuss the phase diagram of this model and find that it exhibits richer transition patterns and contains the physics of the LRTIAFF model.

Susceptibility to Exercise-Induced Muscle Damage: a Cluster Analysis with a Large Sample.

PubMed

Damas, F; Nosaka, K; Libardi, C A; Chen, T C; Ugrinowitsch, C

2016-07-01

We investigated the responses of indirect markers of exercise-induced muscle damage (EIMD) among a large number of young men (N=286) stratified in clusters based on the largest decrease in maximal voluntary contraction torque (MVC) after an unaccustomed maximal eccentric exercise bout of the elbow flexors. Changes in MVC, muscle soreness (SOR), creatine kinase (CK) activity, range of motion (ROM) and upper-arm circumference (CIR) before and for several days after exercise were compared between 3 clusters established based on MVC decrease (low, moderate, and high responders; LR, MR and HR). Participants were allocated to LR (n=61), MR (n=152) and HR (n=73) clusters, which depicted significantly different cluster centers of 82%, 61% and 42% of baseline MVC, respectively. Once stratified by MVC decrease, all muscle damage markers were significantly different between clusters following the same pattern: small changes for LR, larger changes for MR, and the largest changes for HR. Stratification of individuals based on the magnitude of MVC decrease post-exercise greatly increases the precision in estimating changes in EIMD by proxy markers such as SOR, CK activity, ROM and CIR. This indicates that the most commonly used markers are valid and MVC orchestrates their responses, consolidating the role of MVC as the best EIMD indirect marker. © Georg Thieme Verlag KG Stuttgart · New York.

Response to environmental change in rainbow trout selected for divergent stress coping styles.

PubMed

Ruiz-Gomez, Maria de Lourdes; Huntingford, Felicity A; Øverli, Øyvind; Thörnqvist, Per-Ove; Höglund, Erik

2011-03-01

An extensive literature has documented differences in the way individual animals cope with environmental challenges and stressors. Two broad patterns of individual variability in behavioural and physiological stress responses are described as the proactive and reactive stress coping styles. In addition to variability in the stress response, contrasting coping styles may encompass a general difference in behavioural flexibility as opposed to routine formation in response to more subtle environmental changes and non-threatening novelties. In the present study two different manipulations, relocating food from a previously learned location, and introducing a novel object yielded contrasting responses in rainbow trout selected for high (HR) and low (LR) post stress plasma cortisol levels. No difference was seen in the rate of learning the original food location; however, proactive LR fish were markedly slower than reactive HR fish in altering their food seeking behaviour in response to relocated food. In contrast, LR fish largely ignored a novel object which disrupted feeding in HR fish. Hence, it appears that the two lines appraise environmental cues differently. This observation suggests that differences in responsiveness to environmental change are an integral component of heritable stress coping styles, which in this particular case, had opposite effects on foraging efficiency in different situations. Context dependent fitness effects may thus explain the persistence of stable divergence of this evolutionary widespread trait complex. 2010 Elsevier Inc. All rights reserved.

Genetic basis of human left-right asymmetry disorders.

PubMed

Deng, Hao; Xia, Hong; Deng, Sheng

2015-01-27

Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.

Adsorption of microcystin-LR on mesoporous carbons and its potential use in drinking water source.

PubMed

Park, Jeong-Ann; Jung, Sung-Mok; Yi, In-Geol; Choi, Jae-Woo; Kim, Song-Bae; Lee, Sang-Hyup

2017-06-01

Microcystin-LR (MC-LR) is a common toxin derived from cyanobacterial blooms an effective, rapid and non-toxic method needs to be developed for its removal from drinking water treatment plants (DWTP). For an adsorption-based method, mesoporous carbon can be a promising supplemental adsorbent. The effect of mesoporous carbon (MC1, MC2, and MC3) properties and water quality parameters on the adsorption of MC-LR were investigated and the results were analyzed by kinetic, isotherm, thermodynamic, Derjaguin-Landau-Verwey-Overbeek (DLVO), and intraparticle diffusion models. MC1 was the most appropriate type for the removal of MC-LR with a maximum adsorption capacity of 35,670.49 μg/g. Adsorption of MC-LR is a spontaneous reaction dominated by van der Waals interactions. Pore sizes of 8.5-14 nm enhance the pore diffusion of MC-LR from the surface to the mesopores of MC1. The adsorption capacity was not sensitive to changes in the pH (3.2-8.0) and the existence of organic matter (2-5 mg/L). Furthermore, the final concentration of MC-LR was below the WHO guideline level after a 10-min reaction with 20 mg/L of MC1 in the Nak-Dong River, a drinking water source. The MC-LR adsorption mainly competed with humic substances (500-1000 g/mole); however, they did not have a great effect on adsorption. Copyright © 2017. Published by Elsevier Ltd.

The Influence of Aerosol Hygroscopicity on Retrieving the Aerosol Extincting Coefficient from MPL Data

NASA Astrophysics Data System (ADS)

Zhao, G.; Zhao, C.

2016-12-01

Micro-pulse Lidar (MPL) measurements have been widely used to profile the ambient aerosol extincting coefficient(). Lidar Ratio (LR) ,which highly depends on the particle number size distribution (PNSD) and aerosol hygroscopicity, is the most important factor to retrieve the profile. A constant AOD constrained LR is usually used in current algorithms, which would lead to large bias when the relative humidity (RH) in the mixed layer is high. In this research, the influences of PNSD, aerosol hygroscopicity and RH profiles on the vertical variation of LR were investigated based on the datasets from field measurements in the North China Plain (NCP). Results show that LR can have an enhancement factor of more than 120% when the RH reaches to 92%. A new algorithm of retrieving the profile is proposed based on the variation of LR due to aerosol hygroscopicity. The magnitude and vertical structures of retrieved using this method can be significantly different to that of the fiexed LR method. The relative difference can reach up to 40% when the RH in the mixed layer is higher than 90% . Sensitivity studies show that RH profile and PNSD affect most on the retrieved by fiexed LR method. In view of this, a scheme of LR enhancement factor by RH is proposed in the NCP. The relative differnce of the calculated between using this scheme and the new algorithm with the variable LR can be less than 10%.

The durable wheat disease resistance gene Lr34 confers common rust and northern corn leaf blight resistance in maize.

PubMed

Sucher, Justine; Boni, Rainer; Yang, Ping; Rogowsky, Peter; Büchner, Heike; Kastner, Christine; Kumlehn, Jochen; Krattinger, Simon G; Keller, Beat

2017-04-01

Maize (corn) is one of the most widely grown cereal crops globally. Fungal diseases of maize cause significant economic damage by reducing maize yields and by increasing input costs for disease management. The most sustainable control of maize diseases is through the release and planting of maize cultivars with durable disease resistance. The wheat gene Lr34 provides durable and partial field resistance against multiple fungal diseases of wheat, including three wheat rust pathogens and wheat powdery mildew. Because of its unique qualities, Lr34 became a cornerstone in many wheat disease resistance programmes. The Lr34 resistance is encoded by a rare variant of an ATP-binding cassette (ABC) transporter that evolved after wheat domestication. An Lr34-like disease resistance phenotype has not been reported in other cereal species, including maize. Here, we transformed the Lr34 resistance gene into the maize hybrid Hi-II. Lr34-expressing maize plants showed increased resistance against the biotrophic fungal disease common rust and the hemi-biotrophic disease northern corn leaf blight. Furthermore, the Lr34-expressing maize plants developed a late leaf tip necrosis phenotype, without negative impact on plant growth. With this and previous reports, it could be shown that Lr34 is effective against various biotrophic and hemi-biotrophic diseases that collectively parasitize all major cereal crop species. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

In vitro translocation experiments with RxLR-reporter fusion proteins of Avr1b from Phytophthora sojae and AVR3a from Phytophthora infestans fail to demonstrate specific autonomous uptake in plant and animal cells.

PubMed

Wawra, Stephan; Djamei, Armin; Albert, Isabell; Nürnberger, Thorsten; Kahmann, Regine; van West, Pieter

2013-05-01

Plant-pathogenic oomycetes have a large set of secreted effectors that can be translocated into their host cells during infection. One group of these effectors are the RxLR effectors for which it has been shown, in a few cases, that the RxLR motif is important for their translocation. It has been suggested that the RxLR-leader sequences alone are enough to translocate the respective effectors into eukaryotic cells through binding to surface-exposed phosphoinositol-3-phosphate. These conclusions were primary based on translocation experiments conducted with recombinant fusion proteins whereby the RxLR leader of RxLR effectors (i.e., Avr1b from Phytophthora sojae) were fused to the green fluorescent protein reporter-protein. However, we failed to observe specific cellular uptake for a comparable fusion protein where the RxLR leader of the P. infestans AVR3a was fused to monomeric red fluorescent protein. Therefore, we reexamined the ability of the reported P. sojae AVR1b RxLR leader to enter eukaryotic cells. Different relevant experiments were performed in three independent laboratories, using fluorescent reporter fusion constructs of AVR3a and Avr1b proteins in a side-by-side comparative study on plant tissue and human and animal cells. We report that we were unable to obtain conclusive evidence for specific RxLR-mediated translocation.

Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model

PubMed Central

González, Juan C.; López, Catalina; Álvarez, María E.; Pérez, Jorge E.; Carmona, Jorge U.

2016-01-01

Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT. PMID:26781753

Characterization of in vitro effects of microcystin-LR on intestinal epithelial cells.

PubMed

Zhou, Yuan; Xu, Xiaoping; Yu, Beibei; Yu, Guang

2017-05-01

The intestinal epithelium is a single-cell layer that provides an important barrier against natural toxins. Microcystin-LR (MC-LR), a cyclic heptapeptide, is one of the best known toxins able to alter the functions of intestine. This study evaluated the toxic effects and the possible mechanisms of MC-LR on barrier function of the intestinal epithelial cells. Intestinal epithelial cells (IEC-6) were exposed to 0, 6.25, 12.5, 25 and 50 μM MC-LR. Cell viability significantly decreased, while the ratio of apoptotic cells increased after exposure to 12.5μM and higer concentration of MC-LR. As expected, the integrity of a polarized IEC-6 monolayer was affected by MC-LR exposure, as demonstrated by a decrease in the transepithelial electrical resistance (TEER) values, becoming most pronounced at 50μM, 24 h. No effects were detected on the protein expression levels of the tight junction protein claudin at 50μM. However, the expression of occludin and zonula occludens-1 (ZO-1) declined. Furthermore, MC-LR can immigrate into IEC-6 cells. The activity of protein phosphatases 2A (PP2A) decreased from the concentration of 12.5 μM, showing a dose-dependent decline. These results provide new information that strengthens the concept that the intestinal epithelium is important targets for toxic effects of water contaminants like MC-LR. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1539-1547, 2017. © 2016 Wiley Periodicals, Inc.

Defect reduction of patterned media templates and disks

NASA Astrophysics Data System (ADS)

Luo, Kang; Ha, Steven; Fretwell, John; Ramos, Rick; Ye, Zhengmao; Schmid, Gerard; LaBrake, Dwayne; Resnick, Douglas J.; Sreenivasan, S. V.

2010-05-01

Imprint lithography has been shown to be an effective technique for the replication of nano-scale features. Acceptance of imprint lithography for manufacturing will require a demonstration of defect levels commensurate with cost-effective device production. This work summarizes the results of defect inspections of hard disks patterned using Jet and Flash Imprint Lithography (J-FILTM). Inspections were performed with optical based automated inspection tools. For the hard drive market, it is important to understand the defectivity of both the template and the imprinted disk. This work presents a methodology for automated pattern inspection and defect classification for imprint-patterned media. Candela CS20 and 6120 tools from KLA-Tencor map the optical properties of the disk surface, producing highresolution grayscale images of surface reflectivity and scattered light. Defects that have been identified in this manner are further characterized according to the morphology. The imprint process was tested after optimizing both the disk cleaning and adhesion layers processes that precede imprinting. An extended imprint run was performed and both the defect types and trends are reported.

Understanding and reduction of defects on finished EUV masks

NASA Astrophysics Data System (ADS)

Liang, Ted; Sanchez, Peter; Zhang, Guojing; Shu, Emily; Nagpal, Rajesh; Stivers, Alan

2005-05-01

To reduce the risk of EUV lithography adaptation for the 32nm technology node in 2009, Intel has operated a EUV mask Pilot Line since early 2004. The Pilot Line integrates all the necessary process modules including common tool sets shared with current photomask production as well as EUV specific tools. This integrated endeavor ensures a comprehensive understanding of any issues, and development of solutions for the eventual fabrication of defect-free EUV masks. Two enabling modules for "defect-free" masks are pattern inspection and repair, which have been integrated into the Pilot Line. This is the first time we are able to look at real defects originated from multilayer blanks and patterning process on finished masks over entire mask area. In this paper, we describe our efforts in the qualification of DUV pattern inspection and electron beam mask repair tools for Pilot Line operation, including inspection tool sensitivity, defect classification and characterization, and defect repair. We will discuss the origins of each of the five classes of defects as seen by DUV pattern inspection tool on finished masks, and present solutions of eliminating and mitigating them.

Zygotic LvBMP5-8 is required for skeletal patterning and for left-right but not dorsal-ventral specification in the sea urchin embryo.

PubMed

Piacentino, Michael L; Chung, Oliver; Ramachandran, Janani; Zuch, Daniel T; Yu, Jia; Conaway, Evan A; Reyna, Arlene E; Bradham, Cynthia A

2016-04-01

Skeletal patterning in the sea urchin embryo requires coordinated signaling between the pattern-dictating ectoderm and the skeletogenic primary mesenchyme cells (PMCs); recent studies have begun to uncover the molecular basis for this process. Using an unbiased RNA-Seq-based screen, we have previously identified the TGF-ß superfamily ligand, LvBMP5-8, as a skeletal patterning gene in Lytechinus variegatus embryos. This result is surprising, since both BMP5-8 and BMP2/4 ligands have been implicated in sea urchin dorsal-ventral (DV) and left-right (LR) axis specification. Here, we demonstrate that zygotic LvBMP5-8 is required for normal skeletal patterning on the left side, as well as for normal PMC positioning during gastrulation. Zygotic LvBMP5-8 is required for expression of the left-side marker soxE, suggesting that LvBMP5-8 is required for left-side specification. Interestingly, we also find that LvBMP5-8 knockdown suppresses serotonergic neurogenesis on the left side. While LvBMP5-8 overexpression is sufficient to dorsalize embryos, we find that zygotic LvBMP5-8 is not required for normal DV specification or development. In addition, ectopic LvBMP5-8 does not dorsalize LvBMP2/4 morphant embryos, indicating that, in the absence of BMP2/4, BMP5-8 is insufficient to specify dorsal. Taken together, our data demonstrate that zygotic LvBMP5-8 signaling is essential for left-side specification, and for normal left-side skeletal and neural patterning, but not for DV specification. Thus, while both BMP2/4 and BMP5-8 regulate LR axis specification, BMP2/4 but not zygotic BMP5-8 regulates DV axis specification in sea urchin embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Carbon nanohorn sensitized electrochemical immunosensor for rapid detection of microcystin-LR.

PubMed

Zhang, Jing; Lei, Jianping; Xu, Chuanlai; Ding, Lin; Ju, Huangxian

2010-02-01

A sensitive electrochemical immunosensor was proposed by functionalizing single-walled carbon nanohorns (SWNHs) with analyte for microcystin-LR (MC-LR) detection. The functionalization of SWNHs was performed by covalently binding MC-LR to the abundant carboxylic groups on the cone-shaped tips of SWNHs in the presence of linkage reagents and characterized with Raman spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and a transmission electron micrograph. Compared with single-walled carbon nanotubes, SWNHs as immobilization matrixes showed a better sensitizing effect. Using home-prepared horseradish peroxidase-labeled MC-LR antibody for the competitive immunoassay, under optimal conditions, the immunosensor exhibited a wide linear response to MC-LR ranging from 0.05 to 20 microg/L with a detection limit of 0.03 microg/L at a signal-to-noise of 3. This method showed good accuracy, acceptable precision, and reproducibility. The assay results of MC-LR in polluted water were in a good agreement with the reference values. The proposed strategy provided a biocompatible immobilization and sensitized recognition platform for analytes as small antigens and possessed promising application in food and environmental monitoring.

The Molecular Basis of Wound Healing Processes Induced by Lithospermi Radix: A Proteomics and Biochemical Analysis

PubMed Central

Hsiao, Chia-Yen; Tsai, Tung-Hu; Chak, Kin-Fu

2012-01-01

Lithospermi Radix (LR) is an effective traditional Chinese herb in various types of wound healing; however, its mechanism of action remains unknown. A biochemical and proteomic platform was generated to explore the biological phenomena associated with LR and its active component shikonin. We found that both LR ethanol extracts and shikonin are able to promote cell proliferation by up to 25%. The results of proteomic analysis revealed that twenty-two differentially expressed proteins could be identified when fibroblast cells were treated with LR or shikonin. The functions of those proteins are associated with antioxidant activity, antiapoptosis activity, the regulation of cell mobility, the secretion of collagen, the removal of abnormal proteins, and the promotion of cell proliferation, indicating that the efficacy of LR in wound healing may be derived from a synergistic effect on a number of factors induced by the herbal medicine. Furthermore, an animal model confirmed that LR is able to accelerate wound healing on the flank back of the SD rats. Together these findings help to pinpoint the molecular basis of wound healing process induced by LR. PMID:23024692

Governance and management dynamics of landscape restoration at multiple scales: Learning from successful environmental managers in Sweden.

PubMed

Dawson, Lucas; Elbakidze, Marine; Angelstam, Per; Gordon, Johanna

2017-07-15

Due to a long history of intensive land and water use, habitat networks for biodiversity conservation are generally degraded in Sweden. Landscape restoration (LR) is an important strategy for achieving representative and functional green infrastructures. However, outcomes of LR efforts are poorly studied, particularly the dynamics of LR governance and management. We apply systems thinking methods to a series of LR case studies to analyse the causal structures underlying LR governance and management in Sweden. We show that these structures appear to comprise of an interlinked system of at least three sets of drivers and four core processes. This system exhibits many characteristics of a transformative change towards an integrated, adaptive approach to governance and management. Key challenges for Swedish LR projects relate to institutional and regulatory flexibility, the timely availability of sufficient funds, and the management of learning and knowledge production processes. In response, successful project leaders develop several key strategies to manage complexity and risk, and enhance perceptions of the attractiveness of LR projects. Copyright © 2017 Elsevier Ltd. All rights reserved.

EUV patterning improvement toward high-volume manufacturing

NASA Astrophysics Data System (ADS)

Kuwahara, Yuhei; Matsunaga, Koichi; Kawakami, Shinichiro; Nafus, Kathleen; Foubert, Philippe; Goethals, Anne-Marie

2015-03-01

Extreme ultraviolet lithography (EUVL) technology is a promising candidate for a semiconductor process for 18nm half pitch and beyond. So far, the studies of EUV for manufacturability have been focused on particular aspects. It still requires fine resolution, uniform and smooth patterns, and low defectivity, not only after lithography but also after the etch process. Tokyo Electron Limited and imec are continuously collaborating to improve manufacturing quality of the process of record (POR) on a CLEAN TRACKTM LITHIUS ProTMZ-EUV. This next generation coating/developing system has been upgraded with defectivity reduction enhancements which are applied along with TELTM best known methods. We have evaluated process defectivity post lithography and post etch. Apart from defectivity, FIRMTM rinse material and application compatibility with sub 18nm patterning is improved to prevent line pattern collapse and increase process window on next generation resist materials. This paper reports on the progress of defectivity and patterning performance optimization towards the NXE:3300 POR.

Patterning of leaf vein networks by convergent auxin transport pathways.

PubMed

Sawchuk, Megan G; Edgar, Alexander; Scarpella, Enrico

2013-01-01

The formation of leaf vein patterns has fascinated biologists for centuries. Transport of the plant signal auxin has long been implicated in vein patterning, but molecular details have remained unclear. Varied evidence suggests a central role for the plasma-membrane (PM)-localized PIN-FORMED1 (PIN1) intercellular auxin transporter of Arabidopsis thaliana in auxin-transport-dependent vein patterning. However, in contrast to the severe vein-pattern defects induced by auxin transport inhibitors, pin1 mutant leaves have only mild vein-pattern defects. These defects have been interpreted as evidence of redundancy between PIN1 and the other four PM-localized PIN proteins in vein patterning, redundancy that underlies many developmental processes. By contrast, we show here that vein patterning in the Arabidopsis leaf is controlled by two distinct and convergent auxin-transport pathways: intercellular auxin transport mediated by PM-localized PIN1 and intracellular auxin transport mediated by the evolutionarily older, endoplasmic-reticulum-localized PIN6, PIN8, and PIN5. PIN6 and PIN8 are expressed, as PIN1 and PIN5, at sites of vein formation. pin6 synthetically enhances pin1 vein-pattern defects, and pin8 quantitatively enhances pin1pin6 vein-pattern defects. Function of PIN6 is necessary, redundantly with that of PIN8, and sufficient to control auxin response levels, PIN1 expression, and vein network formation; and the vein pattern defects induced by ectopic PIN6 expression are mimicked by ectopic PIN8 expression. Finally, vein patterning functions of PIN6 and PIN8 are antagonized by PIN5 function. Our data define a new level of control of vein patterning, one with repercussions on other patterning processes in the plant, and suggest a mechanism to select cell files specialized for vascular function that predates evolution of PM-localized PIN proteins.

Sheep laterality.

PubMed

Anderson, Dean M; Murray, Leigh W

2013-01-01

Turning preferences among 309 white-faced ewes were individually evaluated in an enclosed, artificially lit T-maze, followed by each ewe choosing either a right or left return alley to return to peers. Data recorded included time in the start box, time in the T-maze, exit arm chosen to leave the T-maze, and return alley. Right and left arms of the T-maze were chosen 65.7% and 34.3% of the time, respectively, while right and left return alleys were chosen 32.4% and 67.6%, respectively. Exit arm and return alley were not independently chosen (p <.0001), with observed counts being higher than expected under independence when ewes made the same choice for exit and alley (RR or LL turn patterns) and being lower than expected for alternating choices (RL or LR). Out of the 309 ewes, 28.2% and 30.1% chose RR and LL turn patterns, respectively, while 37.5% chose the RL turn pattern, but only 13 (4.2%) chose the LR turning pattern. Overall, ewes that initially turned right when presented a second turning opportunity had a slight preference to alternate their turning direction, while ewes that initially turned left tended to continue turning left when given another chance to turn. Exit arm and return alley laterality was not related (α =.05) to time of day the test was administered, ewe's age or genetics, most recent liveweight, or most recent shorn fleece weight. The mean time spent in the start box (21 s) was not related to exit arm (p =.947) or return alley (p =.779). Mean time (15 s) spent in the T-maze was not related to exit arm (p =.086) or return alley (p =.952). More research will be required to understand sheep turning laterality and how it can impact working facilities and research equipment.

A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a Possible Cell of Origin.

PubMed

Hong, Soon Auck; Yoo, Su Hyun; Choi, Jene; Robboy, Stanley J; Kim, Kyu-Rae

2018-04-13

- Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papilloma virus (LR-HPV). - To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. - A total of 26 PIM cases were evaluated by p16 INK4a , cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papilloma virus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR. - Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the 26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or 42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%) with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but p16 INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%) of which showed direct continuity. Identical HPV subtypes were confirmed in separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24, 92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7 (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases of low-grade squamous intraepithelial lesion (LSIL) were negative for both markers. - Our results suggest that PIM is a distinct subset of LSIL showing a productive HPV infection, but PIM involves the transformation zone and is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.

Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive toxicity in testis on male offspring.

PubMed

Zhang, Ling; Zhang, Hui; Zhang, Huan; Benson, Mikael; Han, Xiaodong; Li, Dongmei

2017-07-01

In the present study, we evaluated the toxic effects on the testis of the male offspring of MC-LR exposure during fetal and lactational periods. Pregnant females were distributed into two experimental groups: control group and MC-LR group which were exposed to 0 and 10 μg/L of MC-LR, respectively, through drinking water separately during fetal and lactational periods. At the age of 30 days after birth, the male offspring were euthanized. The body weight, testis index, and histomorphology change were observed and the global changes of piwi-interacting RNA (piRNA) expression were evaluated. The results revealed that MC-LR was found in the testis of male offspring, body weight and testis index decreased significantly, and testicular tissue structure was damaged in the MC-LR group. In addition, the exposure to MC-LR resulted in an altered piRNA expression profile and an increase of the cell apoptosis and a decrease of the cell proliferation in the testis of the male offspring. It was reasonable to speculate that the toxic effects on reproductive system of the male offspring in MC-LR group might be mediated by piRNAs through the regulation of the target genes. As far as we are aware, this is the first report showing that MC-LR could play a role in disorder of proliferative and cell apoptosis in the testis of the male offspring by the maternal transmission effect of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Life-cycle exposure to microcystin-LR interferes with the reproductive endocrine system of male zebrafish.

PubMed

Su, Yujing; Li, Li; Hou, Jie; Wu, Ning; Lin, Wang; Li, Guangyu

2016-06-01

Recently, MC-LR reproductive toxicity drew great attention. Limited information was available on endocrine-disrupting effects of MC-LR on the reproduction system in fish. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L MC-LR for 90 d until they reached sexual maturity. Male zebrafish were selected, and changes in growth and developmental parameters, testicular histological structure as well as the levels of gonadal steroid hormones were studied along with the related-gene transcriptional responses in the hypothalamic-pituitary-gonadal axis (HPG-axis). The results, for the first time, show a life cycle exposure to MC-LR causes growth inhibition, testicular damage and delayed sperm maturation. A significant decrease in T/E2 ratio indicated that MC-LR disrupted sex steroid hormones balance. The changes in transcriptional responses of HPG-axis related genes revealed that MC-LR promoted the conversion of T to E2 in circulating blood. It was also noted that vtg1 mRNA expression in the liver was up-regulated, which implied that MC-LR could induce estrogenic-like effects at environmentally relevant concentrations and long-term exposure. Our findings indicated that a life cycle exposure to MC-LR causes endocrine disruption with organic and functional damage of the testis, which might compromise the quality of life for the survivors and pose a potent threat on fish reproduction and thus population dynamics in MCs-contaminated aquatic environments. Copyright © 2016 Elsevier B.V. All rights reserved.

Automatic Lung-RADS™ classification with a natural language processing system.

PubMed

Beyer, Sebastian E; McKee, Brady J; Regis, Shawn M; McKee, Andrea B; Flacke, Sebastian; El Saadawi, Gilan; Wald, Christoph

2017-09-01

Our aim was to train a natural language processing (NLP) algorithm to capture imaging characteristics of lung nodules reported in a structured CT report and suggest the applicable Lung-RADS™ (LR) category. Our study included structured, clinical reports of consecutive CT lung screening (CTLS) exams performed from 08/2014 to 08/2015 at an ACR accredited Lung Cancer Screening Center. All patients screened were at high-risk for lung cancer according to the NCCN Guidelines ® . All exams were interpreted by one of three radiologists credentialed to read CTLS exams using LR using a standard reporting template. Training and test sets consisted of consecutive exams. Lung screening exams were divided into two groups: three training sets (500, 120, and 383 reports each) and one final evaluation set (498 reports). NLP algorithm results were compared with the gold standard of LR category assigned by the radiologist. The sensitivity/specificity of the NLP algorithm to correctly assign LR categories for suspicious nodules (LR 4) and positive nodules (LR 3/4) were 74.1%/98.6% and 75.0%/98.8% respectively. The majority of mismatches occurred in cases where pulmonary findings were present not currently addressed by LR. Misclassifications also resulted from the failure to identify exams as follow-up and the failure to completely characterize part-solid nodules. In a sub-group analysis among structured reports with standardized language, the sensitivity and specificity to detect LR 4 nodules were 87.0% and 99.5%, respectively. An NLP system can accurately suggest the appropriate LR category from CTLS exam findings when standardized reporting is used.

Automatic Lung-RADS™ classification with a natural language processing system

PubMed Central

Beyer, Sebastian E.; Regis, Shawn M.; McKee, Andrea B.; Flacke, Sebastian; El Saadawi, Gilan; Wald, Christoph

2017-01-01

Background Our aim was to train a natural language processing (NLP) algorithm to capture imaging characteristics of lung nodules reported in a structured CT report and suggest the applicable Lung-RADS™ (LR) category. Methods Our study included structured, clinical reports of consecutive CT lung screening (CTLS) exams performed from 08/2014 to 08/2015 at an ACR accredited Lung Cancer Screening Center. All patients screened were at high-risk for lung cancer according to the NCCN Guidelines®. All exams were interpreted by one of three radiologists credentialed to read CTLS exams using LR using a standard reporting template. Training and test sets consisted of consecutive exams. Lung screening exams were divided into two groups: three training sets (500, 120, and 383 reports each) and one final evaluation set (498 reports). NLP algorithm results were compared with the gold standard of LR category assigned by the radiologist. Results The sensitivity/specificity of the NLP algorithm to correctly assign LR categories for suspicious nodules (LR 4) and positive nodules (LR 3/4) were 74.1%/98.6% and 75.0%/98.8% respectively. The majority of mismatches occurred in cases where pulmonary findings were present not currently addressed by LR. Misclassifications also resulted from the failure to identify exams as follow-up and the failure to completely characterize part-solid nodules. In a sub-group analysis among structured reports with standardized language, the sensitivity and specificity to detect LR 4 nodules were 87.0% and 99.5%, respectively. Conclusions An NLP system can accurately suggest the appropriate LR category from CTLS exam findings when standardized reporting is used. PMID:29221286

Adsorptive removal of microcystin-LR from surface and wastewater using tyre-based powdered activated carbon: Kinetics and isotherms.

PubMed

Mashile, Phodiso P; Mpupa, Anele; Nomngongo, Philiswa N

2018-04-01

Microcystin LR (MC-LR) is a highly toxic compound and it is known for its adverse health effect on both humans and animals. Due to the ineffectiveness of conventional water treatments methods, for the past decades, researchers have been developing cost-effective ways of removing MC-LR from water bodies. This study reports the application of powdered activated carbon (PAC) obtained from the waste tyre for the removal of MC-LR. The choice of the adsorbent was chosen due to its attractive properties. The prepared tyre-based PAC was found to have the large surface area (1111 m 2  g -1 ). The detection of MC-LR was achieved using high performance liquid chromatography (HPLC) coupled with a PDA detector. The experimental parameters (such as optimum pH, dosage and contact time) affecting the removal of MC-LR using tyre based-powdered activated carbon were optimized using response surface methodology (RSM). Maximum removal of MC-LR was achieved under the following optimum conditions; sample pH 4, carbon dosage concentration 10,000 mg L -1 and contact time of 34 min. Under optimum conditions, kinetic studies and adsorption isotherms reflected better fit for pseudo-second-order rate and Langmuir isotherm model, respectively. The optimized method was applied for the removal of MC-LR in wastewater sample. The effluent and influent sample contained initial concentrations ranging from 0.52 to 8.54 μg L -1 and the removal efficiency was 100%. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interactive effects of microcystin and ammonia on the reproductive performance and phenotypic traits of the rotifer Brachionus calyciflorus.

PubMed

Liang, Ye; Lu, Xuxin; Min, Yuanqi; Liu, Lulu; Yang, Jiaxin

2018-01-01

Elevated microcystin-LR (MC-LR) and ammonia (NH 3 -N) concentrations co-occur during the degradation of Microcystis blooms, and are toxic to aquatic organisms. The freshwater rotifer, Brachionus calyciflorus, was exposed to mixtures of MC-LR (0, 10, 30, and 100µgL -1 ) and NH 3 -N (0, 270, and 540µgL -1 ) to assess the combined effects of the two toxicants on reproductive performance and phenotype traits. Single solutions of MC-LR (100µgL -1 ) and NH 3 -N (540µgL -1 ) had negative effects on rotifer reproductive timing and fecundity. Pre- and post-reproductive periods fluctuated with MC-LR and NH 3 -N concentrations, while reproductive period and total offspring per female were reduced in mixtures of MC-LR and NH 3 -N (p < 0.05). Grazing rate of rotifers decreased with grazing time and concentrations of the two toxicants (p < 0.001). MC-LR in combination with NH 3 -N had negative effects on swimming speed and body length but positively stimulated posterolateral spine development (p < 0.001). MC-LR and NH 3 -N had synergetic interactive effects on pre-reproductive period, reproductive period, total offspring per female, grazing rate, swimming speed, and body length (p < 0.05). In contrast, these effects were antagonistic on post-reproductive period and posterolateral spine length (p > 0.05). These results indicate that MC-LR and NH 3 -N act synergistically and antagonistically in causing toxicity to B. calyciflorus regarding reproductive performance and the formation of defensive phenotypes. Copyright © 2017 Elsevier Inc. All rights reserved.

Microcystin-leucine arginine mediates apoptosis and engulfment of Leydig cell by testicular macrophages resulting in reduced serum testosterone levels.

PubMed

Chen, Yabing; Wang, Jing; Chen, Xiang; Li, Dongmei; Han, Xiaodong

2018-06-01

Microcystin-leucine arginine (MC-LR) causes decline of serum testosterone levels resulting in impaired spermatogenesis; however, the underlying molecular mechanisms are not fully understood. In this study, we aimed to investigate the effects of MC-LR exposure on the number of Leydig cells (LCs) in testis. Following chronic low dose exposure to MC-LR, the number of LCs was markedly decreased while macrophages were significantly increased. Then, we established a co-culture system to study the interaction between macrophages and LCs in the presence of MC-LR. No significant apoptosis of LCs cultured alone was observed after MC-LR (< 5 000 nM) treatment; however, apoptosis was robustly increased when LCs were co-cultured with macrophages in the presence of MC-LR. Further studies identified that MC-LR could stimulate macrophage to produce TNF-α, and secreted TNF-α induced LC apoptosis by binding to the tumor necrosis factor receptor 1 (TNFR1) on the LCs and thus activating reactive oxygen species (ROS)-p38MAPK signaling pathway. Furthermore, we also examined increased expression of Axl receptor and growth arrest-specific 6 (Gas6) in macrophages after MC-LR treatment. GAS6 mediates phagocytosis of apoptotic LCs by binding to the Axl receptor on macrophages and phosphatidylserine (PtdSer) on apoptotic LCs. Together, these results suggested that reduced serum testosterone levels may be associated with decrease of LCs as a result of LC apoptosis and phagocytosis by immune cells in MC-LR-treated mice. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

PubMed

Xiong, Xiaolu; Zhong, Anyuan; Xu, Huajun

2014-01-01

Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice. MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

Physiological response, blood chemistry profile and mucus secretion of red sea bream (Pagrus major) fed diets supplemented with Lactobacillus rhamnosus under low salinity stress.

PubMed

Dawood, Mahmoud A O; Koshio, Shunsuke; Ishikawa, Manabu; El-Sabagh, Mabrouk; Yokoyama, Saichiro; Wang, Wei-Long; Yukun, Zhang; Olivier, Adissin

2017-02-01

Environmental stressors caused by inadequate aquaculture management strategies suppress the immune response of fish and make them more susceptible to diseases. Therefore, efforts have been made to relieve stress in fish by using various functional feed additives in the diet, including probiotics. The present work evaluates the effects of Lactobacillus rhamnosus (LR) on physiological stress response, blood chemistry and mucus secretion of red sea bream (Pagrus major) under low salinity stress. Fish were fed four diets supplemented with LR at [0 (LR0), 1 × 10 2 (LR1), 1 × 10 4 (LR2) and 1 × 10 6 (LR3) cells g -1 ] for 56 days. Before stress, blood cortisol, urea nitrogen (BUN) and total bilirubin (T-BIL) showed no significant difference (P > 0.05), whereas plasma glucose and triglyceride (TG) of fish-fed LR2 and LR3 diets were significantly lower (P < 0.05) than those of the other groups. Plasma total cholesterol (T-CHO) of fish-fed LR3 diet was significantly (P < 0.05) lower than that of the other groups. Furthermore, total plasma protein, mucus myeloperoxidase activity and the amount of mucus secretion were significantly enhanced in LR-supplemented groups when compared with the control group (P < 0.05). After the application of the low salinity stress test, plasma cortisol, glucose, T-CHO and TG contents in all groups showed an increased trend significantly (P < 0.01) compared to the fish before the stress challenge. However, plasma total protein and the amount of secreted mucus showed a decreased trend in all groups. On the other hand, BUN, T-BIL and mucus myeloperoxidase activity showed no significant difference after exposure to the low salinity stress (P > 0.05). In addition, the fish that received LR-supplemented diets showed significantly higher tolerance against low salinity stress than the fish-fed LR-free diet (P < 0.05). The physiological status and the detected immune responses, including total plasma protein and mucus myeloperoxidase activity in red sea bream, will provide a more comprehensive outlook of the effects of probiotics to relieve stress in fish.

Analytic Methods for Evaluating Patterns of Multiple Congenital Anomalies in Birth Defect Registries.

PubMed

Agopian, A J; Evans, Jane A; Lupo, Philip J

2018-01-15

It is estimated that 20 to 30% of infants with birth defects have two or more birth defects. Among these infants with multiple congenital anomalies (MCA), co-occurring anomalies may represent either chance (i.e., unrelated etiologies) or pathogenically associated patterns of anomalies. While some MCA patterns have been recognized and described (e.g., known syndromes), others have not been identified or characterized. Elucidating these patterns may result in a better understanding of the etiologies of these MCAs. This article reviews the literature with regard to analytic methods that have been used to evaluate patterns of MCAs, in particular those using birth defect registry data. A popular method for MCA assessment involves a comparison of the observed to expected ratio for a given combination of MCAs, or one of several modified versions of this comparison. Other methods include use of numerical taxonomy or other clustering techniques, multiple regression analysis, and log-linear analysis. Advantages and disadvantages of these approaches, as well as specific applications, were outlined. Despite the availability of multiple analytic approaches, relatively few MCA combinations have been assessed. The availability of large birth defects registries and computing resources that allow for automated, big data strategies for prioritizing MCA patterns may provide for new avenues for better understanding co-occurrence of birth defects. Thus, the selection of an analytic approach may depend on several considerations. Birth Defects Research 110:5-11, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Final Inspection of Lactated Ringer’s Resuscitation Fluid, Intravenous Sodium Chloride Solution, and Sodium Chloride-Glucose Solution Used in the Deglycerolization of Human Red Cells Frozen With 40% W/V Glycerol, Produced by the Sterimatics EDM Reflups System and Stored for 8 Months to 2.3 Years.

DTIC Science & Technology

1994-09-08

SHIP LR500 000218201816 07/28/94 P N N 25 8237 SHIP LR500 000218201905 07/30/94 P N N 26 8301 SHIP LR500 000218201910 07/30/94 P N N 27 7395 SHIP...24 25 8237 SHIP LR500 000218201905 07/30/94 P 561 512 PASS 537 500 PASS 24 26 8301 SHIP LR500 000218201910 07/30/94 P 562 513 PASS 538 501 PASS 24

The analysis method of the DRAM cell pattern hotspot

NASA Astrophysics Data System (ADS)

Lee, Kyusun; Lee, Kweonjae; Chang, Jinman; Kim, Taeheon; Han, Daehan; Hong, Aeran; Kim, Yonghyeon; Kang, Jinyoung; Choi, Bumjin; Lee, Joosung; Lee, Jooyoung; Hong, Hyeongsun; Lee, Kyupil; Jin, Gyoyoung

2015-03-01

It is increasingly difficult to determine degree of completion of the patterning and the distribution at the DRAM Cell Patterns. When we research DRAM Device Cell Pattern, there are three big problems currently, it is as follows. First, due to etch loading, it is difficult to predict the potential defect. Second, due to under layer topology, it is impossible to demonstrate the influence of the hotspot. Finally, it is extremely difficult to predict final ACI pattern by the photo simulation, because current patterning process is double patterning technology which means photo pattern is completely different from final etch pattern. Therefore, if the hotspot occurs in wafer, it is very difficult to find it. CD-SEM is the most common pattern measurement tool in semiconductor fabrication site. CD-SEM is used to accurately measure small region of wafer pattern primarily. Therefore, there is no possibility of finding places where unpredictable defect occurs. Even though, "Current Defect detector" can measure a wide area, every chip has same pattern issue, the detector cannot detect critical hotspots. Because defect detecting algorithm of bright field machine is based on image processing, if same problems occur on compared and comparing chip, the machine cannot identify it. Moreover this instrument is not distinguished the difference of distribution about 1nm~3nm. So, "Defect detector" is difficult to handle the data for potential weak point far lower than target CD. In order to solve those problems, another method is needed. In this paper, we introduce the analysis method of the DRAM Cell Pattern Hotspot.

Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report

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

Samei, Ehsan; Badano, Aldo; Chakraborty, Dev

Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction withmore » specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (L{sub amb}) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/secondary displays are maximum luminance of greater than 170/100 cd/m{sup 2}, LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to ascertain the viewing cone within which contrast conformance to the GSDF is better than 30%/60% and LR is greater than 175/70 for primary/secondary displays, or alternatively, within which the on-axis contrast thresholds of the TG18-CT test pattern remain discernible. The evaluation of luminance spatial uniformity at two distinct luminance levels across the display faceplate using TG18-UNL test patterns should yield nonuniformity coefficients smaller than 30%. The resolution evaluation includes the visual scoring of the CX test target in the TG18-QC or TG18-CX test patterns, which should yield scores greater than 4/6 for primary/secondary displays. Noise evaluation includes visual evaluation of the contrast threshold in the TG18-AFC test pattern, which should yield a minimum of 3/2 targets visible for primary/secondary displays. The guidelines also include methodologies for more quantitative resolution and noise measurements based on MTF and NPS analyses. The display glare test, based on the visibility of the low-contrast targets of the TG18-GV test pattern or the measurement of the glare ratio (GR), is expected to yield scores greater than 3/1 and GRs greater than 400/150 for primary/secondary displays. Chromaticity, measured across a display faceplate or between two display devices, is expected to render a u{sup '},v{sup '} color separation of less than 0.01 for primary displays. The report offers further descriptions of prior standardization efforts, current display technologies, testing prerequisites, streamlined procedures and timelines, and TG18 test patterns.« less

A comparison of faecal microbial populations of South African Windsnyer-type indigenous pigs (SAWIPs) and Large White × Landrace (LW × LR) crosses fed diets containing ensiled maize cobs.

