Connected Gene Communities Underlie Transcriptional Changes in Cornelia de Lange Syndrome.

PubMed

Boudaoud, Imène; Fournier, Éric; Baguette, Audrey; Vallée, Maxime; Lamaze, Fabien C; Droit, Arnaud; Bilodeau, Steve

2017-09-01

Cornelia de Lange syndrome (CdLS) is a complex multisystem developmental disorder caused by mutations in cohesin subunits and regulators. While its precise molecular mechanisms are not well defined, they point toward a global deregulation of the transcriptional gene expression program. Cohesin is associated with the boundaries of chromosome domains and with enhancer and promoter regions connecting the three-dimensional genome organization with transcriptional regulation. Here, we show that connected gene communities, structures emerging from the interactions of noncoding regulatory elements and genes in the three-dimensional chromosomal space, provide a molecular explanation for the pathoetiology of CdLS associated with mutations in the cohesin-loading factor NIPBL and the cohesin subunit SMC1A NIPBL and cohesin are important constituents of connected gene communities that are centrally positioned at noncoding regulatory elements. Accordingly, genes deregulated in CdLS are positioned within reach of NIPBL- and cohesin-occupied regions through promoter-promoter interactions. Our findings suggest a dynamic model where NIPBL loads cohesin to connect genes in communities, offering an explanation for the gene expression deregulation in the CdLS. Copyright © 2017 by the Genetics Society of America.

The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

PubMed

Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

2015-04-01

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

Differential α4(+)/(−)β2 Agonist-binding Site Contributions to α4β2 Nicotinic Acetylcholine Receptor Function within and between Isoforms*

PubMed Central

Lucero, Linda M.; Weltzin, Maegan M.; Eaton, J. Brek; Cooper, John F.; Lindstrom, Jon M.; Lukas, Ronald J.; Whiteaker, Paul

2016-01-01

Two α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) isoforms exist with (α4)2(β2)3 and (α4)3(β2)2 subunit stoichiometries and high versus low agonist sensitivities (HS and LS), respectively. Both isoforms contain a pair of α4(+)/(−)β2 agonist-binding sites. The LS isoform also contains a unique α4(+)/(−)α4 site with lower agonist affinity than the α4(+)/(−)β2 sites. However, the relative roles of the conserved α4(+)/(−)β2 agonist-binding sites in and between the isoforms have not been studied. We used a fully linked subunit concatemeric nAChR approach to express pure populations of HS or LS isoform α4β2*-nAChR. This approach also allowed us to mutate individual subunit interfaces, or combinations thereof, on each isoform background. We used this approach to systematically mutate a triplet of β2 subunit (−)-face E-loop residues to their non-conserved α4 subunit counterparts or vice versa (β2HQT and α4VFL, respectively). Mutant-nAChR constructs (and unmodified controls) were expressed in Xenopus oocytes. Acetylcholine concentration-response curves and maximum function were measured using two-electrode voltage clamp electrophysiology. Surface expression was measured with 125I-mAb 295 binding and was used to define function/nAChR. If the α4(+)/(−)β2 sites contribute equally to function, making identical β2HQT substitutions at either site should produce similar functional outcomes. Instead, highly differential outcomes within the HS isoform, and between the two isoforms, were observed. In contrast, α4VFL mutation effects were very similar in all positions of both isoforms. Our results indicate that the identity of subunits neighboring the otherwise equivalent α4(+)/(−)β2 agonist sites modifies their contributions to nAChR activation and that E-loop residues are an important contributor to this neighbor effect. PMID:26644472

In vivo encapsulation of nucleic acids using an engineered nonviral protein capsid.

PubMed

Lilavivat, Seth; Sardar, Debosmita; Jana, Subrata; Thomas, Geoffrey C; Woycechowsky, Kenneth J

2012-08-15

In Nature, protein capsids function as molecular containers for a wide variety of molecular cargoes. Such containers have great potential for applications in nanotechnology, which often require encapsulation of non-native guest molecules. Charge complementarity represents a potentially powerful strategy for engineering novel encapsulation systems. In an effort to explore the generality of this approach, we engineered a nonviral, 60-subunit capsid, lumazine synthase from Aquifex aeolicus (AaLS), to act as a container for nucleic acid. Four mutations were introduced per subunit to increase the positive charge at the inner surface of the capsid. Characterization of the mutant (AaLS-pos) revealed that the positive charges lead to the uptake of cellular RNA during production and assembly of the capsid in vivo. Surprisingly, AaLS-pos capsids were found to be enriched with RNA molecules approximately 200-350 bases in length, suggesting that this simple charge complementarity approach to RNA encapsulation leads to both high affinity and a degree of selectivity. The ability to control loading of RNA by tuning the charge at the inner surface of a protein capsid could illuminate aspects of genome recognition by viruses and pave the way for the development of improved RNA delivery systems.

Modified rubisco large subunit n-methyltransferase useful for targeting molecules to the active-site vicinity of ribulose-1,5-bisphosphate

DOEpatents

Houtz, Robert L [Lexington, KY

2012-03-20

The present invention generally relates to a modified Rubisco large subunit .sup..epsilon.N-Methyltransferase (Rubisco LSMT, or RLSMT). The present invention also relates to a modified RLSMT-carbonic anhydrase (RLSMT-CA). This modified RLSMT-CA improves the efficiency of the reduction of CO.sub.2 during photosynthesis, which may increase plant growth rates. The present invention also relates to nucleic acids encoding the modified RLSMT-CA or modified RLSMT. Also, the present invention relates to cells including the modified RLSMT-CA or modified RLSMT, plants containing the modified RLSMT-CA or modified RLSMT, and methods using compositions of the present invention. In addition, the present invention relates to antibodies conjugated to CA which may bind to Rubisco, and antibodies which bind a modified RLSMT-CA. The invention also relates to modified forms of the LS and SS of Rubisco where the modified forms are fusions with CA or biologically active fragments thereof. The present invention provides methods of altering Rubisco carboxylase activity and altering plant growth.

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

Greene, T.W.; Chantler, S.E.; Kahn, M.L.

ADPglucose pyrophosphorylase (glucose-1-phosphate adenylytransferase; AD P:{alpha}-D-glucose-1-phosphate adenylyltransferase, EC 2.7.7.27) catalyzes a key regulatory step in {alpha}-glucan synthesis in bacteria and higher plants. We have previously shown that the expression of the cDNA sequences of the potato tuber large (LS) and small (SS) subunits yielded a functional heterotetrameric enzyme capable of complementing a mutation in the single AGP (glgC) structural gene of Escherichia coli. This heterologous complementation provides a powerful genetic approach to obtain biochemical information on the specific roles of LS and SS in enzyme function. By mutagenizing the LS cDNA with hydroxylamine and then coexpressing with wild-type SS inmore » an E. coli glgC{sup {minus}} strain, >350 mutant colonies were identified that were impaired in glycogen production. One mutant exhibited enzymatic and antigen levels comparable to the wild-type recombinant enzyme but required 45-fold greater levels of the activator 3-phosphoglycerate for maximum activity. Sequence analysis identified a single nucleotide change that resulted in the change of Pro-52 to Leu. This heterologous genetic system provides and efficient means to identify residues important for catalysis and allosteric functioning and should lead to novel approaches to increase plant productivity. 31 refs., 4 figs., 1 tab.« less

Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

PubMed

Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

2017-03-01

The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

Esco2 regulates cx43 expression during skeletal regeneration in the zebrafish fin.

PubMed

Banerji, Rajeswari; Eble, Diane M; Iovine, M Kathryn; Skibbens, Robert V

2016-01-01

Roberts syndrome (RBS) is a rare genetic disorder characterized by craniofacial abnormalities, limb malformation, and often severe mental retardation. RBS arises from mutations in ESCO2 that encodes an acetyltransferase and modifies the cohesin subunit SMC3. Mutations in SCC2/NIPBL (encodes a cohesin loader), SMC3 or other cohesin genes (SMC1, RAD21/MCD1) give rise to a related developmental malady termed Cornelia de Lange syndrome (CdLS). RBS and CdLS exhibit overlapping phenotypes, but RBS is thought to arise through mitotic failure and limited progenitor cell proliferation while CdLS arises through transcriptional dysregulation. Here, we use the zebrafish regenerating fin model to test the mechanism through which RBS-type phenotypes arise. esco2 is up-regulated during fin regeneration and specifically within the blastema. esco2 knockdown adversely affects both tissue and bone growth in regenerating fins-consistent with a role in skeletal morphogenesis. esco2-knockdown significantly diminishes cx43/gja1 expression which encodes the gap junction connexin subunit required for cell-cell communication. cx43 mutations cause the short fin (sof(b123) ) phenotype in zebrafish and oculodentodigital dysplasia (ODDD) in humans. Importantly, miR-133-dependent cx43 overexpression rescues esco2-dependent growth defects. These results conceptually link ODDD to cohesinopathies and provide evidence that ESCO2 may play a transcriptional role critical for human development. © 2015 Wiley Periodicals, Inc.

Diversification of Protein Cage Structure Using Circularly Permuted Subunits.

PubMed

Azuma, Yusuke; Herger, Michael; Hilvert, Donald

2018-01-17

Self-assembling protein cages are useful as nanoscale molecular containers for diverse applications in biotechnology and medicine. To expand the utility of such systems, there is considerable interest in customizing the structures of natural cage-forming proteins and designing new ones. Here we report that a circularly permuted variant of lumazine synthase, a cage-forming enzyme from Aquifex aeolicus (AaLS) affords versatile building blocks for the construction of nanocompartments that can be easily produced, tailored, and diversified. The topologically altered protein, cpAaLS, self-assembles into spherical and tubular cage structures with morphologies that can be controlled by the length of the linker connecting the native termini. Moreover, cpAaLS proteins integrate into wild-type and other engineered AaLS assemblies by coproduction in Escherichia coli to form patchwork cages. This coassembly strategy enables encapsulation of guest proteins in the lumen, modification of the exterior through genetic fusion, and tuning of the size and electrostatics of the compartments. This addition to the family of AaLS cages broadens the scope of this system for further applications and highlights the utility of circular permutation as a potentially general strategy for tailoring the properties of cage-forming proteins.

Differential Expression of P450 Genes and nAChR Subunits Associated With Imidacloprid Resistance in Laodelphax striatellus (Hemiptera: Delphacidae).

PubMed

Zhang, Yueliang; Liu, Baosheng; Zhang, Zhichun; Wang, Lihua; Guo, Huifang; Li, Zhong; He, Peng; Liu, Zewen; Fang, Jichao

2018-05-28

Imidacloprid is a key insecticide used for controlling sucking insect pests, including the small brown planthopper (Laodelphax striatellus, Fallén) (Hemiptera: Delphacidae), an important agricultural pest of rice. A strain of L. striatellus (YN-ILR) developed 21-fold resistance when selected with imidacloprid on a susceptible YN strain. An in vitro study on piperonyl butoxide synergism indicated that enhanced detoxification mediated by cytochrome P450s contributed to imidacloprid resistance to some extent, and multiple P450 genes showed altered expression in the imidacloprid-resistant YN-ILR strain compared with the susceptible YN strain (CYP425B1-CYP6BD10 had 1.51- to 11.45-fold higher expression, CYP4CE2-CYP4DD1V2 had 0.12- to 0.57-fold lower expression). While there were no mutations in target nicotinic acetylcholine receptor (nAChR) genes, subunits of Lsα1, Lsβ1, and Lsβ3 in the YN-ILR strain showed 3.86-, 4.39-, and 2.59-fold higher expression and Lsa8 displayed 0.38-fold lower expression than the YN strain. Moreover, 21-fold moderate imidacloprid resistance in individuals of L. striatellus did not produce a fitness cost. The findings suggest that L. striatellus has the capacity to develop resistance to imidacloprid through P450 detoxification and potential target nAChR expression changes, and moderate imidacloprid resistance was not associated with a fitness cost.

The role of heterologous chloroplast sequence elements in transgene integration and expression.

PubMed

Ruhlman, Tracey; Verma, Dheeraj; Samson, Nalapalli; Daniell, Henry

2010-04-01

Heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. Nucleotide sequence identity in the photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. Secondary structure and predicted Gibbs free energy values of the psbA 5' untranslated region (UTR) among different families reflected this variation. Therefore, chloroplast transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt) psbA promoter, 5' UTR and 3' UTR, regulating expression of the anthrax protective antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit (CTB). Unique lettuce flanking sequences were completely eliminated during homologous recombination in the transplastomic tobacco genomes but not unique tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA and 97% CTB-Pins expression when compared with endogenous psbA regulatory elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts containing endogenous 5' UTR were stabilized in nonpolysomal fractions. Stromal RNA-binding proteins were preferentially associated with endogenous psbA 5' UTR. A rapid and reproducible regeneration system was developed for lettuce commercial cultivars by optimizing plant growth regulators. These findings underscore the need for sequencing complete crop chloroplast genomes, utilization of endogenous regulatory elements and flanking sequences, as well as optimization of plant growth regulators for efficient chloroplast transformation.

The Role of Heterologous Chloroplast Sequence Elements in Transgene Integration and Expression1[W][OA

PubMed Central

Ruhlman, Tracey; Verma, Dheeraj; Samson, Nalapalli; Daniell, Henry

2010-01-01

Heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. Nucleotide sequence identity in the photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. Secondary structure and predicted Gibbs free energy values of the psbA 5′ untranslated region (UTR) among different families reflected this variation. Therefore, chloroplast transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt) psbA promoter, 5′ UTR and 3′ UTR, regulating expression of the anthrax protective antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit (CTB). Unique lettuce flanking sequences were completely eliminated during homologous recombination in the transplastomic tobacco genomes but not unique tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA and 97% CTB-Pins expression when compared with endogenous psbA regulatory elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts containing endogenous 5′ UTR were stabilized in nonpolysomal fractions. Stromal RNA-binding proteins were preferentially associated with endogenous psbA 5′ UTR. A rapid and reproducible regeneration system was developed for lettuce commercial cultivars by optimizing plant growth regulators. These findings underscore the need for sequencing complete crop chloroplast genomes, utilization of endogenous regulatory elements and flanking sequences, as well as optimization of plant growth regulators for efficient chloroplast transformation. PMID:20130101

Recombinant plasmids for encoding restriction enzymes DpnI and DpnII of streptococcus pneumontae

DOEpatents

Lacks, Sanford A.

1990-01-01

Chromosomal DNA cassettes containing genes encoding either the DpnI or DpnII restriction endonucleases from Streptococcus pneumoniae are cloned into a streptococcal vector, pLS101. Large amounts of the restriction enzymes are produced by cells containing the multicopy plasmids, pLS202 and pLS207, and their derivatives pLS201, pLS211, pLS217, pLS251 and pLS252.

Recombinant plasmids for encoding restriction enzymes DpnI and DpnII of Streptococcus pneumontae

DOEpatents

Lacks, S.A.

1990-10-02

Chromosomal DNA cassettes containing genes encoding either the DpnI or DpnII restriction endonucleases from Streptococcus pneumoniae are cloned into a streptococcal vector, pLS101. Large amounts of the restriction enzymes are produced by cells containing the multicopy plasmids, pLS202 and pLS207, and their derivatives pLS201, pLS211, pLS217, pLS251 and pLS252. 9 figs.

Characterization of Chloroplastic Fructose 1,6-Bisphosphate Aldolases as Lysine-methylated Proteins in Plants*

PubMed Central

Mininno, Morgane; Brugière, Sabine; Pautre, Virginie; Gilgen, Annabelle; Ma, Sheng; Ferro, Myriam; Tardif, Marianne; Alban, Claude; Ravanel, Stéphane

2012-01-01

In pea (Pisum sativum), the protein-lysine methyltransferase (PsLSMT) catalyzes the trimethylation of Lys-14 in the large subunit (LS) of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), the enzyme catalyzing the CO2 fixation step during photosynthesis. Homologs of PsLSMT, herein referred to as LSMT-like enzymes, are found in all plant genomes, but methylation of LS Rubisco is not universal in the plant kingdom, suggesting a species-specific protein substrate specificity of the methyltransferase. In this study, we report the biochemical characterization of the LSMT-like enzyme from Arabidopsis thaliana (AtLSMT-L), with a focus on its substrate specificity. We show that, in Arabidopsis, LS Rubisco is not naturally methylated and that the physiological substrates of AtLSMT-L are chloroplastic fructose 1,6-bisphosphate aldolase isoforms. These enzymes, which are involved in the assimilation of CO2 through the Calvin cycle and in chloroplastic glycolysis, are trimethylated at a conserved lysyl residue located close to the C terminus. Both AtLSMT-L and PsLSMT are able to methylate aldolases with similar kinetic parameters and product specificity. Thus, the divergent substrate specificity of LSMT-like enzymes from pea and Arabidopsis concerns only Rubisco. AtLSMT-L is able to interact with unmethylated Rubisco, but the complex is catalytically unproductive. Trimethylation does not modify the kinetic properties and tetrameric organization of aldolases in vitro. The identification of aldolases as methyl proteins in Arabidopsis and other species like pea suggests a role of protein lysine methylation in carbon metabolism in chloroplasts. PMID:22547063

Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome.

PubMed

Chen, Byron; Hui, Jessica; Montgomery, Kelsey S; Gella, Alejandro; Bolea, Irene; Sanz, Elisenda; Palmiter, Richard D; Quintana, Albert

2017-01-01

Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4 , a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

Cohesin and Human Disease

PubMed Central

Liu, Jinglan; Krantz, Ian D.

2016-01-01

Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients.

PubMed

Poyau, A; Buchet, K; Bouzidi, M F; Zabot, M T; Echenne, B; Yao, J; Shoubridge, E A; Godinot, C

2000-02-01

We have studied the fibroblasts of three patients suffering from Leigh syndrome associated with cytochrome c oxidase deficiency (LS-COX-). Their mitochondrial DNA was functional and all nuclear COX subunits had a normal sequence. The expression of transcripts encoding mitochondrial and nuclear COX subunits was normal or slightly increased. Similarly, the OXA1 transcript coding for a protein involved in COX assembly was increased. However, several COX-protein subunits were severely depressed, indicating deficient COX assembly. Surf1, a factor involved in COX biogenesis, was recently reported as mutated in LS-COX- patients, all mutations predicting a truncated protein. Sequence analysis of SURF1 gene in our three patients revealed seven heterozygous mutations, six of which were new : an insertion, a nonsense mutation, a splicing mutation of intron 7 in addition to three missense mutations. The mutation G385 A (Gly124-->Glu) changes a Gly that is strictly conserved in Surfl homologs of 12 species. The substitution G618 C (Asp202-->His), changing an Asp that is conserved only in mammals, appears to be a polymorphism. The mutation T751 C changes Ile246 to Thr, a position at which a hydrophobic amino acid is conserved in all eukaryotic and some bacterial species. Replacing Ile246 by Thr disrupts a predicted beta sheet structure present in all higher eukaryotes. COX activity could be restored in fibroblasts of the three patients by complementation with a retroviral vector containing normal SURF1 cDNA. These mutations identify domains essential to Surf1 protein structure and/or function.

Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.

PubMed

Martín, Miguel A; Blázquez, Alberto; Gutierrez-Solana, Luis G; Fernández-Moreira, Daniel; Briones, Paz; Andreu, Antoni L; Garesse, Rafael; Campos, Yolanda; Arenas, Joaquín

2005-04-01

Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect. The proband was a child who displayed the clinical features of LS. Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation. Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.

SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways.

PubMed

Pérez-Rubio, Gloria; Pérez-Rodríguez, Martha E; Fernández-López, Juan Carlos; Ramírez-Venegas, Alejandra; García-Colunga, Jesús; Ávila-Moreno, Federico; Camarena, Angel; Sansores, Raúl H; Falfán-Valencia, Ramcés

2016-07-01

To identify genetic variants associated with greater tobacco consumption in a Mexican population. Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed. Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2. In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

PubMed

Taniguchi, Kan; Matsuura, Kimio; Matsuoka, Takanori; Nakatani, Hajime; Nakano, Takumi; Furuya, Yasuo; Sugimoto, Takeki; Kobayashi, Michiya; Araki, Keijiro

2005-06-01

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Cornelia de Lange syndrome: further delineation of phenotype, cohesin biology and educational focus, 5th Biennial Scientific and Educational Symposium abstracts.

PubMed

Kline, Antonie D; Calof, Anne L; Schaaf, Cheri A; Krantz, Ian D; Jyonouchi, Soma; Yokomori, Kyoko; Gauze, Maria; Carrico, Cheri S; Woodman, Julie; Gerton, Jennifer L; Vega, Hugo; Levin, Alex V; Shirahige, Katsuhiko; Champion, Michele; Goodban, Marjorie T; O'Connor, Julia T; Pipan, Mary; Horsfield, Julia; Deardorff, Matthew A; Ishman, Stacey L; Dorsett, Dale

2014-06-01

Cornelia de Lange syndrome (CdLS) is the prototype for the cohesinopathy disorders that have mutations in genes associated with the cohesin subunit in all cells. Roberts syndrome is the next most common cohesinopathy. In addition to the developmental implications of cohesin biology, there is much translational and basic research, with progress towards potential treatment for these conditions. Clinically, there are many issues in CdLS faced by the individual, parents and caretakers, professionals, and schools. The following abstracts are presentations from the 5th Cornelia de Lange Syndrome Scientific and Educational Symposium on June 20-21, 2012, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting, Lincolnshire, IL. The research committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts and subsequently disseminates the information to the families. In addition to the basic science and clinical discussions, there were educationally-focused talks related to practical aspects of management at home and in school. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. © 2014 Wiley Periodicals, Inc.

Effects of duration of vitamin C supplementation during the finishing period on postmortem protein degradation, tenderness, and meat color of the longissimus muscle of calf-fed steers consuming a 0.31 or 0.59% sulfur diet.