PubMed

Kanengoni, Arnold T; Chimonyo, Michael; Tasara, Taurai; Cormican, Paul; Chapwanya, Aspinas; Ndimba, Bongani K; Dzama, Kennedy

2015-07-01

Faecal microbial communities in South African Windsnyer-type indigenous pigs (SAWIPs) and Large White × Landrace (LW × LR) crosses were investigated using high-throughput sequencing of the 16S rDNA genes. The faecal microbial communities in LW × LR crosses and SAWIPs fed control (CON) and high maize cob (HMC) diets were evaluated through parallel sequencing of 16S rDNA genes. Butrivibrio, Faecalibacterium and Desulfovibrio, although present in LW × LR pigs, were absent from the SAWIP microbial community. Bacteroides, Succiniclasticum, Peptococcus and Akkermansia were found in SAWIPs but not in LW × LR crosses. The ratios of Bacteroidia to Clostridia on the CON and HMC diets were similar (0.37 versus 0.39) in SAWIPs but different (0.24 versus 0.1) in LW × LR crosses. The faecal microbial profiles determined were different between the LW × LR and SAWIP breeds but not between pigs fed the CON and HMC diets. The composition of faecal bacterial communities in SAWIPs was determined for the first time. The differences in microbial communities detected may explain the enhanced ability of SAWIPs to digest fibrous diets compared with the LW × LR crosses. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Multi-wavelength colorimetric determination of large-ring cyclodextrin content for the cyclization activity of 4-α-glucanotransferase.

PubMed

Wang, Jinpeng; Wei, Ren; Tian, Yaoqi; Yang, Na; Xu, Xueming; Zimmermann, Wolfgang; Jin, Zhengyu

2015-05-20

Large-ring cyclodextrins (LR-CDs) have a number of intriguing properties for potential use in pharmaceutical and food industry. To date, no colorimetric method has been reported for LR-CD content quantification. In this study, triple wavelength colorimetry (TWC) and orthogonal-function spectrophotometry (OFS) have been successfully applied to determine ingredient concentrations in a mixture of amylose and LR-CDs. Both TWC and OFS yielded precise amylose content data in good agreement with expected values. For quantification of LR-CD content, OFS provided a higher accuracy than TWC, which resulted in a slight over-determination. As a comparison, single-wavelength colorimetry performed at the corresponding absorption maximum led to a significant over-determination of both amylose and LR-CD contents. The validity of TWC and OFS allowed their application for discriminative detection of the cyclization and total activity of a 4-α-glucanotransferase (4 αGTase) from Thermus aquaticus regarding the synthesis of LR-CDs and the conversion of amylose to small molecules, respectively. High pressure size exclusion chromatography analysis of the post-reaction mixtures following 4 αGTase-catalyzed conversion of amylose revealed the presence of linear malto-oligosaccharides in the LR-CD fraction. By introduction of a correction factor, the interference caused by linear malto-oligosaccharides was eliminated for a more accurate determination of LR-CD cyclization activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Levels of soluble LR11/SorLA are highly increased in the bile of patients with biliary tract and pancreatic cancers.

PubMed

Terai, Kensuke; Jiang, Meizi; Tokuyama, Wataru; Murano, Takeyoshi; Takada, Nobuo; Fujimura, Kengo; Ebinuma, Hiroyuki; Kishimoto, Toshihiko; Hiruta, Nobuyuki; Schneider, Wolfgang J; Bujo, Hideaki

2016-06-01

The utility of molecules derived from cancer cells as biomarkers of the pathological status in biliary tract and pancreatic cancers is still limited. Soluble LDL receptor relative with 11 ligand-binding repeats (sLR11), a molecule released from immature cells, has been shown to be a circulating biomarker for early stage hematological malignancies. We have evaluated the pathological significance of bile sLR11 levels in 147 samples from 72 patients with biliary tract cancer (BTC), pancreatic cancer (PC), or benign diseases. The bile sLR11 levels in the cancer patients were significantly increased compared with those in patients without cancer, independent of cytological detection of cancer cells in bile. The average bile sLR11 levels in cancer patients were significantly higher than in those with benign diseases, while levels of bile carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were not different. LR11 protein was found to be highly expressed in the BTC and PC cells. The LR11 transcript levels in cholangiocarcinoma and pancreatic cancer cell lines were sharply induced during proliferation and significantly increased under hypoxic conditions. Therefore, sLR11 levels in bile may be indicative of cancer cell conditions and may serve as potential novel biomarker in patients with BTC and PC. Copyright © 2016 Elsevier B.V. All rights reserved.

Rearfoot and midfoot or forefoot impacts in habitually shod runners.

PubMed

Boyer, Elizabeth R; Rooney, Brandon D; Derrick, Timothy R

2014-07-01

Shear loading rates (LR) have not been investigated in runners with a mid- or forefoot strike (FFS) versus rearfoot strike (RFS). The purpose of this study was to compare three-dimensional ground reaction forces (GRF) and LR during impact in habitual rearfoot strikers (hRF) and habitual forefoot strikers (hFF) strikers. Thirty competitive runners performed 10 overground running trials with both foot strike styles. Peak three-dimensional and resultant GRF and instantaneous LR during impact were compared. Vertical LR significantly decreased for hRF using an FFS (RFS = 148 ± 36 body weight [BW]·s(-1), FFS = 98 ± 31 BW·s(-1)) but was similar for hFF running with either foot strike (FFS = 136 ± 35 BW·s(-1), RFS = 135 ± 28 BW·s(-1)). Posterior impact forces were present during FFS but not during RFS, and posterior LR was significantly greater for both groups during FFS (-58 ± 17 vs -19 ± 6 BW·s(-1)). Medial impact forces were also present during FFS but not during RFS, and medial LR was significantly larger for both groups during FFS (-21 ± 7 vs -6 ± 6 BW·s(-1)). Interestingly, hFF had greater impact peaks and LR in all directions compared with hRF during FFS. This may be explained by hFF using a smaller strike index (hFF = 62% ± 9%, hRF = 67% ± 9%; P = 0.02), which was significantly inversely related to vertical LR and impact peak. Peak resultant and vertical LR are not ubiquitously lower when using a shod FFS versus RFS despite an absence of resultant and vertical impact peaks. Furthermore, there were impact peaks in the posterior and medial directions, leading also to greater LR in these directions during FFS. Therefore, transitioning from RFS to FFS in traditional running shoes may not offer long-term protection against impact-related running injuries because hFF running with an FFS demonstrated many GRF and LR similar to or greater than RFS.

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

Woźny, Maciej, E-mail: maciej.wozny@uwm.edu.pl

To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg{sup −1}) caused severe liver injurymore » at the beginning of the exposure period, whereas the lower dose (10 μg·kg{sup −1}) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not accumulate over time of exposure despite weekly-repeated injections. • Down-regulation of oatp1d expression may serve as a defence mechanism against MC-LR.« less

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Kohnhorst, Charlotte; von Tresckow, Bastian; Moccia, Alden; Markova, Jana; Meissner, Julia; Kerkhoff, Andrea; Ludwig, Wolf-Dieter; Fuchs, Michael; Borchmann, Peter; Engert, Andreas

2017-05-01

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.

MMPI-2-RF characteristics of custody evaluation litigants.

PubMed

Archer, Elizabeth M; Hagan, Leigh D; Mason, Janelle; Handel, Richard; Archer, Robert P

2012-03-01

The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a 338-item objective self-report measure drawn from the 567 items of the MMPI-2. Although there is a substantial MMPI-2 literature regarding child custody litigants, there has been only one previously published study using MMPI-2-RF data in this population that focused on Validity scales L-r and K-r. The current study evaluated the MMPI-2-RF results of 344 child custody litigants and showed substantial consistency between T-score elevations typically found on MMPI-2 Validity scales L and K, and comparable elevations for MMPI-2-RF validity scales L-r and K-r. Mean T-scores well within normal limits characterized results for clinical scales on both instruments. The RC scale intercorrelation patterns, and alpha coefficient values found for MMPI-2-RF scales in a custody population, were also found to be very similar to those reported for other populations. Directions for future research are presented.

Spatial resolution requirements for urban land cover mapping from space

NASA Technical Reports Server (NTRS)

Todd, William J.; Wrigley, Robert C.

1986-01-01

Very low resolution (VLR) satellite data (Advanced Very High Resolution Radiometer, DMSP Operational Linescan System), low resolution (LR) data (Landsat MSS), medium resolution (MR) data (Landsat TM), and high resolution (HR) satellite data (Spot HRV, Large Format Camera) were evaluated and compared for interpretability at differing spatial resolutions. VLR data (500 m - 1.0 km) is useful for Level 1 (urban/rural distinction) mapping at 1:1,000,000 scale. Feature tone/color is utilized to distinguish generalized urban land cover using LR data (80 m) for 1:250,000 scale mapping. Advancing to MR data (30 m) and 1:100,000 scale mapping, confidence in land cover mapping is greatly increased, owing to the element of texture/pattern which is now evident in the imagery. Shape and shadow contribute to detailed Level II/III urban land use mapping possible if the interpreter can use HR (10-15 m) satellite data; mapping scales can be 1:25,000 - 1:50,000.

Effects of microcystin-LR on the tissue growth and physiological responses of the aquatic plant Iris pseudacorus L.

PubMed

Wang, Naiyu; Wang, Can

2018-04-27

The release of cyanobacterial toxins during algal bloom has adverse effects on aquatic plants and animals. This study aimed to understand the toxic effects and mechanism of microcystin-LR (MC-LR) on the seedling growth and physiological responses of Iris pseudacorus L. (calamus). After a one-month exposure experiment, the growth and development of the calamus leaves were significantly inhibited, and this inhibitory effect was verified to be concentration dependent. Furthermore, the cell membrane system was damaged, and the photosynthesis was also adversely affected by MC-LR. The relative conductivity of the leaves increased from 10.96% to 97.51%, and the total chlorophyll content decreased from 0.89 mg/g to 0.09 mg/g. Notably, the behavior of the roots in the presence of MC-LR was different from that of the leaves. The seedlings needed to absorb more nutrients to maintain the normal growth at low-toxin concentrations, but the high concentration of (over 250 μg/L) MC-LR exceeded the tolerance of plants and inhibited the growth of roots. In addition, MC-LR led to an excessive accumulation of H 2 O 2 , and the seedlings enhanced the activities of catalase, peroxidase, and superoxide dismutase to resist oxidative stress. The presence of MC-LR also affected the capacity of the plants to absorb nitrogen and phosphorus. The removal efficiency of NO 3 - -N, the main source of nitrogen, was 63.53% in the presence of 100 μg/L MC-LR. As a result, the pH increased, and the growth of plants was indirectly inhibited. Therefore, the presence of MC-LR could affect the purification efficiency of calamus in eutrophic water. This study provides theoretical support for the selection of plants in the eutrophic water. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Ligustrum robustum on gut microbes and obesity in rats

PubMed Central

Xie, Zhi-Mei; Zhou, Tao; Liao, Hong-Yu; Ye, Qian; Liu, Shan; Qi, Lu; Huang, Jing; Zuo, Hao-Jiang; Pei, Xiao-Fang

2015-01-01

AIM: To investigate the anti-obesity and antibacterial effects of Ligustrum robustum (L. robustum) in vivo and in vitro and its possible mechanisms. METHODS: The effects of L. robustum aqueous extract (LR) on various gut bacteria in vitro were evaluated. The effects of LR on high-fat diet-fed (HFD) rats in vivo were also assessed. Culture methods, quantitative polymerase chain reaction, and terminal-restriction fragment length polymorphism were used to analyze the effects of LR on gut bacteria. Biochemical tests were also performed to detect the changes in obesity-related indicators after LR treatment. RESULTS: LR treatment lowered adipose weight and decreased Lee’s index, blood glucose, total cholesterol, and lipid in the tested groups relative to control (P < 0.05). To determine the reasons for these changes, we assessed the potential bacteriostatic and bactericidal effects of LR on specific bacterial species in vitro. LR affected the richness, diversity, and evenness of gut bacteria, increased fecal Lactobacillus, and decreased Enterococci in HFD rats (P < 0.05). CONCLUSION: L. robustum may be a safe and effective food for weight loss and obesity control, and the effects of L. robustum might be mediated by the regulation of gut bacteria. PMID:26676281

Statistical strength of experiments to reject local realism with photon pairs and inefficient detectors

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

Zhang Yanbao; Mathematical and Computational Sciences Division, National Institute of Standards and Technology, Boulder, Colorado, 80305; Knill, Emanuel

2010-03-15

Because of the fundamental importance of Bell's theorem, a loophole-free demonstration of a violation of local realism (LR) is highly desirable. Here, we study violations of LR involving photon pairs. We quantify the experimental evidence against LR by using measures of statistical strength related to the Kullback-Leibler (KL) divergence, as suggested by van Dam et al.[W. van Dam, R. D. Gill, and P. D. Grunwald, IEEE Trans. Inf. Theory. 51, 2812 (2005)]. Specifically, we analyze a test of LR with entangled states created from two independent polarized photons passing through a polarizing beam splitter. We numerically study the detection efficiencymore » required to achieve a specified statistical strength for the rejection of LR depending on whether photon counters or detectors are used. Based on our results, we find that a test of LR free of the detection loophole requires photon counters with efficiencies of at least 89.71%, or photon detectors with efficiencies of at least 91.11%. For comparison, we also perform this analysis with ideal unbalanced Bell states, which are known to allow rejection of LR with detector efficiencies above 2/3.« less

Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.

PubMed

Wong, Jacqueline M K; Liu, Dachao; Lurain, John R

2014-01-01

To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.

An Updated Meta-Analysis of Laparoscopic Versus Open Repair for Perforated Peptic Ulcer.

PubMed

Zhou, Chunhua; Wang, Weizhi; Wang, Jiwei; Zhang, Xiaoyu; Zhang, Qun; Li, Bowen; Xu, Zekuan

2015-09-09

Laparoscopic repair (LR) for perforated peptic ulcer (PPU) has been introduced since 1990. Although many studies comparing LR with open repair (OR) have been published, controversy remains regarding the clinical utility of laparoscopic techniques for the treatment of PPU. Thus, it is necessary for us to broaden our knowledge on this subject with the newly published articles. Twenty-four nonrandomized controlled studies (NRS) and five randomized controlled trails (RCTs) were included in our meta-analyses, which comprised 5,268 patients (1,890 in the LR group and 3,378 in the OR group). In the analysis of high quality NRS and RCTs, compared with OR, high quality evidence suggested that LR was associated with a lower incidence of overall postoperative complications; moderate evidence showed that the two procedures had the similar reoperation rate; based on the low quality evidence, LR had reduced hospital mortality and similar operative time; Moreover, LR was observed having the advantages of earlier resumption of oral intake, shorter hospital stay and less analgesic use, which were supported by very low evidence. All the evidences suggest that LR is better than OR for PPU, but more high-quality RCTs are still needed for further validation.

An Updated Meta-Analysis of Laparoscopic Versus Open Repair for Perforated Peptic Ulcer

PubMed Central

Zhou, Chunhua; Wang, Weizhi; Wang, Jiwei; Zhang, Xiaoyu; Zhang, Qun; Li, Bowen; Xu, Zekuan

2015-01-01

Laparoscopic repair (LR) for perforated peptic ulcer (PPU) has been introduced since 1990. Although many studies comparing LR with open repair (OR) have been published, controversy remains regarding the clinical utility of laparoscopic techniques for the treatment of PPU. Thus, it is necessary for us to broaden our knowledge on this subject with the newly published articles. Twenty-four nonrandomized controlled studies (NRS) and five randomized controlled trails (RCTs) were included in our meta-analyses, which comprised 5,268 patients (1,890 in the LR group and 3,378 in the OR group). In the analysis of high quality NRS and RCTs, compared with OR, high quality evidence suggested that LR was associated with a lower incidence of overall postoperative complications; moderate evidence showed that the two procedures had the similar reoperation rate; based on the low quality evidence, LR had reduced hospital mortality and similar operative time; Moreover, LR was observed having the advantages of earlier resumption of oral intake, shorter hospital stay and less analgesic use, which were supported by very low evidence. All the evidences suggest that LR is better than OR for PPU, but more high-quality RCTs are still needed for further validation. PMID:26350958

Pavlovian Fear Conditioning Activates a Common Pattern of Neurons in the Lateral Amygdala of Individual Brains

DTIC Science & Technology

2011-01-12

Abstract Understanding the physical encoding of a memory (the engram ) is a fundamental question in neuroscience. Although it has been established...assembly constitutes a spatial dimension of the engram . Citation: Bergstrom HC, McDonald CG, Johnson LR (2011) Pavlovian Fear Conditioning Activates a Common...competing interests exist. * E-mail: LukeJohnsonPhD@gmail.com Introduction Understanding the physical encoding of a memory (the engram ) in neuronal

LACK OF TERATOGENICITY OF MICROCYSTIN-LR IN THE MOUSE AND TOAD

EPA Science Inventory

Abstract. Microcystin-LR (MC-LR) is a cyanobacterial toxin generated by the organism, Microcystis aeruginosa. Although the hepatotoxicity of this chemical has been characterized, the potential developmental toxicity in vertebrates has not been well studied. The purpose of this...

New insights into cytotoxicity induced by microcystin-LR, estradiol, and ractopamine with mathematical models: Individual and combined effects.

PubMed

Ma, Min; Pi, Fuwei; Wang, Jiasheng; Ji, Jian; Sun, Xiulan

2017-02-01

Humans are most likely to be exposed to microcystins (MCs) combined with other water pollutants rather than to individual compounds through the consumption of contaminated drinking water or through recreational activities, such as swimming. However, the combined effects of MC-LR, estradiol (EST), and ractopamine (RAC) have not been extensively researched. The goal of this study was to investigate the combined effects of these compounds. For this purpose, cytotoxicity was evaluated in HepG2 cells treated with single or combined doses of MC-LR, EST, and RAC based on concentration addition (CA), independent action (IA), and Chou-Talalay's combination-index (CI) methods. Singly applied MC-LR and EST induced HepG2 cellular proliferation at low-concentration levels (1 × 10 -12 -1 × 10 -9  M), and decreased viability at higher doses of exposure (1 × 10 -9 -1 × 10 -6  M). Exposure to binary or ternary mixtures of MC-LR, EST, and RAC exhibited synergistic effects at high concentrations, irrespective of the models used. In contrast, antagonism was observed for the mixture of MC-LR and EST at relatively low concentrations. A synergistic effect on reactive oxygen species (ROS) generation was observed for the combined drugs at high concentrations. Additionally, the ratio of apoptotic cells was increased more by the combined drugs than the single drugs, consistent with the inhibition of cell viability. The ROS increase after treatment with the combined drugs may enhance cytotoxicity and subsequently lead to cell apoptosis. Given the interactions between MC-LR, EST, and RAC, government regulatory standards for MC-LR should consider the toxicological interactions between MC-LR and other environment pollutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis.

PubMed

Satheesan, S; Figarola, J L; Dabbs, T; Rahbar, S; Ermel, R

2014-06-01

We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology. STZ-induced diabetic rats were treated with or without LR-90 (50 mg L(-1) in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra. LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats. Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications. © 2014 The British Pharmacological Society.

Toxicogenomic evaluation of microcystin-LR treated with ultrasonic irradiation

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

Hudder, Alice; Song Weihua; O'Shea, Kevin E.

2007-05-01

Microcystins are a family of toxins produced by cyanobacteria found throughout the world in marine and freshwater environments. The most commonly encountered form of microcystin is microcystin-LR (MC-LR). Humans are exposed to MC-LR by drinking contaminated water. The toxin accumulates rapidly in the liver where it exerts most of its damage. Treatment of water containing MC-LR by ultrasonic irradiation leads to the breakdown of the toxin. Both the parent toxin and the treated toxin reaction products (TTRP) were evaluated for toxic effects in mice. Animals were exposed to purified MC-LR or an equivalent dose of the TTRP and sacrificed aftermore » 4 h or 24 h. Serum was collected and assayed for lactate dehydrogenase (LDH) activity as an indicator of hepatotoxicity. LDH activity was detected in the serum of MC-LR exposed mice indicative of liver damage, but not in control mice. Only a fraction of that activity was detectable in mice exposed to TTRP. Liver RNA was used for microarray analysis and real-time PCR. Individual animals varied in their overall genomic response to the toxin; however, only 20 genes showed consistent changes in expression. These include chaperones which may be part of a generalized stress response; cytochrome P450 which may be involved in metabolizing the toxin; and lipid dystrophy genes such as lipin-2, uridine phosphorylase and a homolog to tribbles, a stress-inducible gene involved in cell death. Of the genes that responded to the MC-LR, none showed significant changes in expression profile in response to TTRP. Taken together, the data indicate that ultrasonic irradiation of MC-LR effectively reduces hepatotoxicity in mice and therefore may be a useful method for detoxification of drinking water.« less

Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery.

PubMed

Hamaji, Masatsugu; Chen, Fengshi; Matsuo, Yukinori; Ueki, Nami; Hiraoka, Masahiro; Date, Hiroshi

2015-11-01

Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

Ultrasound-based logistic regression model LR2 versus magnetic resonance imaging for discriminating between benign and malignant adnexal masses: a prospective study.

PubMed

Shimada, Kanane; Matsumoto, Koji; Mimura, Takashi; Ishikawa, Tetsuya; Munechika, Jiro; Ohgiya, Yoshimitsu; Kushima, Miki; Hirose, Yusuke; Asami, Yuka; Iitsuka, Chiaki; Miyamoto, Shingo; Onuki, Mamiko; Tsunoda, Hajime; Matsuoka, Ryu; Ichizuka, Kiyotake; Sekizawa, Akihiko

2018-06-01

The diagnostic performances of the International Ovarian Tumor Analysis (IOTA) ultrasound-based logistic regression model (LR2) and magnetic resonance imaging (MRI) in discriminating between benign and malignant adnexal masses have not been directly compared in a single study. Using the IOTA LR2 model and subjective interpretation of MRI findings by experienced radiologists, 265 consecutive patients with adnexal masses were preoperatively evaluated in two hospitals between February 2014 and December 2015. Definitive histological diagnosis of excised tissues was used as a gold standard. From the 265 study subjects, 54 (20.4%) tumors were histologically diagnosed as malignant (including 11 borderline and 3 metastatic tumors). Preoperative diagnoses of malignant tumors showed 91.7% total agreement between IOTA LR2 and MRI, with a kappa value of 0.77 [95% confidence interval (CI), 0.68-0.86]. Sensitivity of IOTA LR2 (0.94, 95% CI, 0.85-0.98) for predicting malignant tumors was similar to that of MRI (0.96, 95% CI, 0.87-0.99; P = 0.99), whereas specificity of IOTA LR2 (0.98, 95% CI, 0.95-0.99) was significantly higher than that of MRI (0.91, 95% CI, 0.87-0.95; P = 0.002). Combined IOTA LR2 and MRI results gave the greatest sensitivity (1.00, 95% CI, 0.93-1.00) and had similar specificity (0.91, 95% CI, 0.86-0.94) to MRI. The IOTA LR2 model had a similar sensitivity to MRI for discriminating between benign and malignant tumors and a higher specificity compared with MRI. Our findings suggest that the IOTA LR2 model, either alone or in conjunction with MRI, should be included in preoperative evaluation of adnexal masses.

A Novel Technique for Clinical Assessment of Laryngeal Nerve Conduction: Normal and Abnormal Results

PubMed Central

Sulica, Lucian; Carey, Bridget; Branski, Ryan C.

2014-01-01

Objectives/Hypothesis To describe a novel conduction study of the laryngeal nerves, including normal values and abnormal findings. Study Design Prospective nonrandomized. Methods Seventeen healthy adult volunteers, as well as three patients with clinically identified laryngeal neuropathy, underwent low-level brief electrical stimulation of the laryngeal mucosa by means of a wire inserted via a transnasal flexible laryngoscope. Bilateral hookwire electrodes recorded the result in the laryngeal adductor muscles. Results This study yields an early response ipsilateral to the side of stimulation (LR1), which is uniform and consistent (right 5 13.2 6 0.80 msec; left 5 15.2 6 1.20 msec), and late bilateral responses (ipsilateral LR2 [LR2i] and contralateral LR2 [LR2c]), which exhibit greater variation in latency and morphology (right LR2i 5 50.5 6 3.38 msec; left LR2i 5 52.2 msec; right LR2c 5 50.7 6 4.26; left LR2c 5 50.6 6 4.07). Findings in abnormal patients differ significantly from normal, consistent with the distribution of neuropathy. Conclusions We describe a novel, clinically applicable conduction study of laryngeal nerves. Normative electrodiagnostic values and variations of the reflex responses of the laryngeal adductor muscles in response to irritative stimulation of the laryngeal mucosa (Laryngeal Closure Reflex) are proposed. By enabling the determination of electrophysiological parameters of the superior laryngeal and recurrent laryngeal branches of cranial nerve X (CN X), this procedure, which is used as an adjunct to laryngeal electromyography, may provide earlier and more accurate information regarding the extent and grade of nerve injury. Because injury grade relates directly to prognosis, the information derived from this test may have clinical relevance in determining optimal treatment. Level of Evidence 4. PMID:23835889

The utility of serum tryptase in the diagnosis of food-induced anaphylaxis.

PubMed

Wongkaewpothong, Patcharaporn; Pacharn, Punchama; Sripramong, Chaweewan; Boonchoo, Siribangon; Piboonpocanun, Surapon; Visitsunthorn, Nualanong; Vichyanond, Pakit; Jirapongsananuruk, Orathai

2014-07-01

This study investigates the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis. Patients with a history of shrimp allergy and positive skin prick tests (SPT) to commercial shrimp extract were recruited for shrimp challenges. Serum total tryptase was obtained at baseline and 60 min (peak) after the onset of symptoms. Thirty-nine patients were challenged. There were 12 patients with anaphylaxis, 20 with mild reactions and 7 without symptoms (control group). Characteristic features and baseline tryptase were not different among the 3 groups. The peak tryptase levels were higher than the baseline in anaphylaxis and mild reaction groups (P<0.05). The delta-tryptase (peak minus baseline) and the tryptase ratio (peak divided by baseline) in the anaphylaxis group were higher than the mild reaction and control groups (P<0.01). The optimum cut-off for peak tryptase to confirm anaphylaxis was 2.99 µg/L with 50% sensitivity, 85% specificity, 3.33 positive likelihood ratio (LR) and 0.59 negative LR. The manufacturer's cut-off for peak tryptase was >11.4 µg/L with 17% sensitivity, 100% specificity, infinity positive LR and 0.83 negative LR. The best cut-off for delta-tryptase was ≥0.8 µg/L with 83% sensitivity, 93% specificity, 11.86 positive LR and 0.18 negative LR. The best cut-off for tryptase ratio was ≥1.5 with 92% sensitivity, 96% specificity, 23 positive LR and 0.08 negative LR. The peak tryptase level should be compared with the baseline value to confirm anaphylaxis. The tryptase ratio provide the best sensitivity, specificity, positive and negative LR than a single peak serum tryptase for the confirmation of shrimp-induced anaphylaxis.

Reduced 30-Day Mortality After Laparoscopic Colorectal Cancer Surgery: A Population Based Study From the Dutch Surgical Colorectal Audit (DSCA).

PubMed

Gietelink, Lieke; Wouters, Michel W J M; Bemelman, Willem A; Dekker, Jan Willem; Tollenaar, Rob A E M; Tanis, Pieter J

2016-07-01

To evaluate the impact of a laparoscopic resection on postoperative mortality after colorectal cancer surgery. The question whether laparoscopic resection (LR) compared with open surgery [open resection (OR)] for colorectal cancer influences the risk of postoperative mortality remains unresolved. Several meta-analyses showed a trend but failed to reach statistical significance. The exclusion of high-risk patients and insufficient power might be responsible for that. We analyzed the influence of LR on postoperative mortality in a risk-stratified comparison and secondly, we studied the effect of LR on postoperative morbidity. Data from the Dutch Surgical Colorectal Audit (2010-2013) were used. Homogenous subgroups of patients were defined on the basis of factors influencing the choice of surgical approach and risk factors for postoperative mortality. Crude mortality rates were compared between LR and OR. The influence of LR on postoperative complications was evaluated using both univariable and multivariable analyses. In patients undergoing elective surgery for nonlocally advanced, nonmetastasized colon cancer, LR was associated with a significant lower risk of postoperative mortality than OR in 20/22 subgroups. LR was independently associated with a lower risk of cardiac (odds ratio: 0.73, 95% confidence interval: 0.66-0.82) and respiratory (odds ratio: 0.73, 95% confidence interval: 0.64-0.84) complications. LR reduces the risk of postoperative mortality compared with OR in elective setting in patients with nonlocally advanced, nonmetastasized colorectal cancer. Especially elderly frail patients seem to benefit because of reduced cardiopulmonary complications. These findings support widespread implementation of LR for colorectal cancer also in patients at high operative risk.

Postulation of rust resistance genes in Nordic spring wheat genotypes and identification of widely effective sources of resistance against the Australian rust flora.

PubMed

Randhawa, Mandeep; Bansal, Urmil; Lillemo, Morten; Miah, Hanif; Bariana, Harbans

2016-11-01

Wild relatives, landraces and cultivars from different geographical regions have been demonstrated as the sources of genetic variation for resistance to rust diseases. This study involved assessment of diversity for resistance to three rust diseases among a set of Nordic spring wheat cultivars. These cultivars were tested at the seedling stage against several pathotypes of three rust pathogens in the greenhouse. All stage stem rust resistance genes Sr7b, Sr8a, Sr12, Sr15, Sr17, Sr23 and Sr30, and leaf rust resistance genes Lr1, Lr3a, Lr13, Lr14a, Lr16 and Lr20 were postulated either singly or in different combinations among these cultivars. A high proportion of cultivars were identified to carry linked rust resistance genes Sr15 and Lr20. Although 51 cultivars showed variation against Puccinia striiformis f. sp. tritici (Pst) pathotypes used in this study, results were not clearly contrasting to enable postulation of stripe rust resistance genes in these genotypes. Stripe rust resistance gene Yr27 was postulated in four cultivars and Yr1 was present in cultivar Zebra. Cultivar Tjalve produced low stripe rust response against all Pst pathotypes indicating the presence either of a widely effective resistance gene or combination of genes with compensating pathogenic specificities. Several cultivars carried moderate to high level of APR to leaf rust and stripe rust. Seedling stem rust susceptible cultivar Aston exhibited moderately resistant to moderately susceptible response, whereas other cultivars belonging to this class were rated moderately susceptible or higher. Molecular markers linked with APR genes Yr48, Lr34/Yr18/Sr57, Lr68 and Sr2 detected the presence of these genes in some genotypes.

Microcystin-LR impairs zebrafish reproduction by affecting oogenesis and endocrine system.

PubMed

Zhao, Yanyan; Xie, Liqiang; Yan, Yunjun

2015-02-01

Previous studies have shown that microcystins (MCs) are able to exert negative effects on the reproductive system of fish. However, few data are actually available on the effects of MC-LR on the reproductive system of female fish. In the present study, female zebrafish were exposed to 2, 10, and 50 μg L(-1) of MC-LR for 21 d, and its effects on oogenesis, sex hormones, transcription of genes on the hypothalamic-pituitary-gonad (HPG) axis, and reproduction were investigated for the first time. It was observed that egg production significantly declined at ⩾ 10 μg L(-1) MC-LR. MC-LR exposure to zebrafish increased the concentrations of 17β-estradiol (E2) and vitellogenin (VTG) at 10 μg L(-1) level, whereas concentrations of E2, VTG and testosterone declined at 50 μg L(-1) MC-LR. The transcriptions of steroidogenic pathway gene (cyp19a, cyp19b, 17βhsd, cyp17 and hmgra) changed as well after the exposure and corresponded well with the alterations of hormone levels. A number of intra- and extra-ovarian factors, such as gnrh3, gnrhr1, fshβ, fshr, lhr, bmp15, mrpβ, ptgs2 and vtg1 which regulate oogenesis, were significantly changed with a different dose-related effect. Moreover, MC-LR exposure to female zebrafish resulted in decreased fertilization and hatching rates, and may suggest the possibility of trans-generational effects of MC-LR exposure. The results demonstrate that MC-LR could modulate endocrine function and oogenesis, eventually leading to disruption of reproductive performance in female zebrafish. These data suggest there is a risk for aquatic population living in MC polluted areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of the watermark in immersion lithography process

NASA Astrophysics Data System (ADS)

Kawamura, Daisuke; Takeishi, Tomoyuki; Sho, Koutarou; Matsunaga, Kentarou; Shibata, Naofumi; Ozawa, Kaoru; Shimura, Satoru; Kyoda, Hideharu; Kawasaki, Tetsu; Ishida, Seiki; Toshima, Takayuki; Oonishi, Yasunobu; Ito, Shinichi

2005-05-01

In the liquid immersion lithography, uses of the cover material (C/M) films were discussed to reduce elution of resist components to fluid. With fluctuation of exposure tool or resist process, it is possible to remain of waterdrop on the wafer and watermark (W/M) will be made. The investigation of influence of the W/M on resist patterns, formation process of W/M, and reduction of pattern defect due to W/M will be discussed. Resist patterns within and around the intentionally made W/M were observed in three cases, which were without C/M, TOK TSP-3A and alkali-soluble C/M. In all C/M cases, pattern defect were T-topped shapes. Reduction of pattern defects due to waterdrop was examined. It was found that remained waterdrop made defect. It should be required to remove waterdrop before drying, and/or to remove the defect due to waterdrop. But new dry technique and/or unit will be need for making no W/M. It was examined that the observation of waterdrop through the drying step and simulative reproduction of experiment in order to understand the formation mechanism of W/M. If maximum drying time of waterdrop using immersion exposure tool is estimated 90 seconds, the watermark of which volume and diameter are less than 0.02 uL and 350um will be dried and will make pattern defect. The threshold will be large with wafer speed become faster. From result and speculations in this work, it is considered that it will be difficult to development C/M as single film, which makes no pattern defects due to remained waterdrop.

LR: Compact connectivity representation for triangle meshes

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

Gurung, T; Luffel, M; Lindstrom, P

2011-01-28

We propose LR (Laced Ring) - a simple data structure for representing the connectivity of manifold triangle meshes. LR provides the option to store on average either 1.08 references per triangle or 26.2 bits per triangle. Its construction, from an input mesh that supports constant-time adjacency queries, has linear space and time complexity, and involves ordering most vertices along a nearly-Hamiltonian cycle. LR is best suited for applications that process meshes with fixed connectivity, as any changes to the connectivity require the data structure to be rebuilt. We provide an implementation of the set of standard random-access, constant-time operators formore » traversing a mesh, and show that LR often saves both space and traversal time over competing representations.« less

The Molecular Differentiation of Anatomically Paired Left and Right Mantles of the Pacific Oyster Crassostrea gigas.

PubMed

Wei, Lei; Xu, Fei; Wang, Yuzhi; Cai, Zhongqiang; Yu, Wenchao; He, Cheng; Jiang, Qiuyun; Xu, Xiqiang; Guo, Wen; Wang, Xiaotong

2018-03-28

Left-right (L-R) asymmetry is controlled by gene regulation pathways for the L-R axis, and in vertebrates, the gene Pitx2 in TGF-β signaling pathway plays important roles in the asymmetrical formation of organs. However, less is known about the asymmetries of anatomically identical paired organs, as well as the transcriptional regulation mechanism of the gene Pitx in invertebrates. Here, we report the molecular biological differences between the left and right mantles of an invertebrate, the Pacific oyster Crassostrea gigas, and propose one possible mechanism underlying those differences. RNA sequencing (RNA-seq) analysis indicated that the paired organs showed different gene expression patterns, suggesting possible functional differences in shell formation, pheromone signaling, nerve conduction, the stress response, and other physiological processes. RNA-seq and real-time qPCR analysis indicated high right-side expression of the Pitx homolog (cgPitx) in oyster mantle, supporting a conserved role for Pitx in controlling asymmetry. Methylation-dependent restriction-site associated DNA sequencing (MethylRAD) identified a methylation site in the promoter region of cgPitx and showed significantly different methylation levels between the left and right mantles. This is the first report, to our knowledge, of such a difference in methylation in spiralians, and it was further confirmed in 18 other individuals by using a pyrosequencing assay. The miRNome analysis and the TGF-β receptor/Smad inhibition experiment further supported that several genes in TGF-β signaling pathway may be related with the L/R asymmetry of oyster mantles. These results suggested that the molecular differentiation of the oyster's paired left and right mantles is significant, TGF-β signaling pathway could be involved in establishing or maintaining the asymmetry, and the cgPitx gene as one of genes in this pathway; the different methylation levels in its promoter regions between L/R mantles was the one of possible mechanisms regulating the left-right functional differentiation.

Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

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

Chopra, Supriya; Princess Margaret Hospital, University Health Network, Toronto; Toi, Ants

2012-03-01

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement,more » PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.« less

Myosin1D is an evolutionarily conserved regulator of animal left-right asymmetry.

PubMed

Juan, Thomas; Géminard, Charles; Coutelis, Jean-Baptiste; Cerezo, Delphine; Polès, Sophie; Noselli, Stéphane; Fürthauer, Maximilian

2018-05-16

The establishment of left-right (LR) asymmetry is fundamental to animal development, but the identification of a unifying mechanism establishing laterality across different phyla has remained elusive. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish. Alternatively, LR asymmetry can be established independently of cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton. Here, we show that Myosin1D (Myo1D), a previously identified regulator of Drosophila LR asymmetry, is essential for the formation and function of the zebrafish LR organizer (LRO), Kupffer's vesicle (KV). Myo1D controls the orientation of LRO cilia and interacts functionally with the planar cell polarity (PCP) pathway component VanGogh-like2 (Vangl2), to shape a productive LRO flow. Our findings identify Myo1D as an evolutionarily conserved regulator of animal LR asymmetry, and show that functional interactions between Myo1D and PCP are central to the establishment of animal LR asymmetry.

Highly sensitive detection and discrimination of LR and YR microcystins based on protein phosphatases and an artificial neural network.

PubMed

Covaci, O I; Sassolas, A; Alonso, G A; Muñoz, R; Radu, G L; Bucur, B; Marty, J-L

2012-08-01

The inhibition characteristics of three different protein phosphatases by three microcystin (MC) variants--LR, YR, and RR--were studied. The corresponding K (I) for each enzyme-MC couple was calculated. The toxicity of MC varies in the following order: MC-LR > MC-YR > MC-RR. The sensitivity of the enzymes increased in the following order: mutant PP2A < mutant PP1 < natural PP2A. The best limit of detection obtained was 21.2 pM MC-LR using the most sensible enzyme. Methanol, ethanol, and acetonitrile up to 2 % (v/v) may be used in inhibition measurements. An artificial neural network (ANN) was used to discriminate two MC variants--LR and YR--using the differences in inhibition percentages measured with mutant PP1 and natural PP2A. The ANN is able to analyze mixtures with concentrations ranging from 8 to 98 pM MC-LR and 31 to 373 pM MC-YR.

Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis.

PubMed

Parkin, Patricia C; Macarthur, Colin; Khambalia, Amina; Goldman, Ran D; Friedman, Jeremy N

2010-03-01

To evaluate clinical and laboratory assessment of dehydration severity in children, 1 to 36 months, with acute gastroenteritis. Clinical and laboratory measures and weight change following rehydration were collected for enrolled children. Pediatric emergency department. Likelihood ratio (LR+) and 95% confidence interval (CI): for a clinical score of 0, the LR+ was 2.2 (95% CI = 0.9-5.3); for a clinical score of 1 to 4, the LR+ was 1.3 (95% CI = 0.90-1.74); for a clinical score of 5 to 8, the LR+ was 5.2 (95% CI = 2.2-12.8); for a venous pH <7.32, the LR+ was 7.2 (95% CI = 2.4-21.9); and for serum bicarbonate <18 mmol/L, the LR+ was 11.6 (95% CI = 3.5-38.0). Clinicians may find it useful to incorporate the Clinical Dehydration Scale and laboratory measures into clinical decision-making algorithms to assess dehydration severity in children with acute gastroenteritis.

Dietary n-6:n-3 Fatty Acid Ratios Alter Rumen Fermentation Parameters and Microbial Populations in Goats.

PubMed

Ebrahimi, Mahdi; Rajion, Mohamed Ali; Adeyemi, Kazeem Dauda; Jafari, Saeid; Jahromi, Mohammad Faseleh; Oskoueian, Ehsan; Meng, Goh Yong; Ghaffari, Morteza Hosseini

2017-02-01

Revealing the ruminal fermentation patterns and microbial populations as affected by dietary n-6:n-3 PUFA ratio would be useful for further clarifying the role of the rumen in the lipid metabolism of ruminants. The objective of the present study was to investigate the effects of dietary n-6:n-3 PUFA ratios on fermentation characteristics, fatty acid (FA) profiles, and microbial populations in the rumen of goats. A total of twenty-one goats were randomly assigned to three dietary treatments with different n-6:n-3 PUFA ratios of 2.27:1 (low ratio, LR), 5.01:1 (medium ratio, MR), and 10.38:1 (high ratio, HR). After 100 days of feeding, all goats were slaughtered. Dietary n-6:n-3 PUFA ratios had no effect (P > 0.05) on rumen pH and NH 3 N concentration. Goats fed HR diet had lower (P < 0.05) propionate and total volatile fatty acids and higher (P < 0.05) butyrate compared with those fed the MR and LR diets. The proportion of C18:0 decreased (P < 0.05) as dietary n-6:n-3 PUFA ratios increased. The proportions of C18:1 trans-11, C18:2n-6, cis-9 trans-11 CLA, and C20:4n-6 were greater in the HR goats compared with the MR and LR goats. Lowering dietary n-6:n-3 PUFA ratios enhanced (P < 0.05) the proportion of C18:3n-3 and total n-3 PUFA in the rumen fluid of goats. The populations of R. albus and R. flavefaciens decreased (P < 0.05) as the n-6:n-3 PUFA ratios increased in diet. Diet had no effect (P > 0.05) on the ruminal populations of F. succinogenes, total bacteria, methanogens, total protozoa, Entiodinium, and Holotrich. The population of B. fibrisolvens was lower (P < 0.05) in the LR goats compared with the MR and HR goats. It was concluded that HR would increase the concentration of cis-9 trans-11 CLA and C18:1 trans-11 in the rumen. However, LR whould decrease the B. fibrisolvens population, which is involved in the BH process in the rumen. Further research is needed to evaluate the potential role and contribution of rumen microbiome in the metabolism of FA in the rumen.

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

PubMed Central

McNally, Andrew; Madan, Ashish; Sucosky, Philippe

2017-01-01

The bicuspid aortic valve (BAV) is a major risk factor for secondary aortopathy such as aortic dilation. The heterogeneous BAV morphotypes [left-right-coronary cusp fusion (LR), right-non-coronary cusp fusion (RN), and left-non-coronary cusp fusion (LN)] are associated with different dilation patterns, suggesting a role for hemodynamics in BAV aortopathogenesis. However, assessment of this theory is still hampered by the limited knowledge of the hemodynamic abnormalities generated by the distinct BAV morphotypes. The objective of this study was to compare experimentally the hemodynamics of a normal (i.e., non-dilated) ascending aorta (AA) subjected to tricuspid aortic valve (TAV), LR-BAV, RN-BAV, and NL-BAV flow. Tissue BAVs reconstructed from porcine TAVs were subjected to physiologic pulsatile flow conditions in a left-heart simulator featuring a realistic aortic root and compliant aorta. Phase-locked particle image velocimetry experiments were carried out to characterize the flow in the aortic root and in the tubular AA in terms of jet skewness and displacement, as well as mean velocity, viscous shear stress and Reynolds shear stress fields. While all three BAVs generated skewed and asymmetrical orifice jets (up to 1.7- and 4.0-fold increase in flow angle and displacement, respectively, relative to the TAV at the sinotubular junction), the RN-BAV jet was out of the plane of observation. The LR- and NL-BAV exhibited a 71% increase in peak-systolic orifice jet velocity relative to the TAV, suggesting an inherent degree of stenosis in BAVs. While these two BAV morphotypes subjected the convexity of the aortic wall to viscous shear stress overloads (1.7-fold increase in maximum peak-systolic viscous shear stress relative to the TAV-AA), the affected sites were morphotype-dependent (LR-BAV: proximal AA, NL-BAV: distal AA). Lastly, the LR- and NL-BAV generated high degrees of turbulence in the AA (up to 2.3-fold increase in peak-systolic Reynolds shear stress relative to the TAV) that were sustained from peak systole throughout the deceleration phase. This in vitro study reveals substantial flow abnormalities (increased jet skewness, asymmetry, jet velocity, turbulence, and shear stress overloads) in non-dilated BAV aortas, which differ from those observed in dilated aortas but still coincide with aortic wall regions prone to dilation. PMID:28203207

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

PubMed

Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

2012-05-01

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

High novelty-seeking rats are resilient to negative physiological effects of the early life stress.

PubMed

Clinton, Sarah M; Watson, Stanley J; Akil, Huda

2014-01-01

Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs' already high physiological response to stress - stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs') neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals' response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

Impairment of endoplasmic reticulum is involved in β-cell dysfunction induced by microcystin-LR.

PubMed

Zhao, Yanyan; Cao, Qing; He, Yaojia; Xue, Qingju; Xie, Liqiang; Yan, Yunjun

2017-04-01

Microcystins (MCs) widely distributed in freshwaters have posed a significant risk to human health. Previous studies have demonstrated that exposure to MC-LR impairs pancreatic islet function, however, the underlying mechanisms still remain unclear. In the present study, we explored the role of endoplasmic reticulum (ER) impairment in β-cell dysfunction caused by MC-LR. The result showed that MC-LR modified ER morphology evidenced by increased ER amount and size at low doses (15, 30 or 60 μM) and vacuolar and dilated ER ultrastructure at high doses (100 or 200 μM). Also, insulin content showed increased at 15 or 30 μM but declined at 60, 100, or 200 μM, which was highly accordant with ER morphological alteration. Transcriptomic analysis identified a number of factors and several pathways associated with ER protein processing, ER stress, apoptosis, and diabetes mellitus in the cells treated with MC-LR compared with non-treated cells. Furthermore, MC-LR-induced ER stress significantly promoted the expression of PERK/eIF2α and their downstream targets (ATF4, CHOP, and Gadd34), which indicates that PERK-eIF2α-ATF4 pathway is involved in MC-LR-induced insulin deficiency. These results suggest that ER impairment is an important contributor to MC-LR-caused β-cell failure and provide a new insight into the association between MCs contamination and the occurrence of human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unveiling New Degradation Intermediates/Pathways from the Photocatalytic Degradation of Microcystin-LR

EPA Science Inventory

This study focuses on the identification of reaction intermediates formed during the photocatalytic degradation of the cyanotoxin microcystin-LR with immobilized TiO₂ Tphotocatalysts at neutral pH. To differentiate between impurities already existing in the MC-LR stand...

Importance of ocean mesoscale variability for air-sea interactions in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Putrasahan, D. A.; Kamenkovich, I.; Le Hénaff, M.; Kirtman, B. P.

2017-06-01

Mesoscale variability of currents in the Gulf of Mexico (GoM) can affect oceanic heat advection and air-sea heat exchanges, which can influence climate extremes over North America. This study is aimed at understanding the influence of the oceanic mesoscale variability on the lower atmosphere and air-sea heat exchanges. The study contrasts global climate model (GCM) with 0.1° ocean resolution (high resolution; HR) with its low-resolution counterpart (1° ocean resolution with the same 0.5° atmosphere resolution; LR). The LR simulation is relevant to current generation of GCMs that are still unable to resolve the oceanic mesoscale. Similar to observations, HR exhibits positive correlation between sea surface temperature (SST) and surface turbulent heat flux anomalies, while LR has negative correlation. For HR, we decompose lateral advective heat fluxes in the upper ocean into mean (slowly varying) and mesoscale-eddy (fast fluctuations) components. We find that the eddy flux divergence/convergence dominates the lateral advection and correlates well with the SST anomalies and air-sea latent heat exchanges. This result suggests that oceanic mesoscale advection supports warm SST anomalies that in turn feed surface heat flux. We identify anticyclonic warm-core circulation patterns (associated Loop Current and rings) which have an average diameter of 350 km. These warm anomalies are sustained by eddy heat flux convergence at submonthly time scales and have an identifiable imprint on surface turbulent heat flux, atmospheric circulation, and convective precipitation in the northwest portion of an averaged anticyclone.

Effects of microcystins contamination on soil enzyme activities and microbial community in two typical lakeside soils.

PubMed

Cao, Qing; Steinman, Alan D; Su, Xiaomei; Xie, Liqiang

2017-12-01

A 30-day indoor incubation experiment was conducted to investigate the effects of different concentrations of microcystin (1, 10, 100 and 1000 μg eq. MC-LR L -1 ) on soil enzyme activity, soil respiration, physiological profiles, potential nitrification, and microbial abundance (total bacteria, total fungi, ammonia-oxidizing bacteria and archaea) in two lakeside soils in China (Soil A from the lakeside of Lake Poyanghu at Jiujiang; Soil B from the lakeside of Lake Taihu at Suzhou). Of the enzymes tested, only phenol oxidase activity was negatively affected by microcystin application. In contrast, dehydrogenase activity was stimulated in the 1000 μg treatment, and a stimulatory effect also occurred with soil respiration in contaminated soil. The metabolic profiles of the microbial communities indicated that overall carbon metabolic activity in the soils treated with high microcystin concentrations was inhibited, and high concentrations of microcystin also led to different patterns of potential carbon utilization. High microcystin concentrations (100, 1000 μg eq. MC-LR L -1 in Soil A; 10, 100 1000 μg eq. MC-LR L -1 in Soil B) significantly decreased soil potential nitrification rate. Furthermore, the decrease in soil potential nitrification rate was positively correlated with the decrease of the amoA gene abundance, which corresponds to the ammonia-oxidizing bacterial community. We conclude that application of microcystin-enriched irrigation water can significantly impact soil microbial community structure and function. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Multi-Walled Carbon Nanotube-based Biosensor for Monitoring Microcystin-LR in Sources of Drinking Water Supplies

EPA Science Inventory

A multi-walled carbon nanotube-based electrochemical biosensor is developed for monitoring microcystin-LR (MC-LR), a toxic cyanobacterial toxin, in sources of drinking water supplies. The biosensor electrodes are fabricated using dense, mm-long multi-walled CNT (MWCNT) arrays gro...

ARC-1969-A-36324

NASA Image and Video Library

1966-02-01

MANNED SPACECRAFT SIMULATION BRANCH PERSONNEL - Top row, L-R: Henry C. Lessing, Dallas G. Denery, Richard Acken, Robert E. Coate. Secon row, L-R: Frederick W. Boltz, Kenneth C. White, Gordon H. Hardy, Donald W. Smith. Third row, L-R: Rodney C. Wingrove, Bedford A. Lampkin, Armando E. Lopez, DeLamar W. Watson. Bottom row, L-R: Richard L. Kurkowski, Michele H. Hilliard, Brent Y. Creer, Grace M. Webster, Frederick G. Edwards. Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig 90

A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model.

PubMed

Umbaugh, Charles Samuel; Diaz-Quiñones, Adriana; Neto, Manoel Figueiredo; Shearer, Joseph J; Figueiredo, Marxa L

2018-01-19

Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF balance is a desirable therapeutic outcome, and we sought to identify a small molecule that could recapitulate known signaling properties of PEDF but without the additional complications of peptide formulation or gene delivery safety validation. We used an in silico drug discovery approach to target the interaction interface between PEDF and 37 LR. Following cell based counter screening and binding validation, we characterized a hit compound's anti-viability, activation of PEDF signaling-related genes, anti-wound healing, and anti-cancer signaling properties. This hit compound has potential for future development as a lead compound for treating tumor growth and inhibiting angiogenesis.

The Accuracy of the Physical Examination for the Diagnosis of Midlumbar and Low Lumbar Nerve Root Impingement

PubMed Central

Suri, Pradeep; Rainville, James; Katz, Jeffrey N.; Jouve, Cristin; Hartigan, Carol; Limke, Janet; Pena, Enrique; Li, Ling; Swaim, Bryan; Hunter, David J

2010-01-01

Study Design Cross-sectional study with prospective recruitment. Objective To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement (L2, L3, or L4), low lumbar nerve root impingement (L5 or S1) and level-specific lumbar nerve root impingement on magnetic resonance imaging (MRI), using individual tests and combinations of tests. Summary of Background Data The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied. Methods Sensitivities, specificities and LRs were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar, low lumbar, and specific nerve root levels. Results LRs ≥5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability. For the diagnosis of midlumbar impingement, the femoral stretch test (FST), crossed femoral stretch test (CFST), medial ankle pinprick sensation, and patellar reflex testing demonstrated LRs ≥5.0 (LR ∞). LRs ≥5.0 were seen with the combinations of FST and either patellar reflex testing (LR 7.0; 95% CI 2.3–21), or the sit-to-stand test (LR ∞). For the diagnosis of low lumbar impingement, the Achilles reflex test demonstrated a LR ≥5.0 (LR 7.1; CI 0.96–53); test combinations did not increase LRs. For the diagnosis of level-specific impingement, LRs ≥5.0 were seen for anterior thigh sensation at L2 (LR 13; 95% CI 1.8–87); FST at L3 (LR 5.7 ; 95% CI 2.3–4.4); patellar reflex testing (LR 7.7; 95% CI 1.7–35), medial ankle sensation (LR ∞), or CFST (LR 13; 95% CI 1.8–87) at L4; and hip abductor strength at L5(LR 11; 95% CI 1.3–84). Test combinations increased LRs for level-specific root impingement at the L4 level only. Conclusions Individual physical examination tests may provide clinical information which substantially alters the likelihood that midlumbar impingement, low lumbar impingement, or level-specific impingement is present. Test combinations improve diagnostic accuracy for midlumbar impingement. PMID:20543768

Cingulate neglect in humans: disruption of contralesional reward learning in right brain damage.

PubMed

Lecce, Francesca; Rotondaro, Francesca; Bonnì, Sonia; Carlesimo, Augusto; Thiebaut de Schotten, Michel; Tomaiuolo, Francesco; Doricchi, Fabrizio

2015-01-01

Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of attentional processing as he suffered no contralesional visual or auditory extinction on double simultaneous tachistoscopic and dichotic stimulation and detected, with no exception, single contralesional visual and auditory stimuli. In a separate study, we were able to compare L.R. with another RBD patient, G.P., who had a selective lesion in the right ACC, in the adjacent callosal connections and the medial-basal prefrontal cortex. G.P. had no contralesional neglect and displayed normal reward learning both in the left and right side of space. These findings show that contralesional reward learning is generally preserved in RBD patients with left spatial neglect and that this can be exploited in rehabilitation protocols. Contralesional reward learning is severely disrupted in neglect patients when an additional lesion of the ACC is present: however, as demonstrated by the comparison between L.R. and G.P. cases, selective unilateral lesion of the right ACC does not produce motivational neglect for the contralesional space. Copyright © 2014 Elsevier Ltd. All rights reserved.

No turning, a mouse mutation causing left-right and axial patterning defects.

PubMed

Melloy, P G; Ewart, J L; Cohen, M F; Desmond, M E; Kuehn, M R; Lo, C W

1998-01-01

Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.

Advanced in-production hotspot prediction and monitoring with micro-topography

NASA Astrophysics Data System (ADS)

Fanton, P.; Hasan, T.; Lakcher, A.; Le-Gratiet, B.; Prentice, C.; Simiz, J.-G.; La Greca, R.; Depre, L.; Hunsche, S.

2017-03-01

At 28nm technology node and below, hot spot prediction and process window control across production wafers have become increasingly critical to prevent hotspots from becoming yield-limiting defects. We previously established proof of concept for a systematic approach to identify the most critical pattern locations, i.e. hotspots, in a reticle layout by computational lithography and combining process window characteristics of these patterns with across-wafer process variation data to predict where hotspots may become yield impacting defects [1,2]. The current paper establishes the impact of micro-topography on a 28nm metal layer, and its correlation with hotspot best focus variations across a production chip layout. Detailed topography measurements are obtained from an offline tool, and pattern-dependent best focus (BF) shifts are determined from litho simulations that include mask-3D effects. We also establish hotspot metrology and defect verification by SEM image contour extraction and contour analysis. This enables detection of catastrophic defects as well as quantitative characterization of pattern variability, i.e. local and global CD uniformity, across a wafer to establish hotspot defect and variability maps. Finally, we combine defect prediction and verification capabilities for process monitoring by on-product, guided hotspot metrology, i.e. with sampling locations being determined from the defect prediction model and achieved prediction accuracy (capture rate) around 75%

History, Physical Examination, Laboratory Testing, and Emergency Department Ultrasonography for the Diagnosis of Acute Cholecystitis.

PubMed

Jain, Ashika; Mehta, Ninfa; Secko, Michael; Schechter, Joshua; Papanagnou, Dimitri; Pandya, Shreya; Sinert, Richard

2017-03-01

Acute cholecystitis (AC) is a common differential for patients presenting to the emergency department (ED) with abdominal pain. The diagnostic accuracy of history, physical examination, and bedside laboratory tests for AC have not been quantitatively described. We performed a systematic review to determine the utility of history and physical examination (H&P), laboratory studies, and ultrasonography (US) in diagnosing AC in the ED. We searched medical literature from January 1965 to March 2016 in PubMed, Embase, and SCOPUS using a strategy derived from the following formulation of our clinical question: patients-ED patients suspected of AC; interventions-H&P, laboratory studies, and US findings commonly used to diagnose AC; comparator-surgical pathology or definitive diagnostic radiologic study confirming AC; and outcome-the operating characteristics of the investigations in diagnosing AC were calculated. Sensitivity, specificity, and likelihood ratios (LRs) were calculated using Meta-DiSc with a random-effects model (95% CI). Study quality and risks for bias were assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies. Separate PubMed, Embase, and SCOPUS searches retrieved studies for H&P (n = 734), laboratory findings (n = 74), and US (n = 492). Three H&P studies met inclusion/exclusion criteria with AC prevalence of 7%-64%. Fever had sensitivity ranging from 31% to 62% and specificity from 37% to 74%; positive LR [LR+] was 0.71-1.24, and negative LR [LR-] was 0.76-1.49. Jaundice sensitivity ranged from 11% to 14%, and specificity from 86% to 99%; LR+ was 0.80-13.81, and LR- was 0.87-1.03. Murphy's sign sensitivity was 62% (range = 53%-71%), and specificity was 96% (range = 95%-97%); LR+ was 15.64 (range = 11.48-21.31), and LR- was 0.40 (range = 0.32-0.50). Right upper quadrant pain had sensitivity ranging from 56% to 93% and specificity of 0% to 96%; LR+ ranged from 0.92 to 14.02, and LR- from 0.46 to 7.86. One laboratory study met criteria with a 26% prevalence of AC. Elevated bilirubin had a sensitivity of 40% (range = 12%-74%) and specificity of 93% (range = 77%-99%); LR+ was 5.80 (range = 1.25-26.99), and LR- was 0.64 (range = 0.39-1.08). Five US studies with a prevalence of AC of between 10% and 46%. US sensitivity was 86% (range = 78%-94%) and specificity was 71% (range = 66%-76%); LR+ was 3.23 (range = 1.74-6.00), and LR- was 0.18 (range = 0.10-0.33). Variable disease prevalence, coupled with limited sample sizes, increases the risk of selection bias. Individually, none of these investigations reliably rule out AC. Development of a clinical decision rule to include evaluation of H&P, laboratory data, and US are more likely to achieve a correct diagnosis of AC. © 2016 by the Society for Academic Emergency Medicine.

Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice.

PubMed

Soffe, Z; Radley-Crabb, H G; McMahon, C; Grounds, M D; Shavlakadze, T

2016-02-01

This study compared the capacity of young and old male C57Bl/6J mice to exercise with increasing resistance over 10 weeks, and its impact on muscle mass. Young mice (aged 15-25 weeks) were subjected to low (LR) and high (HR) resistance exercise, whereas only LR was used for old mice (107-117 weeks). Weekly patterns of voluntary wheel activity, food consumption and body weights were measured. Running patterns changed over time and with age, with two peaks of activity detected for young, but only one for old mice: speed and distance run was also less for old mice. The mass for six limb muscles was measured at the end of the experiment. The most pronounced increase in mass in response to exercise was for the soleus in young and old mice, and also quadriceps and gastrocnemius in young mice. Soleus and quadriceps muscles were analyzed histologically for myofiber number and size. A striking feature was the many small myofibers in response to exercise in young (but not old) soleus, whereas these were not present after exercise in young or old quadriceps. Overall, there was a striking difference in response to exercise between muscles and this was influenced by age. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patterns of hand preference for pairs of actions and the classification of handedness.

PubMed

Annett, Marian

2009-08-01

Pairs of actions such as write x throw and throw x racquet were examined for items of the Annett hand preference questionnaire (AHPQ). Right (R) and left (L) responses were described for frequencies of RR, RL, LR, and LL pairings (write x throw etc.) in a large representative combined sample with the aim of discovering the distribution over the population as a whole. The frequencies of RL pairings varied significantly over the different item pairs but the frequencies of LR pairings were fairly constant. An important difference was found between primary actions (originally write, throw, racquet, match, toothbrush, hammer with the later addition of scissors for right-handers) and non-primary actions (needle and thread, broom, spade, dealing playing cards, and unscrewing the lid of a jar). For primary actions, there were similar numbers of right and left writers using the 'other' hand. For non-primary actions more right-handers used the left hand than for primary actions but more left-handers did not use the right hand. That is, different frequencies of response to primary versus non-primary actions were found for right-handers but not for left-handers. The pattern of findings was repeated for a corresponding analysis of left-handed throwing x AHPQ actions. The findings have implications for the classification of hand preferences and for analyses of the nature of hand skill.

Defect-mediated turbulence in ribbons of viscoelastic Taylor-Couette flow.

PubMed

Latrache, Noureddine; Abcha, Nizar; Crumeyrolle, Olivier; Mutabazi, Innocent

2016-04-01

Transition to defect-mediated turbulence in the ribbon patterns observed in a viscoelastic Taylor-Couette flow is investigated when the rotation rate of the inner cylinder is increased while the outer cylinder is fixed. In four polymer solutions with different values of the elasticity number, the defects appear just above the onset of the ribbon pattern and trigger the appearance of disordered oscillations when the rotation rate is increased. The flow structure around the defects is determined and the statistical properties of these defects are analyzed in the framework of the complex Ginzburg-Landau equation.

Prospective evaluation of the ability of clinical scoring systems and physician-determined likelihood of appendicitis to obviate the need for CT.

PubMed

Golden, Sean K; Harringa, John B; Pickhardt, Perry J; Ebinger, Alexander; Svenson, James E; Zhao, Ying-Qi; Li, Zhanhai; Westergaard, Ryan P; Ehlenbach, William J; Repplinger, Michael D

2016-07-01

To determine whether clinical scoring systems or physician gestalt can obviate the need for computed tomography (CT) in patients with possible appendicitis. Prospective, observational study of patients with abdominal pain at an academic emergency department (ED) from February 2012 to February 2014. Patients over 11 years old who had a CT ordered for possible appendicitis were eligible. All parameters needed to calculate the scores were recorded on standardised forms prior to CT. Physicians also estimated the likelihood of appendicitis. Test characteristics were calculated using clinical follow-up as the reference standard. Receiver operating characteristic curves were drawn. Of the 287 patients (mean age (range), 31 (12-88) years; 60% women), the prevalence of appendicitis was 33%. The Alvarado score had a positive likelihood ratio (LR(+)) (95% CI) of 2.2 (1.7 to 3) and a negative likelihood ratio (LR(-)) of 0.6 (0.4 to 0.7). The modified Alvarado score (MAS) had LR(+) 2.4 (1.6 to 3.4) and LR(-) 0.7 (0.6 to 0.8). The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score had LR(+) 1.3 (1.1 to 1.5) and LR(-) 0.5 (0.4 to 0.8). Physician-determined likelihood of appendicitis had LR(+) 1.3 (1.2 to 1.5) and LR(-) 0.3 (0.2 to 0.6). When combined with physician likelihoods, LR(+) and LR(-) was 3.67 and 0.48 (Alvarado), 2.33 and 0.45 (RIPASA), and 3.87 and 0.47 (MAS). The area under the curve was highest for physician-determined likelihood (0.72), but was not statistically significantly different from the clinical scores (RIPASA 0.67, Alvarado 0.72, MAS 0.7). Clinical scoring systems performed equally well as physician gestalt in predicting appendicitis. These scores do not obviate the need for imaging for possible appendicitis when a physician deems it necessary. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Observed to expected or logistic regression to identify hospitals with high or low 30-day mortality?

PubMed Central

Helgeland, Jon; Clench-Aas, Jocelyne; Laake, Petter; Veierød, Marit B.

2018-01-01

Introduction A common quality indicator for monitoring and comparing hospitals is based on death within 30 days of admission. An important use is to determine whether a hospital has higher or lower mortality than other hospitals. Thus, the ability to identify such outliers correctly is essential. Two approaches for detection are: 1) calculating the ratio of observed to expected number of deaths (OE) per hospital and 2) including all hospitals in a logistic regression (LR) comparing each hospital to a form of average over all hospitals. The aim of this study was to compare OE and LR with respect to correctly identifying 30-day mortality outliers. Modifications of the methods, i.e., variance corrected approach of OE (OE-Faris), bias corrected LR (LR-Firth), and trimmed mean variants of LR and LR-Firth were also studied. Materials and methods To study the properties of OE and LR and their variants, we performed a simulation study by generating patient data from hospitals with known outlier status (low mortality, high mortality, non-outlier). Data from simulated scenarios with varying number of hospitals, hospital volume, and mortality outlier status, were analysed by the different methods and compared by level of significance (ability to falsely claim an outlier) and power (ability to reveal an outlier). Moreover, administrative data for patients with acute myocardial infarction (AMI), stroke, and hip fracture from Norwegian hospitals for 2012–2014 were analysed. Results None of the methods achieved the nominal (test) level of significance for both low and high mortality outliers. For low mortality outliers, the levels of significance were increased four- to fivefold for OE and OE-Faris. For high mortality outliers, OE and OE-Faris, LR 25% trimmed and LR-Firth 10% and 25% trimmed maintained approximately the nominal level. The methods agreed with respect to outlier status for 94.1% of the AMI hospitals, 98.0% of the stroke, and 97.8% of the hip fracture hospitals. Conclusion We recommend, on the balance, LR-Firth 10% or 25% trimmed for detection of both low and high mortality outliers. PMID:29652941

Effect of calcium and magnesium on the antimicrobial action of enterocin LR/6 produced by Enterococcus faecium LR/6.

PubMed

Kumar, Manoj; Srivastava, Sheela

2011-06-01

Enterococci are well-known producers of antimicrobial peptides (enterocins) that possess potential as biopreservatives in food. In this study, divalent cations and release of intracellular potassium were used to assess the mechanism of interaction and killing of enterocin LR/6 produced by Enterococcus faecium LR/6 on three target Gram-positive and Gram-negative bacteria, namely Micrococcus luteus, Enterococcus sp. strain LR/3 and Escherichia coli K-12. Whilst treatment with enterocin LR/6 in all cases led to a significant loss of viability, suggesting a bactericidal mode of action, E. coli K-12 showed better tolerance than the other two strains. Bacteriocins have generally been reported to create pores in the membrane of sensitive cells and this function is diminished by divalent cations. In this study it was shown that Ca(2+) and Mg(2+) markedly improved the viability of enterocin LR/6-treated cells in a concentration-dependent manner. K(+) release as a sign of membrane leakiness was higher in M. luteus compared with the other two test strains. In agreement with the viability response, pre-exposure to Ca(2+) and Mg(2+) substantially reduced the amount of K(+) leakage by M. luteus and Enterococcus sp.; in the case of E. coli K-12, no leakage of K(+) was recorded. These results suggest that enterocin LR/6, which possesses good antibacterial potential, may not be very effective as a preservative in foods containing high concentrations of calcium and magnesium. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Functional relationships of landfill and landraise capacity with design and operation parameters.

PubMed

Aivaliotis, Vassilis; Dokas, Ioannis; Hatzigiannakou, Maria; Panagiotakopoulos, Demetrios

2004-08-01

Solid waste management presses for effective landfill design and operation. While planning and operating a landfill (LF) or a landraise (LR), choices need to be made regarding: (1) LF-LR morphology (base shape, side slopes, final cover thickness, LR/LF height/depth); (2) cell geometry (height, length, slopes); and (3) operation parameters (waste density, working face length, cover thicknesses). These parameters affect LF/LR capacity, operation lifespan and construction/ operation costs. In this paper, relationships are generated between capacity (C, space available for waste) and the above parameters. Incorporating real data into simulation kgamma A1.38, runs, two types of functions are developed: first, C = where A is the LF/LR base area size and kgamma a base shape-dependent coefficient; and second, C = alpha(p,gamma,A) + delta(p,gamma,A)Xp for every parameter p, where Xp is the value of p and alpha(p,gamma,A) and delta(p,gamma,A) are parameter- and base (shape/size)-specific coefficients. Moreover, the relationship between LF depth and LR height that balances excavation volume with cover material, is identified. Another result is that, for a symmetrical combination of LF/LR, with base surface area shape between square and 1:2 orthogonal, and final density between 500 and 800 kg m(-3), waste quantity placed ranges from 1.76A1.38 to 2.55A1.38 tons. The significance of such functions is obvious, as they allow the analyst to investigate alternative LF/LR schemes and make trade-off analyses.

The effect of intravenous lactated Ringer's solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers.

PubMed

Williams, E L; Hildebrand, K L; McCormick, S A; Bedel, M J

1999-05-01

Animal studies have shown that large volumes of IV lactated Ringer's solution (LR) decrease serum osmolality, thereby increasing cerebral water. These studies have led to recommendations to limit LR to avoid cerebral edema in neurosurgical patients. Eighteen healthy human volunteers aged 20-48 yr received 50 mL/kg LR over 1 h on one occasion and 0.9% sodium chloride (NS) on another. Venous samples were taken at baseline (T1), at infusion end (T2), and 1 h after T2 (T3). Time until first urination was noted. With LR, serum osmolality decreased by 4+/-3 mOsm/kg from T1 to T2 and increased insignificantly with NS. At T3, osmolality returned almost to baseline in the LR group. Blood pH increased from T1 to T2 with LR by 0.04+/-0.04 and decreased with NS by 0.04+/-0.04. These pH changes persisted at T3. Subjective mental changes occurred only with NS. Abdominal discomfort was more common with NS. Time until first urination was longer with NS (106+/-11 min) than with LR (75+/-10 min) (P < 0.001). In healthy humans, an infusion of large volumes of LR, but not NS, transiently decreased serum osmolality, whereas acidosis associated with NS persisted and urinary output was slower with NS. Large volumes of lactated Ringer's solution administered to healthy humans produced small transient changes in serum osmolality. Large volumes of sodium chloride did not change osmolality but resulted in lower pH.

Degradation of [Dha7]MC-LR by a Microcystin Degrading Bacterium Isolated from Lake Rotoiti, New Zealand

PubMed Central

Somdee, Theerasak; Ruck, John; Lys, Isabelle; Allison, Margaret; Page, Rachel

2013-01-01

For the first time a microcystin-degrading bacterium (NV-3 isolate) has been isolated and characterized from a NZ lake. Cyanobacterial blooms in New Zealand (NZ) waters contain microcystin (MC) hepatotoxins at concentrations which are a risk to animal and human health. Degradation of MCs by naturally occurring bacteria is an attractive bioremediation option for removing MCs from drinking and recreational water sources. The NV-3 isolate was identified by 16S rRNA sequence analysis and found to have 100% nucleotide sequence homology with the Sphingomonas MC-degrading bacterial strain MD-1 from Japan. The NV-3 isolate (concentration of 1.0 × 108 CFU/mL) at 30°C degraded a mixture of [Dha7]MC-LR and MC-LR (concentration 25 μg/mL) at a maximum rate of 8.33 μg/mL/day. The intermediate by-products of [Dha7]MC-LR degradation were detected and similar to MC-LR degradation by-products. The presence of three genes (mlrA, mlrB, and mlrC), that encode three enzymes involved in the degradation of MC-LR, were identified in the NV-3 isolate. This study confirmed that degradation of [Dha7]MC-LR by the Sphingomonas isolate NV-3 occurred by a similar mechanism previously described for MC-LR by Sphingomonas strain MJ-PV (ACM-3962). This has important implications for potential bioremediation of toxic blooms containing a variety of MCs in NZ waters. PMID:23936728

Estrogenic potency of MC-LR is induced via stimulating steroidogenesis: In vitro and in vivo evidence.

PubMed

Hou, Jie; Su, Yujing; Lin, Wang; Guo, Honghui; Li, Li; Anderson, Donald M; Li, Dapeng; Tang, Rong; Chi, Wei; Zhang, Xi

2018-05-14

Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes. In the in vivo assay, adult male zebrafish were exposed to 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d. Similarly, E2 and T contents in the testis were increased, accompanied by extensive up-regulation of steroidogenic genes, especially cyp19a. Meanwhile, the percentage of spermatid in the testis declined. In the liver, the vtg1 gene was significantly up-regulated while both the transcriptional and protein levels of the estrogenic receptor (ER) declined. These results indicate that MC-LR induced non-dose-dependent estrogenic effects at environmental concentrations, which may result from steroidogenesis stimulation via a non-ER-mediated pathway. Our findings support a paradigm shift in the risk assessment of MC-LR from traditional toxicity to estrogenic risk, particularly at low concentrations, and emphasize the potential threat to the male reproductive capacity of wildlife in bloom areas. Copyright © 2018 Elsevier Ltd. All rights reserved.

A pM leveled photoelectrochemical sensor for microcystin-LR based on surface molecularly imprinted TiO2@CNTs nanostructure.

PubMed

Liu, Meichuan; Ding, Xue; Yang, Qiwei; Wang, Yu; Zhao, Guohua; Yang, Nianjun

2017-06-05

A simple and highly sensitive photoelectrochemical (PEC) sensor towards Microcystin-LR (MC-LR), a kind of typical cyanobacterial toxin in water samples, was developed on a surface molecular imprinted TiO 2 coated multiwalled carbon nanotubes (MI-TiO 2 @CNTs) hybrid nanostructure. It was synthesized using a feasible two-step sol-gel method combining with in situ surface molecular imprinting technique (MIT). With a controllable core-shell tube casing structure, the resultant MI-TiO 2 @CNTs are enhanced greatly in visible-light driven response capacity. In comparison with the traditional TiO 2 (P25) and non-imprinted (NI-)TiO 2 @CNTs, the MI-TiO 2 @CNTs based PEC sensor showed a much higher photoelectric oxidation capacity towards MC-LR. Using this sensor, the determination of MC-LR was doable in a wide linear range from 1.0pM to 3.0nM with a high photocurrent response sensitivity. An outstanding selectivity towards MC-LR was further achieved with this sensor, proven by simultaneously monitoring 100-fold potential co-existing interferences. The superiority of the obtained MC-LR sensor in sensitivity and selectivity is mainly attributed to the high specific surface area and excellent photoelectric activity of TiO 2 @CNTs heterojunction structure, as well as the abundant active recognition sites on its functionalized molecular imprinting surface. A promising PEC analysis platform with high sensitivity and selectivity for MC-LR has thus been provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Successful introduction and audit of a step-down oral antibiotic strategy for low risk paediatric febrile neutropaenia in a UK, multicentre, shared care setting.

PubMed

Dommett, R; Geary, J; Freeman, S; Hartley, J; Sharland, M; Davidson, A; Tulloh, R; Taj, M; Stoneham, S; Chisholm, J C

2009-11-01

Patients with febrile neutropaenia (FN) can be stratified according to their risk of significant complications, allowing reduced intensity therapy for low risk (LR) episodes. Serious events are very rare in low risk episodes making randomised trials difficult. Introduction of new evidence-based guidelines followed by re-auditing of the outcome is an alternative strategy. New guidelines for the management of LR FN were implemented in 4 specialist paediatric oncology centres (POCs) and in their associated shared care units (POSCUs). All patients commenced empirical intravenous antibiotic therapy and after 48h those with blood culture negative episodes designated LR were eligible for discharge on oral co-amoxiclav. Prospective data collection on FN episodes in all treatment centres was undertaken over a 1-year period. Seven hundred and sixty two eligible episodes of FN were recorded in 368 patients; 213 episodes were initiated in POCs and 549 episodes were initiated in POSCUs. In 40% of episodes no clinical or microbiological focus of infection was found. At 48h, 212 (27%) episodes were classified as LR and 143 of these (19%) were managed on the LR protocol. There was a low hospital readmission rate (8/143 episodes; 5.6%), no intensive care admissions and no deaths in LR episodes. Almost all LR episodes (209/212) occurred in the shared care setting. Rapid step-down to oral antibiotics was a feasible and safe management strategy for LR FN in the shared care setting in England.

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings

PubMed Central

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca2+]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca2+] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development. PMID:26076049

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings.

PubMed

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca(2+)]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca(2+)] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development.

Microcystin-LR Induced Reactive Oxygen Species Mediate Cytoskeletal Disruption and Apoptosis of Hepatocytes in Cyprinus carpio L.

PubMed Central

Jiang, Jinlin; Shan, Zhengjun; Xu, Weili; Wang, Xiaorong; Zhou, Junying; Kong, Deyang; Xu, Jing

2013-01-01

Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12 - 48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity. PMID:24376844

Effect of lattice defects on Hele-Shaw flow over an etched lattice

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

Decker, E.L.; Ignes-Mullol, J.; Baratt, A.

We examine the patterns formed by injecting nitrogen gas into the center of a horizontal, radial Hele-Shaw cell filled with paraffin oil. We use smooth plates and etched plates with lattices having different amounts of defects (0{endash}10&hthinsp;{percent}). In all cases, a quantitative measure of the pattern ramification shows a regular trend with injection rate and cell gap, such that the dimensionless perimeter scales with the dimensionless time. By adding defects to the lattice, we observe increased branching in the pattern morphologies. However, even in this case, the scaling behavior persists. Only the prefactor of the scaling function shows a dependencemore » on the defect density. For different lattice defect densities, we examine the nature of the different morphology phases. {copyright} {ital 1999} {ital The American Physical Society}« less

Does this adult patient have a blunt intra-abdominal injury?

PubMed

Nishijima, Daniel K; Simel, David L; Wisner, David H; Holmes, James F

2012-04-11

Blunt abdominal trauma often presents a substantial diagnostic challenge. Well-informed clinical examination can identify patients who require further diagnostic evaluation for intra-abdominal injuries after blunt abdominal trauma. To systematically assess the precision and accuracy of symptoms, signs, laboratory tests, and bedside imaging studies to identify intra-abdominal injuries in patients with blunt abdominal trauma. We conducted a structured search of MEDLINE (1950-January 2012) and EMBASE (1980-January 2012) to identify English-language studies examining the identification of intra-abdominal injuries. A separate, structured search was conducted for studies evaluating bedside ultrasonography. We included studies of diagnostic accuracy for intra-abdominal injury that compared at least 1 finding with a reference standard of abdominal computed tomography, diagnostic peritoneal lavage, laparotomy, autopsy, and/or clinical course for intra-abdominal injury. Twelve studies on clinical findings and 22 studies on bedside ultrasonography met inclusion criteria for data extraction. Critical appraisal and data extraction were independently performed by 2 authors. The prevalence of intra-abdominal injury in adult emergency department patients with blunt abdominal trauma among all evidence level 1 and 2 studies was 13% (95% CI, 10%-17%), with 4.7% (95% CI, 2.5%-8.6%) requiring therapeutic surgery or angiographic embolization of injuries. The presence of a seat belt sign (likelihood ratio [LR] range, 5.6-9.9), rebound tenderness (LR, 6.5; 95% CI, 1.8-24), hypotension (LR, 5.2; 95% CI, 3.5-7.5), abdominal distention (LR, 3.8; 95% CI, 1.9-7.6), or guarding (LR, 3.7; 95% CI, 2.3-5.9) suggest an intra-abdominal injury. The absence of abdominal tenderness to palpation does not rule out an intra-abdominal injury (summary LR, 0.61; 95% CI, 0.46-0.80). The presence of intraperitoneal fluid or organ injury on bedside ultrasound assessment is more accurate than any history and physical examination findings (adjusted summary LR, 30; 95% CI, 20-46); conversely, a normal ultrasound result decreases the chance of injury detection (adjusted summary LR, 0.26; 95% CI, 0.19-0.34). Test results increasing the likelihood of intra-abdominal injury include a base deficit less than -6 mEq/L (LR, 18; 95% CI, 11-30), elevated liver transaminases (LR range, 2.5-5.2), hematuria (LR range, 3.7-4.1), anemia (LR range, 2.2-3.3), and abnormal chest radiograph (LR range, 2.5-3.8). Symptoms and signs may be most useful in combination, particularly in identification of patients who do not need further diagnostic workup. Bedside ultrasonography has the highest accuracy of all individual findings, but a normal result does not rule out an intra-abdominal injury. Combinations of clinical findings may be most useful to determine which patients do not require further evaluation, but the ideal combination of variables for identifying patients without intra-abdominal injury requires further study.

HISTOPATHOLOGICAL EVIDENCE OF REGENERATION FOLLOWING HEPATOTOXIC EFFECTS OF THE CYANOTOXIN MICROCYSTIN-LR IN THE HARDHEAD CATFISH AND GULF KILLIFISH.

EPA Science Inventory

The cyanobacterial toxin, microcystin-LR (MC-LR), causes liver damage in several freshwater fish species. The damage appears to be acute and irreversible. In the present study, two estuarine species, hardhead catfish, Arius felis, and gulf killifish, Fundulus grandis, were inject...

Hepatotoxicity of Microcystin-LR in Fed and Fasted Rats

DTIC Science & Technology

1990-04-20

a free radical scavenger, silymarin , prot’cted mice against MCYST-LR (MEREISH et al., 1989). One of the more dramatic changes in liver after exposure...Microcystin-LR hepatotoxicity by silymarin in mice and rats. The FASEB J. 3, A1190. MERILUOTO, J. A. 0., SANDSTROM, A., ERIKSSON, J. E., REMAUD, G

77 FR 15818 - License Renewal Interim Staff Guidance LR-ISG-2011-05: Ongoing Review of Operating Experience

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...-05: Ongoing Review of Operating Experience AGENCY: Nuclear Regulatory Commission. ACTION: Interim... License Renewal Interim Staff Guidance (LR-ISG), LR-ISG-2011-05, ``Ongoing Review of Operating Experience... industry-wide operating experience as an attribute of aging management programs used at nuclear power...

Uptake and biotransformation of pure commercial microcystin-LR versus microcystin-LR from a natural cyanobacterial bloom extract in the aquatic fungus Mucor hiemalis.

PubMed

Esterhuizen-Londt, Maranda; Hertel, Stefanie; Pflugmacher, Stephan

2017-10-01

To evaluate the remediation efficiency of Mucor hiemalis by comparing media elimination, uptake, and biotransformation of microcystin-LR with exposure to pure toxin versus a crude bloom extract. With exposure to the extract, the elimination rate of microcystin-LR from the media, which was 0.28 ng MC-LR l -1  h -1 , was significantly higher compared to that achieved with exposure to the pure toxin (0.16 ng MC-LR l -1  h -1 ) after 24 h. However, intracellular breakdown of microcystin-LR was significantly lower in the extract exposed pellets compared to the pure toxin treated fungal pellets over time. This coincided with reduced intracellular glutathione S-transferase activity with crude extract exposure which could be responsible for the detection of only the glutathione conjugate of microcystin-LR. This paper signifies the importance of using laboratory exposure scenarios which resemble conditions in nature to fully understand and evaluate remediation efficiency. There is merit in using M. hiemalis for mycoremediation of cyanotoxins in surface waters.

[Analysis of fragments of intergenome spacers of human body observed in chromosomes containing no nuclear organization].

PubMed

Kupriyanova, N S; Nechvolodov, K K; Korsunenko, A V

2014-01-01

Tandem repetitions of rDNA provide so-called nuclear organizations (NOR). On the other hand, rDNA-structures are observed in some NOR chromosomes. It was demonstrated that, in addition to ribosome biogenesis, nucleoli provided a number of functions: cell cycle regulation, stress-induced response, transcription regulation, which often induced cell cascades. The mechanisms of the induction of rDNA segments in NOR chromosomes are obscure and require further research. About 1/3 repetitions are associated with nucleoli and SINE/Alu repetitions, homogeneous repetition, and tandem repetition. Perhaps, relative position of nucleoli and chromosomes may facilitate/prevent interaction of chromosomes with rDNA clusters. The variability of two larger repetitions in the central part of rMGS, LR1, and LR2 similar by -90% and separated by several hundred pairs of bases from each other was studied in our previous works. This work was devoted to the search for the LR1-LR2 segments in other chromosomes, characterization of their terminal tips at rupture points and genome areas of incorporation of the LR1-LR2 segments.

Association of swine leukocyte antigen class II haplotypes and immune-related traits in a swine line selected for resistance to mycoplasmal pneumonia.