PubMed

Pogge, D J; Lonergan, S M; Hansen, S L

2015-05-01

High-S (HS) diets have been identified as a causative agent in the development of oxidative stress in cattle, which in postmortem muscle can negatively alter meat quality. Vitamin C (VC) is a potent antioxidant produced endogenously by cattle; however, exogenous supplementation of VC may be useful when HS diets are fed to cattle. The objective of this study was to examine the impact of duration of VC supplementation, for the first 56, 90, or 127 d, during the finishing period on meat color and tenderness of the longissimus thoracis (LT) collected from calf-fed steers consuming a 0.31 or 0.59% S diet. Angus steers ( n= 42) were stratified to pens by initial BW (304 ± 13 kg) and GeneMax marbling score (4.3 ± 0.12), and each pen was randomly assigned to 1 of 7 treatments (6 steers/pen, 1 pen/treatment), including HS (0.59% S, a combination of dried distillers grains plus solubles and sodium sulfate) control (HS CON), HS CON + 10 g VC·steer·(-1)d(-1) for the first 56 d (HS VC56), 90 d (HS VC90), or 127 d (HS VC127), low S (LS; 0.31% S) + 10 g VC·steer·(-1)d(-1) for the first 56 d (LS VC56), 90 d (LS VC90), or 127 d (LS VC127). Steers were harvested (n = 40) and, after a 24-h chill, rib sections (LT) were collected. pH was determined on each rib section before division into 3 sections for determination of 1) 7-d retail display and color and Warner-Bratzler shear force (WBSF), 2) 14-d WBSF determination, and 3) protein degradation and collagen content (2 d postmortem). Data were analyzed by ANOVA as a completely randomized design, with the fixed effect of treatment. Individual feed intake was recorded, and steer was the experimental unit. The HS steers had a greater and lesser percent of the 80- and 76-kDa subunits of calpain-1 (P ≤ 0.05), respectively, and tended to have less (P = 0.08) troponin T degradation (d2), and more (P = 0.02) collagen than LS steers. Increasing days of VC supplementation decreased (P = 0.05) the percentage of the 80 kDa subunit of calpain-1 in HS steers but actually increased it in LS steers (P= 0.003). Supplementing VC, regardless of dietary S, did not affect meat collagen, WBSF, or color (P ≥ 0.12). a* and b* values were greater (P ≤ 0.05) in the LS treatments compared to the HS treatments. Increasing the days of VC supplementation to steers fed a HS diet appears to alleviate the negative effects of the HS diet on calpain-1 but has no effect on muscle tenderness or meat color.

Preparation of Gd Loaded Liquid Scintillator for Daya Bay Neutrino Experiment

NASA Astrophysics Data System (ADS)

Ya-yun, Ding; Zhi-yong, Zhang

2010-05-01

Gadolinium loaded liquid scintillator (Gd-LS) is an excellent target material for reactor antineutrino experiments. Ideal Gd-LS should have long attenuation length, high light yield, long term stability, low toxicity, and should be compatible with the material used to build the detector. We have developed a new Gd-LS recipe in which carboxylic acid 3,5,5-trimethylhexanoic acid is used as the complexing ligand to gadolinium, 2,5-diphenyloxazole (PPO) and 1,4-bis[2-methylstyryl]benzene (bis-MSB) are used as primary fluor and wavelength shifter, respectively. The scintillator base is linear alkyl benzene (LAB). Eight hundred liters of Gd-LS has been synthesized and tested in a prototype detector. Results show that the Gd-LS has high quality and is suitable for underground experiments in large quantity. Large scale production facility has been built. A full batch production of 4 t Gd-LS has been produced and monitored for several months. The production of 180 t Gd-LS will be carried out in the near future.

Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.

PubMed

Minoia, Francesca; Bertamino, Marta; Picco, Paolo; Severino, Mariasavina; Rossi, Andrea; Fiorillo, Chiara; Minetti, Carlo; Nesti, Claudia; Santorelli, Filippo Maria; Di Rocco, Maja

2017-01-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.

Preparation of Gd Loaded Liquid Scintillator for Daya Bay Neutrino Experiment

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

Ding Yayun; Zhang Zhiyong

2010-05-12

Gadolinium loaded liquid scintillator (Gd-LS) is an excellent target material for reactor antineutrino experiments. Ideal Gd-LS should have long attenuation length, high light yield, long term stability, low toxicity, and should be compatible with the material used to build the detector. We have developed a new Gd-LS recipe in which carboxylic acid 3,5,5-trimethylhexanoic acid is used as the complexing ligand to gadolinium, 2,5-diphenyloxazole (PPO) and 1,4-bis[2-methylstyryl]benzene (bis-MSB) are used as primary fluor and wavelength shifter, respectively. The scintillator base is linear alkyl benzene (LAB). Eight hundred liters of Gd-LS has been synthesized and tested in a prototype detector. Results showmore » that the Gd-LS has high quality and is suitable for underground experiments in large quantity. Large scale production facility has been built. A full batch production of 4 t Gd-LS has been produced and monitored for several months. The production of 180 t Gd-LS will be carried out in the near future.« less

The unpredictability of lymphatic drainage from the ear in melanoma patients, and its implications for management.

PubMed

Peach, Howard S; van der Ploeg, Augustinus P T; Haydu, Lauren E; Stretch, Jonathan R; Shannon, Kerwin F; Uren, Roger F; Thompson, John F

2013-05-01

The ear is known to have variable lymphatic drainage. The purpose of this study was to define better the lymphatic drainage patterns of the ear by correlating the location of primary tumors, classified according to the embryologically derived anatomical subunits of the ear, with their mapped sentinel nodes (SNs) identified by lymphoscintigraphy (LS). Lymphatic drainage data for patients with a primary melanoma of the ear were reviewed and correlated with the precise primary melanoma site. Between 1993 and 2010, LS was performed in 111 patients with a primary melanoma on the ear, identifying 281 SNs in 195 lymph node (LN) fields. The mean numbers of SNs and LN fields identified by LS per patient were 2.65 and 1.76. SN biopsy was performed in 71 patients (64 %). The mean number of SNs removed was 2.36. The 111 ear melanomas were mostly located on the helical rim (55 %), followed by the lobule (24.3 %). The five different primary ear sites drained mainly to SNs in level CII, level CV and the preauricular region. Drainage was most often to level CII (36.4 %). Drainage to the contralateral neck was not observed. Lymphatic drainage of the ear has no predictable pattern and can be to SNs anywhere in the ipsilateral neck. Most commonly drainage is to cervical level II and the preauricular and postauricular LN fields. LS defines the lymphatic drainage pattern in individual melanoma patients and is essential for accurate SN identification and reliable SN biopsy.

Design of a large magnetic-bearing turbomolecular pump for NET

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

Bernhardt, K.H.; Conrad, A.; Dinner, P.J.

1988-09-01

The feasibility of development of large vacuum components for operation in fusion machines have been investigated in the framework of the European Fusion Technology Programme. The requirements and the results of the feasibility study for the large turbomolecular pump units (TMP) are presented. Design parameters for single flow 50.000 l/s TMP and a double flow 15.000 and a 50.000 l/s TMP have been compared.

Exploring connectivity with large-scale Granger causality on resting-state functional MRI.

PubMed

DSouza, Adora M; Abidin, Anas Z; Leistritz, Lutz; Wismüller, Axel

2017-08-01

Large-scale Granger causality (lsGC) is a recently developed, resting-state functional MRI (fMRI) connectivity analysis approach that estimates multivariate voxel-resolution connectivity. Unlike most commonly used multivariate approaches, which establish coarse-resolution connectivity by aggregating voxel time-series avoiding an underdetermined problem, lsGC estimates voxel-resolution, fine-grained connectivity by incorporating an embedded dimension reduction. We investigate application of lsGC on realistic fMRI simulations, modeling smoothing of neuronal activity by the hemodynamic response function and repetition time (TR), and empirical resting-state fMRI data. Subsequently, functional subnetworks are extracted from lsGC connectivity measures for both datasets and validated quantitatively. We also provide guidelines to select lsGC free parameters. Results indicate that lsGC reliably recovers underlying network structure with area under receiver operator characteristic curve (AUC) of 0.93 at TR=1.5s for a 10-min session of fMRI simulations. Furthermore, subnetworks of closely interacting modules are recovered from the aforementioned lsGC networks. Results on empirical resting-state fMRI data demonstrate recovery of visual and motor cortex in close agreement with spatial maps obtained from (i) visuo-motor fMRI stimulation task-sequence (Accuracy=0.76) and (ii) independent component analysis (ICA) of resting-state fMRI (Accuracy=0.86). Compared with conventional Granger causality approach (AUC=0.75), lsGC produces better network recovery on fMRI simulations. Furthermore, it cannot recover functional subnetworks from empirical fMRI data, since quantifying voxel-resolution connectivity is not possible as consequence of encountering an underdetermined problem. Functional network recovery from fMRI data suggests that lsGC gives useful insight into connectivity patterns from resting-state fMRI at a multivariate voxel-resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization

PubMed Central

Gouzil, Julie; Fablet, Aurore; Lara, Estelle; Caignard, Grégory; Cochet, Marielle; Kundlacz, Cindy; Palmarini, Massimo; Varela, Mariana; Breard, Emmanuel; Sailleau, Corinne; Viarouge, Cyril; Coulpier, Muriel; Zientara, Stéphan

2016-01-01

ABSTRACT Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded nonstructural protein, termed NSs, is a major virulence factor of SBV, and it is known to promote the degradation of Rpb1, a subunit of the RNA polymerase II (Pol II) complex, and therefore hampers global cellular transcription. In this study, we found that NSs is mainly localized in the nucleus of infected cells and specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein. NSs colocalizes with nucleolar markers such as B23 (nucleophosmin) and fibrillarin. We observed that in SBV-infected cells, B23 undergoes a nucleolus-to-nucleoplasm redistribution, evocative of virus-induced nucleolar disruption. In contrast, the nucleolar pattern of B23 was unchanged upon infection with an SBV recombinant mutant with NSs lacking the NoLS motif (SBVΔNoLS). Interestingly, unlike wild-type SBV, the inhibitory activity of SBVΔNoLS toward RNA Pol II transcription is impaired. Overall, our results suggest that a putative link exists between NSs-induced nucleolar disruption and its inhibitory function on cellular transcription, which consequently precludes the cellular antiviral response and/or induces cell death. IMPORTANCE Schmallenberg virus (SBV) is an emerging arbovirus of ruminants that spread in Europe between 2011 and 2013. SBV induces fetal abnormalities during gestation, with the central nervous system being one of the most affected organs. The virus-encoded NSs protein acts as a virulence factor by impairing host cell transcription. Here, we show that NSs contains a nucleolar localization signal (NoLS) and induces disorganization of the nucleolus. The NoLS motif in the SBV NSs is absolutely necessary for virus-induced inhibition of cellular transcription. To our knowledge, this is the first report of nucleolar functions for NSs within the Bunyaviridae family. PMID:27795408

Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization.

PubMed

Gouzil, Julie; Fablet, Aurore; Lara, Estelle; Caignard, Grégory; Cochet, Marielle; Kundlacz, Cindy; Palmarini, Massimo; Varela, Mariana; Breard, Emmanuel; Sailleau, Corinne; Viarouge, Cyril; Coulpier, Muriel; Zientara, Stéphan; Vitour, Damien

2017-01-01

Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded nonstructural protein, termed NSs, is a major virulence factor of SBV, and it is known to promote the degradation of Rpb1, a subunit of the RNA polymerase II (Pol II) complex, and therefore hampers global cellular transcription. In this study, we found that NSs is mainly localized in the nucleus of infected cells and specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein. NSs colocalizes with nucleolar markers such as B23 (nucleophosmin) and fibrillarin. We observed that in SBV-infected cells, B23 undergoes a nucleolus-to-nucleoplasm redistribution, evocative of virus-induced nucleolar disruption. In contrast, the nucleolar pattern of B23 was unchanged upon infection with an SBV recombinant mutant with NSs lacking the NoLS motif (SBVΔNoLS). Interestingly, unlike wild-type SBV, the inhibitory activity of SBVΔNoLS toward RNA Pol II transcription is impaired. Overall, our results suggest that a putative link exists between NSs-induced nucleolar disruption and its inhibitory function on cellular transcription, which consequently precludes the cellular antiviral response and/or induces cell death. Schmallenberg virus (SBV) is an emerging arbovirus of ruminants that spread in Europe between 2011 and 2013. SBV induces fetal abnormalities during gestation, with the central nervous system being one of the most affected organs. The virus-encoded NSs protein acts as a virulence factor by impairing host cell transcription. Here, we show that NSs contains a nucleolar localization signal (NoLS) and induces disorganization of the nucleolus. The NoLS motif in the SBV NSs is absolutely necessary for virus-induced inhibition of cellular transcription. To our knowledge, this is the first report of nucleolar functions for NSs within the Bunyaviridae family. Copyright © 2016 Gouzil et al.

Longitudinal monitoring of liver stiffness by acoustic radiation force impulse imaging in patients with chronic hepatitis B receiving entecavir.

PubMed

Wu, Sheng-Di; Ding, Hong; Liu, Li-Li; Zhuang, Yuan; Liu, Yun; Cheng, Li-Sha; Wang, Si-Qi; Tseng, Yu-Jen; Wang, Ji-Yao; Jiang, Wei

2018-06-01

Acoustic radiation force impulse (ARFI) imaging measures liver stiffness (LS), which significantly correlates with the stage of liver fibrosis in treatment-naive patients with chronic hepatitis B (CHB). We aimed to prospectively assess the clinical usefulness of ARFI during long-term antiviral therapy in CHB. Seventy-one CHB patients were consecutively recruited and paired liver biopsies were performed in 27 patients. LS was assessed by ARFI semiannually during entecavir therapy. LS gradually decreased with treatment and continued to decrease after normalization of alanine aminotransaminase. Overall, 97.2% patients achieved improvement of LS, whereas 19.7% patients had more than 30% reduction in LS values between baseline and week 104. Multivariate linear regression analysis showed that the degree of LS reduction significantly correlated with the baseline levels of LS value, platelet and cholinesterase. In the 27 patients who underwent paired liver biopsies, LS significantly correlated with stage of fibrosis and inflammatory grade at baseline. LS values decreased more significantly in patients with fibrosis regression than those with static histological fibrosis. In CHB patients, LS assessed by ARFI was gradually reduced during antiviral therapy. Longitudinal monitoring of LS may be a promising noninvasive assessment of fibrosis regression during long-term antiviral therapy in CHB. Further large sample studies are needed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Validity and Reliability of Assessing Body Composition Using a Mobile Application.

PubMed

Macdonald, Elizabeth Z; Vehrs, Pat R; Fellingham, Gilbert W; Eggett, Dennis; George, James D; Hager, Ronald

2017-12-01

The purpose of this study was to determine the validity and reliability of the LeanScreen (LS) mobile application that estimates percent body fat (%BF) using estimates of circumferences from photographs. The %BF of 148 weight-stable adults was estimated once using dual-energy x-ray absorptiometry (DXA). Each of two administrators assessed the %BF of each subject twice using the LS app and manually measured circumferences. A mixed-model ANOVA and Bland-Altman analyses were used to compare the estimates of %BF obtained from each method. Interrater and intrarater reliabilities values were determined using multiple measurements taken by each of the two administrators. The LS app and manually measured circumferences significantly underestimated (P < 0.05) the %BF determined using DXA by an average of -3.26 and -4.82 %BF, respectively. The LS app (6.99 %BF) and manually measured circumferences (6.76 %BF) had large limits of agreement. All interrater and intrarater reliability coefficients of estimates of %BF using the LS app and manually measured circumferences exceeded 0.99. The estimates of %BF from manually measured circumferences and the LS app were highly reliable. However, these field measures are not currently recommended for the assessment of body composition because of significant bias and large limits of agreements.

Large spot transpupillary thermotherapy: a quicker laser for treatment of high risk prethreshold retinopathy of prematurity - a randomized study.

PubMed

Shah, Parag K; Narendran, V; Kalpana, N

2011-01-01

To compare structural and functional outcome and time efficiency between standard spot sized conventional pulsed mode diode laser and continuous mode large spot transpupillary thermotherapy (LS TTT) for treatment of high risk prethreshold retinopathy of prematurity (ROP). Ten eyes of five preterm babies having bilateral symmetrical high risk prethreshold ROP were included in this study. One eye of each baby was randomized to get either standard spot sized conventional pulsed mode diode laser or continuous mode LS TTT. There was no significant difference between structural or functional outcome in either group. The mean time taken for conventional diode laser was 20.07 minutes, while that for LS TTT was 12.3 minutes. LS TTT was 40% more time efficient than the conventional laser. It may be better suited for the very small fragile premature infants as it is quicker than the conventional laser.

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

PubMed

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

1995-12-01

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

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

Jack Preiss

Conversion of the Potato tuber ADP-glucose Pyrophopshorylase Regulatory Subunit into a Catalytic Subunit. ADP-glucose synthesis, a rate-limiting reaction in starch synthesis, is catalyzed by ADP-glucose pyrophosphorylase (ADPGlc PPase). The enzyme in plants is allosterically activated by 3-phosphoglycerate (3PGA) and inhibited by inorganic phosphate (Pi) and is composed of two subunits as a heterotetramer, a2b2. Subunit a is the catalytic subunit and subunit b is designated as the regulatory subunit.The b subunit increases the affinty of the activator for the catalytic subunit. Recent results have shown that the subunits are derived from the same ancestor subunit as the regulatory subunit canmore » be converted to a catalytically subunit via mutation of just two amino acids. Lys44 and Thr54 in the large subunit from potato tuber were converted to the homologous catalytic subunit residues, Arg33 and Lys43. The activity of the large subunit mutants cannot be readily tested with a co-expressed wild-type small (catalytic) subunit because of the intrinsic activity of the latter. We co-expressed the regulatory-subunit mutants with SmallD145N, an inactive S subunit in which the catalytic Asp145 was mutated. The activity of the small (catalytic) subunit was reduced more than three orders of magnitude. Coexpression of the L subunit double mutant LargeK44R/T54K with SmallD145N generated an enzyme with considerable activity, 10% and 18% of the wildtype enzyme, in the ADP-glucose synthetic and pyrophosphorolytic direction, respectively. Replacement of those two residues in the small subunit by the homologous amino acids in the L subunits (mutations R33K and K43T) decreased the activity one and two orders of magnitude. The wild-type enzyme and SmallD145NLargeK44R/T54K had very similar kinetic properties indicating that the substrate site has been conserved. The fact that only two mutations in the L subunit restored enzyme activity is very strong evidence that the large subunit is derived from the catalytic ancestor. Previous results showed that Asp145 in the small subunit of the wild-type is essential for catalysis, whereas the homologous Asp160 in the Large WT subunit is not. However, in this study, mutation D160N or D160E in the LK44R/T54K subunit abolished the activity, which shows the ancestral essential role of this residue and confirms that the catalysis of SmallD145NLarge K44R/T54K occurs in the L(b) subunit. A phylogenetic tree of the ADP-Glc PPases present in photosynthetic eukaryotes also sheds information about the origin of the subunits. The tree showed that plant Small and Large subunits can be divided into two and four distinct groups, respectively. The two main groups of S subunits are from dicot and monocot plants, whereas Large subunit groups correlate better with their documented tissue expression. The first Large-subunit group is generally expressed in photosynthetic tissues and comprises Large subunits from dicots and monocots. Group II displays a broader expression pattern, whereas groups III and IV are expressed in storage organs (roots, stems, tubers, seeds). Subunits from group III are only from dicot plants, whereas group IV are seed-specific subunits from monocots. These last two groups stem from the same branch of the phylogenetic tree and split before monocot and dicot separation. Thus few as two mutations turned the L subunit from Solanum tuberosum catalytic, showing that L and S subunits share a common catalytic ancestor, rather than a non-catalytic one. The L subunit evolved to have a regulatory role, lost catalytic residues more than 130 million years ago before monocots and dicots diverged, and preserved, possibly as a byproduct, the active site domain.« less

Genetic sequence data identifies the cercaria of Drepanocephalus spathans (Digenea: Echinostomatidae), a parasite of the double-crested cormorant (Phalacrocorax auritus), with notes on its pathology in juvenile channel catfish (Ictalurus punctatus).

PubMed

Griffin, Matt J; Khoo, Lester H; Quiniou, Sylvie M; O'Hear, Mary M; Pote, Linda M; Greenway, Terrence E; Wise, David J

2012-10-01

An unidentified xiphidio-type cercaria, previously thought inconsequential to catfish health, was found to be released from marsh rams-horn snails (Planorbella trivolvis) inhabiting ponds on a commercial catfish operation in the Mississippi Delta. A preliminary challenge of cohabiting channel catfish ( Ictalurus punctatus ) with snails actively shedding the unidentified cercariae resulted in death of some fish. A second cohabitation trial yielded similar results, as did a third challenge of 250 cercariae/fish. Histopathology revealed developing metacercariae concentrated in the cranial region, especially within the branchial chamber, with several metacercariae at the base of the branchial arches within, or adjacent to, blood vessels, possibly the proximate cause of death. Genetic sequence analysis of the 18S small subunit ribosomal DNA (ssDNA), 28S large subunit rDNA (lsDNA), and cytochrome oxidase (Cox1) genes all matched the cercariae to Drepanocephalus spathans (Digenea: Echinostomatidae), a parasite of the double-crested cormorant (Phalacrocorax auritus), a piscivorous bird endemic on most catfish farms. This is the first commentary regarding pathology of D. spathans in juvenile channel catfish as well as the first report of the marsh rams-horn snail as an intermediate host in the D. spathans life cycle. The data presented here suggest this parasite could have limiting effects on catfish production, further supporting the need for adequate snail control programs to reduce trematode prevalence on commercial catfish operations.

Development of layer 1 neurons in the mouse neocortex.

PubMed

Ma, Jian; Yao, Xing-Hua; Fu, Yinghui; Yu, Yong-Chun

2014-10-01

Layer 1 of the neocortex harbors a unique group of neurons that play crucial roles in synaptic integration and information processing. Although extensive studies have characterized the properties of layer 1 neurons in the mature neocortex, it remains unclear how these neurons progressively acquire their distinct morphological, neurochemical, and physiological traits. In this study, we systematically examined the dynamic development of Cajal-Retzius cells and γ-aminobutyric acid (GABA)-ergic interneurons in layer 1 during the first 2 postnatal weeks. Cajal-Retzius cells underwent morphological degeneration after birth and gradually disappeared from layer 1. The majority of GABAergic interneurons showed clear expression of at least 1 of the 6 distinct neurochemical markers, including Reelin, GABA-A receptor subunit delta (GABAARδ), neuropeptide Y, vasoactive intestinal peptide (VIP), calretinin, and somatostatin from postnatal day 8. Furthermore, according to firing pattern, layer 1 interneurons can be divided into 2 groups: late-spiking (LS) and burst-spiking (BS) neurons. LS neurons preferentially expressed GABAARδ, whereas BS neurons preferentially expressed VIP. Interestingly, both LS and BS neurons exhibited a rapid electrophysiological and morphological development during the first postnatal week. Our results provide new insights into the molecular, morphological, and functional developments of the neurons in layer 1 of the neocortex. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Extension of a GIS procedure for calculating the RUSLE equation LS factor

NASA Astrophysics Data System (ADS)

Zhang, Hongming; Yang, Qinke; Li, Rui; Liu, Qingrui; Moore, Demie; He, Peng; Ritsema, Coen J.; Geissen, Violette

2013-03-01

The Universal Soil Loss Equation (USLE) and revised USLE (RUSLE) are often used to estimate soil erosion at regional landscape scales, however a major limitation is the difficulty in extracting the LS factor. The geographic information system-based (GIS-based) methods which have been developed for estimating the LS factor for USLE and RUSLE also have limitations. The unit contributing area-based estimation method (UCA) converts slope length to unit contributing area for considering two-dimensional topography, however is not able to predict the different zones of soil erosion and deposition. The flowpath and cumulative cell length-based method (FCL) overcomes this disadvantage but does not consider channel networks and flow convergence in two-dimensional topography. The purpose of this research was to overcome these limitations and extend the FCL method through inclusion of channel networks and convergence flow. We developed LS-TOOL in Microsoft's.NET environment using C♯ with a user-friendly interface. Comparing the LS factor calculated with the three methodologies (UCA, FCL and LS-TOOL), LS-TOOL delivers encouraging results. In particular, LS-TOOL uses breaks in slope identified from the DEM to locate soil erosion and deposition zones, channel networks and convergence flow areas. Comparing slope length and LS factor values generated using LS-TOOL with manual methods, LS-TOOL corresponds more closely with the reality of the Xiannangou catchment than results using UCA or FCL. The LS-TOOL algorithm can automatically calculate slope length, slope steepness, L factor, S factor, and LS factors, providing the results as ASCII files which can be easily used in some GIS software. This study is an important step forward in conducting more accurate large area erosion evaluation.

A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification.

PubMed

Tognetto, Alessia; Michelazzo, Maria Benedetta; Calabró, Giovanna Elisa; Unim, Brigid; Di Marco, Marco; Ricciardi, Walter; Pastorino, Roberta; Boccia, Stefania

2017-01-01

Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3-5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS. We performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate. We identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%. This systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

Geranyl diphosphate synthase large subunit, and methods of use

DOEpatents

Croteau, Rodney B.; Burke, Charles C.; Wildung, Mark R.

2001-10-16

A cDNA encoding geranyl diphosphate synthase large subunit from peppermint has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Replicable recombinant cloning vehicles are provided which code for geranyl diphosphate synthase large subunit). In another aspect, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding geranyl diphosphate synthase large subunit. In yet another aspect, the present invention provides isolated, recombinant geranyl diphosphate synthase protein comprising an isolated, recombinant geranyl diphosphate synthase large subunit protein and an isolated, recombinant geranyl diphosphate synthase small subunit protein. Thus, systems and methods are provided for the recombinant expression of geranyl diphosphate synthase.

Solving Fuzzy Optimization Problem Using Hybrid Ls-Sa Method

NASA Astrophysics Data System (ADS)

Vasant, Pandian

2011-06-01

Fuzzy optimization problem has been one of the most and prominent topics inside the broad area of computational intelligent. It's especially relevant in the filed of fuzzy non-linear programming. It's application as well as practical realization can been seen in all the real world problems. In this paper a large scale non-linear fuzzy programming problem has been solved by hybrid optimization techniques of Line Search (LS), Simulated Annealing (SA) and Pattern Search (PS). As industrial production planning problem with cubic objective function, 8 decision variables and 29 constraints has been solved successfully using LS-SA-PS hybrid optimization techniques. The computational results for the objective function respect to vagueness factor and level of satisfaction has been provided in the form of 2D and 3D plots. The outcome is very promising and strongly suggests that the hybrid LS-SA-PS algorithm is very efficient and productive in solving the large scale non-linear fuzzy programming problem.

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.).

PubMed

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2017-01-01

Lettuce ( Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce.

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.)

PubMed Central

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2018-01-01

Lettuce (Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce. PMID:29403510

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency.

PubMed

Péquignot, M O; Dey, R; Zeviani, M; Tiranti, V; Godinot, C; Poyau, A; Sue, C; Di Mauro, S; Abitbol, M; Marsac, C

2001-05-01

Cytochrome c oxidase (COX) deficiency is one of the major causes of Leigh Syndrome (LS), a fatal encephalopathy of infancy or childhood, characterized by symmetrical lesions in the basal ganglia and brainstem. Mutations in the nuclear genes encoding COX subunits have not been found in patients with LS and COX deficiency, but mutations have been identified in SURF1. SURF1 encodes a factor involved in COX biogenesis. To date, 30 different mutations have been reported in 40 unrelated patients. We aim to provide an overview of all known mutations in SURF1, and to propose a common nomenclature. Twelve of the mutations were insertion/deletion mutations in exons 1, 4, 6, 8, and 9; 10 were missense/nonsense mutations in exons 2, 4, 5, 7, and 8; and eight were detected at splicing sites in introns 3 to 7. The most frequent mutation was 312_321del 311_312insAT which was found in 12 patients out of 40. Twenty mutations have been described only once. We also list all polymorphisms discovered to date. Copyright 2001 Wiley-Liss, Inc.

Influence of Terraced area DEM Resolution on RUSLE LS Factor

NASA Astrophysics Data System (ADS)

Zhang, Hongming; Baartman, Jantiene E. M.; Yang, Xiaomei; Gai, Lingtong; Geissen, Viollette

2017-04-01

Topography has a large impact on the erosion of soil by water. Slope steepness and slope length are combined (the LS factor) in the universal soil-loss equation (USLE) and its revised version (RUSLE) for predicting soil erosion. The LS factor is usually extracted from a digital elevation model (DEM). The grid size of the DEM will thus influence the LS factor and the subsequent calculation of soil loss. Terracing is considered as a support practice factor (P) in the USLE/RUSLE equations, which is multiplied with the other USLE/RUSLE factors. However, as terraces change the slope length and steepness, they also affect the LS factor. The effect of DEM grid size on the LS factor has not been investigated for a terraced area. We obtained a high-resolution DEM by unmanned aerial vehicles (UAVs) photogrammetry, from which the slope steepness, slope length, and LS factor were extracted. The changes in these parameters at various DEM resolutions were then analysed. The DEM produced detailed LS-factor maps, particularly for low LS factors. High (small valleys, gullies, and terrace ridges) and low (flats and terrace fields) spatial frequencies were both sensitive to changes in resolution, so the areas of higher and lower slope steepness both decreased with increasing grid size. Average slope steepness decreased and average slope length increased with grid size. Slope length, however, had a larger effect than slope steepness on the LS factor as the grid size varied. The LS factor increased when the grid size increased from 0.5 to 30-m and increased significantly at grid sizes >5-m. The LS factor was increasingly overestimated as grid size decreased. The LS factor decreased from grid sizes of 30 to 100-m, because the details of the terraced terrain were gradually lost, but the factor was still overestimated.

Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi Arabian Patients with Laron Syndrome.

PubMed

Al-Ashwal, Abdullah A; Al-Sagheir, Afaf; Ramzan, Khushnooda; Al-Owain, Mohammed; Allam, Rabab; Qari, Alya; Al-Numair, Nouf S; Imtiaz, Faiqa

2017-01-01

Laron syndrome (LS) is an autosomal recessive disease characterized by marked short stature and very low serum IGF-1 and IGFBP-3 levels. This study assessed the clinical and endocrine features alongside determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian patients with LS in order to establish whether or not a genotype/phenotype correlation is evident in this large cohort. A total of 40 Saudi Arabian patients with a suspected diagnosis of LS were recruited and subjected to a full clinical and endocrine investigation together with direct sequencing of the coding regions of the GHR gene. GHR mutations were identified in 34 patients from 22 separate nuclear families. All 34 molecularly confirmed patients had the typical clinical and endocrinological manifestations of LS. Eleven different mutations (9 previously unreported) were detected in this cohort of patients, all inherited in an autosomal recessive homozygous form. No genotype/phenotype correlation was apparent. The identification of pathogenic mutations causing LS will be of tremendous use for the molecular diagnosis of patients in Saudi Arabia and the region in general, with respect to prevention of this disease in the forms of future carrier testing, prenatal testing, premarital screening and preimplantation genetic diagnosis. © 2017 S. Karger AG, Basel.

Inverse European Latitudinal Cline at the timeless Locus of Drosophila melanogaster Reveals Selection on a Clock Gene: Population Genetics of ls-tim.

PubMed

Zonato, Valeria; Vanin, Stefano; Costa, Rodolfo; Tauber, Eran; Kyriacou, Charalambos P

2018-02-01

The spread of adaptive genetic variants in populations is a cornerstone of evolutionary theory but with relatively few biologically well-understood examples. Previous work on the ls-tim variant of timeless, which encodes the light-sensitive circadian regulator in Drosophila melanogaster, suggests that it may have originated in southeastern Italy. Flies characterized by the new allele show photoperiod-related phenotypes likely to be adaptive in seasonal environments. ls-tim may be spreading from its point of origin in Italy by directional selection, but there are alternative explanations for its observed clinal geographical distribution, including balancing selection and demography. From population analyses of ls-tim frequencies collected on the eastern side of the Iberian Peninsula, we show that ls-tim frequencies are inverted compared with those in Italy. This pattern is consistent with a scenario of directional selection rather than latitude-associated balancing selection. Neutrality tests further reveal the signature of directional selection at the ls-tim site, which is reduced a few kb pairs either side of ls-tim. A reanalysis of allele frequencies from a large number of microsatellite loci do not demonstrate any frequent ls-tim-like spatial patterns, so a general demographic effect or population expansion from southeastern Italy cannot readily explain current ls-tim frequencies. Finally, a revised estimate of the age of ls-tim allele using linkage disequilibrium and coalescent-based approaches reveals that it may be only 300 to 3000 years old, perhaps explaining why it has not yet gone to fixation. ls-tim thus provides a rare temporal snapshot of a new allele that has come under selection before it reaches equilibrium.

[Epidemiology of bone and joint disease - the present and future - . Epidemiology of lumbar spondylosis in Japan : the ROAD study].

PubMed

Yoshimura, Noriko

2014-05-01

To clarify the prevalence and estimate the number of people with osteoarthritis, and osteoporosis in Japan, we established a large-scale population-based cohort study entitled Research on Osteoarthritis/osteoporosis Against Disability (ROAD). The prevalence of lumbar spondylosis (LS) in men and women was 80.6% and 61.5%, respectively with utilizing the ROAD baseline data. The cumulative incidence of LS in men and women was 15.2%/y and 10.4%/y, respectively with using the follow-up data. The estimated number of prevalent cases and incident cases/y of LS in Japan was approximately 38 million and 9 million, respectively. Older age, male-sex, and greater BMI were associated with the occurrence of LS.

Cloning, Purification, and Characterization of a Heterodimeric β-Galactosidase from Lactobacillus kefiranofaciens ZW3.

PubMed

He, Xi; Han, Ning; Wang, Yan-Ping

2016-01-01

Lactobacillus kefiranofaciens ZW3 was obtained from kefir grains, which have high lactose hydrolytic activity. In this study, a heterodimeric LacLM-type β-galactosidase gene (lacLM) from ZW3 was isolated, which was composed of two overlapping genes, lacL (1,884 bp) and lacM (960 bp) encoding large and small subunits with calculated molecular masses of 73,620 and 35,682 Da, respectively. LacLM, LacL, and LacM were expressed in Escherichia coli BL21(DE3) and these recombinant proteins were purified and characterized. The results showed that, compared with the recombinant holoenzyme, the recombinant large subunit exhibits obviously lower thermostability and hydrolytic activity. Moreover, the optimal temperature and pH of the holoenzyme and large subunit are 60°C and 7.0, and 50°C and 8.0, respectively. However, the recombinant small subunit alone has no activity. Interestingly, the activity and thermostability of the large subunit were greatly improved after mixing it with the recombinant small subunit. Therefore, the results suggest that the small subunit might play an important role in maintaining the stability of the structure of the catalytic center located in the large subunit.

Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants*

PubMed Central

Chen, Lie; Bi, Danlei; Tian, Lijun; McClafferty, Heather; Steeb, Franziska; Ruth, Peter; Knaus, Hans Guenther; Shipston, Michael J.

2013-01-01

Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels. PMID:23504458

Error mechanism analyses of an ultra-precision stage for high speed scan motion over a large stroke

NASA Astrophysics Data System (ADS)

Wang, Shaokai; Tan, Jiubin; Cui, Jiwen

2015-02-01

Reticle Stage (RS) is designed to complete scan motion with high speed in nanometer-scale over a large stroke. Comparing with the allowable scan accuracy of a few nanometers, errors caused by any internal or external disturbances are critical and must not be ignored. In this paper, RS is firstly introduced in aspects of mechanical structure, forms of motion, and controlling method. Based on that, mechanisms of disturbances transferred to final servo-related error in scan direction are analyzed, including feedforward error, coupling between the large stroke stage (LS) and the short stroke stage (SS), and movement of measurement reference. Especially, different forms of coupling between SS and LS are discussed in detail. After theoretical analysis above, the contributions of these disturbances to final error are simulated numerically. The residual positioning error caused by feedforward error in acceleration process is about 2 nm after settling time, the coupling between SS and LS about 2.19 nm, and the movements of MF about 0.6 nm.

Time Harmonic Elastography Reveals Sensitivity of Liver Stiffness to Water Ingestion.

PubMed

Ipek-Ugay, Selcan; Tzschätzsch, Heiko; Hudert, Christian; Marticorena Garcia, Stephan Rodrigo; Fischer, Thomas; Braun, Jürgen; Althoff, Christian; Sack, Ingolf

2016-06-01

The aim of the study was to test the sensitivity of liver stiffness (LS) measured by time harmonic elastography in large tissue windows to water uptake and post-prandial effects. Each subject gave written informed consent to participate in this institutional review board-approved prospective study. LS was measured by time harmonic elastography in 10 healthy volunteers pre- and post-prandially, as well as before, directly after and 2 h after drinking water. The LS-time function during water intake was measured in 14 scans over 3 h in five volunteers. LS increased by 10% (p = 0.0015) post-prandially and by 11% (p = 0.0024) after pure water ingestion, and decreased to normal values after 2 h. LS was lower after overnight fasting than after 2-h fasting (3%, p = 0.04). Over the time course, LS increased to post-water peak values 15 min after drinking 0.25 L water and remained unaffected by further ingestion of water. In conclusion, our study indicates that LS measured by time harmonic elastography represents an effective-medium property sensitive to physiologic changes in vascular load of the liver. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The Behavioural Phenotype of Cornelia de Lange Syndrome: A Study of 56 Individuals

ERIC Educational Resources Information Center

Basile, Emanuele; Villa, L.; Selicorni, A.; Molteni, M.

2007-01-01

Background: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. Methods: In total, 56 individuals with CdLS…

Regional-scale calculation of the LS factor using parallel processing

NASA Astrophysics Data System (ADS)

Liu, Kai; Tang, Guoan; Jiang, Ling; Zhu, A.-Xing; Yang, Jianyi; Song, Xiaodong

2015-05-01

With the increase of data resolution and the increasing application of USLE over large areas, the existing serial implementation of algorithms for computing the LS factor is becoming a bottleneck. In this paper, a parallel processing model based on message passing interface (MPI) is presented for the calculation of the LS factor, so that massive datasets at a regional scale can be processed efficiently. The parallel model contains algorithms for calculating flow direction, flow accumulation, drainage network, slope, slope length and the LS factor. According to the existence of data dependence, the algorithms are divided into local algorithms and global algorithms. Parallel strategy are designed according to the algorithm characters including the decomposition method for maintaining the integrity of the results, optimized workflow for reducing the time taken for exporting the unnecessary intermediate data and a buffer-communication-computation strategy for improving the communication efficiency. Experiments on a multi-node system show that the proposed parallel model allows efficient calculation of the LS factor at a regional scale with a massive dataset.

Detection of expansion at large angle grain boundaries using electron diffraction

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

Balluffi, R.W.; Bristowe, P.D.

1984-02-01

Lamarre and Sass (LS) (Scripta Metall. 17: 1141(1983)) observed a grain boundary electron diffraction effect from a large angle twist boundary which they claim can be used to obtain the volume expansion at the grain boundary in a direction normal to it. This paper considers the case where the intensity from the grain boundary region, is close to lattice reflections on the same element of the boundary diffraction lattice. Analysis of this complex problem show that the simplified model of LS is misleading in this case. (DLC)

Examining the relationships between life satisfaction and alcohol, tobacco and marijuana use among school-aged children.

PubMed

Lew, D; Xian, H; Qian, Z; Vaughn, M G

2018-05-03

There are many known risk factors associated with youth substance use. Nonetheless, the impact of life satisfaction (LS) on the use of alcohol, tobacco and marijuana by adolescents still remains largely unknown. The present analysis utilized data from the Health Behavior in School-Aged Children 2009-10 US study. Multilevel logistic regression models were used to assess the relationship between LS and individual substance use. Multilevel multinomial regression models examined the relationship with total number of substances used. After controlling for numerous variables associated with substance use, individuals reporting low LS were significantly more likely to ever use tobacco (OR = 1.34, 95% CI = [1.01, 1.78]), alcohol (OR = 1.45, 95% CI = [1.10, 1.92]) and marijuana (OR = 1.98, 95% CI = [1.39, 2.82]). Additionally, students with low LS were significantly more likely to use two substances (OR = 1.90, 95% CI = [1.15, 3.14]) and three substances concurrently (OR = 2.00, 95% CI = [1.27, 3.16]). The present study identified strong associations between LS and individual, as well as concurrent, substance use among adolescents. Interventions aiming to reduce adolescent substance use may benefit from incorporating components to improve LS.

The βγ-crystallin domain of Lysinibacillus sphaericus phosphatidylinositol phospholipase C plays a central role in protein stability.

PubMed

Cerminati, Sebastián; Paoletti, Luciana; Peirú, Salvador; Menzella, Hugo G; Castelli, María Eugenia

2018-06-16

βγ-crystallin has emerged as a superfamily of structurally homologous proteins with representatives across all domains of life. A major portion of this superfamily is constituted by microbial members. This superfamily has also been recognized as a novel group of Ca 2+ -binding proteins with a large diversity and variable properties in Ca 2+ binding and stability. We have recently described a new phosphatidylinositol phospholipase C from Lysinibacillus sphaericus (LS-PIPLC) which was shown to efficiently remove phosphatidylinositol from crude vegetable oil. Here, the role of the C-terminal βγ-crystallin domain of LS-PIPLC was analyzed in the context of the whole protein. A truncated protein in which the C-terminal βγ-crystallin domain was deleted (LS-PIPLC ΔCRY ) is catalytically as efficient as the full-length protein (LS-PIPLC). However, the thermal and chemical stability of LS-PIPLC ΔCRY are highly affected, demonstrating a stabilizing role for this domain. It is also shown that the presence of Ca 2+ increases the thermal and chemical stability of the protein both in aqueous media and in oil, making LS-PIPLC an excellent candidate for use in industrial soybean oil degumming.

Some aspects of large-scale travelling ionospheric disturbances

NASA Astrophysics Data System (ADS)

Bowman, G. G.

1992-06-01

On two occasions the speeds and directions of travel of large-scale traveling ionospheric disturbances (LS-TIDs) following geomagnetic substorm onsets, have been calculated for the propagation of these disturbances in both hemispheres of the earth. N(h) analyses have been used to produce height change profiles at a fixed frequency from which time shifts between stations (used for the speed and direction-of-travel values) have been calculated. Fixed-frequency phase path measurements at Bribie Island for two events reveal wavetrains with periodicities around 17 min associated with these disturbances. Another event recorded a periodicity of 19 min. Also, for two of the events additional periodicities around 30 min were found. These wavetrains along with the macroscale height changes and electron density depletions associated with these LS-TIDs are essentially the same as the ionospheric structure changes observed during the passage of night-time medium-scale traveling ionospheric disturbances (MS-TIDs). However, unlike these MS-TIDs, the LS-TIDs are generally not associated with the recording of spread-F on ionograms. Possible reasons for this difference are discussed as well as the special conditions which probably prevail on the few occasions when spread-F is associated with LS-TIDs.

A threshold-based fixed predictor for JPEG-LS image compression

NASA Astrophysics Data System (ADS)

Deng, Lihua; Huang, Zhenghua; Yao, Shoukui

2018-03-01

In JPEG-LS, fixed predictor based on median edge detector (MED) only detect horizontal and vertical edges, and thus produces large prediction errors in the locality of diagonal edges. In this paper, we propose a threshold-based edge detection scheme for the fixed predictor. The proposed scheme can detect not only the horizontal and vertical edges, but also diagonal edges. For some certain thresholds, the proposed scheme can be simplified to other existing schemes. So, it can also be regarded as the integration of these existing schemes. For a suitable threshold, the accuracy of horizontal and vertical edges detection is higher than the existing median edge detection in JPEG-LS. Thus, the proposed fixed predictor outperforms the existing JPEG-LS predictors for all images tested, while the complexity of the overall algorithm is maintained at a similar level.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Delivery of Iron-Sulfur Clusters to the Hydrogen-Oxidizing [NiFe]-Hydrogenases in Escherichia coli Requires the A-Type Carrier Proteins ErpA and IscA

PubMed Central

Pinske, Constanze; Sawers, R. Gary

2012-01-01

During anaerobic growth Escherichia coli synthesizes two membrane-associated hydrogen-oxidizing [NiFe]-hydrogenases, termed hydrogenase 1 and hydrogenase 2. Each enzyme comprises a catalytic subunit containing the [NiFe] cofactor, an electron-transferring small subunit with a particular complement of [Fe-S] (iron-sulfur) clusters and a membrane-anchor subunit. How the [Fe-S] clusters are delivered to the small subunit of these enzymes is unclear. A-type carrier (ATC) proteins of the Isc (iron-sulfur-cluster) and Suf (sulfur mobilization) [Fe-S] cluster biogenesis pathways are proposed to traffic pre-formed [Fe-S] clusters to apoprotein targets. Mutants that could not synthesize SufA had active hydrogenase 1 and hydrogenase 2 enzymes, thus demonstrating that the Suf machinery is not required for hydrogenase maturation. In contrast, mutants devoid of the IscA, ErpA or IscU proteins of the Isc machinery had no detectable hydrogenase 1 or 2 activities. Lack of activity of both enzymes correlated with the absence of the respective [Fe-S]-cluster-containing small subunit, which was apparently rapidly degraded. During biosynthesis the hydrogenase large subunits receive their [NiFe] cofactor from the Hyp maturation machinery. Subsequent to cofactor insertion a specific C-terminal processing step occurs before association of the large subunit with the small subunit. This processing step is independent of small subunit maturation. Using western blotting experiments it could be shown that although the amount of each hydrogenase large subunit was strongly reduced in the iscA and erpA mutants, some maturation of the large subunit still occurred. Moreover, in contrast to the situation in Isc-proficient strains, these processed large subunits were not membrane-associated. Taken together, our findings demonstrate that both IscA and ErpA are required for [Fe-S] cluster delivery to the small subunits of the hydrogen-oxidizing hydrogenases; however, delivery of the Fe atom to the active site might have different requirements. PMID:22363723

Mass Cytometry Identifies Distinct Lung CD4+ T Cell Patterns in Löfgren’s Syndrome and Non-Löfgren’s Syndrome Sarcoidosis

PubMed Central

Kaiser, Ylva; Lakshmikanth, Tadepally; Chen, Yang; Mikes, Jaromir; Eklund, Anders; Brodin, Petter; Achour, Adnane; Grunewald, Johan

2017-01-01

Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4+ T cells in the lungs. Disease phenotypes Löfgren’s syndrome (LS) and “non-LS” differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03+ LS and four HLA-DRB1*03− non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers. Differentially regulated CD4+ T cell populations were identified using the Citrus algorithm, and t-stochastic neighborhood embedding was applied for dimensionality reduction and single-cell data visualization. We identified 19 individual CD4+ T cell clusters differing significantly in abundance between LS and non-LS patients. Seven clusters more frequent in LS patients were characterized by significantly higher expression of regulatory receptors CTLA-4, PD-1, and ICOS, along with low expression of adhesion marker CD44. In contrast, 12 clusters primarily found in non-LS displayed elevated expression of activation and effector markers HLA-DR, CD127, CD39, as well as CD44. Hierarchical clustering further indicated functional heterogeneity and diverse origins of T cell receptor Vα2.3/Vβ22-restricted cells in LS. Finally, a near-complete overlap of CD8 and Ki-67 expression suggested larger influence of CD8+ T cell activity on sarcoid inflammation than previously appreciated. In this study, we provide detailed characterization of pulmonary T cells and immunological parameters that define separate disease pathways in LS and non-LS. With direct association to clinical parameters, such as granuloma persistence, resolution, or chronic inflammation, these results provide a valuable foundation for further exploration and potential clinical application. PMID:28955342

Characterization of Lactobacillus salivarius strains B37 and B60 capable of inhibiting IL-8 production in Helicobacter pylori-stimulated gastric epithelial cells.