PubMed

Ando, Asako; Shigenari, Atsuko; Kojima-Shibata, Chihiro; Nakajoh, Mitsuru; Suzuki, Keiichi; Kitagawa, Hitoshi; Shiina, Takashi; Inoko, Hidetoshi; Uenishi, Hirohide

2016-10-01

By selective breeding for five generations, a Landrace line has been recently established to improve resistance to mycoplasmal pneumonia of swine (MPS), daily gain (DG), back fat thickness (BF), and plasma cortisol concentrations (COR). To clarify the involvement of swine leukocyte antigen (SLA) polymorphisms in the selection process, we investigated possible associations of 11 SLA-class II haplotypes with selected traits or immune parameters. Pigs with the low-resolution SLA haplotype Lr-0.23 or Lr-0.13, which increased in frequency with the passage of generations, had less severe pathological lesions of MPS, increased leukocyte phagocytic activity, and higher white blood cell counts. In contrast, Lr-0.12 and Lr-0.2, which decreased in subsequent generations, were weakly associated with more severe pathological lesions of MPS. Therefore, in the studied Landrace line, the Lr-0.23 and Lr-0.13 haplotypes are potentially useful genetic markers for selecting and breeding animals with less severe pathological lesions of MPS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluating practical vs. theoretical inspection system capability with a new programmed defect test mask designed for 3X and 4X technology nodes

NASA Astrophysics Data System (ADS)

Glasser, Joshua; Pratt, Tim

2008-10-01

Programmed defect test masks serve the useful purpose of evaluating inspection system sensitivity and capability. It is widely recognized that when evaluating inspection system capability, it is important to understand the actual sensitivity of the inspection system in production; yet unfortunately we have observed that many test masks are a more accurate judge of theoretical sensitivity rather than real-world usable capability. Use of ineffective test masks leave the purchaser of inspection equipment open to the risks of over-estimating the capability of their inspection solution and overspecifying defect sensitivity to their customers. This can result in catastrophic yield loss for device makers. In this paper we examine some of the lithography-related technology advances which place an increasing burden on mask inspection complexity, such as MEEF, defect printability estimation, aggressive OPC, double patterning, and OPC jogs. We evaluate the key inspection system component contributors to successful mask inspection, including what can "go wrong" with these components. We designed and fabricated a test mask which both (a) more faithfully represents actual production use cases; and (b) stresses the key components of the inspection system. This mask's patterns represent 32nm, 36nm, and 45nm logic and memory technology including metal and poly like background patterns with programmed defects. This test mask takes into consideration requirements of advanced lithography, such as MEEF, defect printability, assist features, nearly-repetitive patterns, and data preparation. This mask uses patterns representative of 32nm, 36nm, and 45nm logic, flash, and DRAM technology. It is specifically designed to have metal and poly like background patterns with programmed defects. The mask is complex tritone and was designed for annular immersion lithography.

Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study.

PubMed

Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

2015-06-01

Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and 'relaxed' after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal.

Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study1

PubMed Central

Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

2015-01-01

Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and ‘relaxed’ after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal. PMID:26089755

Pattern formation in rotating Bénard convection

NASA Astrophysics Data System (ADS)

Fantz, M.; Friedrich, R.; Bestehorn, M.; Haken, H.

1992-12-01

Using an extension of the Swift-Hohenberg equation we study pattern formation in the Bénard experiment close to the onset of convection in the case of rotating cylindrical fluid containers. For small Taylor numbers we emphasize the existence of slowly rotating patterns and describe behaviour exhibiting defect motion. Finally, we study pattern formation close to the Küppers-Lortz instability. The instability is nucleated at defects and proceeds through front propagation into the bulk patterns.

The Impact of Pre-Hospital Administration of Lactated Ringer's Solution versus Normal Saline in Patients with Traumatic Brain Injury

PubMed Central

Rowell, Susan E.; Barbosa, Ronald R.; Watters, Jennifer M.; Bulger, Eileen M.; Holcomb, John B.; Cohen, Mitchell J.; Rahbar, Mohammad H.; Fox, Erin E.; Schreiber, Martin A.

2016-01-01

Abstract Lactated Ringer's (LR) and normal saline (NS) are both used for resuscitation of injured patients. NS has been associated with increased resuscitation volume, blood loss, acidosis, and coagulopathy compared with LR. We sought to determine if pre-hospital LR is associated with improved outcome compared with NS in patients with and without traumatic brain injury (TBI). We included patients receiving pre-hospital LR or NS from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients with TBI (Abbreviated Injury Scale [AIS] head ≥3) and without TBI (AIS head ≤2) were compared. Cox proportional hazards models including Injury Severity Score (ISS), AIS head, AIS extremity, age, fluids, intubation status, and hospital site were generated for prediction of mortality. Linear regression models were generated for prediction of red blood cell (RBC) and crystalloid requirement, and admission biochemical/physiological parameters. Seven hundred ninety-one patients received either LR (n = 117) or NS (n = 674). Median ISS, AIS head, AIS extremity, and pre-hospital fluid volume were higher in TBI and non-TBI patients receiving LR compared with NS (p < 0.01). In patients with TBI (n = 308), LR was associated with higher adjusted mortality compared with NS (hazard rate [HR] = 1.78, confidence interval [CI] 1.04–3.04, p = 0.035). In patients without TBI (n = 483), no difference in mortality was demonstrated (HR = 1.49, CI 0.757–2.95, p = 0.247). Fluid type had no effect on admission biochemical or physiological parameters, 6-hour RBC, or crystalloid requirement in either group. LR was associated with increased mortality compared with NS in patients with TBI. These results underscore the need for a prospective randomized trial comparing pre-hospital LR with NS in patients with TBI. PMID:26914721

A double-blind randomized study comparing the association of Retinol and LR2412 with tretinoin 0.025% in photoaged skin.

PubMed

Bouloc, Anne; Vergnanini, Andre Luiz; Issa, Maria Claudia

2015-03-01

Topical tretinoin is considered the gold standard to treat photoaged skin, but it is associated with side effects and only available upon prescription. To compare the efficacy, tolerance, and perception of a fixed proprietary combination (Retinol 0.2%/LR2412 2%) vs. tretinoin 0.025% cream in women with photoaged skin. In this randomized, parallel, double-blind, controlled clinical study, women applied to the entire face for 3 months in the morning a SPF 50 sunscreen and in the evening either the association of Retinol 0.2%/LR2412 2% or tretinoin 0.025%. Clinical and instrumental parameters were assessed at days 0, 28, 56, and 84. Subject perception of the efficacy, tolerance and cosmeticity of the tested products were assessed at days 28, 56, and 84. A total of 120 women (60 to Retinol 0.2%/LR2412 2% cream and 60 to tretinoin 0.025% cream) were included in the study. Both products improved considerably wrinkles, mottled pigmentation, pores, and global photodamage. No statistically significant differences were noted between Retinol 0.2%/LR2412 2% cream and tretinoin 0.025% cream. Adverse effects were mostly graded mild. Overall, Retinol 0.2%/LR2412 2% cream was better tolerated than tretinoin 0.025% cream. At all visits, subject perception of the association of Retinol 0.2%/LR2412 2% was either comparable to or better than tretinoin 0.025% cream. The treatment outcome of Retinol 0.2%/LR2412 2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results were not statistically different. Furthermore, Retinol 0.2%/LR2412 2% cream is better tolerated and better perceived by women used to rejuvenation procedures. © 2015 The Authors Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

Greater power and computational efficiency for kernel-based association testing of sets of genetic variants

PubMed Central

Lippert, Christoph; Xiang, Jing; Horta, Danilo; Widmer, Christian; Kadie, Carl; Heckerman, David; Listgarten, Jennifer

2014-01-01

Motivation: Set-based variance component tests have been identified as a way to increase power in association studies by aggregating weak individual effects. However, the choice of test statistic has been largely ignored even though it may play an important role in obtaining optimal power. We compared a standard statistical test—a score test—with a recently developed likelihood ratio (LR) test. Further, when correction for hidden structure is needed, or gene–gene interactions are sought, state-of-the art algorithms for both the score and LR tests can be computationally impractical. Thus we develop new computationally efficient methods. Results: After reviewing theoretical differences in performance between the score and LR tests, we find empirically on real data that the LR test generally has more power. In particular, on 15 of 17 real datasets, the LR test yielded at least as many associations as the score test—up to 23 more associations—whereas the score test yielded at most one more association than the LR test in the two remaining datasets. On synthetic data, we find that the LR test yielded up to 12% more associations, consistent with our results on real data, but also observe a regime of extremely small signal where the score test yielded up to 25% more associations than the LR test, consistent with theory. Finally, our computational speedups now enable (i) efficient LR testing when the background kernel is full rank, and (ii) efficient score testing when the background kernel changes with each test, as for gene–gene interaction tests. The latter yielded a factor of 2000 speedup on a cohort of size 13 500. Availability: Software available at http://research.microsoft.com/en-us/um/redmond/projects/MSCompBio/Fastlmm/. Contact: heckerma@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25075117

Validation of the WristOx 3100 oximeter for the diagnosis of sleep apnea/hypopnea syndrome.

PubMed

Nigro, Carlos Alberto; Aimaretti, Silvia; Gonzalez, Sergio; Rhodius, Edgardo

2009-05-01

To evaluate the diagnostic accuracy of the Nonin WristOx 3100 and its software (nVision 5.0) in patients with suspicion of sleep apnea/hypopnea syndrome (SAHS). All participants (168) had the oximetry and polysomnography simultaneously. The two recordings were interpreted blindly. The software calculated: adjusted O(2) desaturation index [ADI]-mean number of O(2) desaturation per hour of total recording analyzed time of > or = 2%, 3%, 4%, 5%, and 6% (ADI2, 3, 4, 5, and 6) and AT90-accumulated time at SO(2) < 90%. The ADI2, 3, 4, 5, and 6 and the AT90 cutoff points that better discriminated between subjects with or without SAHS arose from the receiver operating characteristic curve analysis. The sensitivity (S), specificity (E), and positive and negative likelihood ratio (LR+, LR-) for the different thresholds for ADI were calculated. One hundred and fifty-four patients were included (119 men, mean age 51, median apnea/hypopnea index [AHI] 14, median body mass index [BMI] 28.3 kg/m(2)). The best cutoff points of ADI were: SAHS = AHI > or = 5: ADI2 > 19.3 (S 89%, E 94%, LR+ 15.5 LR- 0.11); SAHS =AHI > or = 10: ADI3 > 10.5 (S 88%, E 94%, LR+ 15 LR- 0.12); SAHS = AHI > or = 15: ADI3 > 13.4 (S 88%, E 90%, LR+ 8.9, LR- 0.14). AT90 had the lowest diagnosis accuracy. An ADI2 < or = 12.2 excluded SAHS (AHI > or = 5 and 10; S 100%, LR- 0) and ADI3 > 4.3 (AHI > or = 5 and 10) or 32 (AHI > or = 15) confirmed SAHS (E 100%). A negative oximetry defined as ADI2 < or = 12.2 excluded SAHS defined as AHI > or = 5 or 10 with a sensitivity and negative likelihood ratio of 100% and 0%, respectively. Furthermore, a positive oximetry defined as an ADI3 > 32 (SAHS = AHI > or = 15) had a specificity of 100% to confirm the pathology.

Greater power and computational efficiency for kernel-based association testing of sets of genetic variants.

PubMed

Lippert, Christoph; Xiang, Jing; Horta, Danilo; Widmer, Christian; Kadie, Carl; Heckerman, David; Listgarten, Jennifer

2014-11-15

Set-based variance component tests have been identified as a way to increase power in association studies by aggregating weak individual effects. However, the choice of test statistic has been largely ignored even though it may play an important role in obtaining optimal power. We compared a standard statistical test-a score test-with a recently developed likelihood ratio (LR) test. Further, when correction for hidden structure is needed, or gene-gene interactions are sought, state-of-the art algorithms for both the score and LR tests can be computationally impractical. Thus we develop new computationally efficient methods. After reviewing theoretical differences in performance between the score and LR tests, we find empirically on real data that the LR test generally has more power. In particular, on 15 of 17 real datasets, the LR test yielded at least as many associations as the score test-up to 23 more associations-whereas the score test yielded at most one more association than the LR test in the two remaining datasets. On synthetic data, we find that the LR test yielded up to 12% more associations, consistent with our results on real data, but also observe a regime of extremely small signal where the score test yielded up to 25% more associations than the LR test, consistent with theory. Finally, our computational speedups now enable (i) efficient LR testing when the background kernel is full rank, and (ii) efficient score testing when the background kernel changes with each test, as for gene-gene interaction tests. The latter yielded a factor of 2000 speedup on a cohort of size 13 500. Software available at http://research.microsoft.com/en-us/um/redmond/projects/MSCompBio/Fastlmm/. heckerma@microsoft.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

COMPUTERIZED EXPERT SYSTEM FOR EVALUATION OF AUTOMATED VISUAL FIELDS FROM THE ISCHEMIC OPTIC NEUROPATHY DECOMPRESSION TRIAL: METHODS, BASELINE FIELDS, AND SIX-MONTH LONGITUDINAL FOLLOW-UP

PubMed Central

Feldon, Steven E

2004-01-01

ABSTRACT Purpose To validate a computerized expert system evaluating visual fields in a prospective clinical trial, the Ischemic Optic Neuropathy Decompression Trial (IONDT). To identify the pattern and within-pattern severity of field defects for study eyes at baseline and 6-month follow-up. Design Humphrey visual field (HVF) change was used as the outcome measure for a prospective, randomized, multi-center trial to test the null hypothesis that optic nerve sheath decompression was ineffective in treating nonarteritic anterior ischemic optic neuropathy and to ascertain the natural history of the disease. Methods An expert panel established criteria for the type and severity of visual field defects. Using these criteria, a rule-based computerized expert system interpreted HVF from baseline and 6-month visits for patients randomized to surgery or careful follow-up and for patients who were not randomized. Results A computerized expert system was devised and validated. The system was then used to analyze HVFs. The pattern of defects found at baseline for patients randomized to surgery did not differ from that of patients randomized to careful follow-up. The most common pattern of defect was a superior and inferior arcuate with central scotoma for randomized eyes (19.2%) and a superior and inferior arcuate for nonrandomized eyes (30.6%). Field patterns at 6 months and baseline were not different. For randomized study eyes, the superior altitudinal defects improved (P = .03), as did the inferior altitudinal defects (P = .01). For nonrandomized study eyes, only the inferior altitudinal defects improved (P = .02). No treatment effect was noted. Conclusions A novel rule-based expert system successfully interpreted visual field defects at baseline of eyes enrolled in the IONDT. PMID:15747764

Coater/developer based techniques to improve high-resolution EUV patterning defectivity

NASA Astrophysics Data System (ADS)

Hontake, Koichi; Huli, Lior; Lemley, Corey; Hetzer, Dave; Liu, Eric; Ko, Akiteru; Kawakami, Shinichiro; Shimoaoki, Takeshi; Hashimoto, Yusaku; Tanaka, Koichiro; Petrillo, Karen; Meli, Luciana; De Silva, Anuja; Xu, Yongan; Felix, Nelson; Johnson, Richard; Murray, Cody; Hubbard, Alex

2017-10-01

Extreme ultraviolet lithography (EUVL) technology is one of the leading candidates under consideration for enabling the next generation of devices, for 7nm node and beyond. As the focus shifts to driving down the 'effective' k1 factor and enabling the full scaling entitlement of EUV patterning, new techniques and methods must be developed to reduce the overall defectivity, mitigate pattern collapse, and eliminate film-related defects. In addition, CD uniformity and LWR/LER must be improved in terms of patterning performance. Tokyo Electron Limited (TEL™) and IBM Corporation are continuously developing manufacturing quality processes for EUV. In this paper, we review the ongoing progress in coater/developer based processes (coating, developing, baking) that are required to enable EUV patterning.

Classification and printability of EUV mask defects from SEM images

NASA Astrophysics Data System (ADS)

Cho, Wonil; Price, Daniel; Morgan, Paul A.; Rost, Daniel; Satake, Masaki; Tolani, Vikram L.

2017-10-01

Classification and Printability of EUV Mask Defects from SEM images EUV lithography is starting to show more promise for patterning some critical layers at 5nm technology node and beyond. However, there still are many key technical obstacles to overcome before bringing EUV Lithography into high volume manufacturing (HVM). One of the greatest obstacles is manufacturing defect-free masks. For pattern defect inspections in the mask-shop, cutting-edge 193nm optical inspection tools have been used so far due to lacking any e-beam mask inspection (EBMI) or EUV actinic pattern inspection (API) tools. The main issue with current 193nm inspection tools is the limited resolution for mask dimensions targeted for EUV patterning. The theoretical resolution limit for 193nm mask inspection tools is about 60nm HP on masks, which means that main feature sizes on EUV masks will be well beyond the practical resolution of 193nm inspection tools. Nevertheless, 193nm inspection tools with various illumination conditions that maximize defect sensitivity and/or main-pattern modulation are being explored for initial EUV defect detection. Due to the generally low signal-to-noise in the 193nm inspection imaging at EUV patterning dimensions, these inspections often result in hundreds and thousands of defects which then need to be accurately reviewed and dispositioned. Manually reviewing each defect is difficult due to poor resolution. In addition, the lack of a reliable aerial dispositioning system makes it very challenging to disposition for printability. In this paper, we present the use of SEM images of EUV masks for higher resolution review and disposition of defects. In this approach, most of the defects detected by the 193nm inspection tools are first imaged on a mask SEM tool. These images together with the corresponding post-OPC design clips are provided to KLA-Tencor's Reticle Decision Center (RDC) platform which provides ADC (Automated Defect Classification) and S2A (SEM-to-Aerial printability) analysis of every defect. First, a defect-free or reference mask SEM is rendered from the post-OPC design, and the defective signature is detected from the defect-reference difference image. These signatures help assess the true nature of the defect as evident in e-beam imaging; for example, excess or missing absorber, line-edge roughness, contamination, etc. Next, defect and reference contours are extracted from the grayscale SEM images and fed into the simulation engine with an EUV scanner model to generate corresponding EUV defect and reference aerial images. These are then analyzed for printability and dispositioned using an Aerial Image Analyzer (AIA) application to automatically measure and determine the amount of CD errors. Thus by integrating EUV ADC and S2A applications together, every defect detection is characterized for its type and printability which is essential for not only determining which defects to repair, but also in monitoring the performance of EUV mask process tools. The accuracy of the S2A print modeling has been verified with other commercially-available simulators, and will also be verified with actual wafer print results. With EUV lithography progressing towards volume manufacturing at 5nm technology, and the likelihood of EBMI inspectors approaching the horizon, the EUV ADC-S2A system will continue serving an essential role of dispositioning defects off e-beam imaging.

[Congenital talipes equinovarus--family occurrence].

PubMed

Kołecka, Ewa; Niedzielski, Kryspin Ryszard; Cukras, Zbigniew; Piotrowicz, Małgorzata

2011-01-01

Although congenital talipes equinovarus (CTEV) is one of the most frequently occurring congenital defects of locomotor organs, its ethiopathogenesis is still not fully known. Amongst the others, the inheritance patterns of that defect are not fully known, and that restricts genetic therapeutics and development of new treatment technologies. The aim of this study was analysis of family lineages of 205 children with CTEV (298 feet) treated at our centre in the years 1998-2008. The family occurrence of CTEV was found in 16 cases (8% of analysed group). 6 lineages, in which CTEV occurred in successive generations, were analysed in detail. Particularly interesting is the lineage of the family 1, in which the defect occurred in three successive generations. In case of that family, an autosomal dominant inheritance pattern is possible. Previously that pattern of CTEV inheritance was described only for isolated populations of Polynesians. In own material the family occurrence of CTEV was found to be less frequent than in bibliographic references. The defect occurred twice as often in boys, while the severe form was more frequently observed in girls, and that is consisted with data in the available bibliography. The analysis of presented lineages of families with CTEV did not allow unambiguous defining of the inheritance pattern for that defect. To confirm the autosomal dominant pattern of CTEV inheritance in the family in which the defect occurred in three successive generations, genetic tests would be necessary.

Local recurrence after laparoscopic radiofrequency ablation of malignant liver tumors: Results of a contemporary series.

PubMed

Takahashi, Hideo; Akyuz, Muhammet; Aksoy, Erol; Karabulut, Koray; Berber, Eren

2017-06-01

The aims of this study were to determine the incidence of Local recurrence (LR) in patients at long-term follow-up after laparoscopic RFA (LRFA) and also to determine the risk factors for LR from a contemporary series. Patients undergoing LRFA between 2005 and 2014 by a single surgeon were reviewed. Demographic and perioperative data were analyzed from a prospective database. LRFA was performed on 316 patients with 901 lesions. Median follow-up was 25 months, with 76% of whom completed at least one year of follow-up. The LR rate was 18.4%. The LR in patients followed for less than 12 months was 13.8%, 20.3% for 12 months, and 19.7% for 18 months (P = 0.02). One-fourth of the LRs developed after the 1st year. Morbidity was 8.9% and mortality 0.3%. Tumor type, size, ablation margin, and surgeon experience affected LR, with tumor type, size, and ablation margin being independent. This study shows that 14% of malignant liver tumors will develop LR within a year after LRFA. Additional 4% of the lesions will demonstrate recurrence within 1 cm of the ablation zone, mostly as part of a multifocal recurrence. Ablation margin is the only parameter that the surgeon can manipulate to decrease LR. © 2017 Wiley Periodicals, Inc.

Bioaccumulation and harmful effects of microcystin-LR in the aquatic plants Lemna minor and Wolffia arrhiza and the filamentous alga Chladophora fracta.

PubMed

Mitrovic, Simon M; Allis, Orla; Furey, Ambrose; James, Kevin J

2005-07-01

Although the toxic effects of cyanotoxins on animals have been examined extensively, little research has focused on their effects on higher plants and macroalgae, and the potential for bioaccumulation in the food web through plants. Two aquatic plants, Lemna minor and Wolffia arrhiza, and one filamentous alga, Chladophora fracta, were exposed to the cyanotoxin microcystin-LR. Growth of L. minor (as weight and frond number) and root length were significantly reduced and peroxidase activity was significantly increased after 5 days of exposure to concentrations of 10 and 20 microg mL(-1) microcystin-LR. Growth of W. arrhiza (as frond number) was significantly reduced after 5 days of exposure to 15 microg mL(-1) microcystin-LR. Growth and peroxidase activity of C. fracta were not affected by microcystin-LR at concentrations up to 10 microg mL(-1). L. minor also accumulated microcystin-LR up to a concentration of 0.288 +/- 0.009 ng mg(-1) wet wt. plant material over the 5 days of the experiment, equivalent to an accumulation rate of 0.058 ng mg(-1) day(-1). C. fracta accumulated a microcystin-LR concentration of 0.042 +/- 0.015 ng mg(-1) wet wt. plant material over the 5 days of the experiment, equivalent to an accumulation rate of 0.008 ng mg(-1) day(-1).

Cell chirality: its origin and roles in left–right asymmetric development

PubMed Central

Inaki, Mikiko; Liu, Jingyang

2016-01-01

An item is chiral if it cannot be superimposed on its mirror image. Most biological molecules are chiral. The homochirality of amino acids ensures that proteins are chiral, which is essential for their functions. Chirality also occurs at the whole-cell level, which was first studied mostly in ciliates, single-celled protozoans. Ciliates show chirality in their cortical structures, which is not determined by genetics, but by ‘cortical inheritance’. These studies suggested that molecular chirality directs whole-cell chirality. Intriguingly, chirality in cellular structures and functions is also found in metazoans. In Drosophila, intrinsic cell chirality is observed in various left–right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. In other invertebrates, such as snails and Caenorhabditis elegans, blastomere chirality is responsible for subsequent LR asymmetric development. Various cultured cells of vertebrates also show intrinsic chirality in their cellular behaviours and intracellular structural dynamics. Thus, cell chirality may be a general property of eukaryotic cells. In Drosophila, cell chirality drives the LR asymmetric development of individual organs, without establishing the LR axis of the whole embryo. Considering that organ-intrinsic LR asymmetry is also reported in vertebrates, this mechanism may contribute to LR asymmetric development across phyla. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821533

Cell chirality: its origin and roles in left-right asymmetric development.

PubMed

Inaki, Mikiko; Liu, Jingyang; Matsuno, Kenji

2016-12-19

An item is chiral if it cannot be superimposed on its mirror image. Most biological molecules are chiral. The homochirality of amino acids ensures that proteins are chiral, which is essential for their functions. Chirality also occurs at the whole-cell level, which was first studied mostly in ciliates, single-celled protozoans. Ciliates show chirality in their cortical structures, which is not determined by genetics, but by 'cortical inheritance'. These studies suggested that molecular chirality directs whole-cell chirality. Intriguingly, chirality in cellular structures and functions is also found in metazoans. In Drosophila, intrinsic cell chirality is observed in various left-right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. In other invertebrates, such as snails and Caenorhabditis elegans, blastomere chirality is responsible for subsequent LR asymmetric development. Various cultured cells of vertebrates also show intrinsic chirality in their cellular behaviours and intracellular structural dynamics. Thus, cell chirality may be a general property of eukaryotic cells. In Drosophila, cell chirality drives the LR asymmetric development of individual organs, without establishing the LR axis of the whole embryo. Considering that organ-intrinsic LR asymmetry is also reported in vertebrates, this mechanism may contribute to LR asymmetric development across phyla.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Authors.

LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

PubMed Central

Figarola, James L.; Singhal, Jyotsana; Rahbar, Samuel; Awasthi, Sanjay

2014-01-01

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound known to induce cellular injury and cytoxicity, including apoptosis in vascular cells. Vascular endothelial cell apoptosis has been implicated in the pathophysiology and progression of atherosclerosis. We investigated whether the advanced glycation end-product inhibitor LR-90 could prevent MGO-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). HUVECs were pre-treated with LR-90 and then stimulated with MGO. Cell morphology, cytotoxicity and apoptosis were evaluated by light microscopy, MTT assay, and Annexin V-FITC and propidium iodide double staining, respectively. Levels of Bax, Bcl-2, cytochrome c, mitogen-activated protein kinases (MAPKs) and caspase activities were assessed by Western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. LR-90 dose-dependently prevented MGO-associated HUVEC cytotoxicity and apoptotic biochemical changes such as loss of MMP, increased Bax/Bcl-2 protein ratio, mitochondrial cytochrome c release and activation of caspase-3 and 9. Additionally, LR-90 blocked intracellular ROS formation and MAPK (p44/p42, p38, JNK) activation, though the latter seem to be not directly involved in MGO-induced HUVEC apoptosis. LR-90 prevents MGO-induced HUVEC apoptosis by inhibiting ROS and associated mitochondrial-dependent apoptotic signaling cascades, suggesting that LR-90 possess cytoprotective ability which could be beneficial in prevention of diabetic related-atherosclerosis. PMID:24615331

Effects of laser remelting on microstructures and immersion corrosion performance of arc sprayed Al coating in 3.5% NaCl solution

NASA Astrophysics Data System (ADS)

Sun, Ze; Zhang, Donghui; Yan, Baoxu; Kong, Dejun

2018-02-01

An arc sprayed aluminum (Al) coating on S355 steel was processed using a laser remelting (LR). The microstructures, chemical element composition, and phases of the obtained Al coating were analyzed using a field mission scanning electronic microscope (FESEM), energy dispersive spectrometer (EDS), and X-ray diffractometer (XRD), respectively, and the residual stresses were measured using an X-ray diffraction stress tester. The immersion corrosion tests and potentiodynamic polarization of Al coating in 3.5% NaCl solution were performed to investigate the effects of LR on its immersion corrosion behaviors, and the corrosion mechanism of Al coating was also discussed. The results show that the arc sprayed Al coating is composed of Al phase, while that by LR is composed of Al-Fe and AlO4FeO6 phases, and the porosities and cracks in the arc sprayed Al coating are eliminated by LR, The residual stress of arc sprayed Al coating is -5.6 ± 18 MPa, while that after LR is 137.9 ± 12 MPa, which deduces the immersion corrosion resistance of Al coating. The corrosion mechanism of arc sprayed Al coating is pitting corrosion and crevice corrosion, while that by LR is uniform corrosion and pitting corrosion. The corrosion potential of arc sprayed Al coating by LR shifts positively, which improves its immersion corrosion resistance.

Low rank alternating direction method of multipliers reconstruction for MR fingerprinting.

PubMed

Assländer, Jakob; Cloos, Martijn A; Knoll, Florian; Sodickson, Daniel K; Hennig, Jürgen; Lattanzi, Riccardo

2018-01-01

The proposed reconstruction framework addresses the reconstruction accuracy, noise propagation and computation time for magnetic resonance fingerprinting. Based on a singular value decomposition of the signal evolution, magnetic resonance fingerprinting is formulated as a low rank (LR) inverse problem in which one image is reconstructed for each singular value under consideration. This LR approximation of the signal evolution reduces the computational burden by reducing the number of Fourier transformations. Also, the LR approximation improves the conditioning of the problem, which is further improved by extending the LR inverse problem to an augmented Lagrangian that is solved by the alternating direction method of multipliers. The root mean square error and the noise propagation are analyzed in simulations. For verification, in vivo examples are provided. The proposed LR alternating direction method of multipliers approach shows a reduced root mean square error compared to the original fingerprinting reconstruction, to a LR approximation alone and to an alternating direction method of multipliers approach without a LR approximation. Incorporating sensitivity encoding allows for further artifact reduction. The proposed reconstruction provides robust convergence, reduced computational burden and improved image quality compared to other magnetic resonance fingerprinting reconstruction approaches evaluated in this study. Magn Reson Med 79:83-96, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Does This Older Adult With Lower Extremity Pain Have the Clinical Syndrome of Lumbar Spinal Stenosis?

PubMed Central

Suri, Pradeep; Rainville, James; Kalichman, Leonid; Katz, Jeffrey N.

2012-01-01

Context The clinical syndrome of lumbar spinal stenosis (LSS) is a common diagnosis in older adults presenting with lower extremity pain. Objective To systematically review the accuracy of the clinical examination for the diagnosis of the clinical syndrome of LSS. Data Sources MEDLINE, EMBASE, and CINAHL searches of articles published from January 1966 to September 2010. Study Selection Studies were included if they contained adequate data on the accuracy of the history and physical examination for diagnosing the clinical syndrome of LSS, using a reference standard of expert opinion with radiographic or anatomic confirmation. Data Extraction Two authors independently reviewed each study to determine eligibility, extract data, and appraise levels of evidence. Data Synthesis Four studies evaluating 741 patients were identified. Among patients with lower extremity pain, the likelihood of the clinical syndrome of LSS was increased for individuals older than 70 years (likelihood ratio [LR], 2.0; 95% confidence interval [CI], 1.6–2.5), and was decreased for those younger than 60 years (LR, 0.40; 95% CI, 0.29–0.57). The most useful symptoms for increasing the likelihood of the clinical syndrome of LSS were having no pain when seated (LR, 7.4; 95% CI, 1.9–30), improvement of symptoms when bending forward (LR, 6.4; 95% CI, 4.1–9.9), the presence of bilateral buttock or leg pain (LR, 6.3; 95% CI, 3.1–13), and neurogenic claudication (LR, 3.7; 95% CI, 2.9–4.8). Absence of neurogenic claudication (LR, 0.23; 95% CI, 0.17–0.31) decreased the likelihood of the diagnosis. A wide-based gait (LR, 13; 95% CI, 1.9–95) and abnormal Romberg test result (LR, 4.2; 95% CI, 1.4–13) increased the likelihood of the clinical syndrome of LSS. A score of 7 or higher on a diagnostic support tool including history and examination findings increased the likelihood of the clinical syndrome of LSS (LR, 3.3; 95% CI, 2.7–4.0), while a score lower than 7 made the diagnosis much less likely (LR, 0.10; 95% CI, 0.06–0.16). Conclusions The diagnosis of the clinical syndrome of LSS requires the appropriate clinical picture and radiographic findings. Absence of pain when seated and improvement of symptoms when bending forward are the most useful individual findings. Combinations of findings are most useful for identifying patients who are unlikely to have the diagnosis. PMID:21156951

A comparison of logistic regression analysis and an artificial neural network using the BI-RADS lexicon for ultrasonography in conjunction with introbserver variability.

PubMed

Kim, Sun Mi; Han, Heon; Park, Jeong Mi; Choi, Yoon Jung; Yoon, Hoi Soo; Sohn, Jung Hee; Baek, Moon Hee; Kim, Yoon Nam; Chae, Young Moon; June, Jeon Jong; Lee, Jiwon; Jeon, Yong Hwan

2012-10-01

To determine which Breast Imaging Reporting and Data System (BI-RADS) descriptors for ultrasound are predictors for breast cancer using logistic regression (LR) analysis in conjunction with interobserver variability between breast radiologists, and to compare the performance of artificial neural network (ANN) and LR models in differentiation of benign and malignant breast masses. Five breast radiologists retrospectively reviewed 140 breast masses and described each lesion using BI-RADS lexicon and categorized final assessments. Interobserver agreements between the observers were measured by kappa statistics. The radiologists' responses for BI-RADS were pooled. The data were divided randomly into train (n = 70) and test sets (n = 70). Using train set, optimal independent variables were determined by using LR analysis with forward stepwise selection. The LR and ANN models were constructed with the optimal independent variables and the biopsy results as dependent variable. Performances of the models and radiologists were evaluated on the test set using receiver-operating characteristic (ROC) analysis. Among BI-RADS descriptors, margin and boundary were determined as the predictors according to stepwise LR showing moderate interobserver agreement. Area under the ROC curves (AUC) for both of LR and ANN were 0.87 (95% CI, 0.77-0.94). AUCs for the five radiologists ranged 0.79-0.91. There was no significant difference in AUC values among the LR, ANN, and radiologists (p > 0.05). Margin and boundary were found as statistically significant predictors with good interobserver agreement. Use of the LR and ANN showed similar performance to that of the radiologists for differentiation of benign and malignant breast masses.

Microcystin-LR affects the hypothalamic-pituitary-inter-renal (HPI) axis in early life stages (embryos and larvae) of zebrafish.

PubMed

Chen, Liang; Wang, Yeke; Giesy, John P; Chen, Feng; Shi, Ting; Chen, Jun; Xie, Ping

2018-05-22

Frequencies and durations of blooms of cyanobacteria are increasing. Some cyanobacteria can produce cyanotoxins including microcystins (MCs). MCs are the most common toxic products of hazardous algal blooms (HABs), with the greatest potential for exposure and to cause toxicity. Recently, MCs have been shown to disrupt endocrine functions. In this study, for the first time, effects of MC-LR on the hypothalamic-pituitary-inter-renal (HPI) axis during early embryonic development (embryos/larvae) of zebrafish (Danio rerio), were investigated. Embryos/larvae of zebrafish were exposed to 1, 10, 100, or 300 μg MC-LR/L during the period of 4-168 h post-fertilization (hpf). Exposure to 300 μg MC-LR/L resulted in significantly greater concentrations of whole-body cortisol than those in controls. Expressions of genes along the HPI axis and mineralocorticoid receptor (MR-) and glucocorticoid receptor (GR-) centered gene networks were evaluated by use of quantitative real-time PCR. Expression of mRNA for crh was significantly down-regulated by exposure to 300 μg MC-LR/L, while expressions of crhbp, crhr1, and crhr2 were significantly up-regulated, relative to controls. MC-LR caused significantly lesser levels of mRNA for steroidogenic genes including hmgra, star, and cyp17, but expression of mRNA for hsd20b was significantly greater than that of controls. Treatment with MC-LR also altered profiles of transcription of MR- and GR-centered gene networks, which might result in multiple responses. Taken together, these results demonstrated that MC-LR affected the corticosteroid-endocrine system of larvae of zebrafish. This study provided valuable insights into molecular mechanisms behind potential toxicity and endocrine disruption of MCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early embryonic programming of neuronal left/right asymmetry in C. elegans.

PubMed

Poole, Richard J; Hobert, Oliver

2006-12-05

Nervous systems are largely bilaterally symmetric on a morphological level but often display striking degrees of functional left/right (L/R) asymmetry. How L/R asymmetric functional features are superimposed onto an essentially bilaterally symmetric structure and how nervous-system laterality relates to the L/R asymmetry of internal organs are poorly understood. We address these questions here by using the establishment of L/R asymmetry in the ASE chemosensory neurons of C. elegans as a paradigm. This bilaterally symmetric neuron pair is functionally lateralized in that it senses a distinct class of chemosensory cues and expresses a putative chemoreceptor family in a L/R asymmetric manner. We show that the directionality of the asymmetry of the two postmitotic ASE neurons ASE left (ASEL) and ASE right (ASER) in adults is dependent on a L-/R-symmetry-breaking event at a very early embryonic stage, the six-cell stage, which also establishes the L/R asymmetric placement of internal organs. However, the L/R asymmetry of the ASE neurons per se is dependent on an even earlier anterior-posterior (A/P) Notch signal that specifies embryonic ABa/ABp blastomere identities at the four-cell stage. This Notch signal, which functions through two T box genes, acts genetically upstream of a miRNA-controlled bistable feedback loop that regulates the L/R asymmetric gene-expression program in the postmitotic ASE cells. Our results link adult neuronal laterality to the generation of the A/P axis at the two-cell stage and raise the possibility that neural asymmetries observed across the animal kingdom are similarly established by very early embryonic interactions.

The prevalence of tarsal tunnel syndrome in patients with lumbosacral radiculopathy.

PubMed

Zheng, Chaojun; Zhu, Yu; Jiang, Jianyuan; Ma, Xiaosheng; Lu, Feizhou; Jin, Xiang; Weber, Robert

2016-03-01

Tarsal tunnel syndrome (TTS) is a painful foot condition. Lumbosacral radiculopathy (LR) may also present with symptoms occurring in TTS. However, no studies have been reported to determine the possible coexistence of these two conditions. The aim of our study was to identify the prevalence of TTS in patients with confirmed LR and to analyze the clinical and electrodiagnostic features of patients with both TTS and LR. Medial and lateral plantar nerve mixed studies, peroneal motor studies and deep peroneal sensory studies were performed in 81 normal subjects and 561 patients with LR. The Tinel's test and other provocative tests were performed in the LR patient group, and the clinical symptoms of TTS were also analyzed. The frequency of TTS was investigated in all radiculopathy group patients with different nerve root lesions. Concomitant TTS was found in 27 (4.8%) patients with LR. Abnormal results of sensory/mixed conduction tests were observed in 25/27 (92.6%) patients, and 11/27 (40.7%) patients had abnormal results of motor conduction tests. Positivity for the Tinel's test and special provocative tests was found in 15/27 (55.6%) and 17/27 (63.0%) patients, respectively. Overall, 9/27 (33.3%) patients had typical symptoms, and suspicious clinical symptoms were found in the other 14/27 (51.9%) patients. The frequency of coexisting TTS was not statistically different among the single-level L4, L5 or S1 radiculopathy, or between the single-level and multi-level radiculopathies (P > 0.05). The findings suggest that the prevalence of TTS is significant in patients with LR. Thus, more caution should be paid when diagnosing and managing patients with LR due to the possible existence of TTS, as their management strategies are quite different.

Rapid Isolation of a Single-Chain Antibody against the Cyanobacterial Toxin Microcystin-LR by Phage Display and Its Use in the Immunoaffinity Concentration of Microcystins from Water

PubMed Central

McElhiney, Jacqui; Drever, Mathew; Lawton, Linda A.; Porter, Andy J.

2002-01-01

A naïve (unimmunized) human semisynthetic phage display library was employed to isolate recombinant antibody fragments against the cyanobacterial hepatotoxin microcystin-LR. Selected antibody scFv genes were cloned into a soluble expression vector and expressed in Escherichia coli for characterization against purified microcystin-LR by competition enzyme-linked immunosorbent assay (ELISA). The most sensitive single-chain antibody (scAb) isolated was capable of detecting microcystin-LR at levels below the World Health Organization limit in drinking water (1 μg liter−1) and cross-reacted with three other purified microcystin variants (microcystin-RR, -LW, and -LF) and the related cyanotoxin nodularin. Extracts of the cyanobacterium Microcystis aeruginosa were assayed by ELISA, and quantifications of microcystins in toxic samples showed good correlation with analysis by high-performance liquid chromatography. Immobilized scAb was also used to prepare immunoaffinity columns, which were assessed for the ability to concentrate microcystin-LR from water for subsequent analysis by high-performance liquid chromatography. Anti-microcystin-LR scAb was immobilized on columns via a hexahistidine tag, ensuring maximum exposure of antigen binding sites, and the performance of the columns was evaluated by directly applying 150 ml of distilled water spiked with 4 μg of purified microcystin-LR. The procedure was simple, and a recovery rate of 94% was achieved following elution in 1 ml of 100% methanol. Large-scale, low-cost production of anti-microcystin-LR scAb in E. coli is an exciting prospect for the development of biosensors and on-line monitoring systems for microcystins and will also facilitate a range of immunoaffinity applications for the cleanup and concentration of these toxins from environmental samples. PMID:12406716

IMAGING OF BRAIN FUNCTION BASED ON THE ANALYSIS OF FUNCTIONAL CONNECTIVITY - IMAGING ANALYSIS OF BRAIN FUNCTION BY FMRI AFTER ACUPUNCTURE AT LR3 IN HEALTHY INDIVIDUALS.

PubMed

Zheng, Yu; Wang, Yuying; Lan, Yujun; Qu, Xiaodong; Lin, Kelin; Zhang, Jiping; Qu, Shanshan; Wang, Yanjie; Tang, Chunzhi; Huang, Yong

2016-01-01

This Study observed the relevant brain areas activated by acupuncture at the Taichong acupoint (LR3) and analyzed the functional connectivity among brain areas using resting state functional magnetic resonance imaging (fMRI) to explore the acupoint specificity of the Taichong acupoint. A total of 45 healthy subjects were randomly divided into the Taichong (LR3) group, sham acupuncture group and sham acupoint group. Subjects received resting state fMRI before acupuncture, after true (sham) acupuncture in each group. Analysis of changes in connectivity among the brain areas was performed using the brain functional connectivity method. The right cerebrum temporal lobe was selected as the seed point to analyze the functional connectivity. It had a functional connectivity with right cerebrum superior frontal gyrus, limbic lobe cingulate gyrus and left cerebrum inferior temporal gyrus (BA 37), inferior parietal lobule compared by before vs. after acupuncture at LR3, and right cerebrum sub-lobar insula and left cerebrum middle frontal gyrus, medial frontal gyrus compared by true vs. sham acupuncture at LR3, and right cerebrum occipital lobe cuneus, occipital lobe sub-gyral, parietal lobe precuneus and left cerebellum anterior lobe culmen by acupuncture at LR3 vs. sham acupoint. Acupuncture at LR3 mainly specifically activated the brain functional network that participates in visual function, associative function, and emotion cognition, which are similar to the features on LR3 in tradition Chinese medicine. These brain areas constituted a neural network structure with specific functions that had specific reference values for the interpretation of the acupoint specificity of the Taichong acupoint.

LumenRECON Guidewire: Pilot Study of a Novel, Nonimaging Technology for Accurate Vessel Sizing and Delivery of Therapy in Femoropopliteal Disease.