PubMed

Panpetch, Wimonrat; Spinler, Jennifer K; Versalovic, James; Tumwasorn, Somying

2016-10-18

Interleukin (IL)-8 is the key agent for initiating an inflammatory response to infection with Helicobacter pylori. Some strains of Lactobacillus spp. are known to colonize the stomach and suppress inflammation caused by H. pylori. In this study, we characterized two gastric-derived lactobacilli, Lactobacillus salivarius (LS) strains B37 and B60, capable of inhibiting H. pylori-induced IL-8 production by gastric epithelial cells. Conditioned media from LS-B37 and LS-B60 suppressed H. pylori-induced IL-8 production and mRNA expression from AGS cells without inhibiting H. pylori growth. These conditioned media suppressed the activation of NF-κB but did not suppress c-Jun activation. IL-8 inhibitory substances in conditioned media of LS-B37 and LS-B60 are heat-stable and larger than 100 kDa in size. The inhibitory activity of LS-B37 was abolished when the conditioned medium was treated with α-amylase but still remained when treated with either proteinase K, trypsin, lipase or lysozyme. The activity of LS-B60 was abolished when the conditioned medium was treated with either amylase or proteinase K but still remained when treated with lysozyme. Treatment with lipase and trypsin also significantly affected the inhibitory activity of LS-B60 although the conditioned medium retained IL-8 suppression statistically different from media control. These results suggest that L. salivarius strains B37 and B60 produce different immunomodulatory factors capable of suppressing H. pylori-induced IL-8 production from gastric epithelial cells. Our results suggest that the large, heat-stable immunomodulatory substance(s) present in the LCM of LS-B37 is a polysaccharide, while the one(s) of LS-B60 is either complex consisting of components of polysaccharide, lipid and protein or includes multiple components such as glycoprotein and lipoprotein.

Lhermitte's sign: Review with special emphasis in oncology practice.

PubMed

Gemici, Cengiz

2010-05-01

Lhermitte's sign (LS) is characterized by electric shock like sensation, spreading along the spine in a cervico-caudal direction and also into both arms and legs, which is felt upon forward flexion of the neck. It is a myelopathy resulting from damage to sensory axons at the dorsal columns of the cervical or thoracic spinal cord and a well-known clinical sign in neurology practice. Patients with cancer may present with LS due to various causes either related to the tumor itself or to its treatment. Spinal cord tumors, radiotherapy and chemotherapy are possible causes of LS observed in oncology practice. While LS is observed with a frequency of 3.6-13% in large patient groups receiving radiotherapy for head and neck and thoracic malignancies, the true incidence of chemotherapy and spinal cord tumor induced LS is unknown with only few reported cases in the literature. In the present article, various pathologies causing Lhermitte's sign are reviewed with special emphasis on the implications of this sign in oncology practice. 2009 Elsevier Ireland Ltd. All rights reserved.

Subunit Conformations and Assembly States of a DNA Translocating Motor: The Terminase of Bacteriophage P22

PubMed Central

Němeček, Daniel; Gilcrease, Eddie B.; Kang, Sebyung; Prevelige, Peter E.; Casjens, Sherwood; Thomas, George J.

2007-01-01

Bacteriophage P22, a podovirus infecting strains of Salmonella typhimurium, packages a 42 kbp genome using a headful mechanism. DNA translocation is accomplished by the phage terminase, a powerful molecular motor consisting of large and small subunits. Although many of the structural proteins of the P22 virion have been well characterized, little is known about the terminase subunits and their molecular mechanism of DNA translocation. We report here structural and assembly properties of ectopically expressed and highly purified terminase large and small subunits. The large subunit (gp2), which contains the nuclease and ATPase activities of terminase, exists as a stable monomer with an α/β fold. The small subunit (gp3), which recognizes DNA for packaging and may regulate gp2 activity, exhibits a highly α-helical secondary structure and self-associates to form a stable oligomeric ring in solution. For wildtype gp3, the ring contains nine subunits, as demonstrated by hydrodynamic measurements, electron microscopy and native mass spectrometry. We have also characterized a gp3 mutant (Ala 112 → Thr) that forms a ten subunit ring, despite a subunit fold indistinguishable from wildtype. Both the nonameric and decameric gp3 rings exhibit nonspecific DNA binding activity, and gp2 is able to bind strongly to the DNA/gp3 complex but not to DNA alone. We propose a scheme for the roles of P22 terminase large and small subunits in the recruitment and packaging of viral DNA and discuss the model in relation to proposals for terminase-driven DNA translocation in other phages. PMID:17945256

Elastic Differential Cross Sections

NASA Technical Reports Server (NTRS)

Werneth, Charles M.; Maung, Khin M.; Ford, William P.; Norbury, John W.; Vera, Michael D.

2014-01-01

The eikonal, partial wave (PW) Lippmann-Schwinger, and three-dimensional Lippmann-Schwinger (LS3D) methods are compared for nuclear reactions that are relevant for space radiation applications. Numerical convergence of the eikonal method is readily achieved when exact formulas of the optical potential are used for light nuclei (A less than or equal to 16) and the momentum-space optical potential is used for heavier nuclei. The PW solution method is known to be numerically unstable for systems that require a large number of partial waves, and, as a result, the LS3D method is employed. The effect of relativistic kinematics is studied with the PW and LS3D methods and is compared to eikonal results. It is recommended that the LS3D method be used for high energy nucleon- nucleus reactions and nucleus-nucleus reactions at all energies because of its rapid numerical convergence and stability.

Nuclear Cross Sections for Space Radiation Applications

NASA Technical Reports Server (NTRS)

Werneth, C. M.; Maung, K. M.; Ford, W. P.; Norbury, J. W.; Vera, M. D.

2015-01-01

The eikonal, partial wave (PW) Lippmann-Schwinger, and three-dimensional Lippmann-Schwinger (LS3D) methods are compared for nuclear reactions that are relevant for space radiation applications. Numerical convergence of the eikonal method is readily achieved when exact formulas of the optical potential are used for light nuclei (A = 16) and the momentum-space optical potential is used for heavier nuclei. The PW solution method is known to be numerically unstable for systems that require a large number of partial waves, and, as a result, the LS3D method is employed. The effect of relativistic kinematics is studied with the PW and LS3D methods and is compared to eikonal results. It is recommended that the LS3D method be used for high energy nucleon-nucleus reactions and nucleus-nucleus reactions at all energies because of its rapid numerical convergence and stability for both non-relativistic and relativistic kinematics.

LS Bound based gene selection for DNA microarray data.

PubMed

Zhou, Xin; Mao, K Z

2005-04-15

One problem with discriminant analysis of DNA microarray data is that each sample is represented by quite a large number of genes, and many of them are irrelevant, insignificant or redundant to the discriminant problem at hand. Methods for selecting important genes are, therefore, of much significance in microarray data analysis. In the present study, a new criterion, called LS Bound measure, is proposed to address the gene selection problem. The LS Bound measure is derived from leave-one-out procedure of LS-SVMs (least squares support vector machines), and as the upper bound for leave-one-out classification results it reflects to some extent the generalization performance of gene subsets. We applied this LS Bound measure for gene selection on two benchmark microarray datasets: colon cancer and leukemia. We also compared the LS Bound measure with other evaluation criteria, including the well-known Fisher's ratio and Mahalanobis class separability measure, and other published gene selection algorithms, including Weighting factor and SVM Recursive Feature Elimination. The strength of the LS Bound measure is that it provides gene subsets leading to more accurate classification results than the filter method while its computational complexity is at the level of the filter method. A companion website can be accessed at http://www.ntu.edu.sg/home5/pg02776030/lsbound/. The website contains: (1) the source code of the gene selection algorithm; (2) the complete set of tables and figures regarding the experimental study; (3) proof of the inequality (9). ekzmao@ntu.edu.sg.

Proteopedia Entry: The Large Ribosomal Subunit of "Haloarcula Marismortui"

ERIC Educational Resources Information Center

Decatur, Wayne A.

2010-01-01

This article presents a "Proteopedia" page that shows the refined version of the structure of the "Haloarcula" large ribosomal subunit as solved by the laboratories of Thomas Steitz and Peter Moore. The landmark structure is of great impact as it is the first atomic-resolution structure of the highly conserved ribosomal subunit which harbors…

Incidence and risk factors for radiographic lumbar spondylosis and lower back pain in Japanese men and women: the ROAD study.

PubMed

Muraki, S; Akune, T; Oka, H; Ishimoto, Y; Nagata, K; Yoshida, M; Tokimura, F; Nakamura, K; Kawaguchi, H; Yoshimura, N

2012-07-01

To determine the incidence of radiographic lumbar spondylosis (LS)and lower back pain, and their risk factors in Japan using a large-scale population from the nationwide cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD) Study. Participants in the ROAD study who had been recruited between 2005 and 2007 were followed up with lumbar spine radiography for 3 years. A total of 2,282 paired radiographs (75% of the original sample) were scored using Kellgren and Lawrence (KL) grades, and the incidence and progression rate of radiographic LS was analyzed. The incidence of lower back pain was also examined. In addition, associations between risk factors and incident and progressive radiographic LS as well as incident lower back pain were tested. Given a 3.3-year follow-up, the incidence of KL≥2 radiographic LS was 50.0% and 34.4% (15.3% and 10.5% per year), while that of KL≥3 LS was 15.3% and 23.7% (4.6% and 7.2% per year) in men and women, respectively. The progression rate of LS was 20.5% and 27.4% (6.2% and 8.3% per year) in men and in women, respectively. In addition, the incidence of lower back pain was 28.3% and 31.2% (8.6% and 9.5% per year) in men and women. Lower back pain was not significantly associated with incident radiographic LS, while a more severe KL grade at baseline was associated with incident lower back pain. The present longitudinal study revealed a high incidence of radiographic LS in Japan. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

2003 Mars Report from Cooperative Observation Networks. II. After the Opposition

NASA Astrophysics Data System (ADS)

Nakakushi, Takashi; Adachi, Makoto; Iga, Yuichi; Ikemura, Toshihiko; Tokimasa, Noritaka; Narumi, Yasunori

2005-06-01

This is the second report on Mars in 2003 by two networks for cooperative Mars observations in Japan: Nishi-Harima Astronomical Observatory Mars Cooperative Observation and Association of Lunar and Planetary Observers in Japan. This paper is a summary of 4145 data for 226 nights collected by the two networks during the second half of the last apparition from 2003 September 1 through 2004 June 22, corresponding to a period of Ls ˜ 252°--51° (Ls is the areocentric longitude of the Sun). During this period, many interesting phenomena were observed: (1) Albedo features did not show a large difference from the first half of the period. (2) Blue clearings due to the opposition effect and due to the cloud effect were, respectively, observed. (3) South polar cap (SPC) recession was usual. The recession rate in ˜ 210°--270°W increased and that in ˜ 30°--60°W decreased after Ls ˜ 230°. (4) North polar hood (NPH) had a topography-synchronous wave structure with a wave number = 1. (5) Many water ice clouds (WICs) were observed. Some particular regions frequently had prominent WICs. Some of them were related to topography. (6) Dust storm ``2003c'' was detected on December 9 (Ls = 314°) in Chryse. The storm grew rapidly to a very large dimension in the southern mid-latitudes, encircling over half of Mars. Another dust core occurred on December 23 around Aurorae Sinus. (7) Another dust storm is suspected in Ls = 20° over the south polar region.

High capacity hard carbon derived from lotus stem as anode for sodium ion batteries

NASA Astrophysics Data System (ADS)

Zhang, Nan; Liu, Qing; Chen, Weilun; Wan, Min; Li, Xiaocheng; Wang, Lili; Xue, Lihong; Zhang, Wuxing

2018-02-01

Porous hard carbons are synthesized via carbonizing lotus stems with naturally hierarchical structures. The hard carbon carbonized at 1400 °C (LS1400) delivers a total capacity 350 mAh g-1 in the current density of 100 mA g-1 and a plateau capacity of 250 mAh g-1. Even cycled at 100 mA g-1 after 450 cycles, the capacity still retains 94%. Further investigation shows that the sodium storage of LS carbons involves Na+ adsorption in the defect sites, Na+ insertion and Na metal deposition in the closed pores. However, the Na metal deposition in closed pores mainly contribute to the plateau capacity, leading to the excellent sodium storage performance of LS1400 with a large closed pore ratio of 66%. The results show that the intrinsic structure of natural biomass can inspire us to design hard carbon with large closed pore ratio as excellent anode for sodium ion batteries.

Large Scale Triboelectric Nanogenerator and Self-Powered Pressure Sensor Array Using Low Cost Roll-to-Roll UV Embossing

PubMed Central

Dhakar, Lokesh; Gudla, Sudeep; Shan, Xuechuan; Wang, Zhiping; Tay, Francis Eng Hock; Heng, Chun-Huat; Lee, Chengkuo

2016-01-01

Triboelectric nanogenerators (TENGs) have emerged as a potential solution for mechanical energy harvesting over conventional mechanisms such as piezoelectric and electromagnetic, due to easy fabrication, high efficiency and wider choice of materials. Traditional fabrication techniques used to realize TENGs involve plasma etching, soft lithography and nanoparticle deposition for higher performance. But lack of truly scalable fabrication processes still remains a critical challenge and bottleneck in the path of bringing TENGs to commercial production. In this paper, we demonstrate fabrication of large scale triboelectric nanogenerator (LS-TENG) using roll-to-roll ultraviolet embossing to pattern polyethylene terephthalate sheets. These LS-TENGs can be used to harvest energy from human motion and vehicle motion from embedded devices in floors and roads, respectively. LS-TENG generated a power density of 62.5 mW m−2. Using roll-to-roll processing technique, we also demonstrate a large scale triboelectric pressure sensor array with pressure detection sensitivity of 1.33 V kPa−1. The large scale pressure sensor array has applications in self-powered motion tracking, posture monitoring and electronic skin applications. This work demonstrates scalable fabrication of TENGs and self-powered pressure sensor arrays, which will lead to extremely low cost and bring them closer to commercial production. PMID:26905285

Laparoscopic Splenectomy with Technical Standardization and Selection Criteria for Standard or Hand-Assisted Approach in 390 Patients with Liver Cirrhosis and Portal Hypertension.

PubMed

Kawanaka, Hirofumi; Akahoshi, Tomohiko; Kinjo, Nao; Harimoto, Norifumi; Itoh, Shinji; Tsutsumi, Norifumi; Matsumoto, Yoshihiro; Yoshizumi, Tomoharu; Shirabe, Ken; Maehara, Yoshihiko

2015-08-01

Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension. We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS. Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014). Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

PubMed

Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

2016-02-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. Copyright © 2016 by the American Society of Nephrology.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

PubMed Central

Qi, Ying; Wang, Xiaojing; Rose, Kristie L.; MacDonald, W. Hayes; Zhang, Bing; Schey, Kevin L.

2016-01-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. PMID:26113616

Nipbl and mediator cooperatively regulate gene expression to control limb development.

PubMed

Muto, Akihiko; Ikeda, Shingo; Lopez-Burks, Martha E; Kikuchi, Yutaka; Calof, Anne L; Lander, Arthur D; Schilling, Thomas F

2014-09-01

Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

Highly conserved small subunit residues influence rubisco large subunit catalysis.

PubMed

Genkov, Todor; Spreitzer, Robert J

2009-10-30

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

Liver Stiffness Reflecting Right-Sided Filling Pressure Can Predict Adverse Outcomes in Patients With Heart Failure.

PubMed

Taniguchi, Tatsunori; Ohtani, Tomohito; Kioka, Hidetaka; Tsukamoto, Yasumasa; Onishi, Toshinari; Nakamoto, Kei; Katsimichas, Themistoklis; Sengoku, Kaoruko; Chimura, Misato; Hashimoto, Haruko; Yamaguchi, Osamu; Sawa, Yoshiki; Sakata, Yasushi

2018-01-12

This study sought to investigate whether elevated liver stiffness (LS) values at discharge reflect residual liver congestion and are associated with worse outcomes in patients with heart failure (HF). Transient elastography is a newly developed, noninvasive method for assessing LS, which can be highly reflective of right-sided filling pressure associated with passive liver congestion in patients with HF. LS values were determined for 171 hospitalized patients with HF before discharge using a Fibroscan device. The median LS value was 5.6 kPa (interquartile range: 4.4 to 8.1; range 2.4 to 39.7) and that of right-sided filling pressure, which was estimated based on LS, was 5.7 mm Hg (interquartile range: 4.1 to 8.2 mm Hg; range 0.1 to 18.9 mm Hg). The patients in the highest LS tertile (>6.9 kPa, corresponding to an estimated right-sided filling pressure of >7.1 mm Hg) had advanced New York Heart Association functional class, high prevalence of jugular venous distention and moderate/severe tricuspid regurgitation, large inferior vena cava (IVC) diameter, low hemoglobin and hematocrit levels, high serum direct bilirubin level, and a similar left ventricular ejection fraction compared with the lower tertiles. During follow-up periods (median: 203 days), 8 (5%) deaths and 33 (19%) hospitalizations for HF were observed. The patients in the highest LS group had a significantly higher mortality rate and HF rehospitalization (hazard ratio: 3.57; 95% confidence interval: 1.93 to 6.83; p < 0.001) compared with the other tertiles. Although LS correlated with IVC diameter and serum direct bilirubin and brain natriuretic peptide levels, LS values were predictive of worse outcomes, even after adjustment for these indices. These data suggest that LS is a useful index for assessing systemic volume status and predicting the severity of HF, and that the presence of liver congestion at discharge is associated with worse outcomes in patients with HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

LS-SNP: large-scale annotation of coding non-synonymous SNPs based on multiple information sources.

PubMed

Karchin, Rachel; Diekhans, Mark; Kelly, Libusha; Thomas, Daryl J; Pieper, Ursula; Eswar, Narayanan; Haussler, David; Sali, Andrej

2005-06-15

The NCBI dbSNP database lists over 9 million single nucleotide polymorphisms (SNPs) in the human genome, but currently contains limited annotation information. SNPs that result in amino acid residue changes (nsSNPs) are of critical importance in variation between individuals, including disease and drug sensitivity. We have developed LS-SNP, a genomic scale software pipeline to annotate nsSNPs. LS-SNP comprehensively maps nsSNPs onto protein sequences, functional pathways and comparative protein structure models, and predicts positions where nsSNPs destabilize proteins, interfere with the formation of domain-domain interfaces, have an effect on protein-ligand binding or severely impact human health. It currently annotates 28,043 validated SNPs that produce amino acid residue substitutions in human proteins from the SwissProt/TrEMBL database. Annotations can be viewed via a web interface either in the context of a genomic region or by selecting sets of SNPs, genes, proteins or pathways. These results are useful for identifying candidate functional SNPs within a gene, haplotype or pathway and in probing molecular mechanisms responsible for functional impacts of nsSNPs. http://www.salilab.org/LS-SNP CONTACT: rachelk@salilab.org http://salilab.org/LS-SNP/supp-info.pdf.

Robust Least-Squares Support Vector Machine With Minimization of Mean and Variance of Modeling Error.

PubMed

Lu, Xinjiang; Liu, Wenbo; Zhou, Chuang; Huang, Minghui

2017-06-13

The least-squares support vector machine (LS-SVM) is a popular data-driven modeling method and has been successfully applied to a wide range of applications. However, it has some disadvantages, including being ineffective at handling non-Gaussian noise as well as being sensitive to outliers. In this paper, a robust LS-SVM method is proposed and is shown to have more reliable performance when modeling a nonlinear system under conditions where Gaussian or non-Gaussian noise is present. The construction of a new objective function allows for a reduction of the mean of the modeling error as well as the minimization of its variance, and it does not constrain the mean of the modeling error to zero. This differs from the traditional LS-SVM, which uses a worst-case scenario approach in order to minimize the modeling error and constrains the mean of the modeling error to zero. In doing so, the proposed method takes the modeling error distribution information into consideration and is thus less conservative and more robust in regards to random noise. A solving method is then developed in order to determine the optimal parameters for the proposed robust LS-SVM. An additional analysis indicates that the proposed LS-SVM gives a smaller weight to a large-error training sample and a larger weight to a small-error training sample, and is thus more robust than the traditional LS-SVM. The effectiveness of the proposed robust LS-SVM is demonstrated using both artificial and real life cases.

The little-studied cluster Berkeley 90. I. LS III +46 11: a very massive O3.5 If* + O3.5 If* binary

NASA Astrophysics Data System (ADS)

Maíz Apellániz, J.; Negueruela, I.; Barbá, R. H.; Walborn, N. R.; Pellerin, A.; Simón-Díaz, S.; Sota, A.; Marco, A.; Alonso-Santiago, J.; Sanchez Bermudez, J.; Gamen, R. C.; Lorenzo, J.

2015-07-01

Context. It appears that most (if not all) massive stars are born in multiple systems. At the same time, the most massive binaries are hard to find owing to their low numbers throughout the Galaxy and the implied large distances and extinctions. Aims: We want to study LS III +46 11, identified in this paper as a very massive binary; another nearby massive system, LS III +46 12; and the surrounding stellar cluster, Berkeley 90. Methods: Most of the data used in this paper are multi-epoch high S/N optical spectra, although we also use Lucky Imaging and archival photometry. The spectra are reduced with dedicated pipelines and processed with our own software, such as a spectroscopic-orbit code, CHORIZOS, and MGB. Results: LS III +46 11 is identified as a new very early O-type spectroscopic binary [O3.5 If* + O3.5 If*] and LS III +46 12 as another early O-type system [O4.5 V((f))]. We measure a 97.2-day period for LS III +46 11 and derive minimum masses of 38.80 ± 0.83 M⊙ and 35.60 ± 0.77 M⊙ for its two stars. We measure the extinction to both stars, estimate the distance, search for optical companions, and study the surrounding cluster. In doing so, a variable extinction is found as well as discrepant results for the distance. We discuss possible explanations and suggest that LS III +46 12 may be a hidden binary system where the companion is currently undetected.

Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex

PubMed Central

Lyumkis, Dmitry; Oliveira dos Passos, Dario; Tahara, Erich B.; Webb, Kristofor; Bennett, Eric J.; Vinterbo, Staal; Potter, Clinton S.; Carragher, Bridget; Joazeiro, Claudio A. P.

2014-01-01

All organisms have evolved mechanisms to manage the stalling of ribosomes upon translation of aberrant mRNA. In eukaryotes, the large ribosomal subunit-associated quality control complex (RQC), composed of the listerin/Ltn1 E3 ubiquitin ligase and cofactors, mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. How RQC recognizes stalled ribosomes and performs its functions has not been understood. Using single-particle cryoelectron microscopy, we have determined the structure of the RQC complex bound to stalled 60S ribosomal subunits. The structure establishes how Ltn1 associates with the large ribosomal subunit and properly positions its E3-catalytic RING domain to mediate nascent chain ubiquitylation. The structure also reveals that a distinguishing feature of stalled 60S particles is an exposed, nascent chain-conjugated tRNA, and that the Tae2 subunit of RQC, which facilitates Ltn1 binding, is responsible for selective recognition of stalled 60S subunits. RQC components are engaged in interactions across a large span of the 60S subunit surface, connecting the tRNA in the peptidyl transferase center to the distally located nascent chain tunnel exit. This work provides insights into a mechanism linking translation and protein degradation that targets defective proteins immediately after synthesis, while ignoring nascent chains in normally translating ribosomes. PMID:25349383

Identification and functional characterization of HIV-associated neurocognitive disorders with large-scale Granger causality analysis on resting-state functional MRI

NASA Astrophysics Data System (ADS)

Chockanathan, Udaysankar; DSouza, Adora M.; Abidin, Anas Z.; Schifitto, Giovanni; Wismüller, Axel

2018-02-01

Resting-state functional MRI (rs-fMRI), coupled with advanced multivariate time-series analysis methods such as Granger causality, is a promising tool for the development of novel functional connectivity biomarkers of neurologic and psychiatric disease. Recently large-scale Granger causality (lsGC) has been proposed as an alternative to conventional Granger causality (cGC) that extends the scope of robust Granger causal analyses to high-dimensional systems such as the human brain. In this study, lsGC and cGC were comparatively evaluated on their ability to capture neurologic damage associated with HIV-associated neurocognitive disorders (HAND). Functional brain network models were constructed from rs-fMRI data collected from a cohort of HIV+ and HIV- subjects. Graph theoretic properties of the resulting networks were then used to train a support vector machine (SVM) model to predict clinically relevant parameters, such as HIV status and neuropsychometric (NP) scores. For the HIV+/- classification task, lsGC, which yielded a peak area under the receiver operating characteristic curve (AUC) of 0.83, significantly outperformed cGC, which yielded a peak AUC of 0.61, at all parameter settings tested. For the NP score regression task, lsGC, with a minimum mean squared error (MSE) of 0.75, significantly outperformed cGC, with a minimum MSE of 0.84 (p < 0.001, one-tailed paired t-test). These results show that, at optimal parameter settings, lsGC is better able to capture functional brain connectivity correlates of HAND than cGC. However, given the substantial variation in the performance of the two methods at different parameter settings, particularly for the regression task, improved parameter selection criteria are necessary and constitute an area for future research.

Distinct cellular distributions of Kv4 pore-forming and auxiliary subunits in rat dorsal root ganglion neurons.

PubMed

Matsuyoshi, Hiroko; Takimoto, Koichi; Yunoki, Takakazu; Erickson, Vickie L; Tyagi, Pradeep; Hirao, Yoshihiko; Wanaka, Akio; Yoshimura, Naoki

2012-09-17

Dorsal root ganglia contain heterogeneous populations of primary afferent neurons that transmit various sensory stimuli. This functional diversity may be correlated with differential expression of voltage-gated K(+) (Kv) channels. Here, we examine cellular distributions of Kv4 pore-forming and ancillary subunits that are responsible for fast-inactivating A-type K(+) current. Expression pattern of Kv α-subunit, β-subunit and auxiliary subunit was investigated using immunohistochemistry, in situ hybridization and RT-PCR technique. The two pore-forming subunits Kv4.1 and Kv4.3 show distinct cellular distributions: Kv4.3 is predominantly in small-sized C-fiber neurons, whereas Kv4.1 is seen in DRG neurons in various sizes. Furthermore, the two classes of Kv4 channel auxiliary subunits are also distributed in different-sized cells. KChIP3 is the only significantly expressed Ca(2+)-binding cytosolic ancillary subunit in DRGs and present in medium to large-sized neurons. The membrane-spanning auxiliary subunit DPP6 is seen in a large number of DRG neurons in various sizes, whereas DPP10 is restricted in small-sized neurons. Distinct combinations of Kv4 pore-forming and auxiliary subunits may constitute A-type channels in DRG neurons with different physiological roles. Kv4.1 subunit, in combination with KChIP3 and/or DPP6, form A-type K(+) channels in medium to large-sized A-fiber DRG neurons. In contrast, Kv4.3 and DPP10 may contribute to A-type K(+) current in non-peptidergic, C-fiber somatic afferent neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

Coupled Research in Ocean Acoustics and Signal Processing for the Next Generation of Underwater Acoustic Communication Systems

DTIC Science & Technology

2016-08-05

technique which used unobserved ”intermediate” variables to break a high-dimensional estimation problem such as least- squares (LS) optimization of a large...Least Squares (GEM-LS). The estimator is iterative and the work in this time period focused on characterizing the convergence properties of this...ap- proach by relaxing the statistical assumptions which is termed the Relaxed Approximate Graph-Structured Recursive Least Squares (RAGS-RLS). This

A Two-Layer Least Squares Support Vector Machine Approach to Credit Risk Assessment

NASA Astrophysics Data System (ADS)

Liu, Jingli; Li, Jianping; Xu, Weixuan; Shi, Yong

Least squares support vector machine (LS-SVM) is a revised version of support vector machine (SVM) and has been proved to be a useful tool for pattern recognition. LS-SVM had excellent generalization performance and low computational cost. In this paper, we propose a new method called two-layer least squares support vector machine which combines kernel principle component analysis (KPCA) and linear programming form of least square support vector machine. With this method sparseness and robustness is obtained while solving large dimensional and large scale database. A U.S. commercial credit card database is used to test the efficiency of our method and the result proved to be a satisfactory one.

Protection Conferred by recombinant Yersinia pestis Antigens Produced by a Rapid and Highly Scalable Plant Expression System

DTIC Science & Technology

2006-01-24

translational fusions with dsRED (lanes 8), and cytosol-targeted GFP (lanes 9). RbcL, large subunit of Rubisco . 862 ! www.pnas.org"cgi"doi൒.1073...analysis of F1-V expression with SDS"PAGE-Coomassie staining was difficult because the chimeric protein comigrates with the large subunit of Rubisco , a...contaminated by the Rubisco large subunit, which is very similar in size to F1-V. Analysis of Purified Plant-Produced Antigens. Western blots were

Prospective comparison of speckle tracking longitudinal bidimensional strain between two vendors.

PubMed

Castel, Anne-Laure; Szymanski, Catherine; Delelis, François; Levy, Franck; Menet, Aymeric; Mailliet, Amandine; Marotte, Nathalie; Graux, Pierre; Tribouilloy, Christophe; Maréchaux, Sylvestre

2014-02-01

Speckle tracking is a relatively new, largely angle-independent technique used for the evaluation of myocardial longitudinal strain (LS). However, significant differences have been reported between LS values obtained by speckle tracking with the first generation of software products. To compare LS values obtained with the most recently released equipment from two manufacturers. Systematic scanning with head-to-head acquisition with no modification of the patient's position was performed in 64 patients with equipment from two different manufacturers, with subsequent off-line post-processing for speckle tracking LS assessment (Philips QLAB 9.0 and General Electric [GE] EchoPAC BT12). The interobserver variability of each software product was tested on a randomly selected set of 20 echocardiograms from the study population. GE and Philips interobserver coefficients of variation (CVs) for global LS (GLS) were 6.63% and 5.87%, respectively, indicating good reproducibility. Reproducibility was very variable for regional and segmental LS values, with CVs ranging from 7.58% to 49.21% with both software products. The concordance correlation coefficient (CCC) between GLS values was high at 0.95, indicating substantial agreement between the two methods. While good agreement was observed between midwall and apical regional strains with the two software products, basal regional strains were poorly correlated. The agreement between the two software products at a segmental level was very variable; the highest correlation was obtained for the apical cap (CCC 0.90) and the poorest for basal segments (CCC range 0.31-0.56). A high level of agreement and reproducibility for global but not for basal regional or segmental LS was found with two vendor-dependent software products. This finding may help to reinforce clinical acceptance of GLS in everyday clinical practice. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Assessing medicare beneficiaries’ strength‐of‐preference scores for health care options: how engaging does the elicitation technique need to be?

PubMed Central

Crump, Trafford; Llewellyn‐Thomas, Hilary A.

2011-01-01

Abstract Objective  The objective was to determine if participants’ strength‐of‐preference scores for elective health care interventions at the end‐of‐life (EOL) elicited using a non‐engaging technique are affected by their prior use of an engaging elicitation technique. Design  Medicare beneficiaries were randomly selected from a larger survey sample. During a standardized interview, participants considered four scenarios involving a choice between a relatively less‐ or more‐intense EOL intervention. For each scenario, participants indicated their favoured intervention, then used a 7‐point Leaning Scale (LS1) to indicate how strongly they preferred their favoured intervention relative to the alternative. Next, participants engaged in a Threshold Technique (TT), which, depending on the participant’s initially favoured intervention, systematically altered a particular attribute of the scenario until the participant switched preferences. Finally, they repeated the LS (LS2) to indicate how strongly they preferred their initially‐favoured intervention. Results  Two hundred and two participants were interviewed (189–198 were included in this study). The concordance of individual participants’ LS1 and LS2 scores was assessed using Kendall tau‐b correlation coefficients; scores of 0.74, 0.84, 0.85 and 0.89 for scenarios 1–4, respectively, were observed. Conclusion  Kendall tau‐b statistics indicate a high concordance between LS scores, implying that the interposing engaging TT exercise had no significant effects on the LS2 strength‐of‐preference scores. Future investigators attempting to characterize the distributions of strength‐of‐preference scores for EOL care from a large, diverse community could use non‐engaging elicitation methods. The potential limitations of this study require that further investigation be conducted into this methodological issue. PMID:21323819

Fourfold increased detection of Lynch syndrome by raising age limit for tumour genetic testing from 50 to 70 years is cost-effective.

PubMed

Sie, A S; Mensenkamp, A R; Adang, E M M; Ligtenberg, M J L; Hoogerbrugge, N

2014-10-01

Recognising colorectal cancer (CRC) patients with Lynch syndrome (LS) can increase life expectancy of these patients and their close relatives. To improve identification of this under-diagnosed disease, experts suggested raising the age limit for CRC tumour genetic testing from 50 to 70 years. The present study evaluates the efficacy and cost-effectiveness of this strategy. Probabilistic efficacy and cost-effectiveness analyses were carried out comparing tumour genetic testing of CRC diagnosed at age 70 or below (experimental strategy) versus CRC diagnosed at age 50 or below (current practice). The proportions of LS patients identified and cost-effectiveness including cascade screening of relatives, were calculated by decision analytic models based on real-life data. Using the experimental strategy, four times more LS patients can be identified among CRC patients when compared with current practice. Both the costs to detect one LS patient (€9437/carrier versus €4837/carrier), and the number needed to test for detecting one LS patient (42 versus 19) doubled. When family cascade screening was included, the experimental strategy was found to be highly cost-effective according to Dutch standards, resulting in an overall ratio of €2703 per extra life-year gained in additionally tested patients. Testing all CRC tumours diagnosed at or below age 70 for LS is cost-effective. Implementation is important as relatives from the large number of LS patients that are missed by current practice, can benefit from life-saving surveillance. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A comparison between Lynch syndrome and sporadic colorectal cancer survivors' satisfaction with their healthcare providers.

PubMed

Burton-Chase, Allison M; Parker, Wendy M; Polivka, Katrina M; Gritz, Ellen R; Amos, Christopher I; Lu, Karen H; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; Nancy You, Y; Peterson, Susan K

2017-03-01

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case-case-matched CRC survivors with (n = 75) or without (n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Long-Term Monitoring Of The High-Energy γ-Ray Emission From Ls I +61°303 And Ls 5039

DOE PAGES

Hadasch, D.; Torres, D. F.; Tanaka, T.; ...

2012-03-22

The Fermi Large Area Telescope (LAT) reported the first definitive GeV detections of the binaries LS I +61°303 and LS 5039 in the first year after its launch in 2008 June. These detections were unambiguous as a consequence of the reduced positional uncertainty and the detection of modulated γ-ray emission on the corresponding orbital periods. An analysis of new data from the LAT, comprising 30 months of observations, identifies a change in the γ-ray behavior of LS I +61°303. An increase in flux is detected in 2009 March and a steady decline in the orbital flux modulation is observed. Significantmore » emission up to 30 GeV is detected by the LAT; prior data sets led to upper limits only. Contemporaneous TeV observations no longer detected the source, or found it—in one orbit—close to periastron, far from the phases at which the source previously appeared at TeV energies. The detailed numerical simulations and models that exist within the literature do not predict or explain many of these features now observed at GeV and TeV energies. New ideas and models are needed to fully explain and understand this behavior. A detailed phase-resolved analysis of the spectral characterization of LS I +61°303 in the GeV regime ascribes a power law with an exponential cutoff spectrum along each analyzed portion of the system's orbit. The on-source exposure of LS 5039 is also substantially increased with respect to our prior publication. In this case, whereas the general γ-ray properties remain consistent, the increased statistics of the current data set allows for a deeper investigation of its orbital and spectral evolution.« less

Long-Term Monitoring of the High-Energy Gamma-Ray Emission from LS I +61 deg 303 and LS 5039

NASA Technical Reports Server (NTRS)

Hadasch, D.; Torres, D. F.; Tanaka, T.; Corbet, R. H. D.; Hill, A. B.; Dubois, R.; Dubus, G.; Glanzman, T.; Corbel, S.; Li, J.;

Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.

PubMed

Parfitt, Gustavo Morrone; Nguyen, Robin; Bang, Jee Yoon; Aqrabawi, Afif J; Tran, Matthew M; Seo, D Kanghoon; Richards, Blake A; Kim, Jun Chul

2017-07-01

Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioral contribution at circuit level. We targeted LS-projecting vHPC cells and mPFC-projecting vHPC cells by injecting the retrogradely propagating canine adenovirus encoding Cre recombinase into the LS or mPFC, and injecting a Cre-responsive AAV (AAV8-hSyn-FLEX-hM3D or hM4D) into the vHPC. Consequences of manipulating these neurons were examined in well-established tests of anxiety. Chemogenetic manipulation of LS-projecting vHPC cells led to bidirectional changes in anxiety: activation of LS-projecting vHPC cells decreased anxiety whereas inhibition of these cells produced opposite anxiety-promoting effects. The observed anxiety-reducing function of LS-projecting cells was in contrast with the function of mPFC-projecting cells, which promoted anxiety. In addition, double retrograde tracing demonstrated that LS- and mPFC-projecting cells represent two largely anatomically distinct cell groups. Altogether, our findings suggest that the vHPC houses discrete populations of cells that either promote or suppress anxiety through differences in their projection targets. Disruption of the intricate balance in the activity of these two neuron populations may drive inappropriate behavioral responses seen in anxiety disorders.

EP of a Different Class: The Challenges of Testing for MW Missions

DTIC Science & Technology

2012-07-20

that the pumping capacity of the Large Vacuum Test Facility (LVTF) at PEPL (Figure 3) at 520,000 l/s on air makes it most suitable for initial checkout...evaluation of the thruster. NASA Glenn Research Center’s Vacuum Facility 5 (VF5) (Figure 4), with its increased pumping speed of 3,500,000 l/s on air...reader to Dr. Dan Goebel’s IEPC 2011 paper.41 IV. Facility Selection and Preparation Facility Size and Pumping High T/P thruster testing

Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior

PubMed Central

Bredewold, Remco; Schiavo, Jennifer K.; van der Hart, Marieke; Verreij, Michelle; Veenema, Alexa H.

2015-01-01

Social play is a motivated and rewarding behavior that is displayed by nearly all mammals and peaks in the juvenile period. Moreover, social play is essential for the development of social skills and is impaired in social disorders like autism. We recently showed that the lateral septum (LS) is involved in the regulation of social play behavior in juvenile male and female rats. The LS is largely modulated by GABA and glutamate neurotransmission, but their role in social play behavior is unknown. Here, we determined whether social play behavior is associated with changes in the extracellular release of GABA and glutamate in the LS and to what extent such changes modulate social play behavior in male and female juvenile rats. Using intracerebral microdialysis in freely behaving rats, we found no sex difference in extracellular GABA concentrations, but extracellular glutamate concentrations are higher in males than in females under baseline condition and during social play. This resulted in a higher glutamate/GABA concentration ratio in males versus females and thus, an excitatory predominance in the LS of males. Furthermore, social play behavior in both sexes is associated with significant increases in extracellular release of GABA and glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with bicuculline (100 ng/0.5 µl, 250 ng/0.5 µl) dose-dependently decreased the duration of social play behavior in both sexes. In contrast, pharmacological blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in the LS with AP-5 + CNQX (2 mM+0.4 mM/0.5 µl, 30 mM+3 mM/0.5 µl) dose-dependently decreased the duration of social play behavior in females, but did not alter social play behavior in males. Together, these data suggest a role for GABA neurotransmission in the LS in the regulation of juvenile social play behavior in both sexes, while glutamate neurotransmission in the LS is involved in the sex-specific regulation of juvenile social play behavior. PMID:26318330

Characterization of the replication region of the Bacillus subtilis plasmid pLS20: a novel type of replicon.

PubMed Central

Meijer, W J; de Boer, A J; van Tongeren, S; Venema, G; Bron, S

1995-01-01

A 3.1 kb fragment of the large (approximately 55 kb) Bacillus subtilis plasmid pLS20 containing all the information for autonomous replication was cloned and sequenced. In contrast to the parental plasmid, derived minireplicons were unstably maintained. Using deletion analysis the fragment essential and sufficient for replication was delineated to 1.1 kb. This 1.1 kb fragment is located between two divergently transcribed genes, denoted orfA and orfB, neither of which is required for replication. orfA shows homology to the B.subtilis chromosomal genes rapA (spoOL, gsiA) and rapB (spoOP). The 1.1 kb fragment, which is characterized by the presence of several regions of dyad symmetry, contains no open reading frames of more than 85 codons and shows no similarity with other known plasmid replicons. The structural organization of the pLS20 minimal replicon is entirely different from that of typical rolling circle plasmids from Gram-positive bacteria. The pLS20 minireplicons replicate in polA5 and recA4 B.subtilis strains. Taken together, these results strongly suggest that pLS20 belongs to a new class of theta replicons. PMID:7667098

Three Generations of FPGA DAQ Development for the ATLAS Pixel Detector

NASA Astrophysics Data System (ADS)

Mayer, Joseph A., II

The Large Hadron Collider (LHC) at the European Center for Nuclear Research (CERN) tracks a schedule of long physics runs, followed by periods of inactivity known as Long Shutdowns (LS). During these LS phases both the LHC, and the experiments around its ring, undergo maintenance and upgrades. For the LHC these upgrades improve their ability to create data for physicists; the more data the LHC can create the more opportunities there are for rare events to appear that physicists will be interested in. The experiments upgrade so they can record the data and ensure the event won't be missed. Currently the LHC is in Run 2 having completed the first LS of three. This thesis focuses on the development of Field-Programmable Gate Array (FPGA)-based readout systems that span across three major tasks of the ATLAS Pixel data acquisition (DAQ) system. The evolution of Pixel DAQ's Readout Driver (ROD) card is presented. Starting from improvements made to the new Insertable B-Layer (IBL) ROD design, which was part of the LS1 upgrade; to upgrading the old RODs from Run 1 to help them run more efficiently in Run 2. It also includes the research and development of FPGA based DAQs and integrated circuit emulators for the ITk upgrade which will occur during LS3 in 2025.

Density-Dependent Quantized Least Squares Support Vector Machine for Large Data Sets.

PubMed

Nan, Shengyu; Sun, Lei; Chen, Badong; Lin, Zhiping; Toh, Kar-Ann

2017-01-01

Based on the knowledge that input data distribution is important for learning, a data density-dependent quantization scheme (DQS) is proposed for sparse input data representation. The usefulness of the representation scheme is demonstrated by using it as a data preprocessing unit attached to the well-known least squares support vector machine (LS-SVM) for application on big data sets. Essentially, the proposed DQS adopts a single shrinkage threshold to obtain a simple quantization scheme, which adapts its outputs to input data density. With this quantization scheme, a large data set is quantized to a small subset where considerable sample size reduction is generally obtained. In particular, the sample size reduction can save significant computational cost when using the quantized subset for feature approximation via the Nyström method. Based on the quantized subset, the approximated features are incorporated into LS-SVM to develop a data density-dependent quantized LS-SVM (DQLS-SVM), where an analytic solution is obtained in the primal solution space. The developed DQLS-SVM is evaluated on synthetic and benchmark data with particular emphasis on large data sets. Extensive experimental results show that the learning machine incorporating DQS attains not only high computational efficiency but also good generalization performance.

Decon2LS: An open-source software package for automated processing and visualization of high resolution mass spectrometry data

PubMed Central

Jaitly, Navdeep; Mayampurath, Anoop; Littlefield, Kyle; Adkins, Joshua N; Anderson, Gordon A; Smith, Richard D

2009-01-01

Background Data generated from liquid chromatography coupled to high-resolution mass spectrometry (LC-MS)-based studies of a biological sample can contain large amounts of biologically significant information in the form of proteins, peptides, and metabolites. Interpreting this data involves inferring the masses and abundances of biomolecules injected into the instrument. Because of the inherent complexity of mass spectral patterns produced by these biomolecules, the analysis is significantly enhanced by using visualization capabilities to inspect and confirm results. In this paper we describe Decon2LS, an open-source software package for automated processing and visualization of high-resolution MS data. Drawing extensively on algorithms developed over the last ten years for ICR2LS, Decon2LS packages the algorithms as a rich set of modular, reusable processing classes for performing diverse functions such as reading raw data, routine peak finding, theoretical isotope distribution modelling, and deisotoping. Because the source code is openly available, these functionalities can now be used to build derivative applications in relatively fast manner. In addition, Decon2LS provides an extensive set of visualization tools, such as high performance chart controls. Results With a variety of options that include peak processing, deisotoping, isotope composition, etc, Decon2LS supports processing of multiple raw data formats. Deisotoping can be performed on an individual scan, an individual dataset, or on multiple datasets using batch processing. Other processing options include creating a two dimensional view of mass and liquid chromatography (LC) elution time features, generating spectrum files for tandem MS data, creating total intensity chromatograms, and visualizing theoretical peptide profiles. Application of Decon2LS to deisotope different datasets obtained across different instruments yielded a high number of features that can be used to identify and quantify peptides in the biological sample. Conclusion Decon2LS is an efficient software package for discovering and visualizing features in proteomics studies that require automated interpretation of mass spectra. Besides being easy to use, fast, and reliable, Decon2LS is also open-source, which allows developers in the proteomics and bioinformatics communities to reuse and refine the algorithms to meet individual needs. Decon2LS source code, installer, and tutorials may be downloaded free of charge at . PMID:19292916

Decon2LS: An open-source software package for automated processing and visualization of high resolution mass spectrometry data.