PubMed

Nair, Pradeep K; Carr, Jeffrey G; Bigelow, Brian; Bhatt, Deepak L; Berwick, Zachary C; Adams, George

2018-01-01

Proper vessel sizing during endovascular interventions is crucial to avoid adverse procedural and clinical outcomes. LumenRECON (LR) is a novel, nonimaging, 0.035-inch wire-based technology that uses the physics-based principle of Ohm's law to provide a simple, real-time luminal size while also providing a platform for therapy delivery. This study evaluated the accuracy, reliability, and safety of the LR system in patients presenting for a femoropopliteal artery intervention. This multicenter, prospective pilot study of 24 patients presenting for peripheral intervention compared LR measurements of femoropopliteal artery size to angiographic visual estimation, duplex ultrasound, quantitative angiography, and intravascular ultrasound. The primary effectiveness and safety end point was comparison against core laboratory adjudicated intravascular ultrasound values and major adverse events, respectively. Additional preclinical studies were also performed in vitro and in vivo in swine to determine the accuracy of the LR guidewire system. No intra- or postprocedure device-related adverse events occurred. A balloon or stent was successfully delivered in 12 patients (50%) over the LR wire. Differences in repeatability between successive LR measurements was 2.5±0.40% ( R 2 =0.96) with no significant bias. Differences in measurements of LR to other modalities were 0.5±1.7%, 5.0±1.8%, -1.5±2.0%, and 6.8±3.4% for intravascular ultrasound core laboratory, quantitative angiography, angiographic, and duplex ultrasound, respectively. This study demonstrates that through a physics-based principle, LR provides a real-time, safe, reproducible, and accurate vessel size of the femoropopliteal artery during intervention and can additionally serve as a conduit for therapy delivery over its wire-based platform. © 2018 American Heart Association, Inc.

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

Byun, Eui-Baek; Choi, Han-Gyu; Sung, Nak-Yun

Highlights: Black-Right-Pointing-Pointer Expressions of CD80, CD86, and MHC class I/II were inhibited by EGCG via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited LPS-induced pro-inflammatory cytokines via 67LR. Black-Right-Pointing-Pointer EGCG-treated DCs inhibited MAPKs activation and NF-{kappa}B p65 translocation via 67LR. Black-Right-Pointing-Pointer EGCG elevated the expression of the Tollip protein through 67LR in DCs. -- Abstract: Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecularmore » basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-{alpha}, interleukin [IL]-1{beta}, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor {kappa}B (NF-{kappa}B) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.« less

Actinic inspection of EUV reticles with arbitrary pattern design

NASA Astrophysics Data System (ADS)

Mochi, Iacopo; Helfenstein, Patrick; Rajeev, Rajendran; Fernandez, Sara; Kazazis, Dimitrios; Yoshitake, Shusuke; Ekinci, Yasin

2017-10-01

The re ective-mode EUV mask scanning lensless imaging microscope (RESCAN) is being developed to provide actinic mask inspection capabilities for defects and patterns with high resolution and high throughput, for 7 nm node and beyond. Here we, will report on our progress and present the results on programmed defect detection on random, logic-like patterns. The defects we investigated range from 200 nm to 50 nm size on the mask. We demonstrated the ability of RESCAN to detect these defects in die-to-die and die-to-database mode with a high signal to noise ratio. We also describe future plans for the upgrades to increase the resolution, the sensitivity, and the inspection speed of the demo tool.

Pattern of congenital heart diseases in Rwandan children with genetic defects

PubMed Central

Teteli, Raissa; Uwineza, Annette; Butera, Yvan; Hitayezu, Janvier; Murorunkwere, Seraphine; Umurerwa, Lamberte; Ndinkabandi, Janvier; Hellin, Anne-Cécile; Jamar, Mauricette; Caberg, Jean-Hubert; Muganga, Narcisse; Mucumbitsi, Joseph; Rusingiza, Emmanuel Kamanzi; Mutesa, Leon

2014-01-01

Introduction Congenital heart diseases (CHD) are commonly associated with genetic defects. Our study aimed at determining the occurrence and pattern of CHD association with genetic defects among pediatric patients in Rwanda. Methods A total of 125 patients with clinical features suggestive of genetic defects were recruited. Echocardiography and standard karyotype studies were performed in all patients. Results CHDs were detected in the majority of patients with genetic defects. The commonest isolated CHD was ventricular septal defect found in many cases of Down syndrome. In total, chromosomal abnormalities represented the majority of cases in our cohort and were associated with various types of CHDs. Conclusion Our findings showed that CHDs are common in Rwandan pediatric patients with genetic defects. These results suggest that a routine echocardiography assessment combined with systematic genetic investigations including standard karyotype should be mandatory in patients presenting characteristic clinical features in whom CHD is suspected to be associated with genetic defect. PMID:25722758

Method for characterizing mask defects using image reconstruction from X-ray diffraction patterns

DOEpatents

Hau-Riege, Stefan Peter [Fremont, CA

2007-05-01

The invention applies techniques for image reconstruction from X-ray diffraction patterns on the three-dimensional imaging of defects in EUVL multilayer films. The reconstructed image gives information about the out-of-plane position and the diffraction strength of the defect. The positional information can be used to select the correct defect repair technique. This invention enables the fabrication of defect-free (since repaired) X-ray Mo--Si multilayer mirrors. Repairing Mo--Si multilayer-film defects on mask blanks is a key for the commercial success of EUVL. It is known that particles are added to the Mo--Si multilayer film during the fabrication process. There is a large effort to reduce this contamination, but results are not sufficient, and defects continue to be a major mask yield limiter. All suggested repair strategies need to know the out-of-plane position of the defects in the multilayer.

Simulation of pattern and defect detection in periodic amplitude and phase structures using photorefractive four-wave mixing

NASA Astrophysics Data System (ADS)

Nehmetallah, Georges; Banerjee, Partha; Khoury, Jed

2015-03-01

The nonlinearity inherent in four-wave mixing in photorefractive (PR) materials is used for adaptive filtering. Examples include script enhancement on a periodic pattern, scratch and defect cluster enhancement, periodic pattern dislocation enhancement, etc. through intensity filtering image manipulation. Organic PR materials have large space-bandwidth product, which makes them useful in adaptive filtering techniques in quality control systems. For instance, in the case of edge enhancement, phase conjugation via four-wave mixing suppresses the low spatial frequencies of the Fourier spectrum of an aperiodic image and consequently leads to image edge enhancement. In this work, we model, numerically verify, and simulate the performance of a four wave mixing setup used for edge, defect and pattern detection in periodic amplitude and phase structures. The results show that this technique successfully detects the slightest defects clearly even with no enhancement. This technique should facilitate improvements in applications such as image display sharpness utilizing edge enhancement, production line defect inspection of fabrics, textiles, e-beam lithography masks, surface inspection, and materials characterization.

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

Engineering topological defect patterns of Bose condensates in shaken optical lattices

NASA Astrophysics Data System (ADS)

Feng, Lei; Clark, Logan W.; Gaj, Anita; Chin, Cheng

2017-04-01

Topological defects emerge and play an essential role in the dynamics of systems undergoing continuous, symmetry-breaking phase transitions. Here, we study the topological defects (domain walls) which form when a Bose condensate in a shaken optical lattice undergoes a quantum phase transition and separates into domains of superfluid with finite momentum. Here, we experimentally demonstrate the ability to control the pattern of domain walls using a digital micromirror device. We further explore implementations of this technique to study dynamics near the phase transition and the evolution of topological defects.

A Comparison Study of the Effectiveness of the Lexia Reading Programme

ERIC Educational Resources Information Center

Ness, Mike; Couperus, Josh; Willey, Matthew

2013-01-01

This study evaluates the efficacy of the Lexia Reading (LR) programme with a cohort of 37 students in a Decile 1 primary school. The students were randomly assigned to experimental (who used LR) and control groups (who did not use LR). The WIAT-II was used to provide pre and post measures of literacy skills. Results indicated that students who…

77 FR 36015 - Atomic Safety and Licensing Board; Entergy Nuclear Operations, Inc. (Indian Point Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247-LR and 50-286-LR; ASLBP No. 07-858-03-LR-BD01] Atomic Safety and Licensing Board; Entergy Nuclear Operations, Inc. (Indian Point Nuclear Generating Units 2 and 3); Notice of Hearing (Application for License Renewal) June 8, 2012. Before Administrative Judges: Lawrence G. McDade, Chairman, Dr....

Removal of MCs by Bi2O2CO3: adsorption and the potential of photocatalytic degradation.

PubMed

Wang, Yujiao; Cao, Yanqiu; Li, Hongmei; Gong, Aijun; Han, Jintao; Qian, Zhen; Chao, Wenran

2018-04-01

Microcystins (MCs) is a kind of hepatotoxin, which is the secondary metabolite of cyanobacteria. Bi 2 O 2 CO 3 (BOC) is a kind of cheap and nontoxic semiconductor material. BOC was synthetized by solvothermal method and then microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were removed by BOC, through adsorption and photocatalytic degradation. When the dosage of BOC is 6 g/L, the MC-LR and MC-RR in the natural water sample can be completely adsorbed in 30 min and then after 12 h irradiation, MC-LR and MC-RR were photocatalytically degraded by BOC.

Steganalysis using logistic regression

NASA Astrophysics Data System (ADS)

Lubenko, Ivans; Ker, Andrew D.

2011-02-01

We advocate Logistic Regression (LR) as an alternative to the Support Vector Machine (SVM) classifiers commonly used in steganalysis. LR offers more information than traditional SVM methods - it estimates class probabilities as well as providing a simple classification - and can be adapted more easily and efficiently for multiclass problems. Like SVM, LR can be kernelised for nonlinear classification, and it shows comparable classification accuracy to SVM methods. This work is a case study, comparing accuracy and speed of SVM and LR classifiers in detection of LSB Matching and other related spatial-domain image steganography, through the state-of-art 686-dimensional SPAM feature set, in three image sets.

Antilisterial activity of a broad-spectrum bacteriocin, enterocin LR/6 from Enterococcus faecium LR/6.

PubMed

Kumar, Manoj; Srivastava, Sheela

2010-10-01

Enterocin LR/6, a purified bacteriocin, exhibited broad inhibitory spectrum both against related as well as some food-borne pathogens such as Listeria monocytogenes, Yersinia enterocolitica, Aeromonas sp., Shigella sp., and Bacillus licheniformis. In this investigation, we have focused on L. monocytogenes as the target organism, as it is not only an important pathogen but can also survive over a wide range of environmental conditions such as refrigeration temperature, low pH, and high-salt concentration. This allows the pathogen to overcome many food preservation and safety barriers and poses a potential risk to human health. The enterocin LR/6 showed a bactericidal action against L. monocytogenes and completely inhibited the growth on agar plates, supplemented with 200 AU/ml of enterocin LR/6. The effectiveness of enterocin LR/6 in completely killing a population of acid-adapted (pH 5.2, 2 h) L. monocytogenes exposed to different temperatures (4-37 degrees C), pH (2.5-8.0), and osmotic (up to 30% NaCl) stress is reported here. This paper focuses on the key issue of killing of the acid-adapted L. monocytogenes cells under adverse environmental conditions.

Dynamics of Total Microcystin LR Concentration in Three Subtropical Hydroelectric Generation Reservoirs in Uruguay, South America.

PubMed

González-Piana, Mauricio; Fabián, Daniel; Piccardo, Andrea; Chalar, Guillermo

2017-10-01

This study analyzed the temporal dynamics of total microcystin LR concentrations between the years of 2012 and 2015 in the Bonete, Baygorria and Palmar hydroelectric generation reservoirs in the central region of the Negro River, Uruguay. The three reservoirs showed differents total microcystin LR concentration, with no significant differences among them. Over 20 sampling dates, the three reservoirs exhibited total microcystin LR concentrations on eight occasions that corresponded to a slight to moderate human health risk according to WHO guideline values for recreational waters. By determining the concentration of microcystin LR in cyanobacterial biomass, we identified cyanobacterial populations that occurred over time with varying degrees of toxin production (maximal 85.4 µg/mm 3 ). The microcystin LR concentration in Bonete was positively correlated with temperature (r = 0.587) and cyanobacterial biomass (r = 0.736), in Baygorria with cyanobacterial biomass (r = 0.521), and in Palmar with temperature (r = 0.500) and negatively correlated with ammonia (r = -0.492). Action is needed to reduce the presence of toxic cyanobacteria in these systems. A decrease in the use of agrochemicals and management changes in the reservoir basins could be successful long-term measures.

Super-resolution method for face recognition using nonlinear mappings on coherent features.

PubMed

Huang, Hua; He, Huiting

2011-01-01

Low-resolution (LR) of face images significantly decreases the performance of face recognition. To address this problem, we present a super-resolution method that uses nonlinear mappings to infer coherent features that favor higher recognition of the nearest neighbor (NN) classifiers for recognition of single LR face image. Canonical correlation analysis is applied to establish the coherent subspaces between the principal component analysis (PCA) based features of high-resolution (HR) and LR face images. Then, a nonlinear mapping between HR/LR features can be built by radial basis functions (RBFs) with lower regression errors in the coherent feature space than in the PCA feature space. Thus, we can compute super-resolved coherent features corresponding to an input LR image according to the trained RBF model efficiently and accurately. And, face identity can be obtained by feeding these super-resolved features to a simple NN classifier. Extensive experiments on the Facial Recognition Technology, University of Manchester Institute of Science and Technology, and Olivetti Research Laboratory databases show that the proposed method outperforms the state-of-the-art face recognition algorithms for single LR image in terms of both recognition rate and robustness to facial variations of pose and expression.

Labour room Continuous Positive Airway Pressure (LR CPAP) in preterm neonates <34 weeks: An Indian experience.

PubMed

Desai, Saumil Ashvinkumar; Tule, Pankaj; Nanavati, Ruchi Nimish

2017-01-01

Early continuous positive airway pressure (CPAP) has proven to be beneficial in reducing ventilator dependence and subsequent chronic lung disease in neonates suffering from Respiratory distress syndrome (RDS). However, the efficacy of initiating labour room (LR) CPAP has not been determined prospectively in resource limited settings like India. Hence the objective of the present study was to study the efficacy of LR CPAP in preterm neonates with RDS in resource limited Indian settings. This was a prospective observational study including preterm neonates (26-34 weeks with RDS) carried out over a period of 6 months (January to June 2016) when the CPAP was initiated in LR. The outcome was compared with a similar population during the corresponding period of the previous year when CPAP was initiated in NICU. The historical controls were retrieved from case records and matched for gestational age and birth weight with the study population. There was 36% absolute risk reduction in the need for surfactant and 56% for mechanical ventilation in the LR CPAP group respectively. LR CPAP reduces the need for mechanical ventilation and surfactant in preterm neonates with RDS in resource limited settings.

An iterated Laplacian based semi-supervised dimensionality reduction for classification of breast cancer on ultrasound images.

PubMed

Liu, Xiao; Shi, Jun; Zhou, Shichong; Lu, Minhua

2014-01-01

The dimensionality reduction is an important step in ultrasound image based computer-aided diagnosis (CAD) for breast cancer. A newly proposed l2,1 regularized correntropy algorithm for robust feature selection (CRFS) has achieved good performance for noise corrupted data. Therefore, it has the potential to reduce the dimensions of ultrasound image features. However, in clinical practice, the collection of labeled instances is usually expensive and time costing, while it is relatively easy to acquire the unlabeled or undetermined instances. Therefore, the semi-supervised learning is very suitable for clinical CAD. The iterated Laplacian regularization (Iter-LR) is a new regularization method, which has been proved to outperform the traditional graph Laplacian regularization in semi-supervised classification and ranking. In this study, to augment the classification accuracy of the breast ultrasound CAD based on texture feature, we propose an Iter-LR-based semi-supervised CRFS (Iter-LR-CRFS) algorithm, and then apply it to reduce the feature dimensions of ultrasound images for breast CAD. We compared the Iter-LR-CRFS with LR-CRFS, original supervised CRFS, and principal component analysis. The experimental results indicate that the proposed Iter-LR-CRFS significantly outperforms all other algorithms.

Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses.

PubMed

Di Legge, A; Testa, A C; Ameye, L; Van Calster, B; Lissoni, A A; Leone, F P G; Savelli, L; Franchi, D; Czekierdowski, A; Trio, D; Van Holsbeke, C; Ferrazzi, E; Scambia, G; Timmerman, D; Valentin, L

2012-09-01

To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

The long-term prognosis of newly diagnosed epilepsy in Egypt: A retrospective cohort study from an epilepsy center in Greater Cairo.

PubMed

Ashmawi, Ayman; Hosny, Hassan; Abdelalim, Ahmed; Bianchi, Elisa; Beghi, Ettore

2016-10-01

To investigate the long-term prognosis and prognostic patterns of epilepsy in a single practice study from a developing country. Consecutive patients first seen in an epilepsy clinic in Cairo, Egypt between January 1994 and December 2009 with at least 4 years of follow-up were included. Demographic, clinical, EEG and imaging findings at diagnosis were recorded. At follow-up, treatment was adjusted as clinically indicated. The response to the first drug was defined as 6-month seizure remission. Outcome measures included 2-year remission (R) and 2-year sustained remission (SR). Prognostic patterns were early (ER) and late remission (LR), relapsing-remitting (RR) course, worsening course (WC) and no remission. Included were 287 patients aged 1-66 years and followed for 2237.0 person-years (mean 7.8 years). 244 (85%) attained 2-year R. The cumulative time dependent probability of R was 86.7% at 10 years. Only the response to the first drug predicted R. 82 (28.6%) attained 2-year SR. The probability of SR was 40.9% at 10 years. Poor treatment response and nocturnal seizures predicted lowered SR. R and SR were inversely correlated to the number of drugs. 208 patients (72.5%) entered ER, 36 (12.5%) entered LR, 138 (48.1%) had RR course. A WC was present in 24 (8.4%), 43 (15.0%) never entered remission. Prognostic patterns varied with neurological examination, MRI findings, pre-treatment seizure frequency, seizure type, number of seizure types, etiology, syndrome and response to first drug. The long-term prognosis of newly diagnosed epilepsy patients from a developing country is in keeping with published reports. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data.

PubMed

Ibrahim, Heba; Saad, Amr; Abdo, Amany; Sharaf Eldin, A

2016-04-01

Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among the elements which composed a pattern. The average performance of the method showed 85% precision, 80% negative predictive value, 81% sensitivity and 84% specificity. The LR modeling could provide the statistical context to guard against spurious DIAEs. The proposed method could efficiently detect DIAE signals from SRS data as well as, identifying rare adverse drug reactions (ADRs). Copyright © 2016 Elsevier Inc. All rights reserved.

Comb-push Ultrasound Shear Elastography (CUSE): A Novel Method for Two-dimensional Shear Elasticity Imaging of Soft Tissues

PubMed Central

Song, Pengfei; Zhao, Heng; Manduca, Armando; Urban, Matthew W.; Greenleaf, James F.; Chen, Shigao

2012-01-01

Fast and accurate tissue elasticity imaging is essential in studying dynamic tissue mechanical properties. Various ultrasound shear elasticity imaging techniques have been developed in the last two decades. However, to reconstruct a full field-of-view 2D shear elasticity map, multiple data acquisitions are typically required. In this paper, a novel shear elasticity imaging technique, comb-push ultrasound shear elastography (CUSE), is introduced in which only one rapid data acquisition (less than 35 ms) is needed to reconstruct a full field-of-view 2D shear wave speed map (40 mm × 38 mm). Multiple unfocused ultrasound beams arranged in a comb pattern (comb-push) are used to generate shear waves. A directional filter is then applied upon the shear wave field to extract the left-to-right (LR) and right-to-left (RL) propagating shear waves. Local shear wave speed is recovered using a time-of-flight method based on both LR and RL waves. Finally a 2D shear wave speed map is reconstructed by combining the LR and RL speed maps. Smooth and accurate shear wave speed maps are reconstructed using the proposed CUSE method in two calibrated homogeneous phantoms with different moduli. Inclusion phantom experiments demonstrate that CUSE is capable of providing good contrast (contrast-to-noise-ratio ≥ 25 dB) between the inclusion and background without artifacts and is insensitive to inclusion positions. Safety measurements demonstrate that all regulated parameters of the ultrasound output level used in CUSE sequence are well below the FDA limits for diagnostic ultrasound. PMID:22736690

Left-right asymmetry specification in amphioxus: review and prospects.

PubMed

Soukup, Vladimir

2017-01-01

Extant bilaterally symmetrical animals usually show asymmetry in the arrangement of their inner organs. However, the exaggerated left-right (LR) asymmetry in amphioxus represents a true peculiarity among them. The amphioxus larva shows completely disparate fates of left and right body sides, so that organs associated with pharynx are either positioned exclusively on the left or on the right side. Moreover, segmented paraxial structures such as muscle blocks and their neuronal innervation show offset arrangement between the sides making it difficult to propose any explanation or adaptivity to larval and adult life. First LR asymmetries can be traced back to an early embryonic period when morphological asymmetries are preceded by molecular asymmetries driven by the action of the Nodal signaling pathway. This review sums up recent advances in understanding LR asymmetry specification in amphioxus and proposes upstream events that may regulate asymmetric Nodal signaling. These events include the presence of the vertebrate-like LR organizer and a cilia-driven fluid flow that may be involved in the breaking of bilateral symmetry. The upstream pathways comprising the ion flux, Delta/Notch, Wnt/β-catenin and Wnt/PCP are hypothesized to regulate both formation of the LR organizer and expression of the downstream Nodal signaling pathway genes. These suggestions are in line with what we know from vertebrate and ambulacrarian LR axis specification and are directly testable by experimental manipulations. Thanks to the phylogenetic position of amphioxus, the proposed mechanisms may be helpful in understanding the evolution of LR axis specification across deuterostomes.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

The value of reasons for encounter in early detection of colorectal cancer.

PubMed

van Boxtel-Wilms, Susan J M; van Boven, Kees; Bor, J H Hans; Bakx, J Carel; Lucassen, Peter; Oskam, Sibo; van Weel, Chris

2016-06-01

Symptoms with a high predictive power for colorectal cancer (CRC) do not exist. To explore the predictive value of patients' reason for encounter (RFE) in the two years prior to the diagnosis of CRC. A retrospective nested case-control study using prospectively collected data from electronic records in general practice over 20 years. Matching was done based on age (within two years), gender and practice. The positive likelihood ratios (LR+) and odds ratios (OR) were calculated for RFE between cases and controls in the two years before the index date. We identified 184 CRC cases and matched 366 controls. Six RFEs had significant LR + and ORs for CRC, which may have high predictive power. These RFEs are part of four chapters in the International Classification of Primary Care (ICPC) that include tiredness (significant at 3-6 months prior to the diagnosis; LR+ 2.6 and OR 3.07; and from 0 to 3 months prior to the diagnosis; LR+ 2.0 and OR 2.36), anaemia (significant at three months before diagnosis; LR+ 9.8 and OR 16.54), abdominal pain, rectal bleeding and constipation (significant at 3-6 months before diagnosis; LR+ 3.0 and OR 3.33; 3 months prior to the diagnosis LR+ 8.0 and OR 18.10) and weight loss (significant at three months before diagnosis; LR+ 14.9 and OR 14.53). Data capture and organization in ICPC permits study of the predictive value of RFE for CRC in primary care.

Photodegradation of microcystin-LR catalyzed by metal phthalocyanines immobilized on TiO2-SiO2 under visible-light irradiation.

PubMed

Peng, Guotao; Fan, Zhengqiu; Wang, Xiangrong; Sui, Xin; Chen, Chen

2015-01-01

Microcystins (MCs) are a group of monocyclic heptapeptide toxins produced by species of cyanobacteria. Since MCs exhibit acute and chronic effects on humans and wildlife by damaging the liver, they are of increasing concern worldwide. In this study, we investigated the ability of the phthalocyanine compound (ZnPc-TiO2-SiO2) to degrade microcystin-LR (MC-LR) in the presence of visible light. X-ray diffraction (XRD) and UV-Visible diffuse reflectance spectra (UV-Vis DRS) were utilized to characterize the crystalline phase and the absorption behavior of this catalyst. According to the results, XRD spectra of ZnPc-TiO2-SiO2 powders taken in the 2θ configuration exhibited the peaks characteristic of the anatase phase. UV-Vis DRS showed that the absorption band wavelength shifted to the visible range when ZnPc was supported on the surface of TiO2-SiO2. Subsequently, several parameters including catalyst dose, MC-LR concentrations and pH were investigated. The MC-LR was quantified in each sample through high-performance liquid chromatography (HPLC). The maximum MC-LR degradation rate of 80.2% can be obtained within 300 minutes under the following conditions: catalyst dose of 7.50 g/L, initial MC-LR concentration of 17.35 mg/L, pH 6.76 and the first cycling run of the photocatalytic reaction. Moreover, the degradation process fitted well with the pseudo-first-order kinetic model.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.

PubMed

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-08-12

To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

Dictionary learning based noisy image super-resolution via distance penalty weight model

PubMed Central

Han, Yulan; Zhao, Yongping; Wang, Qisong

2017-01-01

In this study, we address the problem of noisy image super-resolution. Noisy low resolution (LR) image is always obtained in applications, while most of the existing algorithms assume that the LR image is noise-free. As to this situation, we present an algorithm for noisy image super-resolution which can achieve simultaneously image super-resolution and denoising. And in the training stage of our method, LR example images are noise-free. For different input LR images, even if the noise variance varies, the dictionary pair does not need to be retrained. For the input LR image patch, the corresponding high resolution (HR) image patch is reconstructed through weighted average of similar HR example patches. To reduce computational cost, we use the atoms of learned sparse dictionary as the examples instead of original example patches. We proposed a distance penalty model for calculating the weight, which can complete a second selection on similar atoms at the same time. Moreover, LR example patches removed mean pixel value are also used to learn dictionary rather than just their gradient features. Based on this, we can reconstruct initial estimated HR image and denoised LR image. Combined with iterative back projection, the two reconstructed images are applied to obtain final estimated HR image. We validate our algorithm on natural images and compared with the previously reported algorithms. Experimental results show that our proposed method performs better noise robustness. PMID:28759633

Phytophthora parasitica Effector PpRxLR2 Suppresses Nicotiana benthamiana Immunity.

PubMed

Dalio, R J D; Maximo, H J; Oliveira, T S; Dias, R O; Breton, M C; Felizatti, H; Machado, M

2018-04-01

Phytophthora species secrete several classes of effector proteins during interaction with their hosts. These proteins can have multiple functions including modulation of host physiology and immunity. The RxLR effectors have the ability to enter plant cells using the plant machinery. Some of these effectors have been characterized as immunity suppressors; however, very little is known about their functions in the interaction between Phytophthora parasitica and its hosts. Using a bioinformatics pipeline, we have identified 172 candidate RxLR effectors (CREs) in the isolate IAC 01_95 of P. parasitica. Of these 172 CREs, 93 were found to be also present in eight other genomes of P. parasitica, isolated from different hosts and continents. After transcriptomics and gene expression analysis, we have found five CREs to be up-regulated in in-vitro and in-planta samples. Subsequently, we selected three CREs for functional characterization in the model plant Nicotiana benthamiana. We show that PpRxLR2 is able to completely suppress INF-1-induced cell death, whereas PpRxLR3 and PpRxLR5 moderately suppressed N. benthamiana immunity in a less-extensive manner. Moreover, we confirmed the effector-triggered susceptibility activity of these proteins after transient transformation and infection of N. benthamiana plants. All three CREs enhanced virulence of P. parasitica during the interaction with N. benthamiana. These effectors, in particular PpRxLR2, can be targeted for the development of biotechnology-based control strategies of P. parasitica diseases.

Scanning electron microscope automatic defect classification of process induced defects

NASA Astrophysics Data System (ADS)

Wolfe, Scott; McGarvey, Steve

2017-03-01

With the integration of high speed Scanning Electron Microscope (SEM) based Automated Defect Redetection (ADR) in both high volume semiconductor manufacturing and Research and Development (R and D), the need for reliable SEM Automated Defect Classification (ADC) has grown tremendously in the past few years. In many high volume manufacturing facilities and R and D operations, defect inspection is performed on EBeam (EB), Bright Field (BF) or Dark Field (DF) defect inspection equipment. A comma separated value (CSV) file is created by both the patterned and non-patterned defect inspection tools. The defect inspection result file contains a list of the inspection anomalies detected during the inspection tools' examination of each structure, or the examination of an entire wafers surface for non-patterned applications. This file is imported into the Defect Review Scanning Electron Microscope (DRSEM). Following the defect inspection result file import, the DRSEM automatically moves the wafer to each defect coordinate and performs ADR. During ADR the DRSEM operates in a reference mode, capturing a SEM image at the exact position of the anomalies coordinates and capturing a SEM image of a reference location in the center of the wafer. A Defect reference image is created based on the Reference image minus the Defect image. The exact coordinates of the defect is calculated based on the calculated defect position and the anomalies stage coordinate calculated when the high magnification SEM defect image is captured. The captured SEM image is processed through either DRSEM ADC binning, exporting to a Yield Analysis System (YAS), or a combination of both. Process Engineers, Yield Analysis Engineers or Failure Analysis Engineers will manually review the captured images to insure that either the YAS defect binning is accurately classifying the defects or that the DRSEM defect binning is accurately classifying the defects. This paper is an exploration of the feasibility of the utilization of a Hitachi RS4000 Defect Review SEM to perform Automatic Defect Classification with the objective of the total automated classification accuracy being greater than human based defect classification binning when the defects do not require multiple process step knowledge for accurate classification. The implementation of DRSEM ADC has the potential to improve the response time between defect detection and defect classification. Faster defect classification will allow for rapid response to yield anomalies that will ultimately reduce the wafer and/or the die yield.

Planarization of Isolated Defects on ICF Target Capsule Surfaces by Pulsed Laser Ablation

DOE PAGES

Alfonso, Noel; Carlson, Lane C.; Bunn, Thomas L.

2016-08-09

Demanding surface quality requirements for inertial confinement fusion (ICF) capsules motivated the development of a pulsed laser ablation method to reduce or eliminate undesirable surface defects. The pulsed laser ablation technique takes advantage of a full surface (4π) capsule manipulation system working in combination with an optical profiling (confocal) microscope. Based on the defect topography, the material removal rate, the laser pulse energy and its beam profile, a customized laser raster pattern is derived to remove the defect. The pattern is a table of coordinates and number of pulses that dictate how the defect will be vaporized until its heightmore » is level with the capsule surface. This paper explains how the raster patterns are optimized to minimize surface roughness and how surface roughness after laser ablation is simulated. The simulated surfaces are compared with actual ablated surfaces. Large defects are reduced to a size regime where a tumble finishing process produces very high quality surfaces devoid of high mode defects. The combined polishing processes of laser ablation and tumble finishing have become routine fabrication steps for National Ignition Facility capsule production.« less

Optical Metrology for Directed Self-assembly Patterning Using Mueller Matrix Spectroscopic Ellipsometry Based Scatterometry

NASA Astrophysics Data System (ADS)

Dixit, Dhairya J.

The semiconductor industry continues to drive patterning solutions that enable devices with higher memory storage capacity, faster computing performance, lower cost per transistors, and higher transistor density. These developments in the field of semiconductor manufacturing along with the overall minimization of the size of transistors require cutting-edge metrology tools for characterization. Directed self-assembly (DSA) patterning process can be used to fabricate nanoscale line-space patterns and contact holes via thermodynamically driven micro-phase separation of block copolymer (BCP) films with boundary constraints from guiding templates. Its main advantages are high pattern resolution (~10 nm), high throughput, no requirement of a high-resolution mask, and compatibility with standard fab-equipment and processes. Although research into DSA patterning has demonstrated a high potential as a nanoscale patterning process, there are critical challenges that must be overcome before transferring DSA into high volume manufacturing, including achievement of low defect density and high process stability. For this, advances in critical dimension (CD) and overlay measurement as well as rapid defect characterization are required. Both scatterometry and critical dimension-scanning electron microscopy (CD-SEM) are routinely used for inline dimensional metrology. CD-SEM inspection is limited, as it does not easily provide detailed line-shape information, whereas scatterometry has the capability of measuring important feature dimensions including: line-width, line-shape, sidewall-angle, and thickness of the patterned samples quickly and non-destructively. The present work describes the application of Mueller matrix spectroscopic ellipsometry (MMSE) based scatterometry to optically characterize DSA patterned line- space grating and contact hole structures fabricated with phase-separated polystyrene-b-polymethylmethacrylate (PS-b-PMMA) at various integration steps of BCP DSA based patterning process. This work focuses on understanding the efficacy of MMSE base scatterometry for characterizing complex DSA structures. For example, the use of symmetry-antisymmetry properties associated with Mueller matrix (MM) elements to understand the topography of the periodic nanostructures and measure defectivity. Simulations (the forward problem approach of scatterometry) are used to investigate MM elements' sensitivity to changes in DSA structure such as one vs. two contact hole patterns and predict sensitivity to dimensional changes. A regression-based approach is used to extract feature shape parameters of the DSA structures by fitting simulated optical spectra to experimental optical spectra. Detection of the DSA defects is a key to reducing defect density for eventual manufacturability and production use of DSA process. Simulations of optical models of structures containing defects are used to evaluate the sensitivity of MM elements to DSA defects. This study describes the application of MMSE to determine the DSA pattern defectivity via spectral comparisons based on optical anisotropy and depolarization. The use of depolarization and optical anisotropy for characterization of experimental MMSE data is a very recent development in scatterometry. In addition, reconstructed scatterometry models are used to calculate line edge roughness in 28 nm pitch Si fins fabricated using DSA patterning process.

40 CFR 272.951 - Louisiana State-administered program: Final authorization.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 1997. Copies of the document can be obtained from EPA Region 6, 1445 Ross Avenue, Dallas, Texas 75202... November 20, 1988 LR 18:1375 December 20, 1992. LAC § 303.K.1 (previously LHWR § 3.2(k)(1)) July 20, 1984 LR 14:790 November 20, 1988. LAC § 901 (LHWR § 6.1) March 20, 1984 LR 20:1000 September 20, 1994. LAC...

Two small secreted proteins from Puccinia triticina induce reduction of ß-glucoronidase transient expression in wheat isolines containing Lr9, Lr24, and Lr26

USDA-ARS?s Scientific Manuscript database

Little is known about the molecular interaction of wheat and leaf rust (Puccinia triticina Eriks). However, genomic tools are now becoming available so that the host-pathogen interaction can be understood. In this work, a cDNA library was made from haustoria isolated from P. triticina race PBJL inf...

40 CFR 52.970 - Identification of plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for Notification for Interstate Pollution Dec. 1987, LR13:741 03/08/89, 54 FR 09795 Ref 52.999(c)(49... 1101 Control of Air Pollution from Smoke: Purpose and Control of Smoke Dec. 1987, LR13:741 03/08/89, 54... Exemptions Dec. 1987, LR13:741 03/08/89, 54 FR 09795 Ref 52.999(c)(49) Section 1109 Control of Air Pollution...

Securing SSL-VPN with LR-AKE to access personal health record.

PubMed

Eizen, Kimura; Masato, Saito; Kazukuni, Kobara; Yoshihito, Nakato; Takuji, Kuroda; Ken, Ishihara

2013-01-01

Using SSL-VPN requires special considerations for well-known issues such as attackers exploiting web browser vulnerabilities and phishing sites using man-in-the-middle attacks. We used leakage-resilient authenticated key exchange (LR-AKE) to develop a comprehensive solution to SSL-VPN issues. Our results show that the LR-AKE should contribute to building a robust infrastructure for personal health records.

Liver Resection versus Radiofrequency Ablation plus Transcatheter Arterial Chemoembolization in Cirrhotic Patients with Solitary Large Hepatocellular Carcinoma.

PubMed

Saviano, Antonio; Iezzi, Roberto; Giuliante, Felice; Salvatore, Lucia; Mele, Caterina; Posa, Alessandro; Ardito, Francesco; De Gaetano, Anna Maria; Pompili, Maurizio

2017-11-01

To compare liver resection (LR) with single-step, balloon-occluded radiofrequency (RF) ablation plus drug-eluting embolics transarterial chemoembolization in cirrhotic patients with single hepatocellular carcinoma (HCC) ≥ 3 cm. From 2010 to 2014, 25 patients with compensated cirrhosis and single HCC ≥ 3 cm (median size 4.5 cm; range, 3.0-6.8 cm) not suitable for LR or liver transplantation were treated with RF ablation plus transarterial chemoembolization in a prospective observational single-center pilot study; all patients had complete tumor necrosis after treatment. A retrospective control group included 29 patients (median HCC size 4.0 cm; range, 3.0-7.4 cm) who underwent LR. RF ablation plus transarterial chemoembolization group included more patients with severe portal hypertension (65.5% vs 35.0%, P = .017). Primary endpoints were overall survival (OS) and tumor recurrence (TR) rates. One death and 1 major complication (4%) were observed in LR group. No major complications were reported in RF ablation plus transarterial chemoembolization group (P = .463). OS rates at 1 and 3 years were 91.8% and 79.3% in LR group and 89.4% and 48.2% in RF ablation plus transarterial chemoembolization group (P = 0.117). TR rates at 1 and 3 years were 29.5% and 45.0% in LR group and 42.4% and 76.0% in RF ablation plus transarterial chemoembolization group (P = .034). Local tumor progression (LTP) rates at 3 years were significantly lower in LR group (21.8% vs 58.1%, P = .005). Similar results were found in patients with HCC ≤ 5 cm (TR rates 35.4% vs 75.1%, P = .016; LTP 16.0% vs 55.7%, P = .013). LR achieved lower TR and LTP rates than RF ablation plus transarterial chemoembolization, but 3-years OS rates were not statistically different between the 2 groups. RF ablation plus transarterial chemoembolization is an effective treatment option in patients with compensated cirrhosis and solitary HCC ≥ 3 cm unsuitable for LR. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Microcystin-LR nanobody screening from an alpaca phage display nanobody library and its expression and application.

PubMed

Xu, Chongxin; Yang, Ying; Liu, Liwen; Li, Jianhong; Liu, Xiaoqin; Zhang, Xiao; Liu, Yuan; Zhang, Cunzheng; Liu, Xianjin

2018-04-30

Microcystin-LR (MC-LR) is a type of biotoxin that pollutes the ecological environment and food. The study aimed to obtain new nanobodies from phage nanobody library for determination of MC-LR. The toxin was conjugated to keyhole limpet haemocyanin (KLH) and bovine serum albumin (BSA), respectively, then the conjugates were used as coated antigens for enrichment (coated MC-LR-KLH) and screening (coated MC-LR-BSA) of MC-LR phage nanobodies from an alpaca phage display nanobody library. The antigen-specific phage particles were enriched effectively with four rounds of biopanning. At the last round of enrichment, total 20 positive monoclonal phage nanobodies were obtained from the library, which were analyzed after monoclonal phage enzyme linked immunosorbent assay (ELISA), colony PCR and DNA sequencing. The most three positive nanobody genes, ANAb12, ANAb9 and ANAb7 were cloned into pET26b vector, then the nanobodies were expressed in Escherichia coli BL21 respectively. After being purified, the molecular weight (M.W.) of all nanobodies were approximate 15kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The purified nanobodies, ANAb12, ANAb9 and ANAb7 were used to establish the indirect competitive ELISA (IC-ELISA) for MC-LR, and their half-maximum inhibition concentrations (IC 50 ) were 0.87, 1.17 and 1.47μg/L, their detection limits (IC 10 ) were 0.06, 0.08 and 0.12μg/L, respectively. All of them showed strong cross-reactivity (CRs) of 82.7-116.9% for MC-RR, MC-YR and MC-WR, and weak CRs of less than 4.56% for MC-LW, less than 0.1% for MC-LY and MC-LF. It was found that all the IC-ELISAs for MC-LR spiked in tap water samples detection were with good accuracy, stability and repeatability, their recoveries were 84.0-106.5%, coefficient of variations (CVs) were 3.4-10.6%. These results showed that IC-ELISA based on the nanobodies from the alpaca phage display antibody library were promising for high sensitive determination of multiple MCs. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta-analysis.

PubMed

Valachis, Antonios; Mamounas, Eleftherios P; Mittendorf, Elizabeth A; Hayashi, Naoki; Ishitobi, Makoto; Natoli, Clara; Fitzal, Florian; Rubio, Isabel T; Tiezzi, Daniel G; Shin, Hee-Chul; Anderson, Stewart J; Hunt, Kelly K; Matsuda, Naoko; Ohsumi, Shozo; Totomi, Athina; Nilsson, Cecilia

2018-05-03

Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT. Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively. A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively. BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Bedside clinical signs associated with impending death in patients with advanced cancer: preliminary findings of a prospective, longitudinal cohort study.

PubMed

Hui, David; Dos Santos, Renata; Chisholm, Gary; Bansal, Swati; Souza Crovador, Camila; Bruera, Eduardo

2015-03-15

Five highly specific physical signs associated with death within 3 days among cancer patients were recently reported that may aid in the diagnosis of impending death. In this study, the frequency and onset of another 52 bedside physical signs and their diagnostic performance for impending death were examined. Three hundred fifty-seven consecutive patients with advanced cancer who had been admitted to acute palliative care units at 2 tertiary care cancer centers were enrolled. Fifty-two physical signs were systematically documented every 12 hours from admission to death or discharge. The frequency and median time of onset of each sign from death backwards were examined, and the likelihood ratios (LRs) associated with death within 3 days were calculated. Two hundred three of the 357 patients (57%) died at the end of the admission. Eight physical signs that were highly diagnostic of impending death were identified. These signs occurred in 5% to 78% of the patients within the last 3 days of life, had a late onset, and had a high specificity (>95%) and a high positive LR for death within 3 days. They included nonreactive pupils (positive LR, 16.7; 95% confidence interval [CI], 14.9-18.6), a decreased response to verbal stimuli (positive LR, 8.3; 95% CI, 7.7-9), a decreased response to visual stimuli (positive LR, 6.7; 95% CI, 6.3-7.1), an inability to close eyelids (positive LR, 13.6; 95% CI, 11.7-15.5), drooping of the nasolabial fold (positive LR, 8.3; 95% CI, 7.7-8.9), hyperextension of the neck (positive LR, 7.3; 95% CI, 6.7-8), grunting of vocal cords (positive LR, 11.8; 95% CI, 10.3-13.4), and upper gastrointestinal bleeding (positive LR, 10.3; 95% CI, 9.5-11.1). Eight highly specific physical signs associated with death within 3 days among cancer patients were identified. These signs may inform the diagnosis of impending death. © 2015 American Cancer Society.

Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba

PubMed Central

Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdődi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba

2012-01-01

Background and Aims Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Methods Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Key Results Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL−1 MCY-LR, accelerated cell cycle at 10 µg mL−1 MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. Conclusions MCY-LR delayed metaphase–anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent. The toxin may be a useful tool in the study of plant cell cycle regulation. PMID:22819947

Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba.