PubMed

Jaitly, Navdeep; Mayampurath, Anoop; Littlefield, Kyle; Adkins, Joshua N; Anderson, Gordon A; Smith, Richard D

2009-03-17

Data generated from liquid chromatography coupled to high-resolution mass spectrometry (LC-MS)-based studies of a biological sample can contain large amounts of biologically significant information in the form of proteins, peptides, and metabolites. Interpreting this data involves inferring the masses and abundances of biomolecules injected into the instrument. Because of the inherent complexity of mass spectral patterns produced by these biomolecules, the analysis is significantly enhanced by using visualization capabilities to inspect and confirm results. In this paper we describe Decon2LS, an open-source software package for automated processing and visualization of high-resolution MS data. Drawing extensively on algorithms developed over the last ten years for ICR2LS, Decon2LS packages the algorithms as a rich set of modular, reusable processing classes for performing diverse functions such as reading raw data, routine peak finding, theoretical isotope distribution modelling, and deisotoping. Because the source code is openly available, these functionalities can now be used to build derivative applications in relatively fast manner. In addition, Decon2LS provides an extensive set of visualization tools, such as high performance chart controls. With a variety of options that include peak processing, deisotoping, isotope composition, etc, Decon2LS supports processing of multiple raw data formats. Deisotoping can be performed on an individual scan, an individual dataset, or on multiple datasets using batch processing. Other processing options include creating a two dimensional view of mass and liquid chromatography (LC) elution time features, generating spectrum files for tandem MS data, creating total intensity chromatograms, and visualizing theoretical peptide profiles. Application of Decon2LS to deisotope different datasets obtained across different instruments yielded a high number of features that can be used to identify and quantify peptides in the biological sample. Decon2LS is an efficient software package for discovering and visualizing features in proteomics studies that require automated interpretation of mass spectra. Besides being easy to use, fast, and reliable, Decon2LS is also open-source, which allows developers in the proteomics and bioinformatics communities to reuse and refine the algorithms to meet individual needs.Decon2LS source code, installer, and tutorials may be downloaded free of charge at http://http:/ncrr.pnl.gov/software/.

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

PubMed

Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

2013-03-19

Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

γ-Aminobutyric Acid Type A α4, β2, and δ Subunits Assemble to Produce More Than One Functionally Distinct Receptor Type

PubMed Central

Eaton, Megan M.; Bracamontes, John; Shu, Hong-Jin; Li, Ping; Mennerick, Steven; Steinbach, Joe Henry

2014-01-01

Native γ-aminobutyric acid (GABA)A receptors consisting of α4, β1–3, and δ subunits mediate responses to the low, tonic concentration of GABA present in the extracellular milieu. Previous studies on heterologously expressed α4βδ receptors have shown a large degree of variability in functional properties, including sensitivity to the transmitter. We studied properties of α4β2δ receptors employing free subunits and concatemeric constructs, expressed in Xenopus oocytes, HEK 293 cells, and cultured hippocampal neurons. The expression system had a strong effect on the properties of receptors containing free subunits. The midpoint of GABA activation curve was 10 nM for receptors in oocytes versus 2300 nM in HEK cells. Receptors activated by the steroid alfaxalone had an estimated maximal open probability of 0.6 in oocytes and 0.01 in HEK cells. Irrespective of the expression system, receptors resulting from combining the tandem construct β2-δ and a free α4 subunit exhibited large steroid responses. We propose that free α4, β2, and δ subunits assemble in different configurations with distinct properties in oocytes and HEK cells, and that subunit linkage can overcome the expression system-dependent preferential assembly of free subunits. Hippocampal neurons transfected with α4 and the picrotoxin-resistant δ(T269Y) subunit showed large responses to alfaxalone in the presence of picrotoxin, suggesting that α4βδ receptors may assemble in a similar configuration in neurons and oocytes. PMID:25238745

The morphological and chemical characteristics of striatal neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the rat.

PubMed

Waldvogel, H J; Kubota, Y; Trevallyan, S C; Kawaguchi, Y; Fritschy, J M; Mohler, H; Faull, R L

1997-10-01

The distribution, morphology and chemical characteristics of neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of the basal ganglia in the rat brain were investigated at the light, confocal and electron microscope levels using single, double and triple immunohistochemical labelling techniques. The results showed that alpha1-subunit immunoreactive neurons were sparsely distributed throughout the rat striatum. Double and triple labelling results showed that all the alpha1-subunit-immunoreactive neurons were positive for glutamate decarboxylase and immunoreactive for the beta2,3 and gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit-immunoreactive neurons were identified in the striatum on the basis of cellular morphology and chemical characteristics. The most numerous alpha1-subunit-immunoreactive neurons were medium-sized, aspiny neurons with a widely branching dendritic tree. They were parvalbumin-negative and were located mainly in the dorsolateral regions of the striatum. Electron microscopy showed that these neurons had an indented nuclear membrane, typical of striatal interneurons, and were surrounded by small numbers of axon terminals which established alpha1-subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75% of the total population of alpha1-subunit-immunoreactive neurons in the striatum. The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous population of large-sized neurons localized in the ventral and medial regions of the striatum. The most numerous large-sized cells were parvalbumin-negative, had two to three relatively short branching dendrites and were designated type 2 alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2 neurons were characterized by a highly convoluted nuclear membrane and were sparsely covered with small axon terminals. The type 2 neurons comprised 20% of the total population of alpha1-subunit-immunoreactive neurons. The remaining large-sized alpha1-immunoreactive cells were designated type 3 cells; they were positive for parvalbumin and were distinguished by long branching dendrites extending dorsally for 600-800 microm into the striatum. These neurons comprised 5% of the total population of alpha1-subunit-immunoreactive neurons and were surrounded by enkephalin-immunoreactive terminals. Electron microscopy showed that the alpha1-subunit type 3 neurons had an indented nuclear membrane and were densely covered with small axon terminals which established alpha1-subunit-immunoreactive symmetrical synaptic contacts with the soma and dendrites. These results provide a detailed characterization of the distribution, morphology and chemical characteristics of the alpha1-subunit-immunoreactive neurons in the rat striatum and suggest that the type 1 and type 2 neurons comprise of separate populations of striatal interneurons while the type 3 neurons may represent the large striatonigral projection neurons described by Bolam et al. [Bolam J. P., Somogyi P., Totterdell S. and Smith A. D. (1981) Neuroscience 6, 2141-2157.].

Indium-loaded Liquid Scintillator for the Low Energy Neutrino Spectrometer (LENS)

NASA Astrophysics Data System (ADS)

Hu, Liangming; Hans, Sunej; Rosero, Richard; Beriguete, Wanda; Chan, Wai Ting; Cumming, James; Yeh, Minfang; Roundtree, Derek; Vogelaar, Bruce

2012-03-01

The Chemistry Department at Brookhaven National Laboratory has a long history of neutrino research since Ray Davis's Homestake experiment. The Solar Neutrino and Nuclear Chemistry group has been successfully building large neutrino detectors over the past decade for various physics experiments, using tens to hundreds of tons of liquid scintillator. Among them, LENS aims to use 8% indium-loaded LS (In-LS, first investigated by Raghavan in the 1970s) for a real-time measurement of over 95% of sub-MeV solar neutrinos, mainly from pp-, CNO-, and ^7Be-processes. A nearly background-free spectral image from neutrino interactions on ^115In can be obtained via a triple coincidence tag in space and time. LENS detector R&D has made major progress in the recent years. The development of In-LS, in collaboration with Virginia Tech, now meets the challenging requirements of light yield, optical clarity, and chemical stability; and the collaboration is in the process of building a 410-L prototype (miniLENS). In this talk, the preparation and properties of In-LS for the miniLENS detector will be presented.

Multiple emitters in a waveguide: Nonreciprocity and correlated photons at perfect elastic transmission

NASA Astrophysics Data System (ADS)

Fang, Yao-Lung L.; Baranger, Harold U.

2017-07-01

We investigate interference and correlation effects when several detuned emitters are placed along a one-dimensional photonic waveguide. Such a setup allows multiple interactions between the photons and the strongly coupled emitters, and underlies proposed devices for quantum information processing. We show, first, that a pair of detuned two-level systems (2LS) separated by a half wavelength mimic a driven Λ -type three-level system (3LS) in both the single- and two-photon sectors. There is an interference-induced transparency peak at which the fluorescence is quenched, leaving the transmitted photons completely uncorrelated. Slightly away from this separation, we find that the inelastic scattering (fluorescence) is large, leading to nonlinear effects such as nonreciprocity (rectification). We connect this nonreciprocity to inelastic scattering caused by driving a dark pole and so derive a condition for maximum rectification. Finally, by placing a true 3LS midway between the two 2LS, we show that elastic scattering produces only transmission, but inelastic scattering nevertheless occurs (the fluorescence is not quenched) causing substantial photon correlations.

Propagation and transmission of optical vortex beams through turbid scattering wall with orbital angular momentums

NASA Astrophysics Data System (ADS)

Wang, W. B.; Gozali, Richard; Nguyen, Thien An; Alfano, R. R.

2015-03-01

Light scattering and transmission of optical Laguerre Gaussian (LG) vortex beams with different orbital angular momentum (OAM) states in turbid scattering media were investigated in comparison with Gaussian (G) beam. The scattering media used in the experiments consist of various sizes and concentrations of latex beads in water solutions. The LG beams were generated using a spatial light modulator in reflection mode. The ballistic transmissions of LG and G beams were measured with different ratios of thickness of samples (z) to scattering mean free path (ls) of the turbid media, z/ls. The results show that in the ballistic region where z/ls is small, the LG and G beams show no significant difference, while in the diffusive region where z/ls is large, LG beams show higher transmission than Gaussian beam. In the diffusive region, the LG beams with higher orbital angular momentum L values show higher transmission than the beams with lower L values. The transition points from ballistic to diffusive regions for different scattering media were studied and determined.

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

Spreitzer, Robert Joseph

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of CO 2 fixation in photosynthesis. However, it is a slow enzyme, and O 2 competes with CO 2 at the active site. Oxygenation initiates the photorespiratory pathway, which also results in the loss of CO 2. If carboxylation could be increased or oxygenation decreased, an increase in net CO 2 fixation would be realized. Because Rubisco provides the primary means by which carbon enters all life on earth, there is much interest in engineering Rubisco to increase the production of food and renewable energy. Rubisco is located in the chloroplasts of plants,more » and it is comprised of two subunits. Much is known about the chloroplast-gene-encoded large subunit (rbcL gene), which contains the active site, but much less is known about the role of the nuclear-gene-encoded small subunit in Rubisco function (rbcS gene). Both subunits are coded by multiple genes in plants, which makes genetic engineering difficult. In the eukaryotic, green alga Chlamydomonas reinhardtii, it has been possible to eliminate all the Rubisco genes. These Rubisco-less mutants can be maintained by providing acetate as an alternative carbon source. In this project, focus has been placed on determining whether the small subunit might be a better genetic-engineering target for improving Rubisco. Analysis of a variable-loop structure (βA-βB loop) of the small subunit by genetic selection, directed mutagenesis, and construction of chimeras has shown that the small subunit can influence CO 2/O 2 specificity. X-ray crystal structures of engineered chimeric-loop enzymes have indicated that additional residues and regions of the small subunit may also contribute to Rubisco function. Structural dynamics of the small-subunit carboxyl terminus was also investigated. Alanine-scanning mutagenesis of the most-conserved small-subunit residues has identified a possible structural pathway between the small-subunit βA-βB loop and alpha-helix 8 of the large-subunit α/β-barrel active site. Hybrid enzymes were also created comprised of plant small subunits and Chlamydomonas large subunits, and these enzymes have increases in CO 2/O 2 specificity, further indicating that small subunits may be the key for ultimately engineering an improved Rubisco enzyme.« less

Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

PubMed

Lewis, Brian A

2010-01-15

The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

Engineering of chimeric eukaryotic/bacterial Rubisco large subunits in Escherichia coli.

PubMed

Koay, Teng Wei; Wong, Hann Ling; Lim, Boon Hoe

2016-11-26

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a rate-limiting photosynthetic enzyme that catalyzes carbon fixation in the Calvin cycle. Much interest has been devoted to engineering this ubiquitous enzyme with the goal of increasing plant growth. However, experiments that have successfully produced improved Rubisco variants, via directed evolution in Escherichia coli, are limited to bacterial Rubisco because the eukaryotic holoenzyme cannot be produced in E. coli. The present study attempts to determine the specific differences between bacterial and eukaryotic Rubisco large subunit primary structure that are responsible for preventing heterologous eukaryotic holoenzyme formation in E. coli. A series of chimeric Synechococcus Rubiscos were created in which different sections of the large subunit were swapped with those of the homologous Chlamydomonas Rubisco. Chimeric holoenzymes that can form in vivo would indicate that differences within the swapped sections do not disrupt holoenzyme formation. Large subunit residues 1-97, 198-247 and 448-472 were successfully swapped without inhibiting holoenzyme formation. In all ten chimeras, protein expression was observed for the separate subunits at a detectable level. As a first approximation, the regions that can tolerate swapping may be targets for future engineering.

Candidate counterparts to the soft gamma-ray flare in the direction of LS I +61 303

NASA Astrophysics Data System (ADS)

Muñoz-Arjonilla, A. J.; Martí, J.; Combi, J. A.; Luque-Escamilla, P.; Sánchez-Sutil, J. R.; Zabalza, V.; Paredes, J. M.

2009-04-01

Context: A short duration burst reminiscent of a soft gamma-ray repeater/anomalous X-ray pulsar behaviour was detected in the direction of LS I +61 303 by the Swift satellite. While the association with this well known gamma-ray binary is likely, a different origin cannot be excluded. Aims: We explore the error box of this unexpected flaring event and establish the radio, near-infrared and X-ray sources in our search for any peculiar alternative counterpart. Methods: We carried out a combined analysis of archive Very Large Array radio data of LS I +61 303 sensitive to both compact and extended emission. We also reanalysed previous near infrared observations with the 3.5 m telescope of the Centro Astronómico Hispano Alemán and X-ray observations with the Chandra satellite. Results: Our deep radio maps of the LS I +61 303 environment represent a significant advancement on previous work and 16 compact radio sources in the LS I +61 303 vicinity are detected. For some detections, we also identify near infrared and X-ray counterparts. Extended emission features in the field are also detected and confirmed. The possible connection of some of these sources with the observed flaring event is considered. Based on these data, we are unable to claim a clear association between the Swift-BAT flare and any of the sources reported here. However, this study represents the most sophisticated attempt to determine possible alternative counterparts other than LS I +61 303.

Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion.

PubMed

Lynch, Henry T; Riegert-Johnson, Douglas L; Snyder, Carrie; Lynch, Jane F; Hagenkord, Jill; Boland, C Richard; Rhees, Jennifer; Thibodeau, Stephen N; Boardman, Lisa A; Davies, Janine; Kuiper, Roland P; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J L

2011-10-01

The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3' end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS. Our study of two large families (USA Family R and Dutch Family A) with an EPCAM deletion was carried out using each institution's standard family study protocol. DNA was extracted from peripheral blood and EPCAM deletion analysis was performed. Both families were found to harbor the same deletion at the 3' end of EPCAM. Analysis showed that the deletion originated from a common ancestor. Family R and Family A members showed segregation of CRC with the presence of this EPCAM mutation. Compared with classic LS, there were almost no extracolonic cancers. Members of Family R and Family A, all with the same EPCAM deletion, predominantly presented with CRC but no LS-associated endometrial cancer, confirming findings seen in other, smaller, LS families with EPCAM mutations. In these EPCAM mutation carriers, cancer surveillance should be focused on CRC.

An application of change-point recursive models to the relationship between litter size and number of stillborns in pigs.

PubMed

Ibáñez-Escriche, N; López de Maturana, E; Noguera, J L; Varona, L

2010-11-01

We developed and implemented change-point recursive models and compared them with a linear recursive model and a standard mixed model (SMM), in the scope of the relationship between litter size (LS) and number of stillborns (NSB) in pigs. The proposed approach allows us to estimate the point of change in multiple-segment modeling of a nonlinear relationship between phenotypes. We applied the procedure to a data set provided by a commercial Large White selection nucleus. The data file consisted of LS and NSB records of 4,462 parities. The results of the analysis clearly identified the location of the change points between different structural regression coefficients. The magnitude of these coefficients increased with LS, indicating an increasing incidence of LS on the NSB ratio. However, posterior distributions of correlations were similar across subpopulations (defined by the change points on LS), except for those between residuals. The heritability estimates of NSB did not present differences between recursive models. Nevertheless, these heritabilities were greater than those obtained for SMM (0.05) with a posterior probability of 85%. These results suggest a nonlinear relationship between LS and NSB, which supports the adequacy of a change-point recursive model for its analysis. Furthermore, the results from model comparisons support the use of recursive models. However, the adequacy of the different recursive models depended on the criteria used: the linear recursive model was preferred on account of its smallest deviance value, whereas nonlinear recursive models provided a better fit and predictive ability based on the cross-validation approach.

MUC1 and MUC4: Switching the Emphasis from Large to Small

PubMed Central

Carraway, Kermit L.

2011-01-01

Summation The MUC1 and MUC4 membrane mucins are each composed of a large alpha (α) and a small beta (β) subunit. The α subunits are fully exposed at the cell surface and contain variable numbers of repeated amino acid sequences that are heavily glycosylated. In contrast, the β subunits are much smaller and are anchored within the cell membrane, with their amino-terminal portions exposed at the cell surface and their carboxy-terminal tails facing the cytosol. Studies over the last several years are challenging the long-held belief that α subunits play the predominant role in cancer by conferring cellular properties that allow tumor cells to evade immune recognition and destruction. Indeed, the β subunits of MUC1 and MUC4 have emerged as oncogenes, as they engage signaling pathways responsible for tumor initiation and progression. Thus, a switch in the emphasis from the large α to the small β subunits offers attractive possibilities for successful clinical application. Such a focus shift is further supported by the absence of allelic polymorphism and variable glycosylation in the β subunit as well as by the presence of the β subunit in most MUC1 and MUC4 isoforms expressed by tumors. MUC1α, also known as CA15.3, is a Food and Drug Administration-approved serum biomarker for breast cancer, but its use is no longer recommended by the American Society of Clinical Oncology. However, comparison of β subunit expression in normal and malignant breast tissues may offer a novel approach to the exploitation of membrane mucins as biomarkers, as MUC1β-induced gene signatures with prognostic and predictive values in breast cancer have been reported. Preclinical studies with peptides that interfere with MUC1β oncogenic functions also look promising. PMID:21728842

First Record of Anopheles oryzalimnetes, Anopheles argyritarsis, and Anopheles sawyeri (Diptera: Culicidae) in the Caatinga Biome, Semiarid Scrubland of Sergipe State, Brazil.

PubMed

Marteis, L S; Sallum, M A M; Natal, D; Oliveira, T M P; Gama, R A; Dolabella, S S; Santos, R L C

2015-09-01

Caatinga is one of the least known biomes of Brazil in relation to biodiversity. The dry condition of semiarid areas has been associated in the past with low richness of fauna and flora, not encouraging studies in this region. There is a lack of mosquito records including anophelines. Thus, to investigate the biodiversity of Anopheles mosquitoes in the Caatinga biome, we collected immature mosquitoes in aquatic habitats in a conservation reserve located in the northwestern portion of Sergipe state. The captured specimens were initially identified as Anopheles albitarsis l.s. and Anopheles argyritarsis l.s. To confirm the morphological identification, sequences were generated by cytochrome oxidase subunit I mitocondrial gene. The results showed that the specimens belong to the species Anopheles oryzalimnetes, An. argyritarsis, and Anopheles sawyeri. These are the first records of these species in this region. The presence of Anopheles in the Caatinga biome, which is characterized by arid and semiarid climatic conditions, encourages the interest in the study of biological, physiological, and behavioral adaptations, selected over time, which allow these mosquito populations to survive through the long periods of drought that is characteristic of this region. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Discovery of high-energy gamma-ray emission from the binary system PSR B1259–63/LS 2883 around periastron with Fermi

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2011-06-28

Here, we report on the discovery of ≥ 100 MeV rays from the binary system PSR B12596–3/LS 2883 using the Large Area Telescope (LAT) on board Fermi. The system comprises a radio pulsar in orbit around a Be star. We report on LAT observations from near apastron to ~60 days after the time of periastron, t p, on 2010 December 15. No γ-ray emission was detected from this source when it was far from periastron.

Identifying Attributes of CO2 Leakage Zones in Shallow Aquifers Using a Parametric Level Set Method

NASA Astrophysics Data System (ADS)

Sun, A. Y.; Islam, A.; Wheeler, M.

2016-12-01

Leakage through abandoned wells and geologic faults poses the greatest risk to CO2 storage permanence. For shallow aquifers, secondary CO2 plumes emanating from the leak zones may go undetected for a sustained period of time and has the greatest potential to cause large-scale and long-term environmental impacts. Identification of the attributes of leak zones, including their shape, location, and strength, is required for proper environmental risk assessment. This study applies a parametric level set (PaLS) method to characterize the leakage zone. Level set methods are appealing for tracking topological changes and recovering unknown shapes of objects. However, level set evolution using the conventional level set methods is challenging. In PaLS, the level set function is approximated using a weighted sum of basis functions and the level set evolution problem is replaced by an optimization problem. The efficacy of PaLS is demonstrated through recovering the source zone created by CO2 leakage into a carbonate aquifer. Our results show that PaLS is a robust source identification method that can recover the approximate source locations in the presence of measurement errors, model parameter uncertainty, and inaccurate initial guesses of source flux strengths. The PaLS inversion framework introduced in this work is generic and can be adapted for any reactive transport model by switching the pre- and post-processing routines.

Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: A meta-analysis of international cohorts

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

Johansson, H.; Kanis, J. A.; Oden, A.

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. In this paper, we studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS–FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculatedmore » using FN BMD. To examine the effect of an adjustment for ΔLS–FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS–FN was greater than 2 SD for 2.5 % of women and between 1 and 2 SD for 21 %. ΔLS–FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95 % CI = 1.04–1.15). In reclassification analyses, only 2.3–3.2 % of the women moved to a higher or lower risk category when using FRAX with ΔLS–FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1–2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. Finally, this might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.« less

Ladder Structures and Magnetic Surveys: New Insights into the Near Surface, Three-Dimensional Shape and Orientation of Plutonic Structures in the Tuolumne Intrusive Suite, Yosemite National Park, California

NASA Astrophysics Data System (ADS)

Boyd, J. D.