PubMed

Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdodi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba

2012-09-01

Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL(-1) MCY-LR, accelerated cell cycle at 10 µg mL(-1) MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. MCY-LR delayed metaphase-anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent. The toxin may be a useful tool in the study of plant cell cycle regulation.

Prevalence of Low Cardiovascular Risk Profile Among Diverse Hispanic/Latino Adults in the United States by Age, Sex, and Level of Acculturation: The Hispanic Community Health Study/Study of Latinos.

PubMed

Daviglus, Martha L; Pirzada, Amber; Durazo-Arvizu, Ramon; Chen, Jinsong; Allison, Matthew; Avilés-Santa, Larissa; Cai, Jianwen; González, Hector M; Kaplan, Robert C; Schneiderman, Neil; Sorlie, Paul D; Talavera, Gregory A; Wassertheil-Smoller, Sylvia; Stamler, Jeremiah

2016-08-20

Favorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [LR]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross-sectional associations of LR with measures of acculturation. The multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008-2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age-adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age-adjusted odds ratios of having LR were 1.64 (95% CI 1.24-2.17) for foreign-born versus US-born women and 1.96 (95% CI 1.49-2.58) for women residing in the United States <10 versus ≥10 years. Among diverse US Hispanic/Latino adults, the prevalence of a LR profile is low. Lower acculturation is associated with higher odds of a LR profile among women but not men. Comprehensive public health strategies are needed to improve the cardiovascular health of US Hispanic/Latino adults. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Bbs8, together with the planar cell polarity protein Vangl2, is required to establish left-right asymmetry in zebrafish.

PubMed

May-Simera, Helen L; Kai, Masatake; Hernandez, Victor; Osborn, Daniel P S; Tada, Masazumi; Beales, Philip L

2010-09-15

Laterality defects such as situs inversus are not uncommonly encountered in humans, either in isolation or as part of another syndrome, but can have devastating developmental consequences. The events that break symmetry during early embryogenesis are highly conserved amongst vertebrates and involve the establishment of unidirectional flow by cilia within an organising centre such as the node in mammals or Kupffer's vesicle (KV) in teleosts. Disruption of this flow can lead to the failure to successfully establish left-right asymmetry. The correct apical-posterior cellular position of each node/KV cilium is critical for its optimal radial movement which serves to sweep fluid (and morphogens) in the same direction as its neighbours. Planar cell polarity (PCP) is an important conserved process that governs ciliary position and posterior tilt; however the underlying mechanism by which this occurs remains unclear. Here we show that Bbs8, a ciliary/basal body protein important for intraciliary/flagellar transport and the core PCP protein Vangl2 interact and are required for establishment and maintenance of left-right asymmetry during early embryogenesis in zebrafish. We discovered that loss of bbs8 and vangl2 results in laterality defects due to cilia disruption at the KV. We showed that perturbation of cell polarity following abrogation of vangl2 causes nuclear mislocalisation, implying defective centrosome/basal body migration and apical docking. Moreover, upon loss of bbs8 and vangl2, we observed defective actin organisation. These data suggest that bbs8 and vangl2 act synergistically on cell polarization to establish and maintain the appropriate length and number of cilia in the KV and thereby facilitate correct LR asymmetry. (c) 2010. Published by Elsevier Inc.

Analysis of the Ush2a gene in medaka fish (Oryzias latipes).

PubMed

Aller, Elena; Sánchez-Sánchez, Ana V; Chicote, Javier U; García-García, Gema; Udaondo, Patricia; Cavallé, Laura; Piquer-Gil, Marina; García-España, Antonio; Díaz-Llopis, Manuel; Millán, José M; Mullor, José L

2013-01-01

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP).

Versatility of the Angularis Oris Axial Pattern Flap for Facial Reconstruction.

PubMed

Losinski, Sara L; Stanley, Bryden J; Schallberger, Sandra P; Nelson, Laura L; Towle Millard, Heather A M

2015-11-01

To describe the versatility of the axial pattern flap based on the cutaneous perforating branch of the angularis oris artery for reconstruction of large facial defects in dogs, including complications and clinical outcomes. Retrospective clinical case series. Client-owned dogs (n = 8). Facial flaps (n = 9) based at the commissure of the lip with a caudodorsal orientation were utilized, with established anatomical borders. Flaps were elevated deep to the panniculus carnosus in a caudal to rostral direction, preserving the angularis oris artery, its cutaneous perforator, and surrounding cutaneous vasculature. Flaps were rotated dorsally or ventrally to cover the defect. Primary closure of the donor site was by direct apposition in all cases. Angularis oris axial pattern flaps were most commonly used to close large defects of the nasomaxillary area rostral to the eyes (6 dogs), followed by orbital (2) and intermandibular (1) defects. Defects occurred because of tumor resection (6 dogs), trauma (2), and a chronic, non-healing wounding (1). All flaps healed with acceptable functional and cosmetic outcomes without major complications. Followup ranged from 10 days to 16 months. Minor postoperative complications included flap edema (8 dogs), partial incisional dehiscence (3), distal tip necrosis (2), and oroantral fistula recurrence (1). Angularis oris axial pattern flaps provided hirsute, full-thickness skin coverage of a variety of large facial defects with minor complications, and should be considered when restructuring large defects of the rostral face or chin. © Copyright 2015 by The American College of Veterinary Surgeons.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

PubMed

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

The Mediterranean Plio-Pleistocene: A reference frame for astronomically paced low and high latitude climate changes (Jean Baptiste Lamarck Medal Lecture)

NASA Astrophysics Data System (ADS)

Lourens, Lucas

2016-04-01

The astronomical theory of climate has revolutionized our understanding of past climate change and the development of highly accurate geologic time scales for the entire Cenozoic. Most of this understanding has started with the construction of high-resolution stable oxygen isotope (18O) records from planktonic and benthic foraminifera of open ocean deep marine sediments explored by the international drilling operations of DSDP, ODP and IODP. These efforts culminated into global ocean isotopic stacked records, which give a clear picture of the evolution of the climate state through time. Fundamental for these reconstructions are the assumptions made between the astronomical forcing and the tuned time series and the accuracy of the astronomical solution. In the past decades, an astronomically calibrated time scale for the Pliocene and Pleistocene of the Mediterranean has been developed, which has become the reference for the standard Geologic Time Scale. Characteristic of the studied marine sediments are the cyclic lithological alternations, reflecting the interference between obliquity and precession-paced low latitude climate variability. These interference patterns allowed to evaluate the accuracy of astronomical solutions and to constrain the dynamical ellipticity of the Earth and tidal dissipation by the Sun and the Moon, which in turn provided the backbone for the widely applied LR04 open ocean benthic isotope stack of the past 5 Myr. So far, the assumed time lags between orbital forcing and the global climate response as reflected in LR04 have not been tested, while these assumptions hark back to SPECMAP, using simple ice sheet models and a limited number of radiometric dates. In addition, LR04 adopted a shorter response time for the smaller ice caps during the Pliocene. Here I present the first benthic 18O record of the Mediterranean reference scale, which strikingly mirrors the LR04. I will use this record to discuss the assumed phase relations and its potential to constrain global sea level changes and their cause over the past 5.3 million years.

Shear wave elastography in medullary thyroid carcinoma diagnostics.

PubMed

Dobruch-Sobczak, Katarzyna; Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-12-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4-15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB.

The interaction between nitrobenzene and Microcystis aeruginosa and its potential to impact water quality.

PubMed

Liu, Zhiquan; Cui, Fuyi; Ma, Hua; Fan, Zhenqiang; Zhao, Zhiwei; Hou, Zhenling; Liu, Dongmei; Jia, Xuebin

2013-08-01

The potential water quality problems caused by the interaction between nitrobezene (NB) and Microcystis aeruginosa was investigated by studying the growth inhibition, the haloacetic acids formation potential (HAAFP) and the secretion of microcystin-LR (MC-LR). The results showed that NB can inhibit the growth of M. aeruginosa, and the value of EC50 increased with the increase of initial algal density. Although NB can hardly react with chlorine to form HAAs, the presence of NB can enhance the HAAFP productivity. The secretion of the intracellular MC-LR is constant under the steady experimental conditions. However, the presence of NB can reduce the MC-LR productivity of M. aeruginosa. Overall, the increased disinfection risk caused by the interaction has more important effect on the safety of drinking water quality than the benefit of the decreased MC-LR productivity, and should be serious considered when the water contained NB and M. aeruginosa is used as drinking water source. Copyright © 2013 Elsevier Ltd. All rights reserved.

Calibration of Herschel SPIRE FTS observations at different spectral resolutions

NASA Astrophysics Data System (ADS)

Marchili, N.; Hopwood, R.; Fulton, T.; Polehampton, E. T.; Valtchanov, I.; Zaretski, J.; Naylor, D. A.; Griffin, M. J.; Imhof, P.; Lim, T.; Lu, N.; Makiwa, G.; Pearson, C.; Spencer, L.

2017-01-01

The SPIRE Fourier Transform Spectrometer on-board the Herschel Space Observatory had two standard spectral resolution modes for science observations: high resolution (HR) and low resolution (LR), which could also be performed in sequence (H+LR). A comparison of the HR and LR resolution spectra taken in this sequential mode revealed a systematic discrepancy in the continuum level. Analysing the data at different stages during standard pipeline processing demonstrates that the telescope and instrument emission affect HR and H+LR observations in a systematically different way. The origin of this difference is found to lie in the variation of both the telescope and instrument response functions, while it is triggered by fast variation of the instrument temperatures. As it is not possible to trace the evolution of the response functions using housekeeping data from the instrument subsystems, the calibration cannot be corrected analytically. Therefore, an empirical correction for LR spectra has been developed, which removes the systematic noise introduced by the variation of the response functions.

Chemical inhibition of prometastatic lysyl-tRNA synthetase–laminin receptor interaction

PubMed Central

Kim, Dae Gyu; Lee, Jin Young; Kwon, Nam Hoon; Fang, Pengfei; Zhang, Qian; Wang, Jing; Young, Nicolas L.; Guo, Min; Cho, Hye Young; Mushtaq, AmeeqUl; Jeon, Young Ho; Choi, Jin Woo; Han, Jung Min; Kang, Ho Woong; Joo, Jae Eun; Hur, Youn; Kang, Wonyoung; Yang, Heekyoung; Nam, Do-Hyun; Lee, Mi-Sook; Lee, Jung Weon; Kim, Eun-Sook; Moon, Aree; Kim, Kibom; Kim, Doyeun; Kang, Eun Joo; Moon, Youngji; Rhee, Kyung Hee; Han, Byung Woo; Yang, Jee Sun; Han, Gyoonhee; Yang, Won Suk; Lee, Cheolju; Wang, Ming-Wei; Kim, Sunghoon

2014-01-01

Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds to KRS, impinged on interaction of KRS with 67LR and suppressed metastasis in 3 different mouse models. The compound inhibited KRS–67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS–67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS. PMID:24212136

Simultaneous Microcystis Algicidal and Microcystin Degrading Capability by a Single Acinetobacter Bacterial Strain.

PubMed

Li, Hong; Ai, Hainan; Kang, Li; Sun, Xingfu; He, Qiang

2016-11-01

Measures for removal of toxic harmful algal blooms often cause lysis of algal cells and release of microcystins (MCs). In this study, Acinetobacter sp. CMDB-2 that exhibits distinct algal lysing activity and MCs degradation capability was isolated. The physiological response and morphological characteristics of toxin-producing Microcystis aeruginosa, the dynamics of intra- and extracellular MC-LR concentration were studied in an algal/bacterial cocultured system. The results demonstrated that Acinetobacter sp. CMDB-2 caused thorough decomposition of algal cells and impairment of photosynthesis within 24 h. Enhanced algal lysis and MC-LR release appeared with increasing bacterial density from 1 × 10 3 to 1 × 10 7 cells/mL; however, the MC-LR was reduced by nearly 94% within 14 h irrespective of bacterial density. Measurement of extracellular and intracellular MC-LR revealed that the toxin was decreased by 92% in bacterial cell incubated systems relative to control and bacterial cell-free filtrate systems. The results confirmed that the bacterial metabolite caused 92% lysis of Microcystis aeruginosa cells, whereas the bacterial cells were responsible for approximately 91% reduction of MC-LR. The joint efforts of the bacterium and its metabolite accomplished the sustainable removal of algae and MC-LR. This is the first report of a single bacterial strain that achieves these dual actions.

Comparison of Prediction Model for Cardiovascular Autonomic Dysfunction Using Artificial Neural Network and Logistic Regression Analysis

PubMed Central

Zeng, Fangfang; Li, Zhongtao; Yu, Xiaoling; Zhou, Linuo

2013-01-01

Background This study aimed to develop the artificial neural network (ANN) and multivariable logistic regression (LR) analyses for prediction modeling of cardiovascular autonomic (CA) dysfunction in the general population, and compare the prediction models using the two approaches. Methods and Materials We analyzed a previous dataset based on a Chinese population sample consisting of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN and LR analysis, and were tested in the validation set. Performances of these prediction models were then compared. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with the prevalence of CA dysfunction (P<0.05). The mean area under the receiver-operating curve was 0.758 (95% CI 0.724–0.793) for LR and 0.762 (95% CI 0.732–0.793) for ANN analysis, but noninferiority result was found (P<0.001). The similar results were found in comparisons of sensitivity, specificity, and predictive values in the prediction models between the LR and ANN analyses. Conclusion The prediction models for CA dysfunction were developed using ANN and LR. ANN and LR are two effective tools for developing prediction models based on our dataset. PMID:23940593

The combined effects of Dolichospermum flos-aquae, light, and temperature on microcystin production by Microcystis aeruginosa

NASA Astrophysics Data System (ADS)

Chen, Ruoqi; Li, Fangfang; Liu, Jiadong; Zheng, Hongye; Shen, Fei; Xue, Yarong; Liu, Changhong

2016-11-01

The effects of light, temperature, and coculture on the intracellular microcystin-LR (MC-LR) quota of Microcystis aeruginosa were evaluated based on coculture experiments with nontoxic Dolichospermum ( Anabaena) flos-aquae. The MC-LR quota and transcription of mcyB and mcyD genes encoding MC synthetases in M. aeruginosa were evaluated on the basis of cell counts, high-performance liquid chromatography, and reverse-transcription quantitative real-time PCR. The MC-LR quotas of M. aeruginosa in coculture with a 1/1 ratio of inoculum of the two species were significantly lower relative to monocultures 6-d after inoculation. Decreased MC-LR quotas under coculture conditions were enhanced by increasing the D. flos-aquae to M. aeruginosa ratio in the inoculum and by environmental factors, such as temperature and light intensity. Moreover, the transcriptional concentrations of mcyB and mcyD genes in M. aeruginosa were significantly inhibited by D. flos-aquae competition in coculture ( P <0.01), lowered to 20% of initial concentrations within 8 days. These data suggested that coculture eff ects by D. flos-aquae not only reduced M. aeruginosa's intracellular MC-LR quota via inhibition of genes encoding MC synthetases, but also that this eff ect was regulated by environmental factors, including temperature and light intensities.

Unilateral vs bilateral hip bone mineral density measurement for the diagnosis of osteoporosis.

PubMed

Ikegami, Shota; Kamimura, Mikio; Uchiyama, Shigeharu; Mukaiyama, Keijiro; Kato, Hiroyuki

2014-01-01

It has not been established whether unilateral or bilateral hip dual-energy X-ray absorptiometry (DXA) is preferable for the diagnosis of osteoporosis. We investigated the discordance in DXA measurements in bilateral hips to determine whether unilateral DXA is valid for osteoporosis diagnosis. The subjects were 2964 Japanese patients without a previous diagnosis of primary osteoporosis. We measured bilateral femoral bone mineral density (BMD) and calculated indices, related to the unilateral results, for predicting contralateral hip osteoporosis. A likelihood ratio (LR) of a negative test (LR [-]) of less than 0.2 was considered to exclude the diagnosis. In the normal spinal BMD group, the sensitivity of unilateral DXA for women was 27-73% and LR (-) was 0.28-0.73; the sensitivity for men was 0-50% and LR (-) was 0.51-1.00; the diagnosis of contralateral osteoporosis was not excluded. Sensitivity increased and LR (-) increased with worsening spinal BMD status; however, LR (-) did not meet the cutoff for exclusion. We could exclude unilateral hip osteoporosis, in women only, by performing contralateral femoral DXA; this necessitated lowering the T-score cutoff from -2.5 to -2.0. Unilateral femoral DXA is not useful for excluding the diagnosis of contralateral hip osteoporosis. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

PubMed

Bousquet, J; Bourret, R; Camuzat, T; Augé, P; Bringer, J; Noguès, M; Jonquet, O; de la Coussaye, J E; Ankri, J; Cesari, M; Guérin, O; Vellas, B; Blain, H; Arnavielhe, S; Avignon, A; Combe, B; Canovas, G; Daien, C; Dray, G; Dupeyron, A; Jeandel, C; Laffont, I; Laune, D; Marion, C; Pastor, E; Pélissier, J Y; Galan, B; Reynes, J; Reuzeau, J C; Bedbrook, A; Granier, S; Adnet, P A; Amouyal, M; Alomène, B; Bernard, P L; Berr, C; Caimmi, D; Claret, P G; Costa, D J; Cristol, J P; Fesler, P; Hève, D; Millot-Keurinck, J; Morquin, D; Ninot, G; Picot, M C; Raffort, N; Roubille, F; Sultan, A; Touchon, J; Attalin, V; Azevedo, C; Badin, M; Bakhti, K; Bardy, B; Battesti, M P; Bobia, X; Boegner, C; Boichot, S; Bonnin, H Y; Bouly, S; Boubakri, C; Bourrain, J L; Bourrel, G; Bouix, V; Bruguière, V; Cade, S; Camu, W; Carre, V; Cavalli, G; Cayla, G; Chiron, R; Coignard, P; Coroian, F; Costa, P; Cottalorda, J; Coulet, B; Coupet, A L; Courrouy-Michel, M C; Courtet, P; Cros, V; Cuisinier, F; Danko, M; Dauenhauer, P; Dauzat, M; David, M; Davy, J M; Delignières, D; Demoly, P; Desplan, J; Dujols, P; Dupeyron, G; Engberink, O; Enjalbert, M; Fattal, C; Fernandes, J; Fouletier, M; Fraisse, P; Gabrion, P; Gellerat-Rogier, M; Gelis, A; Genis, C; Giraudeau, N; Goucham, A Y; Gouzi, F; Gressard, F; Gris, J C; Guillot, B; Guiraud, D; Handweiler, V; Hayot, M; Hérisson, C; Heroum, C; Hoa, D; Jacquemin, S; Jaber, S; Jakovenko, D; Jorgensen, C; Kouyoudjian, P; Lamoureux, R; Landreau, L; Lapierre, M; Larrey, D; Laurent, C; Léglise, M S; Lemaitre, J M; Le Quellec, A; Leclercq, F; Lehmann, S; Lognos, B; Lussert, Cj M; Makinson, A; Mandrick, K; Mares, P; Martin-Gousset, P; Matheron, A; Mathieu, G; Meissonnier, M; Mercier, G; Messner, P; Meunier, C; Mondain, M; Morales, R; Morel, J; Mottet, D; Nérin, P; Nicolas, P; Nouvel, F; Paccard, D; Pandraud, G; Pasdelou, M P; Pasquié, J L; Patte, K; Perrey, S; Pers, Y M; Portejoie, F; Pujol, J L E; Quantin, X; Quéré, I; Ramdani, S; Ribstein, J; Rédini-Martinez, I; Richard, S; Ritchie, K; Riso, J P; Rivier, F; Robine, J M; Rolland, C; Royère, E; Sablot, D; Savy, J L; Schifano, L; Senesse, P; Sicard, R; Stephan, Y; Strubel, D; Tallon, G; Tanfin, M; Tassery, H; Tavares, I; Torre, K; Tribout, V; Uziel, A; Van de Perre, P; Venail, F; Vergne-Richard, C; Vergotte, G; Vian, L; Vialla, F; Viart, F; Villain, M; Viollet, E; Ychou, M; Mercier, J

2016-01-01

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Attenuated migration by green tea extract (-)-epigallocatechin gallate (EGCG): involvement of 67 kDa laminin receptor internalization in macrophagic cells.

PubMed

Ren, Xuezhi; Guo, Xingzhi; Chen, Li; Guo, Minxia; Peng, Ning; Li, Rui

2014-08-01

Excessive activation of the microglia in the brain is involved in the development of several neurodegenerative diseases. Previous studies have indicated that (-)-epigallocatechin gallate (EGCG), a major active constituent of green tea, exhibits potent suppressive effects on the activation of microglia. As the 67 kDa laminin receptor (67LR) is a key element in cellular activation and migration, we investigated the effect of EGCG on cell migration and 67LR in lipopolysaccharide (LPS)-activated macrophagic RAW264.7 cells. The presence of EGCG (1-25 μM) markedly attenuated LPS-induced cell migration in a dose-dependent manner. However, the total amount of 67LR protein in the RAW264.7 cells was unaffected by EGCG, as revealed by Western blot analysis. In addition, confocal immunofluorescence microscopy indicated that EGCG caused a marked membrane translocation of 67LR from the membrane surface towards the cytoplasm. Cell-surface biotinylation analysis confirmed that EGCG induced a significant internalization of 67LR by 24-68% in a dose-dependent manner. This study helps to explain the pharmacological action of EGCG on 67LR, suggesting its potential use in the treatment of diseases associated with macrophage/microglia activation, such as neurodegenerative diseases and cancer.

Degradation of microcystin-LR by highly efficient AgBr/Ag3PO4/TiO2 heterojunction photocatalyst under simulated solar light irradiation

NASA Astrophysics Data System (ADS)

Wang, Xin; Utsumi, Motoo; Yang, Yingnan; Li, Dawei; Zhao, Yingxin; Zhang, Zhenya; Feng, Chuanping; Sugiura, Norio; Cheng, Jay Jiayang

2015-01-01

A novel photocatalyst AgBr/Ag3PO4/TiO2 was developed by a simple facile in situ deposition method and used for degradation of mirocystin-LR. TiO2 (P25) as a cost effective chemical was used to improve the stability of AgBr/Ag3PO4 under simulated solar light irradiation. The photocatalytic activity tests for this heterojunction were conducted under simulated solar light irradiation using methyl orange as targeted pollutant. The results indicated that the optimal Ag to Ti molar ratio for the photocatalytic activity of the resulting heterojunction AgBr/Ag3PO4/TiO2 was 1.5 (named as 1.5 BrPTi), which possessed higher photocatalytic capacity than AgBr/Ag3PO4. The 1.5 BrPTi heterojunction was also more stable than AgBr/Ag3PO4 in photocatalysis. This highly efficient and relatively stable photocatalyst was further tested for degradation of the hepatotoxin microcystin-LR (MC-LR). The results suggested that MC-LR was much more easily degraded by 1.5 BrPTi than by AgBr/Ag3PO4. The quenching effects of different scavengers proved that reactive h+ and •OH played important roles for MC-LR degradation.

Patterned Video Sensors For Low Vision

NASA Technical Reports Server (NTRS)

Juday, Richard D.

1996-01-01

Miniature video cameras containing photoreceptors arranged in prescribed non-Cartesian patterns to compensate partly for some visual defects proposed. Cameras, accompanied by (and possibly integrated with) miniature head-mounted video display units restore some visual function in humans whose visual fields reduced by defects like retinitis pigmentosa.

Atomically resolved structural determination of graphene and its point defects via extrapolation assisted phase retrieval

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

Latychevskaia, Tatiana; Fink, Hans-Werner

Previously reported crystalline structures obtained by an iterative phase retrieval reconstruction of their diffraction patterns seem to be free from displaying any irregularities or defects in the lattice, which appears to be unrealistic. We demonstrate here that the structure of a nanocrystal including its atomic defects can unambiguously be recovered from its diffraction pattern alone by applying a direct phase retrieval procedure not relying on prior information of the object shape. Individual point defects in the atomic lattice are clearly apparent. Conventional phase retrieval routines assume isotropic scattering. We show that when dealing with electrons, the quantitatively correct transmission functionmore » of the sample cannot be retrieved due to anisotropic, strong forward scattering specific to electrons. We summarize the conditions for this phase retrieval method and show that the diffraction pattern can be extrapolated beyond the original record to even reveal formerly not visible Bragg peaks. Such extrapolated wave field pattern leads to enhanced spatial resolution in the reconstruction.« less

Evaluation of crystallographic strain, rotation and defects in functional oxides by the moiré effect in scanning transmission electron microscopy.

PubMed

Naden, A B; O'Shea, K J; MacLaren, D A

2018-04-20

Moiré patterns in scanning transmission electron microscopy (STEM) images of epitaxial perovskite oxides are used to assess strain and defect densities over fields of view extending over several hundred nanometers. The patterns arise from the geometric overlap of the rastered STEM electron beam and the samples' crystal periodicities and we explore the emergence and application of these moiré fringes for rapid strain analysis. Using the epitaxial functional oxide perovskites BiFeO 3 and Pr 1-x Ca x MnO 3 , we discuss the impact of large degrees of strain on the quantification of STEM moiré patterns, identify defects in the fringe patterns and quantify strain and lattice rotation. Such a wide-area analysis of crystallographic strain and defects is crucial for developing structure-function relations of functional oxides and we find the STEM moiré technique to be an attractive means of structural assessment that can be readily applied to low dose studies of damage sensitive crystalline materials.

Evaluation of crystallographic strain, rotation and defects in functional oxides by the moiré effect in scanning transmission electron microscopy

NASA Astrophysics Data System (ADS)

Naden, A. B.; O'Shea, K. J.; MacLaren, D. A.

2018-04-01

Moiré patterns in scanning transmission electron microscopy (STEM) images of epitaxial perovskite oxides are used to assess strain and defect densities over fields of view extending over several hundred nanometers. The patterns arise from the geometric overlap of the rastered STEM electron beam and the samples’ crystal periodicities and we explore the emergence and application of these moiré fringes for rapid strain analysis. Using the epitaxial functional oxide perovskites BiFeO3 and Pr1-x Ca x MnO3, we discuss the impact of large degrees of strain on the quantification of STEM moiré patterns, identify defects in the fringe patterns and quantify strain and lattice rotation. Such a wide-area analysis of crystallographic strain and defects is crucial for developing structure-function relations of functional oxides and we find the STEM moiré technique to be an attractive means of structural assessment that can be readily applied to low dose studies of damage sensitive crystalline materials.

Thermoelectric phonon-glass electron-crystal via ion beam patterning of silicon

NASA Astrophysics Data System (ADS)

Zhu, Taishan; Swaminathan-Gopalan, Krishnan; Stephani, Kelly; Ertekin, Elif

2018-05-01

Ion beam irradiation has recently emerged as a versatile approach to functional materials design. We show in this work that patterned defective regions generated by ion beam irradiation of silicon can create a phonon-glass electron-crystal (PGEC), a long-standing goal of thermoelectrics. By controlling the effective diameter of and spacing between the defective regions, molecular dynamics simulations suggest a reduction of the thermal conductivity by a factor of ˜20 is achievable. Boltzmann theory shows that the thermoelectric power factor remains largely intact in the damaged material. To facilitate the Boltzmann theory, we derive an analytical model for electron scattering with cylindrical defective regions based on partial-wave analysis. Together we predict a figure of merit of Z T ≈0.5 or more at room temperature for optimally patterned geometries of these silicon metamaterials. These findings indicate that nanostructuring of patterned defective regions in crystalline materials is a viable approach to realize a PGEC, and ion beam irradiation could be a promising fabrication strategy.

Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

NASA Astrophysics Data System (ADS)

Gheith, Mostafa E.; Khairy, Maggie A.

2014-02-01

Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial

PubMed Central

Herrera-Marante, Iván; González-Camacho, Verónica; Bonjoch, Laia; Quesada-Vázquez, Noé; Almenta-Saavedra, Isabel; Miralles-Maciá, Cayetano; Acevedo-Piedra, Nelly G; Roger-Ibáñez, Manuela; Sánchez-Marin, Claudia; Osuna-Ligero, Rosa; Gracia, Ángel; Llorens, Pere; Zapater, Pedro; Singh, Vikesh K; Moreu-Martín, Rocío; Closa, Daniel

2017-01-01

Background Little is known regarding the optimal type of fluid resuscitation in acute pancreatitis (AP). Objective The objective of this article was to compare the effect of lactated Ringer’s solution (LR) vs normal saline (NS) in the inflammatory response in AP. Methods We conducted a triple-blind, randomized, controlled trial. Patients ≥ 18 admitted with AP were eligible. Patients were randomized to receive LR or NS. Primary outcome variables were number of systemic inflammatory response syndrome (SIRS) criteria at 24 hours, 48 hours and 72 hours and blood C-reactive protein (CRP) levels at 48 hours and 72 hours. In vitro complementary experiments were performed to further explore the interaction between pH, lactate and inflammation. Results Nineteen patients receiving LR and 21 receiving NS were analyzed. The median (p25–p75) number of SIRS criteria at 48 hours were 1 (1–2) for NS vs 1 (0–1) for LR, p = 0.060. CRP levels (mg/l) were as follows: at 48 hours NS 166 (78–281) vs LR 28 (3–124), p = 0.037; at 72 hours NS 217 (59–323) vs LR 25 (3–169), p = 0.043. In vitro, LR inhibited the induction of inflammatory phenotype of macrophages and NF-κB activation. This effect was not observed when using Ringer’s solution without lactate, suggesting a direct anti-inflammatory effect of lactate. Conclusions Lactated Ringer’s is associated with an anti-inflammatory effect in patients with acute pancreatitis. PMID:29435315

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study

PubMed Central

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-01-01

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917–0.942), 0.918 (0.905–0.930), 0.914 (0.886–0.936) and 0.875 (0.853–0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90–96%, specificity 74–79% and diagnostic odds ratio (DOR) 32.8–50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6–75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference. PMID:24937676

A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation.

PubMed

Libros, R; Philips, C M; Wolfson, M R; Shaffer, T H

2000-01-01

Tidal liquid ventilation is the transport of dissolved respiratory gases via volume exchange of perfluorochemical (PFC) liquid to and from the PFC-filled lung. All gas-liquid surface tension is eliminated, increasing compliance and providing lung protection due to lower inflation pressures. Tidal liquid ventilation is achieved by cycling fluid from a reservoir to and from the lung by a ventilator. Current approaches are microprocessor-based with feedback control. During inspiration, warmed oxygenated PFC liquid is pumped from a fluid reservoir/gas exchanger into the lung. PFC fluid is conserved by condensing (60-80% efficiency) vapor in the expired gas. A feedback-control system was developed to automatically replace PFC lost due to condenser inefficiency. This loss/restoration (L/R) system consists of a PFC-vapor thermal detector (+/- 2.5%), pneumatics, amplifiers, a gas flow detector (+/- 1%), a PFC pump (+/- 5%), and a controller. Gravimetric studies of perflubron loss from a flask due to evaporation were compared with experimental L/R results and found to be within +/- 1.4%. In addition, when L/R studies were conducted with a previously reported liquid ventilation system over a four-hour period, the L/R system maintained system perflubron volume to within +/- 1% of prime volume and 11.5% of replacement volume, and the difference between experimental PFC loss and that of the L/R system was 1.8 mL/hr. These studies suggest that the PFC L/R system may have significant economic (appropriate dosing for PFC loss) as well as physiologic (maintenance of PFC inventory in the lungs and liquid ventilator) impact on liquid ventilation procedures.

Lung recruitment manoeuvres are effective in regaining lung volume and oxygenation after open endotracheal suctioning in acute respiratory distress syndrome

PubMed Central

Dyhr, Thomas; Bonde, Jan; Larsson, Anders

2003-01-01

Introduction Lung collapse is a contributory factor in the hypoxaemia that is observed after open endotracheal suctioning (ETS) in patients with acute lung injury and acute respiratory distress syndrome. Lung recruitment (LR) manoeuvres may be effective in rapidly regaining lung volume and improving oxygenation after ETS. Materials and method A prospective, randomized, controlled study was conducted in a 15-bed general intensive care unit at a university hospital. Eight consecutive mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome were included. One of two suctioning procedures was performed in each patient. In the first procedure, ETS was performed followed by LR manoeuvre and reconnection to the ventilator with positive end-expiratory pressure set at 1 cmH2O above the lower inflexion point, and after 60 min another ETS (but without LR manoeuvre) was performed followed by reconnection to the ventilator with similar positive end-expiratory pressure; the second procedure was the same as the first but conducted in reverse order. Before (baseline) and over 25 min following each ETS procedure, partial arterial oxygen tension (PaO2) and end-expiratory lung volume were measured. Results After ETS, PaO2 decreased by 4.3(0.9–9.7)kPa (median and range; P < 0.005). After LR manoeuvre, PaO2 recovered to baseline. Without LR manoeuvre, PaO2 was reduced (P = 0.05) until 7 min after ETS. With LR manoeuvre end-expiratory lung volume was unchanged after ETS, whereas without LR manoeuvre end-expiratory lung volume was still reduced (approximately 10%) at 5 and 15 min after ETS (P = 0.01). Discussion A LR manoeuvre immediately following ETS was, as an adjunct to positive end-expiratory pressure, effective in rapidly counteracting the deterioration in PaO2 and lung volume caused by open ETS in ventilator-treated patients with acute lung injury or acute respiratory distress syndrome. PMID:12617741

Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study.

PubMed

Schweitzer, Cedric; Korobelnik, Jean-Francois; Le Goff, Melanie; Rahimian, Olivier; Malet, Florence; Rougier, Marie-Benedicte; Delyfer, Marie-Noelle; Dartigues, Jean-Francois; Delcourt, Cecile

2016-11-01

To assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population. The antioxidants, essential lipids, nutrition and ocular maladies study (ALIENOR: "Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires") is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR). A total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05). Parameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.

Lr67/Yr46 confers adult plant resistance to stem rust and powdery mildew in wheat.

PubMed

Herrera-Foessel, Sybil A; Singh, Ravi P; Lillemo, Morten; Huerta-Espino, Julio; Bhavani, Sridhar; Singh, Sukhwinder; Lan, Caixia; Calvo-Salazar, Violeta; Lagudah, Evans S

2014-04-01

We demonstrate that Lr67/Yr46 has pleiotropic effect on stem rust and powdery mildew resistance and is associated with leaf tip necrosis. Genes are designated as Sr55, Pm46 and Ltn3 , respectively. Wheat (Triticum aestivum) accession RL6077, known to carry the pleiotropic slow rusting leaf and yellow rust resistance genes Lr67/Yr46 in Thatcher background, displayed significantly lower stem rust (P. graminis tritici; Pgt) and powdery mildew (Blumeria graminis tritici; Bgt) severities in Kenya and in Norway, respectively, compared to its recurrent parent Thatcher. We investigated the resistance of RL6077 to stem rust and powdery mildew using Avocet × RL6077 F6 recombinant inbred lines (RILs) derived from two photoperiod-insensitive F3 families segregating for Lr67/Yr46. Greenhouse seedling tests were conducted with Mexican Pgt race RTR. Field evaluations were conducted under artificially initiated stem rust epidemics with Pgt races RTR and TTKST (Ug99 + Sr24) at Ciudad Obregon (Mexico) and Njoro (Kenya) during 2010-2011; and under natural powdery mildew epiphytotic in Norway at Ås and Hamar during 2011 and 2012. In Mexico, a mean reduction of 41 % on stem rust severity was obtained for RILs carrying Lr67/Yr46, compared to RILs that lacked the gene, whereas in Kenya the difference was smaller (16 %) but significant. In Norway, leaf tip necrosis was associated with Lr67/Yr46 and RILs carrying Lr67/Yr46 showed a 20 % reduction in mean powdery mildew severity at both sites across the 2 years of evaluation. Our study demonstrates that Lr67/Yr46 confers partial resistance to stem rust and powdery mildew and is associated with leaf tip necrosis. The corresponding pleiotropic, or tightly linked, genes, designated as Sr55, Pm46, and Ltn3, can be utilized to provide broad-spectrum durable disease resistance in wheat.

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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

Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these,more » 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.« less

Lr41, Lr39, and a leaf rust resistance gene from Aegilops cylindrica may be allelic and are located on wheat chromosome 2DS.

PubMed

Singh, Sukhwinder; Franks, C D; Huang, L; Brown-Guedira, G L; Marshall, D S; Gill, B S; Fritz, A

2004-02-01

The leaf rust resistance gene Lr41 in wheat germplasm KS90WGRC10 and a resistance gene in wheat breeding line WX93D246-R-1 were transferred to Triticum aestivum from Aegilops tauschii and Ae. cylindrica, respectively. The leaf rust resistance gene in WX93D246-R-1 was located on wheat chromosome 2D by monosomic analysis. Molecular marker analysis of F(2) plants from non-critical crosses determined that this gene is 11.2 cM distal to marker Xgwm210 on the short arm of 2D. No susceptible plants were detected in a population of 300 F(2) plants from a cross between WX93D246-R-1 and TA 4186 ( Lr39), suggesting that the gene in WX93D246-R-1 is the same as, or closely linked to, Lr39. In addition, no susceptible plants were detected in a population of 180 F(2) plants from the cross between KS90WGRC10 and WX93D246-R-1. The resistance gene in KS90WGRC10, Lr41, was previously reported to be located on wheat chromosome 1D. In this study, no genetic association was found between Lr41 and 51 markers located on chromosome 1D. A population of 110 F(3 )lines from a cross between KS90WGRC10 and TAM 107 was evaluated with polymorphic SSR markers from chromosome 2D and marker Xgdm35 was found to be 1.9 cM proximal to Lr41. When evaluated with diverse isolates of Puccinia triticina, similar reactions were observed on WX93D246-R-1, KS90WGRC10, and TA 4186. The results of mapping, allelism, and race specificity test indicate that these germplasms likely have the same gene for resistance to leaf rust.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE-/- Mice With Unilateral Renal Artery Stenosis.

PubMed

Pathak, Alokkumar S; Huang, Jianhua; Rojas, Mauricio; Bazemore, Taylor C; Zhou, Ruihai; Stouffer, George A

2016-04-03

Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8LR group (22.7% [22.1, 32.7]), compared to sham-surgery, but less than observed with chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR group, and lipid staining in the descending aorta was not increased in either the D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic atheroma in the D4LR and D8LR groups compared to the chronic RAS group. Restoration of renal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Development of COS-SNP and HRM markers for high-throughput and reliable haplotype-based detection of Lr14a in durum wheat (Triticum durum Desf.).

PubMed

Terracciano, Irma; Maccaferri, Marco; Bassi, Filippo; Mantovani, Paola; Sanguineti, Maria C; Salvi, Silvio; Simková, Hana; Doležel, Jaroslav; Massi, Andrea; Ammar, Karim; Kolmer, James; Tuberosa, Roberto

2013-04-01

Leaf rust (Puccinia triticina Eriks. & Henn.) is a major disease affecting durum wheat production. The Lr14a-resistant gene present in the durum wheat cv. Creso and its derivative cv. Colosseo is one of the best characterized leaf-rust resistance sources deployed in durum wheat breeding. Lr14a has been mapped close to the simple sequence repeat markers gwm146, gwm344 and wmc10 in the distal portion of the chromosome arm 7BL, a gene-dense region. The objectives of this study were: (1) to enrich the Lr14a region with single nucleotide polymorphisms (SNPs) and high-resolution melting (HRM)-based markers developed from conserved ortholog set (COS) genes and from sequenced Diversity Array Technology (DArT(®)) markers; (2) to further investigate the gene content and colinearity of this region with the Brachypodium and rice genomes. Ten new COS-SNP and five HRM markers were mapped within an 8.0 cM interval spanning Lr14a. Two HRM markers pinpointed the locus in an interval of <1.0 cM and eight COS-SNPs were mapped 2.1-4.1 cM distal to Lr14a. Each marker was tested for its capacity to predict the state of Lr14a alleles (in particular, Lr14-Creso associated to resistance) in a panel of durum wheat elite germplasm including 164 accessions. Two of the most informative markers were converted into KASPar(®) markers. Single assay markers ubw14 and wPt-4038-HRM designed for agarose gel electrophoresis/KASPar(®) assays and high-resolution melting analysis, respectively, as well as the double-marker combinations ubw14/ubw18, ubw14/ubw35 and wPt-4038-HRM-ubw35 will be useful for germplasm haplotyping and for molecular-assisted breeding.

Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies.

PubMed

Rakovitch, E; Gray, R; Baehner, F L; Sutradhar, R; Crager, M; Gu, S; Nofech-Mozes, S; Badve, S S; Hanna, W; Hughes, L L; Wood, W C; Davidson, N E; Paszat, L; Shak, S; Sparano, J A; Solin, L J

2018-06-01

Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus  > 1-2.5 cm (1.45, 1.47), age ≥ 50 versus < 50 year (0.61, 0.84) and year ≥ 2000 (0.67, 0.49). Utilization of DS combined with tumor size and age at diagnosis predicted more women with very low (≤ 8%) or higher (> 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making.

Comparative Temporal Transcriptome Profiling of Wheat near Isogenic Line Carrying Lr57 under Compatible and Incompatible Interactions

PubMed Central

Yadav, Inderjit S.; Sharma, Amandeep; Kaur, Satinder; Nahar, Natasha; Bhardwaj, Subhash C.; Sharma, Tilak R.; Chhuneja, Parveen

2016-01-01

Leaf rust caused by Puccinia triticina (Pt) is one of the most important diseases of bread wheat globally. Recent advances in sequencing technologies have provided opportunities to analyse the complete transcriptomes of the host as well as pathogen for studying differential gene expression during infection. Pathogen induced differential gene expression was characterized in a near isogenic line carrying leaf rust resistance gene Lr57 and susceptible recipient genotype WL711. RNA samples were collected at five different time points 0, 12, 24, 48, and 72 h post inoculation (HPI) with Pt 77-5. A total of 3020 transcripts were differentially expressed with 1458 and 2692 transcripts in WL711 and WL711+Lr57, respectively. The highest number of differentially expressed transcripts was detected at 12 HPI. Functional categorization using Blast2GO classified the genes into biological processes, molecular function and cellular components. WL711+Lr57 showed much higher number of differentially expressed nucleotide binding and leucine rich repeat genes and expressed more protein kinases and pathogenesis related proteins such as chitinases, glucanases and other PR proteins as compared to susceptible genotype. Pathway annotation with KEGG categorized genes into 13 major classes with carbohydrate metabolism being the most prominent followed by amino acid, secondary metabolites, and nucleotide metabolism. Gene co-expression network analysis identified four and eight clusters of highly correlated genes in WL711 and WL711+Lr57, respectively. Comparative analysis of the differentially expressed transcripts led to the identification of some transcripts which were specifically expressed only in WL711+Lr57. It was apparent from the whole transcriptome sequencing that the resistance gene Lr57 directed the expression of different genes involved in building the resistance response in the host to combat invading pathogen. The RNAseq data and differentially expressed transcripts identified in present study is a genomic resource which can be used for further studying the host pathogen interaction for Lr57 and wheat transcriptome in general. PMID:28066494

Removal of cyanotoxins from surface water resources using reusable molecularly imprinted polymer adsorbents.

PubMed

Krupadam, Reddithota J; Patel, Govind P; Balasubramanian, Rajasekhar

2012-06-01

Microcystins (MCs; cyclic heptapeptides) are produced by freshwater cyanobacteria and cause public health concern in potable water supplies. There are more than 60 types of MCs identified to date, of which MC-LR is the most common found worldwide. For MC-LR, the WHO has established a threshold value of 1 μg L(-1) for drinking water. The present MCs removal methods such as coagulation, flocculation, adsorption, and filtration showed low efficiency for removing dissolved MC fraction from surface waters to the stipulated limit prescribed by WHO based on MC health impacts. The search for cost-effective and efficient removal method is still warranted for remediation of dissolved MC-LR-contaminated water resources. Molecularly imprinted polymer (MIP) adsorbent has been prepared using non-covalent imprinting approach. Using MC-LR as a template, itaconic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linking monomer, a MIP has been synthesized. Computer simulations were used to design effective binding sites for MC-LR binding in aqueous solutions. Batch binding adsorption assay was followed to determine binding capacity of MIP under the influence of environmental parameters such as total dissolved solids and pH. The adsorptive removal of MC-LR from lake water has been investigated using MIPs. The MIP showed excellent adsorption potential toward MC-LR in aqueous solutions with a binding capacity of 3.64 μg mg(-1) which is about 60% and 70% more than the commercially used powdered activated carbon (PAC) and resin XAD, respectively. Environmental parameters such as total organic carbon (represented as chemical oxygen demand (COD)) and total dissolved solids (TDS) showed no significant interference up to 300 mg L(-1) for MC-LR removal from lake water samples. It was found that the binding sites on PAC and XAD have more affinity toward COD and TDS than the MC-LR. Further, the adsorption capacity of the MIP was evaluated rigorously by its repeated contact with fresh lake water, and it was found that the adsorption capacity of the MIP did not change even after seven adsorption/desorption cycles. The contaminated water of MC-LR (1.0 μg L(-1)) of 3,640 L could be treated by 1 g of MIP with an estimated cost of US $1.5. The adsorption capacity of the MIP is 40% more than commercially used PAC and resins and also the polymer showed reusable potential which is one of the important criteria in selection of cyanotoxins remediation methods.

The ability of laying pullets to negotiate two ramp designs as measured by bird preference and behaviour

PubMed Central

Weeks, Claire A.; Norman, Kate I.; Nicol, Christine J.

2017-01-01

Background Laying hens are often kept in barn or free-range systems where they must negotiate level changes in the house to access resources. However, collisions and resultant keel fractures are commonplace. Producers sometimes add ramps to make raised areas more accessible but designs vary and very little research has investigated bird preference or behaviour when using different ramp designs, or the effect of ramp design on falls and collisions. Methods Two ramp designs were studied in an experimental setting—a ramp made of plastic poultry slats (grid ramp, GR) and a ramp made of wooden rungs (ladder ramp, LR). Sixty-four young female hens were trained to move to a food reward and this was used to test their behavioural responses when first negotiating the two different ramps during individual tests. Both upward and downward transitions were studied. Ramp preference was also tested using a room that replicated a commercial single-tier system with both types of ramp available. Birds were placed in this room in groups of 16 for three days and their use of the ramps studied. Results A greater percentage of birds successfully completed (reached the reward bowl) on the GR than the LR during both upward (58% vs 37%) and downward (83% vs 73%) transitions, and a smaller percentage of birds made zero attempts to use the GR than the LR (upwards: 13% vs 56%, downwards: 8% vs 26%). When making a downward transition, more hesitation behaviours were seen (head orientations, stepping on the spot, moving away) for the LR. However, more head orientations were seen for the GR during the upward transition. Birds were more likely to abort attempts (an attempt began when a bird placed both feet on the ramp) to move up the GR than the LR. Birds took longer to negotiate the LR than the GR in both directions, and more pauses were seen during a successful upward transition on the LR. Birds were more likely to move down the GR by walking/running whereas birds tended to jump over the entire LR. More collisions with the food reward bowl were seen for the LR. In the group tests, birds preferred to use the GR, with more transitions seen at all timepoints. However, in these tests, birds preferred to rest on the LR with greater numbers of birds counted on this type of ramp during scan sampling at all timepoints. Discussion Behavioural results suggest that the GR was easier for the birds to use than the LR, particularly on the downward transition. The GR was also less likely to result in collisions. However, the upward transition may be more difficult on the GR for some birds, potentially because of the inability to pause on a level surface during the transition. The results suggest that the GR was preferred by pullets for moving between a raised area and the ground but the LR was preferred for resting. PMID:29177116

Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis.

PubMed

Guerriero, S; Saba, L; Pascual, M A; Ajossa, S; Rodriguez, I; Mais, V; Alcazar, J L

2018-05-01

To perform a systematic review of studies comparing the accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in diagnosing deep infiltrating endometriosis (DIE) including only studies in which patients underwent both techniques. An extensive search was carried out in PubMed/MEDLINE and Web of Science for papers from January 1989 to October 2016 comparing TVS and MRI in DIE. Studies were considered eligible for inclusion if they reported on the use of TVS and MRI in the same set of patients for the preoperative detection of endometriosis in pelvic locations in women with clinical suspicion of DIE and using surgical data as a reference standard. Quality was assessed using the QUADAS-2 tool. A random-effects model was used to determine pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR). Of 375 citations identified, six studies (n = 424) were considered eligible. For MRI in the detection of DIE in the rectosigmoid, pooled sensitivity was 0.85 (95% CI, 0.78-0.90), specificity was 0.95 (95% CI, 0.83-0.99), LR+ was 18.4 (95% CI, 4.7-72.4), LR- was 0.16 (95% CI, 0.11-0.24) and DOR was 116 (95% CI, 23-585). For TVS in the detection of DIE in the rectosigmoid, pooled sensitivity was 0.85 (95% CI, 0.68-0.94), specificity was 0.96 (95% CI, 0.85-0.99), LR+ was 20.4 (95% CI, 4.7-88.5), LR- was 0.16 (95% CI, 0.07-0.38) and DOR was 127 (95% CI, 14-1126). For MRI in the detection of DIE in the rectovaginal septum, pooled sensitivity was 0.66 (95% CI, 0.51-0.79), specificity was 0.97 (95% CI, 0.89-0.99), LR+ was 22.5 (95% CI, 6.7-76.2), LR- was 0.38 (95% CI, 0.23-0.52) and DOR was 65 (95% CI, 21-204). For TVS in the detection of DIE in the rectovaginal septum, pooled sensitivity was 0.59 (95% CI, 0.26-0.86), specificity was 0.97 (95% CI, 0.94-0.99), LR+ was 23.5 (95% CI, 9.1-60.5), LR- was 0.42 (95% CI, 0.18-0.97) and DOR was 56 (95% CI, 11-275). For MRI in the detection of DIE in the uterosacral ligaments, pooled sensitivity was 0.70 (95% CI, 0.55-0.82), specificity was 0.93 (95% CI, 0.87-0.97), LR+ was 10.4 (95% CI, 5.1-21.2), LR- was 0.32 (95% CI, 0.20-0.51) and DOR was 32 (95% CI, 12-85). For TVS in the detection of DIE in the uterosacral ligaments, pooled sensitivity was 0.67 (95% CI, 0.55-0.77), specificity was 0.86 (95% CI, 0.73-0.93), LR+ was 4.8 (95% CI, 2.6-9.0), LR- was 0.38 (95% CI, 0.29-0.50) and DOR was 12 (95% CI, 7-24). Confidence intervals of pooled sensitivities, specificities and DOR were wide for both techniques in all the locations considered. Heterogeneity was moderate or high for sensitivity and specificity for both TVS and MRI in most locations assessed. According to QUADAS-2, the quality of the included studies was considered good for most domains. The diagnostic performance of TVS and MRI is similar for detecting DIE involving rectosigmoid, uterosacral ligaments and rectovaginal septum. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Identification of superficial defects in reconstructed 3D objects using phase-shifting fringe projection

NASA Astrophysics Data System (ADS)

Madrigal, Carlos A.; Restrepo, Alejandro; Branch, John W.

2016-09-01

3D reconstruction of small objects is used in applications of surface analysis, forensic analysis and tissue reconstruction in medicine. In this paper, we propose a strategy for the 3D reconstruction of small objects and the identification of some superficial defects. We applied a technique of projection of structured light patterns, specifically sinusoidal fringes and an algorithm of phase unwrapping. A CMOS camera was used to capture images and a DLP digital light projector for synchronous projection of the sinusoidal pattern onto the objects. We implemented a technique based on a 2D flat pattern as calibration process, so the intrinsic and extrinsic parameters of the camera and the DLP were defined. Experimental tests were performed in samples of artificial teeth, coal particles, welding defects and surfaces tested with Vickers indentation. Areas less than 5cm were studied. The objects were reconstructed in 3D with densities of about one million points per sample. In addition, the steps of 3D description, identification of primitive, training and classification were implemented to recognize defects, such as: holes, cracks, roughness textures and bumps. We found that pattern recognition strategies are useful, when quality supervision of surfaces has enough quantities of points to evaluate the defective region, because the identification of defects in small objects is a demanding activity of the visual inspection.

Reconfigurable interactions and three-dimensional patterning of colloidal particles and defects in lamellar soft media

PubMed Central

Trivedi, Rahul P.; Klevets, Ivan I.; Senyuk, Bohdan; Lee, Taewoo; Smalyukh, Ivan I.

2012-01-01

Colloidal systems find important applications ranging from fabrication of photonic crystals to direct probing of phenomena typically encountered in atomic crystals and glasses. New applications—such as nanoantennas, plasmonic sensors, and nanocircuits—pose a challenge of achieving sparse colloidal assemblies with tunable interparticle separations that can be controlled at will. We demonstrate reconfigurable multiscale interactions and assembly of colloids mediated by defects in cholesteric liquid crystals that are probed by means of laser manipulation and three-dimensional imaging. We find that colloids attract via distance-independent elastic interactions when pinned to the ends of cholesteric oily streaks, line defects at which one or more layers are interrupted. However, dislocations and oily streaks can also be optically manipulated to induce kinks, allowing one to lock them into the desired configurations that are stabilized by elastic energy barriers for structural transformation of the particle-connecting defects. Under the influence of elastic energy landscape due to these defects, sublamellar-sized colloids self-assemble into structures mimicking the cores of dislocations and oily streaks. Interactions between these defect-embedded colloids can be varied from attractive to repulsive by optically introducing dislocation kinks. The reconfigurable nature of defect–particle interactions allows for patterning of defects by manipulation of colloids and, in turn, patterning of particles by these defects, thus achieving desired colloidal configurations on scales ranging from the size of defect core to the sample size. This defect-colloidal sculpturing may be extended to other lamellar media, providing the means for optically guided self-assembly of mesoscopic composites with predesigned properties. PMID:22411822

Selective formation of porous silicon

NASA Technical Reports Server (NTRS)

Fathauer, Jones (Inventor)

1993-01-01

A pattern of porous silicon is produced in the surface of a silicon substrate by forming a pattern of crystal defects in said surface, preferably by applying an ion milling beam through openings in a photoresist layer to the surface, and then exposing said surface to a stain etchant, such as HF:HNO3:H20. The defected crystal will preferentially etch to form a pattern of porous silicon. When the amorphous content of the porous silicon exceeds 70 percent, the porous silicon pattern emits visible light at room temperature.

Empirical Properties of Multilingual Phone-To-Word Transduction

DTIC Science & Technology

2008-01-01

model are described next. Intended words I’m sorry we’ll blame him Intended phones aI m S a r i: w i: l b l ei m H I m Corrupted phones aI m S a r i...w i: D l ei m H I m Recovered words I’m sorry we blame him Table 1. Steps in the noisy channel model 3. DATABASE AND ACOUSTIC MODELS 3.1. CallHome In...respectively that take speci c values such as rs and ls. Then M (L;R) = X L,R P (L,R) log P (L,R) P (L)P (R) ≈ X s log P (rs, ls) P (rs)P (ls) = X s log P

Different bone regeneration patterns in periimplant circumferential gap defects grafted with two types of osteoconductive biomaterial.

PubMed

Lee, Jung-Seok; Sohn, Joo-Yeon; Lim, Hyun-Chang; Jung, Ui-Won; Choi, Seong-Ho

2016-08-01

This study aimed to determine healing patterns in periimplant gap defect grafted with demineralized bovine bone mineral (DBBM) and porous titanium granules (PTG), which are known to induce a minimal tissue reaction and to undergo minimal biodegradation in healing process. Experiments were performed using a standardized periimplant gap-defect model in dogs with two observational periods: 4 and 8 weeks. Circumferential defects were surgically induced around dental implants on unilateral mandibles in five dogs, and collagen barrier membranes were placed over the DBBM and PTG grafts at two experimental sites and over a nongrafted site. Four weeks later, the same procedures were performed on the contralateral mandible, and the animals allowed to heal for a further 4 weeks, after which they were sacrificed and their mandibles with graft/control sites harvested for histologic evaluation. Both types of grafted biomaterials significantly enhanced the defect fill with newly formed bone, but the bone-to-implant contact (BIC) was significantly increased only at sites that had been grafted with DBBM. The two experimental sites exhibited different healing patterns, with new bone formation being observed on the surface of the DBBM particles throughout the defect, while there was no de novo bone formation on the PTG surface, but rather appositional bone growth from the base and lateral walls of the defect. It has been suggested that gap-defect filling with DBBM around dental implants may enhance both BIC and defect fill; however, the present findings show that defect grafting with PTG enhances only defect fill and not BIC. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1202-1209, 2016. © 2015 Wiley Periodicals, Inc.

Simulation based mask defect repair verification and disposition

NASA Astrophysics Data System (ADS)

Guo, Eric; Zhao, Shirley; Zhang, Skin; Qian, Sandy; Cheng, Guojie; Vikram, Abhishek; Li, Ling; Chen, Ye; Hsiang, Chingyun; Zhang, Gary; Su, Bo

2009-10-01

As the industry moves towards sub-65nm technology nodes, the mask inspection, with increased sensitivity and shrinking critical defect size, catches more and more nuisance and false defects. Increased defect counts pose great challenges in the post inspection defect classification and disposition: which defect is real defect, and among the real defects, which defect should be repaired and how to verify the post-repair defects. In this paper, we address the challenges in mask defect verification and disposition, in particular, in post repair defect verification by an efficient methodology, using SEM mask defect images, and optical inspection mask defects images (only for verification of phase and transmission related defects). We will demonstrate the flow using programmed mask defects in sub-65nm technology node design. In total 20 types of defects were designed including defects found in typical real circuit environments with 30 different sizes designed for each type. The SEM image was taken for each programmed defect after the test mask was made. Selected defects were repaired and SEM images from the test mask were taken again. Wafers were printed with the test mask before and after repair as defect printability references. A software tool SMDD-Simulation based Mask Defect Disposition-has been used in this study. The software is used to extract edges from the mask SEM images and convert them into polygons to save in GDSII format. Then, the converted polygons from the SEM images were filled with the correct tone to form mask patterns and were merged back into the original GDSII design file. This merge is for the purpose of contour simulation-since normally the SEM images cover only small area (~1 μm) and accurate simulation requires including larger area of optical proximity effect. With lithography process model, the resist contour of area of interest (AOI-the area surrounding a mask defect) can be simulated. If such complicated model is not available, a simple optical model can be used to get simulated aerial image intensity in the AOI. With built-in contour analysis functions, the SMDD software can easily compare the contour (or intensity) differences between defect pattern and normal pattern. With user provided judging criteria, this software can be easily disposition the defect based on contour comparison. In addition, process sensitivity properties, like MEEF and NILS, can be readily obtained in the AOI with a lithography model, which will make mask defect disposition criteria more intelligent.

Using composite sinusoidal patterns in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food

USDA-ARS?s Scientific Manuscript database

Structured-illumination reflectance imaging (SIRI) provides a new means for enhanced detection of defects in horticultural products. Implementing the technique relies on retrieving amplitude images by illuminating the object with sinusoidal patterns of single spatial frequencies, which, however, are...

Toward optimized light utilization in nanowire arrays using scalable nanosphere lithography and selected area growth.

PubMed

Madaria, Anuj R; Yao, Maoqing; Chi, Chunyung; Huang, Ningfeng; Lin, Chenxi; Li, Ruijuan; Povinelli, Michelle L; Dapkus, P Daniel; Zhou, Chongwu

2012-06-13

Vertically aligned, catalyst-free semiconducting nanowires hold great potential for photovoltaic applications, in which achieving scalable synthesis and optimized optical absorption simultaneously is critical. Here, we report combining nanosphere lithography (NSL) and selected area metal-organic chemical vapor deposition (SA-MOCVD) for the first time for scalable synthesis of vertically aligned gallium arsenide nanowire arrays, and surprisingly, we show that such nanowire arrays with patterning defects due to NSL can be as good as highly ordered nanowire arrays in terms of optical absorption and reflection. Wafer-scale patterning for nanowire synthesis was done using a polystyrene nanosphere template as a mask. Nanowires grown from substrates patterned by NSL show similar structural features to those patterned using electron beam lithography (EBL). Reflection of photons from the NSL-patterned nanowire array was used as a measure of the effect of defects present in the structure. Experimentally, we show that GaAs nanowires as short as 130 nm show reflection of <10% over the visible range of the solar spectrum. Our results indicate that a highly ordered nanowire structure is not necessary: despite the "defects" present in NSL-patterned nanowire arrays, their optical performance is similar to "defect-free" structures patterned by more costly, time-consuming EBL methods. Our scalable approach for synthesis of vertical semiconducting nanowires can have application in high-throughput and low-cost optoelectronic devices, including solar cells.

Effects of microcystin-LR and cylindrospermopsin on plant-soil systems: A review of their relevance for agricultural plant quality and public health

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

Machado, J.; Campos, A.

Toxic cyanobacterial blooms are recognized as an emerging environmental threat worldwide. Although microcystin-LR is the most frequently documented cyanotoxin, studies on cylindrospermopsin have been increasing due to the invasive nature of cylindrospermopsin-producing cyanobacteria. The number of studies regarding the effects of cyanotoxins on agricultural plants has increased in recent years, and it has been suggested that the presence of microcystin-LR and cylindrospermopsin in irrigation water may cause toxic effects in edible plants. The uptake of these cyanotoxins by agricultural plants has been shown to induce morphological and physiological changes that lead to a potential loss of productivity. There is alsomore » evidence that edible terrestrial plants can bioaccumulate cyanotoxins in their tissues in a concentration dependent-manner. Moreover, the number of consecutive cycles of watering and planting in addition to the potential persistence of microcystin-LR and cylindrospermopsin in the environment are likely to result in groundwater contamination. The use of cyanotoxin-contaminated water for agricultural purposes may therefore represent a threat to both food security and food safety. However, the deleterious effects of cyanotoxins on agricultural plants and public health seem to be dependent on the concentrations studied, which in most cases are non-environmentally relevant. Interestingly, at ecologically relevant concentrations, the productivity and nutritional quality of some agricultural plants seem not to be impaired and may even be enhanced. However, studies assessing if the potential tolerance of agricultural plants to these concentrations can result in cyanotoxin and allergen accumulation in the edible tissues are lacking. This review combines the most current information available regarding this topic with a realistic assessment of the impact of cyanobacterial toxins on agricultural plants, groundwater quality and public health. - Highlights: • Deleterious effects of MC-LR/CYN on agricultural plants are concentration-dependent. • Toxic effects of MC-LR and CYN at ecological conditions are scarce. • The bioaccumulation of MC-LR/CYN in vegetables is time- and concentration-dependent. • The persistence of MC-LR/CYN on soil systems can result in groundwater contamination. • A realistic assessment of the impact of MC-LR/CYN on agricultural plants was made.« less

Empirical comparison between different methods for genomic prediction of number of piglets born alive in moderate sized breeding populations.

PubMed

Fangmann, A; Sharifi, R A; Heinkel, J; Danowski, K; Schrade, H; Erbe, M; Simianer, H

2017-04-01

Currently used multi-step methods to incorporate genomic information in the prediction of breeding values (BV) implicitly involve many assumptions which, if violated, may result in loss of information, inaccuracies and bias. To overcome this, single-step genomic best linear unbiased prediction (ssGBLUP) was proposed combining pedigree, phenotype and genotype of all individuals for genetic evaluation. Our objective was to implement ssGBLUP for genomic predictions in pigs and to compare the accuracy of ssGBLUP with that of multi-step methods with empirical data of moderately sized pig breeding populations. Different predictions were performed: conventional parent average (PA), direct genomic value (DGV) calculated with genomic BLUP (GBLUP), a GEBV obtained by blending the DGV with PA, and ssGBLUP. Data comprised individuals from a German Landrace (LR) and Large White (LW) population. The trait 'number of piglets born alive' (NBA) was available for 182,054 litters of 41,090 LR sows and 15,750 litters from 4534 LW sows. The pedigree contained 174,021 animals, of which 147,461 (26,560) animals were LR (LW) animals. In total, 526 LR and 455 LW animals were genotyped with the Illumina PorcineSNP60 BeadChip. After quality control and imputation, 495 LR (424 LW) animals with 44,368 (43,678) SNP on 18 autosomes remained for the analysis. Predictive abilities, i.e., correlations between de-regressed proofs and genomic BV, were calculated with a five-fold cross validation and with a forward prediction for young genotyped validation animals born after 2011. Generally, predictive abilities for LR were rather small (0.08 for GBLUP, 0.19 for GEBV and 0.18 for ssGBLUP). For LW, ssGBLUP had the greatest predictive ability (0.45). For both breeds, assessment of reliabilities for young genotyped animals indicated that genomic prediction outperforms PA with ssGBLUP providing greater reliabilities (0.40 for LR and 0.32 for LW) than GEBV (0.35 for LR and 0.29 for LW). Grouping of animals according to information sources revealed that genomic prediction had the highest potential benefit for genotyped animals without their own phenotype. Although, ssGBLUP did not generally outperform GBLUP or GEBV, the results suggest that ssGBLUP can be a useful and conceptually convincing approach for practical genomic prediction of NBA in moderately sized LR and LW populations.

DSA process window expansion with novel DSA track hardware

NASA Astrophysics Data System (ADS)

Harumoto, Masahiko; Stokes, Harold; Tanaka, Yuji; Kaneyama, Koji; Pieczulewski, Chalres; Asai, Masaya; Argoud, Maxime; Servin, Isabelle; Chamiot-Maitral, Gaëlle; Claveau, Guillaume; Tiron, Raluca; Cayrefourcq, Ian

2017-03-01

PS-b-PMMA block copolymer is a well-known DSA material, and there are many DSA patterning methods that make effective the use of such 1st generation materials. Consequently, this variety of patterning methods opens a wide array of possibilities for DSA application[1-4]. Last year, during the inaugural International DSA Symposium, researchers and lithographers concurred on common key issues for DSA patterning methods such as: defect density, LWR, placement error, etc. Defect density was specifically expressed as the biggest obstacle for new processes. Coat-Develop track systems contribute to the DSA pattern fabrication and also influence the DSA pattern performances[4]. In this study, defectivity was investigated using an atmosphere-controlled chamber on the SOKUDO DUO track. As an initial step for expanding the DSA process window, fingerprint patterns were used for various atmospheric conditions during DSA self-assembly annealing. In this study, we will demonstrate an improved DSA process window, and then we will discuss the mechanism for this atmospheric effect.

Qingshengfania soli gen. nov., sp. nov., a member of the order Rhizobiales isolated from the soil of a pesticide factory.

PubMed

Zhang, Long; Zhou, Qing-Xin; Song, Man; Chen, Xiao-Long; Xu, Xi-Hui; Chen, Kai; Li, Shun-Peng; Jiang, Jian-Dong

2015-12-01

Two Gram-stain negative, coccoid to oval-shaped, non-spore-forming bacteria (LR4T and LR4-1), isolated from the soil of a pesticide factory in Nanjing, China, were investigated for their taxonomic allocation by using a polyphasic approach. Both strains grew optimally at pH 7.0, 30 °C and in the absence of NaCl. Both strains were positive for catalase and oxidase activities. Q-10 was the predominant respiratory ubiquinone. The major polar lipids were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and two unknown aminolipids. The major fatty acids (>10 % of the total fatty acids) were C18:1ω7c/C18:1ω6c (summed feature 8) and C17:1 iso I/C17:1 anteiso B (summed feature 4). Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the two isolates formed a distinct line within a clade containing the genera Chelatococcus, Bosea, Camelimonas, Salinarimonas, Psychroglaciecola, Microvirga, Methylobacterium, Albibacter, Hansschlegelia and Methylopila in the order Rhizobiales, with the highest 16S rRNA gene sequence similarity to Chelatococcus asaccharovorans TE2T (94.12 %), followed by Bosea thiooxidans DSM 9653T (93.25 %). Strains LR4T and LR4-1 were closely related on the basis of DNA-DNA reassociation and therefore represent a single novel species. Based on phenotypic, chemotaxonomic and phylogenetic data, strains LR4T and LR4-1 represent a novel species of a new genus in the order Rhizobiales, for which the name Qingshengfania soli gen. nov., sp. nov. is proposed. The type strain of the type species is LR4T ( = CCTCC AB 2015036T = KCTC 42463T).

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

PubMed

Watters, Jennifer M; Brundage, Susan I; Todd, S Rob; Zautke, Nathan A; Stefater, J A; Lam, J C; Muller, Patrick J; Malinoski, Darren; Schreiber, Martin A

2004-09-01

Lactated Ringer's (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-alpha) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-alpha gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Imaging markers for Alzheimer disease

PubMed Central

Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles

2013-01-01

Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875

Orbital magnetic resonance imaging is useful in age-related distance esotropia.

PubMed

Gómez de Liaño Sanchez, Pilar; Olavarri González, Gloria; Merino Sanz, Pilar; Escribano Villafruela, Jose C

To describe findings for orbital magnetic resonance imaging (MRI) in patients with age-related distance esotropia (ARDE). We compared 31 orbital MRI from patients with ARDE (77±7 SD years) with 2 control groups: 32 orbits from individuals aged 18-50 years (33±8 SD years) and 16 orbits from individuals aged >60 years (77±7 SD years). MRI scans were acquired using 3D fast field echo in T1 sequence without fat saturation. Exclusion criteria for all groups were neurological or thyroid disease and a relevant ophthalmological history (e.g., high myopia, diplopia from another etiology, complicated cataract surgery, etc.). Muscle displacement and characteristics of the lateral rectus-superior rectus (LR-SR) intermuscular band were analyzed. The analysis of the muscles and angles revealed a series of statistically significant differences (p<0.07) between the groups. Subjects with ARDE had LR pulley positions 1.32±0.19mm lower than in younger controls, and the medial rectus (MR) pulley positions were 0.68±0.19mm lower than in younger. Older controls had LR and MR pulley positions 0.85±0.20mm and 0.49±0.23mm lower than in younger. ARDE subjects had LR pulley positions 0.46±0.26mm lower than in older control group. The LR-SR band was absent in 35.5% of ARDE patients and in 12.5% of older control group (p=0.168). MRI showed that displacements of LR and LR-SR band degeneration could facilitate the diagnosis of patients with ARDE. Copyright © 2017 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Dignity Therapy and Life Review for Palliative Care Patients: A Randomized Controlled Trial.

PubMed

Vuksanovic, Dean; Green, Heather J; Dyck, Murray; Morrissey, Shirley A

2017-02-01

Dignity therapy (DT) is a psychotherapeutic intervention with increasing evidence of acceptability and utility in palliative care settings. The aim of this study was to evaluate the legacy creation component of DT by comparing this intervention with life review (LR) and waitlist control (WC) groups. Seventy adults with advanced terminal disease were randomly allocated to DT, LR, or WC followed by DT, of which 56 completed the study protocol. LR followed an identical protocol to DT except that no legacy document was created in LR. Primary outcome measures were the Brief Generativity and Ego-Integrity Questionnaire, Patient Dignity Inventory, Functional Assessment of Cancer Therapy-General, version 4, and treatment evaluation questionnaires. Unlike LR and WC groups, DT recipients demonstrated significantly increased generativity and ego-integrity scores at study completion. There were no significant changes for dignity-related distress or physical, social, emotional, and functional well-being among the three groups. There were also no significant changes in primary outcomes after the provision of DT after the waiting period in the WC group. High acceptability and satisfaction with interventions were noted for recipients of both DT and LR and family/carers of DT participants. This study provides initial evidence that the specific process of legacy creation is able to positively affect sense of generativity, meaning, and acceptance near end of life. High acceptability and satisfaction rates for both DT and LR and positive impacts on families/carers of DT participants provide additional support for clinical utility of these interventions. Further evaluation of specific mechanisms of change post-intervention is required given DT's uncertain efficacy on other primary outcomes. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Exposure of Lycopersicon Esculentum to Microcystin-LR: Effects in the Leaf Proteome and Toxin Translocation from Water to Leaves and Fruits

PubMed Central

Gutiérrez-Praena, Daniel; Campos, Alexandre; Azevedo, Joana; Neves, Joana; Freitas, Marisa; Guzmán-Guillén, Remédios; Cameán, Ana María; Renaut, Jenny; Vasconcelos, Vitor

2014-01-01

Natural toxins such as those produced by freshwater cyanobacteria have been regarded as an emergent environmental threat. However, the impact of these water contaminants in agriculture is not yet fully understood. The aim of this work was to investigate microcystin-LR (MC-LR) toxicity in Lycopersicon esculentum and the toxin accumulation in this horticultural crop. Adult plants (2 month-old) grown in a greenhouse environment were exposed for 2 weeks to either pure MC-LR (100 μg/L) or Microcystis aeruginosa crude extracts containing 100 μg/L MC-LR. Chlorophyll fluorescence was measured, leaf proteome investigated with two-dimensional gel electrophoresis and Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF)/TOF, and toxin bioaccumulation assessed by liquid chromatography-mass spectrometry (LC-MS)/MS. Variations in several protein markers (ATP synthase subunits, Cytochrome b6-f complex iron-sulfur, oxygen-evolving enhancer proteins) highlight the decrease of the capacity of plants to synthesize ATP and to perform photosynthesis, whereas variations in other proteins (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit and ribose-5-phosphate isomerase) suggest an increase of carbon fixation and decrease of carbohydrate metabolism reactions in plants exposed to pure MC-LR and cyanobacterial extracts, respectively. MC-LR was found in roots (1635.21 μg/kg fw), green tomatoes (5.15–5.41 μg/kg fw), mature tomatoes (10.52–10.83 μg/kg fw), and leaves (12,298.18 μg/kg fw). The results raise concerns relative to food safety and point to the necessity of monitoring the bioaccumulation of water toxins in agricultural systems affected by cyanotoxin contamination. PMID:24921194

Exposure of Lycopersicon esculentum to microcystin-LR: effects in the leaf proteome and toxin translocation from water to leaves and fruits.

PubMed

Gutiérrez-Praena, Daniel; Campos, Alexandre; Azevedo, Joana; Neves, Joana; Freitas, Marisa; Guzmán-Guillén, Remédios; Cameán, Ana María; Renaut, Jenny; Vasconcelos, Vitor

2014-06-11

Natural toxins such as those produced by freshwater cyanobacteria have been regarded as an emergent environmental threat. However, the impact of these water contaminants in agriculture is not yet fully understood. The aim of this work was to investigate microcystin-LR (MC-LR) toxicity in Lycopersicon esculentum and the toxin accumulation in this horticultural crop. Adult plants (2 month-old) grown in a greenhouse environment were exposed for 2 weeks to either pure MC-LR (100 μg/L) or Microcystis aeruginosa crude extracts containing 100 μg/L MC-LR. Chlorophyll fluorescence was measured, leaf proteome investigated with two-dimensional gel electrophoresis and Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF)/TOF, and toxin bioaccumulation assessed by liquid chromatography-mass spectrometry (LC-MS)/MS. Variations in several protein markers (ATP synthase subunits, Cytochrome b6-f complex iron-sulfur, oxygen-evolving enhancer proteins) highlight the decrease of the capacity of plants to synthesize ATP and to perform photosynthesis, whereas variations in other proteins (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit and ribose-5-phosphate isomerase) suggest an increase of carbon fixation and decrease of carbohydrate metabolism reactions in plants exposed to pure MC-LR and cyanobacterial extracts, respectively. MC-LR was found in roots (1635.21 μg/kg fw), green tomatoes (5.15-5.41 μg/kg fw), mature tomatoes (10.52-10.83 μg/kg fw), and leaves (12,298.18 μg/kg fw). The results raise concerns relative to food safety and point to the necessity of monitoring the bioaccumulation of water toxins in agricultural systems affected by cyanotoxin contamination.

The relationships of the level of response to alcohol and additional characteristics to alcohol use disorders across adulthood: a discrete-time survival analysis.

PubMed

Trim, Ryan S; Schuckit, Marc A; Smith, Tom L

2009-09-01

A low level of response (LR) to alcohol has been shown to relate to a higher risk for alcohol use disorders (AUDs). However, no previous research has examined the association between LR and the development of AUDs in the context of additional robust risk factors for AUDs. This study evaluated whether LR and other related characteristics predicted the occurrence of AUDs across adulthood using discrete-time survival analysis (DTSA). A total of 297 probands from the San Diego Prospective Study reported on the LR to alcohol, a family history (FH) of AUDs, the typical drinking quantity, the age of drinking onset, the body mass index and the age at the baseline (T1) assessment. Alcohol use disorders (AUDs) were evaluated at the 10-year (T10), T15, T20, and T25 follow-ups. A low LR to alcohol predicted AUD occurrence over the course of adulthood even after controlling for the effects of other robust risk factors. Interaction effects revealed that the impact of FH on AUDs was only observed for subjects with high T1 drinking levels, and probands with high T1 drinking were at high risk for AUDs regardless of their age of onset. The findings illustrate that LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors. The continued investigation of how LR is related to AUD onset later in life will help inform treatment providers about this high-risk population, and future longitudinal evaluations will utilize DTSA to assess rates of AUD remission as well as the onset of drinking outcomes in adolescent samples.

The Relationships of the Level of Response to Alcohol and Additional Characteristics to Alcohol Use Disorders across Adulthood: A Discrete-Time Survival Analysis

PubMed Central

Trim, Ryan S.; Schuckit, Marc A.; Smith, Tom L.

2010-01-01

Background A low level of response (LR) to alcohol has been shown to relate to a higher risk for alcohol use disorders (AUDs). However, no previous research has examined the association between LR and the development of AUDs in the context of additional robust risk factors for AUDs. This study evaluated whether LR and other related characteristics predicted the occurrence of AUDs across adulthood using discrete-time survival analysis (DTSA). Methods 297 probands from the San Diego Prospective Study reported on the LR to alcohol, a family history (FH) of AUDs, the typical drinking quantity, the age of drinking onset, the body mass index and the age at the baseline (T1) assessment. Alcohol use disorders (AUDs) were evaluated at the 10-year (T10), T15, T20, and T25 follow-ups. Results A low LR to alcohol predicted AUD occurrence over the course of adulthood even after controlling for the effects of other robust risk factors. Interaction effects revealed that the impact of FH on AUDs was only observed for subjects with high T1 drinking levels, and probands with high T1 drinking were at high risk for AUDs regardless of their age of onset. Conclusion The findings illustrate that LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors. The continued investigation of how LR is related to AUD onset later in life will help inform treatment providers about this high-risk population, and future longitudinal evaluations will utilize DTSA to assess rates of AUD remission as well as the onset of drinking outcomes in adolescent samples. PMID:19485971

Elimination of microcystin-LR and residual Mn species using permanganate and powdered activated carbon: Oxidation products and pathways.

PubMed

Jeong, Boyoung; Oh, Min-Seok; Park, Hyun-Mee; Park, Chanhyuk; Kim, Eun-Ju; Hong, Seok Won

2017-05-01

The oxidation of microcystin-LR (MC-LR) in deionized water (DI) and river water using potassium permanganate (KMnO 4 ) at a neutral pH and at 23 ± 2 °C was investigated. These two aqueous systems (i.e., DI and river water) gave comparable second-order rate constants (289.9 and 285.5 M -1 s -1 (r 2  > 0.99), respectively), which confirmed the effectiveness of this oxidation process for the treatment of natural surface water. The presence of either humic or fulvic acid reduced the removal efficiency of MC-LR, with the latter exhibiting a greater inhibitory effect. Monitoring of MC-LR and residual Mn 2+ levels with adding KMnO 4 (1 mg/L) and powdered activated carbon (PAC, 5-20 mg L -1 ) before and during coagulation, respectively, revealed that 60 min of permanganate pre-oxidation followed by coagulant addition with PAC was the most effective approach for reducing both levels below limits stated by WHO guidelines. The MC-LR degradation products were the result of oxidation occurring at the diene and aromatic moieties of the Adda (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid) side-chain, in addition to amine bond hydrolysis of the Mdha (N-methyldehydroalanine) moiety. Several toxic by-products with an intact Adda chain were observed during the reaction, but completely disappeared after 60 min. This further supports the conclusion that sufficient contact time with permanganate (i.e., >60 min) is essential to reducing the residual toxicity and maximizing the efficiency of MC-LR oxidation when treating raw water. Copyright © 2017 Elsevier Ltd. All rights reserved.

A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone.

PubMed

Rakovitch, Eileen; Nofech-Mozes, Sharon; Hanna, Wedad; Baehner, Frederick L; Saskin, Refik; Butler, Steven M; Tuck, Alan; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A; Bonin, Michel; Chang, Martin C; Robertson, Susan J; Slodkowska, Elzbieta; Fong, Cindy; Anderson, Joseph M; Jamshidian, Farid; Miller, Dave P; Cherbavaz, Diana B; Shak, Steven; Paszat, Lawrence

2015-07-01

Validated biomarkers are needed to improve risk assessment and treatment decision-making for women with ductal carcinoma in situ (DCIS) of the breast. The Oncotype DX DCIS Score (DS) was shown to predict the risk of local recurrence (LR) in individuals with low-risk DCIS treated by breast-conserving surgery (BCS) alone. Our objective was to confirm these results in a larger population-based cohort of individuals. We used an established population-based cohort of individuals diagnosed with DCIS treated with BCS alone from 1994 to 2003 with validation of treatment and outcomes. Central pathology assessment excluded cases with invasive cancer, DCIS < 2 mm or positive margins. Cox model was used to determine the relationship between independent covariates, the DS (hazard ratio (HR)/50 Cp units (U)) and LR. Tumor blocks were collected for 828 patients. Final evaluable population includes 718 cases, of whom 571 had negative margins. Median follow-up was 9.6 years. 100 cases developed LR following BCS alone (DCIS, N = 44; invasive, N = 57). In the primary pre-specified analysis, the DS was associated with any LR (DCIS or invasive) in ER+ patients (HR 2.26; P < 0.001) and in all patients regardless of ER status (HR 2.15; P < 0.001). DCIS Score provided independent information on LR risk beyond clinical and pathologic variables including size, age, grade, necrosis, multifocality, and subtype (adjusted HR 1.68; P = 0.02). DCIS was associated with invasive LR (HR 1.78; P = 0.04) and DCIS LR (HR 2.43; P = 0.005). The DCIS Score independently predicts and quantifies individualized recurrence risk in a population of patients with pure DCIS treated by BCS alone.

Testing a level of response to alcohol-based model of heavy drinking and alcohol problems in 1,905 17-year-olds.

PubMed

Schuckit, Marc A; Smith, Tom L; Heron, Jon; Hickman, Matthew; Macleod, John; Lewis, Glyn; Davis, John M; Hibbeln, Joseph R; Brown, Sandra; Zuccolo, Luisa; Miller, Laura L; Davey-Smith, George

2011-10-01

The low level of response (LR) to alcohol is one of several genetically influenced characteristics that increase the risk for heavy drinking and alcohol problems. Efforts to understand how LR operates through additional life influences have been carried out primarily in modest-sized U.S.-based samples with limited statistical power, raising questions about generalizability and about the importance of components with smaller effects. This study evaluates a full LR-based model of risk in a large sample of adolescents from the United Kingdom. Cross-sectional structural equation models were used for the approximate first half of the age 17 subjects assessed by the Avon Longitudinal Study of Parents and Children, generating data on 1,905 adolescents (mean age 17.8 years, 44.2% boys). LR was measured with the Self-Rating of the Effects of Alcohol Questionnaire, outcomes were based on drinking quantities and problems, and standardized questionnaires were used to evaluate peer substance use, alcohol expectancies, and using alcohol to cope with stress. In this young and large U.K. sample, a low LR related to more adverse alcohol outcomes both directly and through partial mediation by all 3 additional key variables (peer substance use, expectancies, and coping). The models were similar in boys and girls. These results confirm key elements of the hypothesized LR-based model in a large U.K. sample, supporting some generalizability beyond U.S. groups. They also indicate that with enough statistical power, multiple elements contribute to how LR relates to alcohol outcomes and reinforce the applicability of the model to both genders. Copyright © 2011 by the Research Society on Alcoholism.

The bZIP dimer localizes at DNA full-sites where each basic region can alternately translocate and bind to subsites at the half-site

PubMed Central

Chan, I-San; Al-Sarraj, Taufik; Shahravan, S. Hesam; Fedorova, Anna V.; Shin, Jumi A.

2012-01-01

Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1 or CRE site show how each GCN4 basic region binds to a 4-bp cognate half-site as a single DNA target; however, this may not always fully describe how bZIP proteins interact with their target sites. Previously, we showed that the GCN4 basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR), and that 5H-LR comprises two 4-bp subsites, TTGC and TGCG, which individually are also target sites of the basic region. In this work, we explored how the basic region interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing 5H-LR to investigate in silico the interface between the basic region and 5H-LR. We also performed in vitro investigation of bZIP–DNA interactions at a number of full-sites that contain 5H-LR vs. either subsite: we analyzed results from DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from EMSA titrations to quantify binding affinities. Our computational and experimental results together support a highly dynamic DNA-binding model: when a bZIP dimer localizes to its target full-site, the basic region can alternately recognize either subsite as a distinct target at 5H-LR and translocate between the subsites, potentially by sliding and hopping. This model provides added insights into how α-helical DNA-binding domains of transcription factors can localize to their gene regulatory sequences in vivo. PMID:22856882

The bZIP dimer localizes at DNA full-sites where each basic region can alternately translocate and bind to subsites at the half-site.