2017-12-01

The study of pluton emplacement and growth history offers a window into the evolution of the continental crust. Plutons, however, are often largely homogeneous in outcrop, lacking reliable structural markers for tracking their emplacement and growth through time. The ladder structures exposed on the glacially polished surfaces of the Tuolumne Intrusive Suite (TIS) in Yosemite National Park, California are an exception. Ladder structures (LS) are eye-catching concentrations of alternating mafic and felsic mineral assemblages in dominantly cresent-shaped, meter to sub-meter scale bands in outcrop that locally terminate into a mafic band forming a circular-shaped enclosure. Their geochemistry and modal mineralogy diverge sharply from host rock trends with large quantities of magnetite, titanite, and zircon in the mafic assemblages. The limited exposure of LS in outcrops has led to much debate as to their true geometries and orientations. The high concentration of magnetite in the LS is fortuitous in that it allows these features to be investigated by magnetic techniques. The preliminary results of new high resolution magnetic surveys of these LS are presented here. A grid of total magnetic intensity (TMI) was collected across the ladder structures. The TMI's were then inverted and modeled to determine the orientation of the magnetic bodies with depth using PyGMI freeware. With sufficient contrast in the magnetic susceptibility (Km) between the feature being imaged and the host rock, meter to sub-meter scale features can be resolved. The average Km of the LS mafic bands and the host rock is approximately 200-850 x10-3 and 15-20×10-3 SI units respectively. These measurements along with oriented samples were collected to determine input parameters (e.g. anisotropy and remanence) for the geocellular model used in this study.

Impact of femoral neck and lumbar spine BMD discordances on FRAX probabilities in women: A meta-analysis of international cohorts

DOE PAGES

Johansson, H.; Kanis, J. A.; Oden, A.; ...

2014-09-04

There are occasional marked discordances in BMD T-scores at the lumbar spine (LS) and femoral neck (FN). We investigated whether such discordances could contribute independently to fracture prediction using FRAX. In this paper, we studied 21,158 women, average age 63 years, from 10 prospective cohorts with baseline FRAX variables as well as FN and LS BMD. Incident fractures were collected by self-report and/or radiographic reports. Extended Poisson regression examined the relationship between differences in LS and FN T-scores (ΔLS–FN) and fracture risk, adjusted for age, time since baseline and other factors including FRAX 10-year probability for major osteoporotic fracture calculatedmore » using FN BMD. To examine the effect of an adjustment for ΔLS–FN on reclassification, women were separated into risk categories by their FRAX major fracture probability. High risk was classified using two approaches: being above the National Osteoporosis Guideline Group intervention threshold or, separately, being in the highest third of each cohort. The absolute ΔLS–FN was greater than 2 SD for 2.5 % of women and between 1 and 2 SD for 21 %. ΔLS–FN was associated with a significant risk of fracture adjusted for baseline FRAX (HR per SD change = 1.09; 95 % CI = 1.04–1.15). In reclassification analyses, only 2.3–3.2 % of the women moved to a higher or lower risk category when using FRAX with ΔLS–FN compared with FN-derived FRAX alone. Adjustment of estimated fracture risk for a large LS/FN discrepancy (>2SD) impacts to a large extent on only a relatively small number of individuals. More moderate (1–2SD) discordances in FN and LS T-scores have a small impact on FRAX probabilities. Finally, this might still improve clinical decision-making, particularly in women with probabilities close to an intervention threshold.« less

An improved method to characterise the modulation of small-scale turbulent by large-scale structures

NASA Astrophysics Data System (ADS)

Agostini, Lionel; Leschziner, Michael; Gaitonde, Datta

2015-11-01

A key aspect of turbulent boundary layer dynamics is ``modulation,'' which refers to degree to which the intensity of coherent large-scale structures (LS) cause an amplification or attenuation of the intensity of the small-scale structures (SS) through large-scale-linkage. In order to identify the variation of the amplitude of the SS motion, the envelope of the fluctuations needs to be determined. Mathis et al. (2009) proposed to define this latter by low-pass filtering the modulus of the analytic signal built from the Hilbert transform of SS. The validity of this definition, as a basis for quantifying the modulated SS signal, is re-examined on the basis of DNS data for a channel flow. The analysis shows that the modulus of the analytic signal is very sensitive to the skewness of its PDF, which is dependent, in turn, on the sign of the LS fluctuation and thus of whether these fluctuations are associated with sweeps or ejections. The conclusion is that generating an envelope by use of a low-pass filtering step leads to an important loss of information associated with the effects of the local skewness of the PDF of the SS on the modulation process. An improved Hilbert-transform-based method is proposed to characterize the modulation of SS turbulence by LS structures

Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior.

PubMed

Bredewold, R; Schiavo, J K; van der Hart, M; Verreij, M; Veenema, A H

2015-10-29

Social play is a motivated and rewarding behavior that is displayed by nearly all mammals and peaks in the juvenile period. Moreover, social play is essential for the development of social skills and is impaired in social disorders like autism. We recently showed that the lateral septum (LS) is involved in the regulation of social play behavior in juvenile male and female rats. The LS is largely modulated by GABA and glutamate neurotransmission, but their role in social play behavior is unknown. Here, we determined whether social play behavior is associated with changes in the extracellular release of GABA and glutamate in the LS and to what extent such changes modulate social play behavior in male and female juvenile rats. Using intracerebral microdialysis in freely behaving rats, we found no sex difference in extracellular GABA concentrations, but extracellular glutamate concentrations are higher in males than in females under baseline conditions and during social play. This resulted in a higher glutamate/GABA concentration ratio in males vs. females and thus, an excitatory predominance in the LS of males. Furthermore, social play behavior in both sexes is associated with significant increases in extracellular release of GABA and glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with bicuculline (100 ng/0.5 μl, 250 ng/0.5 μl) dose-dependently decreased the duration of social play behavior in both sexes. In contrast, pharmacological blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in the LS with AP-5+CNQX (2mM+0.4mM/0.5 μl, 30 mM+3mM/0.5 μl) dose-dependently decreased the duration of social play behavior in females, but did not alter social play behavior in males. Together, these data suggest a role for GABA neurotransmission in the LS in the regulation of juvenile social play behavior in both sexes, while glutamate neurotransmission in the LS is involved in the sex-specific regulation of juvenile social play behavior. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Five Years of Monitoring Mars' Daytime Surface Temperatures (Animation)

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site] Animation

This movie shows the daytime temperature of the surface of Mars as measured by the Thermal Emission Spectrometer instrument on NASA's Mars Global Surveyor orbiter. These temperatures clearly show the growth and retreat of the martian northern and southern polar ice caps. The caps grow in winter and are composed of carbon dioxide ice with temperatures as low as minus 125 degrees Celsius (minus 195 degrees Fahrenheit). In the summer the caps retreat to relatively small areas around the poles. The movie also demonstrates the large difference in temperatures between the northern hemisphere's summer (beginning when solar longitude, or Ls, is 90 degrees) and the southern hemisphere's summer (beginning when Ls is 270 degrees). This difference is because the orbit of Mars around the Sun is more elliptical than Earth's orbit. As on Earth, a hemisphere's summer is when that hemisphere is tilted toward the Sun, but on Mars, the planet's distance from the Sun varies much more than on Earth. Mars is closest to the Sun, and therefore warmest, during the southern summer season. In northern summer, when Mars' northern hemisphere is tilted toward the Sun, the planet is farther from the Sun.

Seasons on Mars are determined by the position of Mars in its orbit around the Sun. The position is measured in degrees of solar longitude (Ls) around the orbit, beginning at 0 degrees Ls at the northern spring equinox, progressing to 90 degrees Ls at the start of northern summer, 180 degrees Ls at the fall equinox, 270 degrees Ls at the start of northern winter, and finally back to 360 degrees, or 0 degrees, Ls at the spring equinox.

The Thermal Emission Spectrometer is operated by a team led at Arizona State University, Tempe. Mars Global Surveyor left Earth on Nov. 7, 1996, and began orbiting Mars on Sept. 12, 1997. JPL, a division of the California Institute of Technology, Pasadena, manages Mars Global Surveyor for NASA's Science Mission Directorate, Washington.

Comparison of land-atmosphere interaction at different surface types in the mid- to lower Yangzi River Valley

NASA Astrophysics Data System (ADS)

Guo, Weidong; Wang, Xueqian; Sun, Jianning; Ding, Aijun; Zou, Jun

2016-04-01

The mid- to lower Yangzi River Valley is located within the typical monsoon zone. Rapid urbanization, industrialization, and development of agriculture have led to fast and complicated land use and land cover changes in this region. To investigate land-atmosphere interaction in this region where human activities and monsoon climate are highly interactive with each other, micro-meteorological elements over four different surface types, i.e. urban surface represented by the observational site at Communist Party School in Nanjing (hereafter DX), suburban surface represented by the ground site at Xianling (XL), and grassland and farmland represented by field sites at Lishui County (LS-grass and LS-crop), are analyzed and their differences are revealed. Impacts of different surface parameters applied for different surface types on the radiation budget and surface-atmosphere heat, water, and mass exchanges are investigated. Results indicate that (1) the largest differences in daily average surface air temperature (Ta), surface skin temperature (Ts), and relative humidity (RH) , which are found during the dry periods between DX and LS-crop, can be up to 3.21°C, 7.26°C, and 22.79% respectively. During the growing season, the diurnal ranges of the above three elements are the smallest at DX and the largest at LS-grass, XL and LS-crop; (2) differences in radiative fluxes are mainly reflected in upward shortwave radiation (USR) that is related to surface albedo and upward longwave radiation (ULR) that is related to Ts. USR is the smallest and ULR is the largest at DX. During the growing season, the average difference in ULR between the DX site and other sites with vegetation cover can be up to 20Wm-2. The USR variability is the largest at LS-crop, while the diurnal variation of ULR is the same as that of Ts at all the four sites; (3) the differences in daily average sensible heat (H) and latent heat (LE) between DX and LS-crop are larger than 45 and 95Wm-2, respectively. The proportion of latent heat flux in the net radiation (LE/Rn) keeps increasing with the change of season from the spring to summer. XL site demonstrates a distinct forest feature; (4) surface albedo is small while the Bowen ratio is large at DX (an urban site). The urban heat island effect results in higher Ta and Ts at DX site that is 2°C higher than that at other sites in the nighttime. It is found that surface albedo and roughness length variability both increase at LS-crop during the harvest season and straw burning periods. LE is dominant due to irrigation. Negative H is observed since evaporative cooling leads to low Ts. Daily variability of Ts and Ta is the lowest at LS-crop while RH is the largest. In the summer, the grassland albedo at XL site gradually becomes larger than that at the sites in Lishui. Since the forest-like effects becomes more distinct at XL, LE/Rn increases rapidly. Thereby, although Ts is higher at XL than that at LS-grass , there is no large difference in Ta between the two sites.

Nmd3p Is a Crm1p-Dependent Adapter Protein for Nuclear Export of the Large Ribosomal Subunit

PubMed Central

Ho, Jennifer Hei-Ngam; Kallstrom, George; Johnson, Arlen W.

2000-01-01

In eukaryotic cells, nuclear export of nascent ribosomal subunits through the nuclear pore complex depends on the small GTPase Ran. However, neither the nuclear export signals (NESs) for the ribosomal subunits nor the receptor proteins, which recognize the NESs and mediate export of the subunits, have been identified. We showed previously that Nmd3p is an essential protein from yeast that is required for a late step in biogenesis of the large (60S) ribosomal subunit. Here, we show that Nmd3p shuttles and that deletion of the NES from Nmd3p leads to nuclear accumulation of the mutant protein, inhibition of the 60S subunit biogenesis, and inhibition of the nuclear export of 60S subunits. Moreover, the 60S subunits that accumulate in the nucleus can be coimmunoprecipitated with the NES-deficient Nmd3p. 60S subunit biogenesis and export of truncated Nmd3p were restored by the addition of an exogenous NES. To identify the export receptor for Nmd3p we show that Nmd3p shuttling and 60S export is blocked by the Crm1p-specific inhibitor leptomycin B. These results identify Crm1p as the receptor for Nmd3p export. Thus, export of the 60S subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway. PMID:11086007

LS-align: an atom-level, flexible ligand structural alignment algorithm for high-throughput virtual screening.

PubMed

Hu, Jun; Liu, Zi; Yu, Dong-Jun; Zhang, Yang

2018-02-15

Sequence-order independent structural comparison, also called structural alignment, of small ligand molecules is often needed for computer-aided virtual drug screening. Although many ligand structure alignment programs are proposed, most of them build the alignments based on rigid-body shape comparison which cannot provide atom-specific alignment information nor allow structural variation; both abilities are critical to efficient high-throughput virtual screening. We propose a novel ligand comparison algorithm, LS-align, to generate fast and accurate atom-level structural alignments of ligand molecules, through an iterative heuristic search of the target function that combines inter-atom distance with mass and chemical bond comparisons. LS-align contains two modules of Rigid-LS-align and Flexi-LS-align, designed for rigid-body and flexible alignments, respectively, where a ligand-size independent, statistics-based scoring function is developed to evaluate the similarity of ligand molecules relative to random ligand pairs. Large-scale benchmark tests are performed on prioritizing chemical ligands of 102 protein targets involving 1,415,871 candidate compounds from the DUD-E (Database of Useful Decoys: Enhanced) database, where LS-align achieves an average enrichment factor (EF) of 22.0 at the 1% cutoff and the AUC score of 0.75, which are significantly higher than other state-of-the-art methods. Detailed data analyses show that the advanced performance is mainly attributed to the design of the target function that combines structural and chemical information to enhance the sensitivity of recognizing subtle difference of ligand molecules and the introduces of structural flexibility that help capture the conformational changes induced by the ligand-receptor binding interactions. These data demonstrate a new avenue to improve the virtual screening efficiency through the development of sensitive ligand structural alignments. http://zhanglab.ccmb.med.umich.edu/LS-align/. njyudj@njust.edu.cn or zhng@umich.edu. Supplementary data are available at Bioinformatics online.

LONG-TERM MONITORING OF THE HIGH-ENERGY {gamma}-RAY EMISSION FROM LS I +61 Degree-Sign 303 AND LS 5039

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

Hadasch, D.; Torres, D. F.; Caliandro, G. A.

2012-04-10

The Fermi Large Area Telescope (LAT) reported the first definitive GeV detections of the binaries LS I +61 Degree-Sign 303 and LS 5039 in the first year after its launch in 2008 June. These detections were unambiguous as a consequence of the reduced positional uncertainty and the detection of modulated {gamma}-ray emission on the corresponding orbital periods. An analysis of new data from the LAT, comprising 30 months of observations, identifies a change in the {gamma}-ray behavior of LS I +61 Degree-Sign 303. An increase in flux is detected in 2009 March and a steady decline in the orbital fluxmore » modulation is observed. Significant emission up to 30 GeV is detected by the LAT; prior data sets led to upper limits only. Contemporaneous TeV observations no longer detected the source, or found it-in one orbit-close to periastron, far from the phases at which the source previously appeared at TeV energies. The detailed numerical simulations and models that exist within the literature do not predict or explain many of these features now observed at GeV and TeV energies. New ideas and models are needed to fully explain and understand this behavior. A detailed phase-resolved analysis of the spectral characterization of LS I +61 Degree-Sign 303 in the GeV regime ascribes a power law with an exponential cutoff spectrum along each analyzed portion of the system's orbit. The on-source exposure of LS 5039 is also substantially increased with respect to our prior publication. In this case, whereas the general {gamma}-ray properties remain consistent, the increased statistics of the current data set allows for a deeper investigation of its orbital and spectral evolution.« less

Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women.

PubMed

Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F

2008-12-01

Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

Causes of high O3 in the lower free troposphere over the Pacific Northwest as observed at the Mt. Bachelor Observatory

NASA Astrophysics Data System (ADS)

Ambrose, J. L.; Reidmiller, D. R.; Jaffe, D. A.

2011-09-01

We measured O3, CO, Hg, sub-micron particle scattering of mid-visible light (σsp), and water vapor (WV) at the Mt. Bachelor Observatory (MBO) in central Oregon, USA since 2004. The data were used to identify sources of large ozone enhancements in the lower free troposphere (FT). A total of 25 high-ozone events, defined as time periods when the 8-h averaged O3 mixing ratio was >70.0 ppbv, were recorded. The events occurred between early March and late September. For 18 of the 25 event days we were able to identify sources based on (1) relative enhancements of O3, CO, Hg and WV compared with the corresponding monthly distributions and (2) supporting data from the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model, the Navy Aerosol Analysis and Prediction System (NAAPS) global aerosol model, and Moderate Resolution Imaging Spectroradiometer (MODIS) satellite-derived active fire counts from the Fire Information for Resource Management System (FIRMS). Our analysis suggests that enhanced O3 levels during all the identified events were transported to MBO in the FT and were driven mostly by subsidence of O3-rich air masses from the upper troposphere/lower stratosphere (UT/LS), Asian long range transport (ALRT) and mixed ALRT + UT/LS influences. The UT/LS events were depleted in CO and total atmospheric mercury (TAM) compared to monthly median values. Levels of O3 and CO tended to be anti-correlated during UT/LS events, consistent with transport from clean regions in the UT. Conversely, the ALRT events were characterized by concomitant enhancements in CO and TAM with mean values during each event that were >70th percentile values for the months during which the events occurred. Unlike for UT/LS events, levels of O3 and CO during ALRT events tended to be correlated, consistent with photochemical O3 production in polluted air masses transported across the Pacific. The mixed ALRT + UT/LS events exhibited characteristics that were intermediate between those of the ALRT and UT/LS events. For the classifiable cases the fractional distribution of each event type was: UT/LS, ˜44% (n = 8); ALRT + UT/LS, ˜33% (n = 6); ALRT, ˜22% (n = 4). In terms of the total number of classifiable high-ozone event hours UT/LS, ALRT + UT/LS and ALRT events accounted for ˜52% (t = 85), ˜36% (t = 59) and ˜13% (t = 21), respectively. The results indicate that downward mixing of O3-rich air masses from the UT/LS together with trans-Pacific transport of urban/industrial and biomass burning emissions from the Asian continent are the most important mechanisms for delivering high O3 levels (i.e., 8-h averages >70.0 ppbv) to the lower FT in the Pacific Northwest.

The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin complex.

PubMed

Yang, Guowei; Waterfield, Nicholas R

2013-01-01

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5∶1∶1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man.

Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron Syndrome).

PubMed

Hershkovitz, Israel; Kornreich, Liora; Laron, Zvi

2007-10-01

Comparison between the skeletal remains of Homo floresiensis and the auxological and roentgenological findings in a large Israeli cohort of patients with Laron Syndrome (LS, primary or classical GH insensitivity or resistance) revealed striking morphological similarities, including extremely small stature and reduced cranial volume. LS is an autosomal recessive disease caused by a molecular defect of the Growth Hormone (GH) receptor or in the post-receptor cascades. Epidemiological studies have shown that LS occurs more often in consanguineous families and isolates, and it has been described in several countries in South East Asia. It is our conclusion that the findings from the island of Flores, which were attributed to a new species of the genus Homo, may in fact represent a local, highly inbred, Homo sapiens population in whom a mutation for the GH receptor had occurred. (c) 2007 Wiley-Liss, Inc.

ls1 mardyn: The Massively Parallel Molecular Dynamics Code for Large Systems.

PubMed

Niethammer, Christoph; Becker, Stefan; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

2014-10-14

The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales that were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multicenter rigid potential models based on Lennard-Jones sites, point charges, and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, such as fluids at interfaces, as well as nonequilibrium molecular dynamics simulation of heat and mass transfer.

Using Transport Diagnostics to Understand Chemistry Climate Model Ozone Simulations

NASA Technical Reports Server (NTRS)

Strahan, S. E.; Douglass, A. R.; Stolarski, R. S.; Akiyoshi, H.; Bekki, S.; Braesicke, P.; Butchart, N.; Chipperfield, M. P.; Cugnet, D.; Dhomse, S.;

SOFIA/FIFI-LS Observations of Galactic PDRs

NASA Astrophysics Data System (ADS)

Klein, Randolf; Reedy, Alexander; Colditz, Sebastian; Fadda, Dario; Fischer, Chrisitan; Geis, Norbert; Hönle, Rainer; Iserlohe, Christof; Krabbe, Alfred; Looney, Leslie; Poglitsch, Albrecht; Raab, Walfried; Rebel, Felix; Vacca, William

2018-01-01

Photo-dissociation regions or photon-dominated regions (PDRs) are the interfaces between ionized HII-regions and adjacent molecular clouds usually found in massive star-forming regions. As the places where molecular clouds are destroyed by the UV radiation of the forming massive stars, they are the regions where the effects of star formation on the interstellar medium and the energetics and physical properties of the feedback can be best studied.FIFI-LS, SOFIA's far-infrared (FIR) spectrometer, is well suited to observe galactic PDRs and study them in great detail. The bulk of the energy from PDRs is emitted in the wavelength range of FIFI-LS, which ranges from 50 to 200µm. In this wavelength range, there are many strong atomic and ionic fine-structure lines, which can serve as diagnostic tools to trace these species and to determine densities and temperatures of the ionized and neutral medium in PDRs. FIFI-LS's ability to map large bright regions quickly and in two transitions simultaneously allows researchers to analyse the varying conditions in star-forming regions comprehensively.We will show first results of FIFI-LS observations of M42 and M17. M42 with the Orion Bar, a well-known PDR seen edge-on was one of the very first objects observed with FIFI-LS. Subsequently, we have observed M42 in a growing number of transitions. We also have observed the PDR in M17 in several transitions. The PDRs are clearly identified by the complementary spatial extent of the ionized and neutral species. From the ratios of the [OI] (63 and 146µm) and [OIII] (52 and 88µm) line pairs, the [CII] (158µm) line and combinations thereof, physical conditions in the different phases and the transition regions can be derived. We are presenting preliminary results.

Lynch Syndrome-Associated Extracolonic Tumors Are Rare in Two Extended Families With the Same EPCAM Deletion

PubMed Central

Lynch, Henry T.; Riegert-Johnson, Douglas L.; Snyder, Carrie; Lynch, Jane F.; Hagenkord, Jill; Boland, C. Richard; Rhees, Jennifer; Thibodeau, Stephen N.; Boardman, Lisa A.; Davies, Janine; Kuiper, Roland P.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J.L.

2013-01-01

OBJECTIVES The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3′ end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS. METHODS Our study of two large families (USA Family R and Dutch Family A) with an EPCAM deletion was carried out using each institution’s standard family study protocol. DNA was extracted from peripheral blood and EPCAM deletion analysis was performed. RESULTS Both families were found to harbor the same deletion at the 3′ end of EPCAM. Analysis showed that the deletion originated from a common ancestor. Family R and Family A members showed segregation of CRC with the presence of this EPCAM mutation. Compared with classic LS, there were almost no extracolonic cancers. CONCLUSIONS Members of Family R and Family A, all with the same EPCAM deletion, predominantly presented with CRC but no LS-associated endometrial cancer, confirming findings seen in other, smaller, LS families with EPCAM mutations. In these EPCAM mutation carriers, cancer surveillance should be focused on CRC. PMID:21769135

Physical readiness and obesity among male U.S. Navy personnel with limited exercise availability while at sea.