PubMed

Chan, I-San; Al-Sarraj, Taufik; Shahravan, S Hesam; Fedorova, Anna V; Shin, Jumi A

2012-08-21

Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1 or CRE site show how each GCN4 basic region binds to a 4 bp cognate half-site as a single DNA target; however, this may not always fully describe how bZIP proteins interact with their target sites. Previously, we showed that the GCN4 basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR) and that 5H-LR comprises two 4 bp subsites, TTGC and TGCG, which individually are also target sites of the basic region. In this work, we explore how the basic region interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing 5H-LR to investigate in silico the interface between the basic region and 5H-LR. We also performed in vitro investigation of bZIP-DNA interactions at a number of full-sites that contain 5H-LR versus either subsite: we analyzed results from DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from EMSA titrations to quantify binding affinities. Our computational and experimental results together support a highly dynamic DNA-binding model: when a bZIP dimer localizes to its target full-site, the basic region can alternately recognize either subsite as a distinct target at 5H-LR and translocate between the subsites, potentially by sliding and hopping. This model provides added insights into how α-helical DNA-binding domains of transcription factors can localize to their gene regulatory sequences in vivo.

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

Wong, Philip; Lambert, Christine, E-mail: christine.lambert@muhc.mcgill.ca; Agnihotram, Ramanakumar V.

Purpose: Local recurrence (LR) of ductal carcinoma in situ (DCIS) is reduced by whole-breast irradiation after breast-conserving surgery (BCS). However, the benefit of adding a radiotherapy boost to the surgical cavity for DCIS is unclear. We sought to determine the impact of the boost on LR in patients with DCIS treated at the McGill University Health Centre. Methods and Materials: A total of 220 consecutive cases of DCIS treated with BCS and radiotherapy between January 2000 and December 2006 were reviewed. Of the patients, 36% received a radiotherapy boost to the surgical cavity. Median follow-up was 46 months for themore » boost and no-boost groups. Kaplan-Meier survival analyses and Cox regression analyses were performed. Results: Compared with the no-boost group, patients in the boost group more frequently had positive and <0.1-cm margins (48% vs. 8%) (p < 0.0001) and more frequently were in higher-risk categories as defined by the Van Nuys Prognostic (VNP) index (p = 0.006). Despite being at higher risk for LR, none (0/79) of the patients who received a boost experienced LR, whereas 8 of 141 patients who did not receive a boost experienced an in-breast LR (log-rank p = 0.03). Univariate analysis of prognostic factors (age, tumor size, margin status, histological grade, necrosis, and VNP risk category) revealed only the presence of necrosis to significantly correlate with LR (log-rank p = 0.003). The whole-breast irradiation dose and fractionation schedule did not affect LR rate. Conclusions: Our results suggest that the use of a radiotherapy boost improves local control in DCIS and may outweigh the poor prognostic effect of necrosis.« less

Revisiting the Ceara Rise, equatorial Atlantic Ocean: isotope stratigraphy of ODP Leg 154 from 0 to 5 Ma

NASA Astrophysics Data System (ADS)

Wilkens, Roy H.; Westerhold, Thomas; Drury, Anna J.; Lyle, Mitchell; Gorgas, Thomas; Tian, Jun

2017-07-01

Isotope stratigraphy has become the method of choice for investigating both past ocean temperatures and global ice volume. Lisiecki and Raymo (2005) published a stacked record of 57 globally distributed benthic δ18O records versus age (LR04 stack). In this study LR04 is compared to high-resolution records collected at all of the sites drilled during ODP Leg 154 on the Ceara Rise, in the western equatorial Atlantic Ocean. Newly developed software is used to check data splices of the Ceara Rise sites and better align out-of-splice data with in-splice data. Core images recovered from core table photos are depth and age scaled and greatly assist in the data analysis. The entire splices of ODP sites 925, 926, 927, 928 and 929 were reviewed. Most changes were minor although several were large enough to affect age models based on orbital tuning. A Ceara Rise composite record of benthic δ18O is out of sync with LR04 between 1.80 and 1.90 Ma, where LR04 exhibits two maxima but Ceara Rise data contain only one. The interval between 4.0 and 4.5 Ma in the Ceara Rise compilation is decidedly different from LR04, reflecting both the low amplitude of the signal over this interval and the limited amount of data available for the LR04 stack. A regional difference in benthic δ18O of 0.2 ‰ relative to LR04 was found. Independent tuning of Site 926 images and physical property data to the Laskar et al. (2004) orbital solution and integration of available benthic stable isotope data from the Ceara Rise provides a new regional reference section for the equatorial Atlantic covering the last 5 million years.

Right across the tree of life: the evolution of left-right asymmetry in the Bilateria.

PubMed

Namigai, Erica K O; Kenny, Nathan J; Shimeld, Sebastian M

2014-06-01

Directional left/right (LR) asymmetries, in which there are consistent, heritable differences in morphology between the left and right sides of bilaterally symmetrical organisms, are found in animals across the Bilateria. For many years, we have lacked evidence for shared mechanisms underlying their development. This led to the supposition that the mechanisms driving establishment of LR asymmetries, and consequently the asymmetries themselves, had evolved separately in the three major Superphyla that constitute the Bilateria. The recent discovery that the transforming growth factor-beta (TGF-B) ligand Nodal plays a role in the regulation of LR asymmetry in both Deuterostomia and Lophotrochozoa has reignited debate in this field, as it suggests that at least this aspect of the development of the LR axis is conserved. In this review, we discuss evidence for shared mechanisms of LR asymmetry establishment across the bilaterian tree of life and consider how these mechanisms might have diverged across the Metazoa over the last 500 million years or so of evolution. As well as the likelihood that Nodal is an ancestral mechanism for regulating LR asymmetry, we reemphasize cytoskeletal architecture as a potential shared mechanism underlying symmetry breaking. However, convergent evolution remains a distinct possibility and study of a wider diversity of species will be needed to distinguish between conserved and lineage-specific mechanisms. © 2014 Wiley Periodicals, Inc.

Identifying common donors in DNA mixtures, with applications to database searches.

PubMed

Slooten, K

2017-01-01

Several methods exist to compute the likelihood ratio LR(M, g) evaluating the possible contribution of a person of interest with genotype g to a mixed trace M. In this paper we generalize this LR to a likelihood ratio LR(M 1 , M 2 ) involving two possibly mixed traces M 1 and M 2 , where the question is whether there is a donor in common to both traces. In case one of the traces is in fact a single genotype, then this likelihood ratio reduces to the usual LR(M, g). We explain how our method conceptually is a logical consequence of the fact that LR calculations of the form LR(M, g) can be equivalently regarded as a probabilistic deconvolution of the mixture. Based on simulated data, and using a semi-continuous mixture evaluation model, we derive ROC curves of our method applied to various types of mixtures. From these data we conclude that searches for a common donor are often feasible in the sense that a very small false positive rate can be combined with a high probability to detect a common donor if there is one. We also show how database searches comparing all traces to each other can be carried out efficiently, as illustrated by the application of the method to the mixed traces in the Dutch DNA database. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Noninvasive Assessment of Advanced Fibrosis Based on Hepatic Volume in Patients with Nonalcoholic Fatty Liver Disease.

PubMed

Hayashi, Tatsuya; Saitoh, Satoshi; Fukuzawa, Kei; Tsuji, Yoshinori; Takahashi, Junji; Kawamura, Yusuke; Akuta, Norio; Kobayashi, Masahiro; Ikeda, Kenji; Fujii, Takeshi; Miyati, Tosiaki; Kumada, Hiromitsu

2017-09-15

Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the hepatic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diagnosing fibrosis ≥F3-4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify variables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confidence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associated with the L/R ratio (coefficient, 0.121; p<0.0001). The L/R ratio, which is not influenced by pathological parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD.

Cost-effectiveness assessment of lumpectomy cavity boost in elderly women with early stage estrogen receptor positive breast cancer receiving adjuvant radiotherapy.

PubMed

Lester-Coll, Nataniel H; Rutter, Charles E; Evans, Suzanne B

2016-04-01

Breast radiotherapy (RT) for elderly women with estrogen receptor positive early stage breast cancer (ER+ESBC) improves local recurrence (LR) rates without benefitting overall survival. Breast boost is a common practice, although the absolute benefit decreases with age. Consequently, an analysis of its cost-effectiveness in the elderly ESBC populations is warranted. A Markov model was used to compare cost-effectiveness of RT with or without a boost in elderly ER+ESBC patients. The ten-year probability of LR with boost was derived from the CALGB 9343 trial and adjusted by the hazard ratio for LR from boost radiotherapy trial data, yielding the LR rate without boost. Remaining parameters were estimated using published data. Boost RT was associated with an increase in mean cost ($7139 vs $6193) and effectiveness (5.66 vs 5.64 quality adjusted life years; QALYs) relative to no boost. The incremental cost-effectiveness ratio (ICER) for boost was $55,903 per QALY. On one-way sensitivity analysis, boost remained cost-effective if the hazard ratio of LR with boost was <0.67. Boost RT for ER+ESBC patients was cost-effective over a wide range of assumptions and inputs over commonly accepted willingness-to pay-thresholds, but particularly in women at higher risk for LR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inheritance and Bulked Segregant Analysis of Leaf Rust and Stem Rust Resistance in Durum Wheat Genotypes.

PubMed

Aoun, Meriem; Kolmer, James A; Rouse, Matthew N; Chao, Shiaoman; Bulbula, Worku Denbel; Elias, Elias M; Acevedo, Maricelis

2017-12-01

Leaf rust, caused by Puccinia triticina, and stem rust, caused by P. graminis f. sp. tritici, are important diseases of durum wheat. This study determined the inheritance and genomic locations of leaf rust resistance (Lr) genes to P. triticina race BBBQJ and stem rust resistance (Sr) genes to P. graminis f. sp. tritici race TTKSK in durum accessions. Eight leaf-rust-resistant genotypes were used to develop biparental populations. Accessions PI 192051 and PI 534304 were also resistant to P. graminis f. sp. tritici race TTKSK. The resulting progenies were phenotyped for leaf rust and stem rust response at seedling stage. The Lr and Sr genes were mapped in five populations using single-nucleotide polymorphisms and bulked segregant analysis. Five leaf-rust-resistant genotypes carried single dominant Lr genes whereas, in the remaining accessions, there was deviation from the expected segregation ratio of a single dominant Lr gene. Seven genotypes carried Lr genes different from those previously characterized in durum. The single dominant Lr genes in PI 209274, PI 244061, PI387263, and PI 313096 were mapped to chromosome arms 6BS, 2BS, 6BL, and 6BS, respectively. The Sr gene in PI 534304 mapped to 6AL and is most likely Sr13, while the Sr gene in PI 192051 could be uncharacterized in durum.

The Case for Extant Life on Mars and Its Possible Detection by the Viking Labeled Release Experiment

NASA Astrophysics Data System (ADS)

Levin, Gilbert V.; Straat, Patricia Ann

2016-10-01

The 1976 Viking Labeled Release (LR) experiment was positive for extant microbial life on the surface of Mars. Experiments on both Viking landers, 4000 miles apart, yielded similar, repeatable, positive responses. While the authors eventually concluded that the experiment detected martian life, this was and remains a highly controversial conclusion. Many believe that the martian environment is inimical to life and the LR responses were nonbiological, attributed to an as-yet-unidentified oxidant (or oxidants) in the martian soil. Unfortunately, no further metabolic experiments have been conducted on Mars. Instead, follow-on missions have sought to define the martian environment, mostly searching for signs of water. These missions have collected considerable data regarding Mars as a habitat, both past and present. The purpose of this article is to consider recent findings about martian water, methane, and organics that impact the case for extant life on Mars. Further, the biological explanation of the LR and recent nonbiological hypotheses are evaluated. It is concluded that extant life is a strong possibility, that abiotic interpretations of the LR data are not conclusive, and that, even setting our conclusion aside, biology should still be considered as an explanation for the LR experiment. Because of possible contamination of Mars by terrestrial microbes after Viking, we note that the LR data are the only data we will ever have on biologically pristine martian samples.

In-flight sleep, pilot fatigue and Psychomotor Vigilance Task performance on ultra-long range versus long range flights.

PubMed

Gander, Philippa H; Signal, T Leigh; van den Berg, Margo J; Mulrine, Hannah M; Jay, Sarah M; Jim Mangie, Captain

2013-12-01

This study evaluated whether pilot fatigue was greater on ultra-long range (ULR) trips (flights >16 h on 10% of trips in a 90-day period) than on long range (LR) trips. The within-subjects design controlled for crew complement, pattern of in-flight breaks, flight direction and departure time. Thirty male Captains (mean age = 54.5 years) and 40 male First officers (mean age = 48.0 years) were monitored on commercial passenger flights (Boeing 777 aircraft). Sleep was monitored (actigraphy, duty/sleep diaries) from 3 days before the first study trip to 3 days after the second study trip. Karolinska Sleepiness Scale, Samn-Perelli fatigue ratings and a 5-min Psychomotor Vigilance Task were completed before, during and after every flight. Total sleep in the 24 h before outbound flights and before inbound flights after 2-day layovers was comparable for ULR and LR flights. All pilots slept on all flights. For each additional hour of flight time, they obtained an estimated additional 12.3 min of sleep. Estimated mean total sleep was longer on ULR flights (3 h 53 min) than LR flights (3 h 15 min; P(F) = 0.0004). Sleepiness ratings were lower and mean reaction speed was faster at the end of ULR flights. Findings suggest that additional in-flight sleep mitigated fatigue effectively on longer flights. Further research is needed to clarify the contributions to fatigue of in-flight sleep versus time awake at top of descent. The study design was limited to eastward outbound flights with two Captains and two First Officers. Caution must be exercised when extrapolating to different operations. © 2013 European Sleep Research Society.

Assessment of oximetry-based statistical classifiers as simplified screening tools in the management of childhood obstructive sleep apnea.

PubMed

Crespo, Andrea; Álvarez, Daniel; Kheirandish-Gozal, Leila; Gutiérrez-Tobal, Gonzalo C; Cerezo-Hernández, Ana; Gozal, David; Hornero, Roberto; Del Campo, Félix

2018-02-16

A variety of statistical models based on overnight oximetry has been proposed to simplify the detection of children with suspected obstructive sleep apnea syndrome (OSAS). Despite the usefulness reported, additional thorough comparative analyses are required. This study was aimed at assessing common binary classification models from oximetry for the detection of childhood OSAS. Overnight oximetry recordings from 176 children referred for clinical suspicion of OSAS were acquired during in-lab polysomnography. Several training and test datasets were randomly composed by means of bootstrapping for model optimization and independent validation. For every child, blood oxygen saturation (SpO 2 ) was parameterized by means of 17 features. Fast correlation-based filter (FCBF) was applied to search for the optimum features. The discriminatory power of three statistical pattern recognition algorithms was assessed: linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and logistic regression (LR). The performance of each automated model was evaluated for the three common diagnostic polysomnographic cutoffs in pediatric OSAS: 1, 3, and 5 events/h. Best screening performances emerged using the 1 event/h cutoff for mild-to-severe childhood OSAS. LR achieved 84.3% accuracy (95% CI 76.8-91.5%) and 0.89 AUC (95% CI 0.83-0.94), while QDA reached 96.5% PPV (95% CI 90.3-100%) and 0.91 AUC (95% CI 0.85-0.96%). Moreover, LR and QDA reached diagnostic accuracies of 82.7% (95% CI 75.0-89.6%) and 82.1% (95% CI 73.8-89.5%) for a cutoff of 5 events/h, respectively. Automated analysis of overnight oximetry may be used to develop reliable as well as accurate screening tools for childhood OSAS.

Primary dysmenorrhea: prevalence in adolescent population of Tbilisi, Georgia and risk factors

PubMed Central

Gagua, Tinatin; Tkeshelashvili, Besarion; Gagua, David

2012-01-01

Objective The study aimed to determine the prevalence of dysmenorrhea in female adolescents living in Tbilisi, Georgia; find possible risk factors and establish an association, if any, with nutrition and sleep hygiene. Material and Methods A cross-sectional study was used. A retrospective case control study was used to identify risk factors. Participants: A total of 2561 women consented to participate in the research. 431 participants were included in the case-control study. Interventions: Detailed questionnaire included: reproductive history, demographic features, menstrual pattern, severity of dysmenorrhea and associated symptoms; information about nutrition and sleep hygiene. Results The prevalence of dysmenorrhea was 52.07%. Due to pain, 69.78% reported frequent school absenteeism. The risk of dysmenorrhea in students who had a family history of dysmenorrhea was approximately 6 times higher than in students with no prior history. The prevalence of dysmenorrhea was significantly higher among smokers compared with non-smokers 3.99% vs. 0.68% (p=.0.05 OR:6.102). Those women reporting an increased intake of sugar reported a marked increase of dysmenorrhea compared to women reporting no daily sugar intake (55.61% vs. 44.39%, p=.0023 LR:0.0002). However, alcohol, family atmosphere and nationality showed no correlation with dysmenorrhea. Our study revealed two most important risk factors of dysmenorrhea: meal skipping 59.78% vs. 27.03%, p=.00000 LR: 0.00000 OR:4.014 and sleep hygiene-receiving less sleep 38.77% vs. 19.59%, p=0.000055 LR: 0.000036 OR:2.598. Conclusion Primary dysmenorrhea is a common problem in the adolescent population of Tbilisi Geogia. It adversely affects their educational performance. Meal skipping and sleep quantity are associated with dysmenorrhea and may cause other reproductive dysfunctions. PMID:24592031

Landslide susceptibility mapping using decision-tree based CHi-squared automatic interaction detection (CHAID) and Logistic regression (LR) integration

NASA Astrophysics Data System (ADS)

Althuwaynee, Omar F.; Pradhan, Biswajeet; Ahmad, Noordin

2014-06-01

This article uses methodology based on chi-squared automatic interaction detection (CHAID), as a multivariate method that has an automatic classification capacity to analyse large numbers of landslide conditioning factors. This new algorithm was developed to overcome the subjectivity of the manual categorization of scale data of landslide conditioning factors, and to predict rainfall-induced susceptibility map in Kuala Lumpur city and surrounding areas using geographic information system (GIS). The main objective of this article is to use CHi-squared automatic interaction detection (CHAID) method to perform the best classification fit for each conditioning factor, then, combining it with logistic regression (LR). LR model was used to find the corresponding coefficients of best fitting function that assess the optimal terminal nodes. A cluster pattern of landslide locations was extracted in previous study using nearest neighbor index (NNI), which were then used to identify the clustered landslide locations range. Clustered locations were used as model training data with 14 landslide conditioning factors such as; topographic derived parameters, lithology, NDVI, land use and land cover maps. Pearson chi-squared value was used to find the best classification fit between the dependent variable and conditioning factors. Finally the relationship between conditioning factors were assessed and the landslide susceptibility map (LSM) was produced. An area under the curve (AUC) was used to test the model reliability and prediction capability with the training and validation landslide locations respectively. This study proved the efficiency and reliability of decision tree (DT) model in landslide susceptibility mapping. Also it provided a valuable scientific basis for spatial decision making in planning and urban management studies.

Measurement of locally resonant band gaps in a surface phononic crystal with inverted conical pillars

NASA Astrophysics Data System (ADS)

Hsu, Jin-Chen; Lin, Fan-Shun

2018-07-01

In this paper, we numerically and experimentally study locally resonant (LR) band gaps for surface acoustic waves (SAWs) in a honeycomb array of inverted conical pillars grown on the surface of a 128°YX lithium-niobate substrate. We show that the inverted conical pillars can be used to generate lower LR band gaps below the sound cone. This lowering effect is caused by the increase in the effective pillar mass without increasing the effective stiffness. We employ the finite-element method to calculate the LR band gaps and wideband slanted-finger interdigital transducers to measure the transmission of SAWs. Numerical results show that SAWs are prohibited from propagating through the structure in the lowered LR band gaps. Obvious LR band-gap lowering is observed in the experimental result of a surface phononic crystal with a honeycomb array of inverted conical pillars. The results enable enhanced control over the phononic metamaterial and surface structures, which may have applications in low-frequency waveguiding, acoustic isolation, acoustic absorbers, and acoustic filters.

Determination of microcystin-LR in drinking water using UPLC tandem mass spectrometry-matrix effects and measurement.

PubMed

Li, Wei; Duan, Jinming; Niu, Chaoying; Qiang, Naichen; Mulcahy, Dennis

2011-10-01

A simple detection method using ultra-performance liquid chromatography electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS-MS) coupled with the sample dilution method for determining trace microcystin-LR (MC-LR) in drinking water is presented. The limit of detection (LOD) was 0.04 µg/L and the limit of quantitation (LOQ) was 0.1 µg/L. Water matrix effects of ionic strength, dissolved organic carbon (DOC) and pH were examined. The results indicate that signal detection intensity for MC-LR was significantly suppressed as the ionic strength increased from ultrapure water condition, whereas it increased slightly with solution pH and DOC at low concentrations. However, addition of methanol (MeOH) into the sample was able to counter the signal suppression effects. In this study, dilution of the tap water sample by adding 4% MeOH (v/v) was observed to be adequate to compensate for the signal suppression. The recoveries of the samples fortified with MC-LR (0.2, 1, and 10 µg/L) for three different tap water samples ranged from 84.4% to 112.9%.

Validity of the MMPI-2-RF (restructured form) L-r and K-r scales in detecting underreporting in clinical and nonclinical samples.

PubMed

Sellbom, Martin; Bagby, R Michael

2008-12-01

In the current investigation, the authors examined the validity of the L-r and K-r scales on the recently developed Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Y. S. Ben-Porath & A. Tellegen, in press) in measuring underreported response bias. Three archival samples previously collected for examining MMPI-2 validity scales were reanalyzed in 2 studies. In Study 1 L-r and K-r significantly differentiated 2 groups of participants (patients with schizophrenia and university students) who had been instructed to underreport on the MMPI-2 from participants who took the test under standard instructions. L-r and K-r also added incremental predictive variance to one another in differentiating these groups. In Study 2 a similar set of outcomes emerged through the use of a differential prevalence design in which L-r and K-r significantly differentiated a group of child custody litigants who were administered the MMPI-2 from university students taking the test under standard instructions. (c) 2008 APA, all rights reserved.

A systematic review of trends and patterns of congenital heart disease in children in Nigeria from 1964-2015.

PubMed

Abdulkadir, Mohammed; Abdulkadir, Zainab

2016-06-01

Congenital heart diseases cause significant childhood morbidity and mortality. Several restricted studies have been conducted on the epidemiology in Nigeria. No truly nationwide data on patterns of congenital heart disease exists. To determine the patterns of congenital heart disease in children in Nigeria and examine trends in the occurrence of individual defects across 5 decades. We searched PubMed database, Google scholar, TRIP database, World Health Organisation libraries and reference lists of selected articles for studies on patterns of congenital heart disease among children in Nigeria between 1964 and 2015. Two researchers reviewed the papers independently and extracted the data. Seventeen studies were selected that included 2,953 children with congenital heart disease. The commonest congenital heart diseases in Nigeria are ventricular septal defect (40.6%), patent ductus arteriosus (18.4%), atrial septal defect (11.3%) and tetralogy of Fallot (11.8%). There has been a 6% increase in the burden of VSD in every decade for the 5 decades studied and a decline in the occurrence of pulmonary stenosis. Studies conducted in Northern Nigeria demonstrated higher proportions of atrial septal defects than patent ductus arteriosus. Ventricular septal defects are the commonest congenital heart diseases in Nigeria with a rising burden.

PCB Fault Detection Using Image Processing

NASA Astrophysics Data System (ADS)

Nayak, Jithendra P. R.; Anitha, K.; Parameshachari, B. D., Dr.; Banu, Reshma, Dr.; Rashmi, P.

2017-08-01

The importance of the Printed Circuit Board inspection process has been magnified by requirements of the modern manufacturing environment where delivery of 100% defect free PCBs is the expectation. To meet such expectations, identifying various defects and their types becomes the first step. In this PCB inspection system the inspection algorithm mainly focuses on the defect detection using the natural images. Many practical issues like tilt of the images, bad light conditions, height at which images are taken etc. are to be considered to ensure good quality of the image which can then be used for defect detection. Printed circuit board (PCB) fabrication is a multidisciplinary process, and etching is the most critical part in the PCB manufacturing process. The main objective of Etching process is to remove the exposed unwanted copper other than the required circuit pattern. In order to minimize scrap caused by the wrongly etched PCB panel, inspection has to be done in early stage. However, all of the inspections are done after the etching process where any defective PCB found is no longer useful and is simply thrown away. Since etching process costs 0% of the entire PCB fabrication, it is uneconomical to simply discard the defective PCBs. In this paper a method to identify the defects in natural PCB images and associated practical issues are addressed using Software tools and some of the major types of single layer PCB defects are Pattern Cut, Pin hole, Pattern Short, Nick etc., Therefore the defects should be identified before the etching process so that the PCB would be reprocessed. In the present approach expected to improve the efficiency of the system in detecting the defects even in low quality images

Method for mask repair using defect compensation

DOEpatents

Sweeney, Donald W.; Ray-Chaudhuri, Avijit K.

2001-01-01

A method for repair of amplitude and/or phase defects in lithographic masks. The method involves modifying or altering a portion of the absorber pattern on the surface of the mask blank proximate to the mask defect to compensate for the local disturbance (amplitude or phase) of the optical field due to the defect.

Liver Transcriptome and miRNA Analysis of Silver Carp (Hypophthalmichthys molitrix) Intraperitoneally Injected With Microcystin-LR

PubMed Central

Qu, Xiancheng; Hu, Menghong; Shang, Yueyong; Pan, Lisha; Jia, Peixuan; Fu, Chunxue; Liu, Qigen; Wang, Youji

2018-01-01

Next-generation sequencing was used to analyze the effects of toxic microcystin-LR (MC-LR) on silver carp (Hypophthalmichthys molitrix). Silver carps were intraperitoneally injected with MC-LR, and RNA-seq and miRNA-seq in the liver were analyzed at 0.25, 0.5, and 1 h. The expression of glutathione S-transferase (GST), which acts as a marker gene for MC-LR, was tested to determine the earliest time point at which GST transcription was initiated in the liver tissues of the MC-LR-treated silver carps. Hepatic RNA-seq/miRNA-seq analysis and data integration analysis were conducted with reference to the identified time point. Quantitative PCR (qPCR) was performed to detect the expression of the following genes at the three time points: heme oxygenase 1 (HO-1), interleukin-10 receptor 1 (IL-10R1), apolipoprotein A-I (apoA-I), and heme binding protein 2 (HBP2). Results showed that the liver GST expression was remarkably decreased at 0.25 h (P < 0.05). RNA-seq at this time point revealed that the liver tissue contained 97,505 unigenes, including 184 significantly different unigenes and 75 unknown genes. Gene Ontology (GO) term enrichment analysis suggested that 35 of the 145 enriched GO terms were significantly enriched and mainly related to the immune system regulation network. KEGG pathway enrichment analysis showed that 18 of the 189 pathways were significantly enriched, and the most significant was a ribosome pathway containing 77 differentially expressed genes. miRNA-seq analysis indicated that the longest miRNA had 22 nucleotides (nt), followed by 21 and 23 nt. A total of 286 known miRNAs, 332 known miRNA precursor sequences, and 438 new miRNAs were predicted. A total of 1,048,575 mRNA–miRNA interaction sites were obtained, and 21,252 and 21,241 target genes were respectively predicted in known and new miRNAs. qPCR revealed that HO-1, IL-10R1, apoA-I, and HBP2 were significantly differentially expressed and might play important roles in the toxicity and liver detoxification of MC-LR in fish. These results were consistent with those of high-throughput sequencing, thereby verifying the accuracy of our sequencing data. RNA-seq and miRNA-seq analyses of silver carp liver injected with MC-LR provided valuable and new insights into the toxic effects of MC-LR and the antitoxic mechanisms of MC-LR in fish. The RNA/miRNA data are available from the NCBI database Registration No. : SRP075165. PMID:29692738

Kidney removal - discharge

MedlinePlus

... Schwartz MJ, Rais-Bahrami S, Kavoussi LR. Laparoscopic and robotic surgery of the kidney. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, PA: Elsevier; 2016: ...

Using composite sinusoidal patterns in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food

USDA-ARS?s Scientific Manuscript database

This study presented a first exploration of using composite sinusoidal patterns that integrated two and three spatial frequencies of interest, in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food (e.g., bruises in apples). Three methods based on Fourier tra...

Femtosecond pulsed laser micromachining of single crystalline 3C SiC structures based on a laser-induced defect-activation process

NASA Astrophysics Data System (ADS)

Dong, Yuanyuan; Zorman, Christian; Molian, Pal

2003-09-01

A femtosecond pulsed Ti:sapphire laser with a pulse width of 120 fs, a wavelength of 800 nm and a repetition rate of 1 kHz was employed for direct write patterning of single crystalline 3C-SiC thin films deposited on Si substrates. The ablation mechanism of SiC was investigated as a function of pulse energy. At high pulse energies (>1 µJ), ablation occurred via thermally dominated processes such as melting, boiling and vaporizing of single crystalline SiC. At low pulse energies, the ablation mechanism involved a defect-activation process that included the accumulation of defects, formation of nano-particles and vaporization of crystal boundaries, which contributed to well-defined and debris-free patterns in 3C-SiC thin films. The interactions between femtosecond laser pulses and the intrinsic lattice defects in epitaxially grown 3C-SiC films led to the generation of nano-particles. Micromechanical structures such as micromotor rotors and lateral resonators were patterned into 3C-SiC films using the defect-activation ablation mechanism.

Selective formation of porous silicon

NASA Technical Reports Server (NTRS)

Fathauer, Robert W. (Inventor); Jones, Eric W. (Inventor)

1993-01-01

A pattern of porous silicon is produced in the surface of a silicon substrate by forming a pattern of crystal defects in said surface, preferably by applying an ion milling beam through openings in a photoresist layer to the surface, and then exposing said surface to a stain etchant, such as HF:HNO3:H2O. The defected crystal will preferentially etch to form a pattern of porous silicon. When the amorphous content of the porous silicon exceeds 70 percent, the porous silicon pattern emits visible light at room temperature.

Oil-based paint poisoning

MedlinePlus

... DD. Hydrocarbons. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank's ... Dermatologic principles. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank's ...

Cystometric study

MedlinePlus

... dysfunction. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology. 11th ed. Philadelphia, ... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology. 11th ed. Philadelphia, ...

Uterine prolapse

MedlinePlus

... devices. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... prolapse. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Penis pain

MedlinePlus

... Priapism. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... disease. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Retrograde ejaculation

MedlinePlus

... ejaculation. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... infertility. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Emergence of ultrafast sparsely synchronized rhythms and their responses to external stimuli in an inhomogeneous small-world complex neuronal network.

PubMed

Kim, Sang-Yoon; Lim, Woochang

2017-09-01

We consider an inhomogeneous small-world network (SWN) composed of inhibitory short-range (SR) and long-range (LR) interneurons, and investigate the effect of network architecture on emergence of synchronized brain rhythms by varying the fraction of LR interneurons p long . The betweenness centralities of the LR and SR interneurons (characterizing the potentiality in controlling communication between other interneurons) are distinctly different. Hence, in view of the betweenness, SWNs we consider are inhomogeneous, unlike the "canonical" Watts-Strogatz SWN with nearly the same betweenness centralities. For small p long , the load of communication traffic is much concentrated on a few LR interneurons. However, as p long is increased, the number of LR connections (coming from LR interneurons) increases, and then the load of communication traffic is less concentrated on LR interneurons, which leads to better efficiency of global communication between interneurons. Sparsely synchronized rhythms are thus found to emerge when passing a small critical value p long (c) (≃0.16). The population frequency of the sparsely synchronized rhythm is ultrafast (higher than 100 Hz), while the mean firing rate of individual interneurons is much lower (∼30 Hz) due to stochastic and intermittent neural discharges. These dynamical behaviors in the inhomogeneous SWN are also compared with those in the homogeneous Watts-Strogatz SWN, in connection with their network topologies. Particularly, we note that the main difference between the two types of SWNs lies in the distribution of betweenness centralities. Unlike the case of the Watts-Strogatz SWN, dynamical responses to external stimuli vary depending on the type of stimulated interneurons in the inhomogeneous SWN. We consider two cases of external time-periodic stimuli applied to sub-populations of the LR and SR interneurons, respectively. Dynamical responses (such as synchronization suppression and enhancement) to these two cases of stimuli are studied and discussed in relation to the betweenness centralities of stimulated interneurons, representing the effectiveness for transfer of stimulation effect in the whole network. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

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

Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida; Fulp, William J.

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSImore » and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy–based decisions in breast cancer.« less

Comparison of conventional versus three-dimensional ultrasound in fetal renal pelvis measurement and their potential prediction of neonatal uropathies.

PubMed

Duin, L K; Nijhuis, J G; Scherjon, S A; Vossen, M; Willekes, C

2016-01-01

To establish a threshold value for fetal renal pelvis dilatation measured by automatic volume calculation (SonoAVC) in the third trimester of pregnancy to predict neonatal uropathies, and to compare these results with conventional antero-posterior (AP) measurement, fetal kidney 3D volume and renal parenchymal thickness. In a prospective cohort study, 125 fetuses with renal pelvis AP diameter of ≥5 mm both at 20 weeks of gestation and in the third trimester, underwent an additional 3D volume measurement of the fetal kidney in the third trimester. Receiver operating characteristic (ROC) curves for establishing threshold values for fetal renal pelvis volume, AP measurement, fetal kidney volume and renal parenchymal thickness to predict neonatal uropathies were analyzed. Also, sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. A cut-off point of 1.58 cm³ was identified in the third trimester of pregnancy (AUC 0.865 (95% CI 0.789-0.940), sensitivity 76.3%, specificity 87.4%, LR+ 6.06, LR- 0.27) for measurements with SonoAVC. A cut-off value of 11.5 mm was established in the third trimester of pregnancy (AUC 0.828 (95% CI 0.737-0.918), sensitivity 71.1%, specificity 85.1%, LR+ 4.77, LR- 0.34) for the conventional AP measurement. A cut-off point for fetal kidney volume was calculated at 13.29 cm³ (AUC 0.769 (95% CI 0.657-0.881), sensitivity 71%, specificity 66%, LR+ 2.09, LR- 0.44). For renal parenchymal thickness, a cut-off point of 8.4 mm was established (AUC 0.216 (95% CI 0.117-0.315), sensitivity 31.6%, specificity 32.6%, LR+ 0.47, LR- 2.10). This study demonstrates that 3D fetal renal pelvis volume measurements and AP measurements both have a good and comparable diagnostic performance, fetal renal volume a fair accuracy and renal parenchymal thickness a poor accuracy in predicting postnatal renal outcome.

Revisiting the Ceara Rise, equatorial Atlantic Ocean: isotope stratigraphy of ODP Leg 154

NASA Astrophysics Data System (ADS)

Wilkens, Roy; Drury, Anna Joy; Westerhold, Thomas; Lyle, Mitchell; Gorgas, Thomas; Tian, Jun

2017-04-01

Isotope stratigraphy has become the method of choice for investigating both past ocean temperatures and global ice volume. Lisiecki and Raymo (2005) published a stacked record of 57 globally distributed benthic δ18O records versus age (LR04 stack). In this study LR04 is compared to high resolution records collected at all of the sites drilled during Ocean Drilling Program (ODP) Leg 154 on the Ceara Rise, in the western equatorial Atlantic Ocean. Newly developed software - the Code for Ocean Drilling Data (CODD) - is used to check data splices of the Ceara sites and better align out-of-splice data with in-splice data. CODD allows to depth and age scaled core images recovered from core table photos enormously facilitating data analysis. The entire splices of ODP Sites 925, 926, 927, 928 and 929 were reviewed. Most changes were minor although several large enough to affect age models based on orbital tuning. We revised the astronomically tuned age model for the Ceara Rise by tuning darker, more clay rich layers to Northern Hemisphere insolation minima. Then we assembled a regional composite benthic stable isotope record from published data. This new Ceara Rise stack provides a new regional reference section for the equatorial Atlantic covering the last 5 million years with an independent age model compared to the non-linear ice volume models of the LR04 stack. Comparison shows that the benthic δ18O composite is consistent with the LR04 stack from 0 - 4 Ma despite a short interval between 1.80 and 1.90 Ma, where LR04 exhibits 2 maxima but where Ceara Rise contains only 1. The interval between 4.0 and 4.5 Ma in the Ceara Rise compilation is decidedly different from LR04, reflecting both the low amplitude of the signal over this interval and the limited amount of data available for the LR04 stack. Our results also point out that precession cycles have been misinterpreted as obliquity in the LR04 stack as suggested by the Ceara Rise composite at 4.2 Ma.

EUVL masks: paving the path for commercialization

NASA Astrophysics Data System (ADS)

Mangat, Pawitter J. S.; Hector, Scott D.

2001-09-01

Optical projection lithography has been the principal vehicle of semiconductor manufacturing for more than 20 years and is marching aggressively to satisfy the needs of semiconductor manufacturers for 100nm devices. However, the complexity of optical lithography continues to increase as wavelength reduction continues to 157nm. Extreme Ultraviolet Lithography (EUVL), with wavelength from 13-14 nm, is evolving as a leading next generation lithography option for semiconductor industry to stay on the path laid by Moore's Law. Masks are a critical part of the success of any technology and are considered to be high risk both for optical lithography and NGL technologies for sub-100nm lithography. Two key areas of EUV mask fabrication are reflective multilayer deposition and absorber patterning. In the case of reflective multilayers, delivering defect free multilayers for mask blanks is the biggest challenge. Defect mitigation is being explored as a possible option to smooth the multilayer defects in addition to optimization of the deposition process to reduce defect density. The mask patterning process needs focus on the defect-free absorber stack patterning process, mask cleaning, inspection and repair. In addition, there is considerable effort to understand by simulations, the defect printability, thermal and mechanical distortions, and non-telecentric illumination, to mention a few. To protect the finished mask from defects added during use, a removable pellicle strategy combined with thermophoretic protection during exposure is being developed. Recent migration to square form factor using low thermal expansion material (LTEM) is advantageous as historical developments in optical masks can be applied to EUV mask patterning. This paper addresses recent developments in the EUV mask patterning and highlights critical manufacturing process controls needed to fabricate defect-free full field masks with CD and image placement specifications for sub-70nm node lithography. No technology can be implemented without establishing the commercial infrastructure. The rising cost seems to be a major issue affecting the technology development. With respect to mask fabrication for commercial availability, a virtual mask shop analysis is presented that indicates that the process cost for EUVL masks are comparable to the high end optical mask with a reasonable yield. However, the cost for setting up a new mask facility is considerably high.

Cilia are required for asymmetric nodal induction in the sea urchin embryo.

PubMed

Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

2016-08-23

Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

Patent urachus repair

MedlinePlus

... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... surgery. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Inflatable artificial sphincter

MedlinePlus

... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... women. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Bladder outlet obstruction

MedlinePlus

... failure. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... failure. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Reorientation Timescales and Pattern Dynamics for Titan's Dunes: Does the Tail Wag the Dog or the Dragon?

NASA Astrophysics Data System (ADS)

Hayes, A. G.; Ewing, R. C.; Cassini Radar Science Team, T.

2011-12-01

Fields of bedform patterns persist across many orders of magnitude, from cm-scale sub-aqueous current ripples to km-scale aeolian dunes, and form with surprisingly little difference in expression despite a range of formative environments. Because of the remarkable similarity between and among patterns, extracting information about climate and environment from these patterns is a challenge. For example, crest orientation is not diagnostic of a particular flow regime; similar patterns form under many different flow configurations. On Titan, these challenges have played out with many attempts to reconcile dune-field patterns with modeled and expected wind regimes. We propose that thinking about the change in dune orientation, rather than the orientation itself, can provide new insights on the long-term stability of the dune-field patterns and the formative wind regime. In this work, we apply the re-orientation model presented by Werner and Kocurek [Geology, 1997] to the equatorial dune fields of Titan. We measure variations in pattern parameters (crest spacing, crest length and defect density, which is the number of defect pairs per total crest length) both within and between Titan's dune fields to describe pattern maturity and identify areas where changes in dune orientation are likely to occur (or may already be occurring). Measured defect densities are similar to Earth's largest linear dune fields, such as the Namib Sand Sea and the Simpson Desert. We use measured defect densities in the Werner and Kocurek model to estimate crestline reorientation rates. We find reorientation timescales varying from ten to a hundred thousand times the average migration timescale (time to migrate a bedform one meter, ~1 Titan year according to Tokano (Aeolian Research, 2010)). Well organized patterns have the longest reorientation time scales (~10^5 migration timescales), while the topographically or spatially isolated patches of dunes show the shortest reorientation times (~10^3 migration timescales). In addition, comparisons between spacing and defect density of Titan's dunes and some of the largest fields observed on Earth and Mars reveal that dune patterns on all three planets are geometrically similar, suggesting that growth and organization share common pattern dynamics. Our results suggest that Titan's dunes may react to gross bedform transport averaged over orbital timescales, relaxing the requirement that a single modern wind regime is required to produce the observed pattern.

Prostate resection - minimally invasive - discharge

MedlinePlus

... approaches. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... hyperplasia. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

When the Viking Missions Discovered Life on the Red Planet

NASA Astrophysics Data System (ADS)

Bianciardi, G.; Miller, J. D.; Straat, P. A.; Levin, G. V.

2012-09-01

The first (and only) dedicated life detection experiments on another planet were performed by the Viking Landers of 1976. In the Viking Labeled Release (LR) experiment of Levin and Straat, injections of organic compounds into Martian soil samples caused radioactive gas to evolve approaching plateaus of 10,000 - 15,000 cpm over several sols (Martian days). These "actives" were run at lander sites 1 and 2 with similar results. In contrast, the LR response to the 160o C control sample soils was very low. In conjunction with the active experiment results this negative result from the controls satisfied the pre-mission criteria for life. However, a controversy immediately arose concerning a biologic interpretation of the data. In an attempt to resolve this issue in the current work, we have employed complexity analysis of the Viking LR data for the initial six sols, and of terrestrial LR pilot studies using bacteria-laden, active soil (Biol 5) and sterilized soil (Biol 6). . Measures of mathematical complexity permitted a deep analysis of signal structure. Martian LR active response data were strongly superimposable upon the terrestrial biological time series, forming a welldefined cluster; and the heat-treated control samples, terrestrial and Martian, also clustered together, but distant from the active group, suggesting that the LR had, indeed, detected biological activity on Mars. The results presente herein are a key subset of the details published earlier by the same authors (IJASS, 13 (1), 14-26, 2012).