PubMed

Gregg, Marion A; Jankosky, Christopher J

2012-11-01

To evaluate differences in physical readiness and obesity in worksites with inherent limitations in exercise availability, utilizing data from U.S. Navy personnel assigned to submarines. Cross-sectional study utilizing height, weight, and Physical Readiness Test (PRT) scores of 26,341 individuals assigned to small submarines (SS), large submarines (LS), and aircraft carriers (AC). PRT failure rates were 3.4% (AC), 1.5% (LS), and 2.9% (SS). Prevalence of obesity was 15.1% (AC), 16.9% (LS), and 17.8% (SS). The adjusted prevalence odds ratio of obesity was increased on SS and LS compared to AC, 1.25 (96% CI = 1.14, 1.31) and 1.17 (95% CI = 1.06, 1.29), respectively. Despite limitations in exercise availability, submarine personnel performance on the PRT was similar to that of AC personnel. Although the prevalence of obesity on submarines was slightly higher, it remains below U.S. nonmilitary comparison data. Although limited access to exercise has the potential for adverse health effects in worker populations, in our cohort of young men, the changes in both physical readiness and obesity were small. Further research on a more diverse group of workers is warranted.

IMPATT Diodes Based on 〈111〉, 〈100〉, and 〈110〉 Oriented GaAs: A Comparative Study to Search the Best Orientation for Millimeter-Wave Atmospheric Windows

PubMed Central

Banerjee, Bhadrani; Tripathi, Anvita; Das, Adrija; Singh, Kumari Alka; Banerjee, J. P.

2015-01-01

The authors have carried out the large-signal (L-S) simulation of double-drift region (DDR) impact avalanche transit time (IMPATT) diodes based on 〈111〉, 〈100〉, and 〈110〉 oriented GaAs. A nonsinusoidal voltage excited (NSVE) L-S simulation technique is used to investigate both the static and L-S performance of the above-mentioned devices designed to operate at millimeter-wave (mm-wave) atmospheric window frequencies, such as 35, 94, 140, and 220 GHz. Results show that 〈111〉 oriented GaAs diodes are capable of delivering maximum RF power with highest DC to RF conversion efficiency up to 94 GHz; however, the L-S performance of 〈110〉 oriented GaAs diodes exceeds their other counterparts while the frequency of operation increases above 94 GHz. The results presented in this paper will be helpful for the future experimentalists to choose the GaAs substrate of appropriate orientation to fabricate DDR GaAs IMPATT diodes at mm-wave frequencies. PMID:27347524

Local Time Variation of Water Vapor on Mars using TES Aerobraking Spectra

NASA Astrophysics Data System (ADS)

AlShamsi, M. R.; AlJanaahi, A. A.; Smith, M. D.; Altunaiji, E. S.; Edwards, C. S.

2016-12-01

During the Mars Global Surveyor (MGS) aerobraking phase, the spacecraft was in a large elliptical orbit that enabled the Thermal Emission Spectrometer (TES) instrument to sample many local times of Mars. The observed TES aerobraking spectra during that phase cover the time range between Mars Year 23, Ls=180° and Mars Year 24, Ls=30°. These TES aerobraking spectra have never been analyzed to study local time variations on Mars. Through radiative transfer modeling of the spectra, surface and atmospheric temperature, dust and water ice optical depth, and water vapor were retrieved. Specifically, the water vapor retrievals during aerobraking have similar seasonal and latitudinal trends to those in other Mars years observed by TES. These retrievals show somewhat higher water vapor during the morning hours (09:00-12:00) than in the afternoon (12:00-17:00) during southern summer (Ls=270°-330°) and little variation as a function of local time for southern fall (Ls=0°-30°). These retrievals show water vapor has a positive correlation with surface pressure (or negative correlation with altitude) indicating that water vapor is mixed in the lowest 10-20 km.

Parallel design of JPEG-LS encoder on graphics processing units

NASA Astrophysics Data System (ADS)

Duan, Hao; Fang, Yong; Huang, Bormin

2012-01-01

With recent technical advances in graphic processing units (GPUs), GPUs have outperformed CPUs in terms of compute capability and memory bandwidth. Many successful GPU applications to high performance computing have been reported. JPEG-LS is an ISO/IEC standard for lossless image compression which utilizes adaptive context modeling and run-length coding to improve compression ratio. However, adaptive context modeling causes data dependency among adjacent pixels and the run-length coding has to be performed in a sequential way. Hence, using JPEG-LS to compress large-volume hyperspectral image data is quite time-consuming. We implement an efficient parallel JPEG-LS encoder for lossless hyperspectral compression on a NVIDIA GPU using the computer unified device architecture (CUDA) programming technology. We use the block parallel strategy, as well as such CUDA techniques as coalesced global memory access, parallel prefix sum, and asynchronous data transfer. We also show the relation between GPU speedup and AVIRIS block size, as well as the relation between compression ratio and AVIRIS block size. When AVIRIS images are divided into blocks, each with 64×64 pixels, we gain the best GPU performance with 26.3x speedup over its original CPU code.

Life satisfaction and cardiovascular disease risk in Poland

PubMed Central

Szklarska, Alicja; Lipowicz, Anna; Jankowska, Ewa Anita; Kozieł, Sławomir

2013-01-01

Introduction Cardiovascular disease is the most common cause of death. Life satisfaction is a predictor of morbidity and mortality, irrespectively of objective measures of health status. The aim of the study was to evaluate the relationship between life satisfaction (LS) and cardiovascular disease risk (CVD) assessed with the Framingham Risk Score (FRS) in Polish adults. Material and methods Past, present and projected LS were estimated. The FRS reflecting 10-year CVD risk was calculated from health indices and lifestyle parameters. Relationships between LS and FRS were tested by two-way analysis of variance in 489 men and 591 women, 40–50 years of age. Results Subjects with a reduction in LS over time had a higher FRS compared to peers with an improvement in LS. The relationship between current LS and FRS had a J-shape in men; FRS was lowest in men with an LS of 5–7 (average LS), slightly higher in men with an LS of 8–10 (highest LS), and highest in men with an LS of 1–4 (lowest LS). Among women, there was an inverse linear relationship between LS and FRS: the higher the LS, the lower FRS. There was a strong linear relationship between predicted LS and CVD risk. Highest risk was evident in subjects with low LS in whom low LS was predicted over the next five years. Conclusions Low LS (dissatisfaction) thus has a long-term negative effect on CVD risk in Polish adults of both sexes. PMID:24049521

Crotoxin: Structural Studies, Mechanism of Action and Cloning of its Gene

DTIC Science & Technology

1988-03-01

thirteen amino acids being acidic . Sequencing of the three peptides present in the acidic subunit, two of which are blocked by pyroglutamate ...the sequence determination of both the basic and acidic subunits of crotoxin- The acidic * subunit peptides were d!Tfficult, .sfi~n~e two of-ftflý...fluorescence spectroscopy. Results indicate a large conformational change occurs upon) ccmplex formation between the acidic and basic subunits of all four

Nitrogen oxides and ozone in the tropopause region of the Northern Hemisphere: Measurements from commercial aircraft in 1995/1996 and 1997

NASA Astrophysics Data System (ADS)

Brunner, Dominik; Staehelin, Johannes; Jeker, Dominique; Wernli, Heini; Schumann, Ulrich

2001-11-01

Measurements of nitrogen oxides (NO and NO2) and ozone (O3) were performed from a Swissair B-747 passenger aircraft in two extended time periods (May 1995 to May 1996, August to November 1997) in the framework of the Swiss NOXAR and the European POLINAT 2 project. The measurements were obtained on a total of 623 flights between Europe and destinations in the United States and the Far East. NO2 measurements were obtained only after December 1995 and were less precise than the NO measurements. Therefore daytime NO2 values were derived from measured NO and O3 concentrations assuming photostationary equilibrium. The completed NOx data set (measured NO, measured NO2 during night, and calculated NO2 during day) includes a complete annual cycle and is the most extensive and representative data set currently available for the upper troposphere (UT) and the lower stratosphere (LS) covering a significant proportion of the northern hemisphere between 15°N and 65°N. NOx concentrations in midlatitudes (30°-60°N) showed a marked seasonal variation both in the UT and the LS with a maximum in summer (median/mean values of 159/264 pptv in UT, 199/237 pptv in LS) and a minimum in winter (51/99 pptv in UT, 67/91 pptv in LS). Mean NOx concentrations were generally much higher than the respective median values, in particular in the UT, which reflects the important contribution from comparatively few very high concentrations observed in large-scale convection/lightning and small-scale aircraft plumes. Seasonal mean NOx concentrations in the UT were up to 3-4 times higher over continental regions than over the North Atlantic during summer. Lightning production of NO and convective vertical transport from the polluted boundary layer thus appear to have dominated the upper tropospheric NOx budget over these continental regions, particularly during summer. Ozone concentrations at aircraft cruising levels typically varied by an order of magnitude due to the strong vertical gradient in the LS. Seasonal mean values were dominated by large-scale dynamical processes controlling the altitude of the tropopause and the O3 abundance in the LS. O3 in the UT in midlatitudes showed a broad maximum between June and August, typical of observations in the free troposphere.

Three Years of Monitoring Mars' Atmospheric Dust (Animation)

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site] Animation

This movie shows the daily abundance of dust in the martian atmosphere over a period of three full martian years, from April 1999 through February 2005. The Thermal Emission Spectrometer instrument on NASA's Mars Global Surveyor orbiter has been tracking the weather on Mars for six years. The infrared spectrum observed by this instrument yields information about the spectral properties of the dust and the temperature of the atmosphere. These two properties can then be used to derive how much dust is in the atmosphere.

Of particular interest are large regional and global dust storms that occur during summer in the southern hemisphere each Mars year. The 2001 storm was by far the largest, lasting over six months (June to October, 2001) and covering the entire planet. The storms in the other two Mars years shown here were much smaller and never covered the planet. The most recent storm season (June 2003 through January 2005) actually had two separate storms, one in June and a second in December. Unlike most large martian dust storms that start in the southern hemisphere, the December storm began in the north and swept toward the equator. Between storms the atmosphere becomes quite clear, with much smaller dust storms scattered throughout the year and over the planet.

Seasons on Mars are determined by the position of Mars in its orbit around the Sun. The position is measured in degrees of solar longitude (Ls) around the orbit, beginning at 0 degrees Ls at the northern spring equinox, progressing to 90 degrees Ls at the start of northern summer, 180 degrees Ls at the fall equinox, 270 degrees Ls at the start of northern winter, and finally back to 360 degrees, or 0 degrees, Ls at the spring equinox. Dust abundance is measured as opacity (tau), with values of 0 tau representing a completely clear atmosphere, and values of 2 indicating that it is nearly impossible to see through to the surface.

The Thermal Emission Spectrometer is operated by a team led at Arizona State University, Tempe. Mars Global Surveyor left Earth on Nov. 7, 1996, and began orbiting Mars on Sept. 12, 1997. JPL, a division of the California Institute of Technology, Pasadena, manages Mars Global Surveyor for NASA's Science Mission Directorate, Washington.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

PubMed

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

PubMed Central

Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

2016-01-01

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

Effects of transgene-encoded high-molecular weight glutenin proteins in wheat flour blends and sponge and dough baking

USDA-ARS?s Scientific Manuscript database

HMW glutenin subunits are the most important determinants of wheat (Triticum aestivum L.) bread-making quality, and subunit composition explains a large percentage of the variability observed between genotypes. Experiments were designed to elevate expression of a key native HMW glutenin subunit (1D...

Optimal rotated staggered-grid finite-difference schemes for elastic wave modeling in TTI media

NASA Astrophysics Data System (ADS)

Yang, Lei; Yan, Hongyong; Liu, Hong

2015-11-01

The rotated staggered-grid finite-difference (RSFD) is an effective approach for numerical modeling to study the wavefield characteristics in tilted transversely isotropic (TTI) media. But it surfaces from serious numerical dispersion, which directly affects the modeling accuracy. In this paper, we propose two different optimal RSFD schemes based on the sampling approximation (SA) method and the least-squares (LS) method respectively to overcome this problem. We first briefly introduce the RSFD theory, based on which we respectively derive the SA-based RSFD scheme and the LS-based RSFD scheme. Then different forms of analysis are used to compare the SA-based RSFD scheme and the LS-based RSFD scheme with the conventional RSFD scheme, which is based on the Taylor-series expansion (TE) method. The contrast in numerical accuracy analysis verifies the greater accuracy of the two proposed optimal schemes, and indicates that these schemes can effectively widen the wavenumber range with great accuracy compared with the TE-based RSFD scheme. Further comparisons between these two optimal schemes show that at small wavenumbers, the SA-based RSFD scheme performs better, while at large wavenumbers, the LS-based RSFD scheme leads to a smaller error. Finally, the modeling results demonstrate that for the same operator length, the SA-based RSFD scheme and the LS-based RSFD scheme can achieve greater accuracy than the TE-based RSFD scheme, while for the same accuracy, the optimal schemes can adopt shorter difference operators to save computing time.

High North American Monsoon Lowermost Stratospheric Water Vapor: Signatures of Convective Injection from MLS and Other Satellite Measurements

NASA Astrophysics Data System (ADS)

Schwartz, M. J.; Santee, M. L.; Livesey, N. J.; Read, W. G.

2015-12-01

The summer North American monsoon anticyclone (NAMA) and the Asian monsoon anticyclone (AMA) enclose most of the highest 100 hPa and 83 hPa water vapor (H2O) mixing ratios in the 11-year Aura Microwave Limb Sounder record, both in terms of mean values and in high outliers. The highest NAMA H2O outliers in the central continental United States are almost certainly the result of direct, local injection of ice into the lower stratosphere (LS) by convection that overshoots the tropopause. However, the relative importance of these direct injections in supplying the bulk of the NAMA LS humidity anomaly compared to that of transport from convection on the tropical side of the anticyclone has not been conclusively determined. Large-scale circulation models have reproduced the high NAMA LS water vapor with tropical convection followed by advection and ascent, however the handling of convection in such models is generally a source of uncertainty. NAMA H2O at 100--83 hPa is close to saturation at the low tropopause temperatures on the tropical side of the anticylone, and cold anomalies above this convection have been shown to act as cold traps, leading to an anticorrelation between NAMA LS humidity and tropical convective intensity. In this work we use MLS and other satellite-based observations to investigate the importance of direct convective injection in supplying the high H2O anomalies within the NAMA LS anticyclone.

Clinical genetic research 3: Genetics ELSI (Ethical, Legal, and Social Issues) research.

PubMed

Pullman, Daryl; Etchegary, Holly

2015-01-01

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research areas involved in examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research has become increasingly important in recent years as there has been a greater emphasis on "translational research" that moves genomics from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of research questions and the various methodologies that might be employed in addressing them in an area of ELSI research that is encompassed under the term "public engagement." We conclude with some practical pointers about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

Large conductance Ca(2+)-activated K(+) channel (BKCa) activating properties of a series of novel N-arylbenzamides: Channel subunit dependent effects.

PubMed

Kirby, R W; Martelli, A; Calderone, V; McKay, N G; Lawson, K

2013-07-15

Large conductance calcium activated potassium channels (BKCa) are fundamental in the control of cellular excitability. Thus, compounds that activate BKCa channels could provide potential therapies in the treatment of pathologies of the cardiovascular and central nervous system. A series of novel N-arylbenzamide compounds, and the reference compound NS1619, were evaluated for BKCa channel opener properties in Human Embryonic Kidney (HEK293) cells expressing the human BKCa channel α-subunit alone or α+β1-subunit complex. Channel activity was determined using a non-radioactive Rb(+) efflux assay to construct concentration effect curves for each compound. All N-arylbenzamide compounds and NS1619 evoked significant (p <0.05) concentration related increases in Rb(+) efflux both in cells expressing α-subunit alone or α+β1-subunits. Co-expression of the β1-subunit modified the Rb(+) efflux responses, relative to that obtained in cells expressing the α-subunit alone, for most of the N-arylbenzamide compounds, in contrast to NS1619. The EC40 values of NS1619, BKMe1 and BKOEt1 were not significantly affected by the co-expression of the BKCa channel α+β1-subunits. In contrast, 5 other N-arylbenzamides (BKPr2, BKPr3, BKPr4, BKH1 and BKVV) showed a significant (p <0.05) 2- to 10-fold increase in EC40 values when tested on the BKCa α+β1-subunit expressing cells compared to BKCa α-subunit expressing cells. Further, the Emax values for BKPr4, BKVV and BKH1 were lower in the BKCa channel α+β1-subunit expressing cells. In conclusion, the N-arylbenzamides studied, like NS1619, were able to activate BKCa channels formed of the α-subunit only. The co-expression of the β1-subunit, however, modified the ability of certain compounds to active the channel leading to differentiated pharmacodynamic profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improved purification of brine-shrimp (Artemia saline) (Na+ + K+)-activated adenosine triphosphatase and amino-acid and carbohydrate analyses of the isolated subunits.

PubMed Central

Peterson, G L; Hokin, L E

1980-01-01

Purification of the (Na+ + K+)-activated ATPase has been improved 2-fold the respect to both purity and yield over the previous method [Peterson, Ewing, Hootman & Conte (1978) J. Biol. Chem. 253, 4762-4770] by using Lubrol WX and non-denaturing concentrations of sodium dodecyl sulphate (SDS). The enzyme was purified 200-fold over the homogenate. The preparation had a specific activity of about 600 mumol of Pi/h per mg of protein, and was about 60% pure according to quantification of Coomassie Blue-stained SDS/polyacrylamide gels. The yield of purified enzyme was about 10 mg of protein per 100g of dry brine-shrimp (Artemia salina) cysts. The method is highly suitable for purification either on a small scale (10-25g of dry cysts) or on a large scale (900g of dry cysts) and methods are described for both. The large (Na+ + K+)-activated ATPase subunit (alpha-subunit) was isolated in pure form by SDS-gel filtration on Bio-Gel A 1.5m. The small subunit (beta-subunit) was eluted with other contaminating proteins on the Bio-Gel column, but was isolated in pure form by extraction from SDS/polyacrylamide gels. The amino acid and carbohydrate compositions of both subunits are reported. The alpha-subunit contained 5.2% carbohydrate by weight, and the beta-subunit 9.2%. Sialic acid was absent from both subunits. Images Fig. 3. Fig. 4. PMID:6272692

Are the different gully morphologies due to different formation processes on the Kaiser dune field on Mars?

NASA Astrophysics Data System (ADS)

Pasquon, K.; Gargani, J.; Nachon, M.; Conway, S. J.; Massé, M.; Jouannic, G.; Balme, M. R.; Costard, F.; Vincendon, M.

2017-12-01

Diverse gully morphologies are seen on Mars and differences are often neglected for simplification. Here we describe in detail the morphology and present-day activity of two gully-systems on the Kaiser dune field in the southern hemisphere of Mars. We then compare their activity with that of the morphologically distinct linear dune gullies present on the same dunes. The studied gully-systems have large depositional aprons (named "large apron gullies") and occur on dune faces oriented westward. They are active from mid-autumn to late winter (i.e. from Ls 50° to Ls 180°) coinciding with CO2 ice condensation/sublimation cycles. Sandy material collapses from the alcove flanks onto the alcove floor sporadically throughout this period. This accumulated sand is remobilized by punctuated mass flows which we estimate to be up to 7100 m3 in volume. These flows run out on to the apron and occur between Ls 120° and Ls 160°. These mass flow events occur when the number of "digitate flows" is at its seasonal maximum. Digitate flows are characterized by long-narrow zig-zagging low-albedo tracks and do not seem to transport appreciable sediment, and they can number in the hundreds. Small pits appear at their termini or midway along and sometimes these pits are re-deepened by subsequent flows. These events repeat every year and using volume balance calculations we find that the whole system could be built on a timescale of hundreds of martian ears. These large apron gullies differ in morphology and timing from the linear dune gullies. The linear dune gullies are active in late winter, or beginning of spring when the CO2 frost finally sublimates, which occurs after the activity of the large apron gullies. Due to the difference of orientation between large apron gullies and linear dune as well as timing, we infer that insolation, which may influence (i) the depth to ground ice, (ii) the amount of volatiles deposits, is the main cause their differences. Sediment transport by CO2 sublimation seems to be a good candidate for the present-day activity of large apron gullies and linear dune gullies. However, we cannot rule out the possibility that the linear gullies are formed by a completely different process to the large apron gullies, namely flows of brine occurring as the temperature warms rapidly after the final removal of the CO2 ice.

Structural Variation of Type I-F CRISPR RNA Guided DNA Surveillance.

PubMed

Pausch, Patrick; Müller-Esparza, Hanna; Gleditzsch, Daniel; Altegoer, Florian; Randau, Lennart; Bange, Gert

2017-08-17

CRISPR-Cas systems are prokaryotic immune systems against invading nucleic acids. Type I CRISPR-Cas systems employ highly diverse, multi-subunit surveillance Cascade complexes that facilitate duplex formation between crRNA and complementary target DNA for R-loop formation, retention, and DNA degradation by the subsequently recruited nuclease Cas3. Typically, the large subunit recognizes bona fide targets through the PAM (protospacer adjacent motif), and the small subunit guides the non-target DNA strand. Here, we present the Apo- and target-DNA-bound structures of the I-Fv (type I-F variant) Cascade lacking the small and large subunits. Large and small subunits are functionally replaced by the 5' terminal crRNA cap Cas5fv and the backbone protein Cas7fv, respectively. Cas5fv facilitates PAM recognition from the DNA major groove site, in contrast to all other described type I systems. Comparison of the type I-Fv Cascade with an anti-CRISPR protein-bound I-F Cascade reveals that the type I-Fv structure differs substantially at known anti-CRISPR protein target sites and might therefore be resistant to viral Cascade interception. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of UT1-UTC, LOD and AAM χ3 by combination of least-squares and multivariate stochastic methods

NASA Astrophysics Data System (ADS)

Niedzielski, Tomasz; Kosek, Wiesław

2008-02-01

This article presents the application of a multivariate prediction technique for predicting universal time (UT1-UTC), length of day (LOD) and the axial component of atmospheric angular momentum (AAM χ 3). The multivariate predictions of LOD and UT1-UTC are generated by means of the combination of (1) least-squares (LS) extrapolation of models for annual, semiannual, 18.6-year, 9.3-year oscillations and for the linear trend, and (2) multivariate autoregressive (MAR) stochastic prediction of LS residuals (LS + MAR). The MAR technique enables the use of the AAM χ 3 time-series as the explanatory variable for the computation of LOD or UT1-UTC predictions. In order to evaluate the performance of this approach, two other prediction schemes are also applied: (1) LS extrapolation, (2) combination of LS extrapolation and univariate autoregressive (AR) prediction of LS residuals (LS + AR). The multivariate predictions of AAM χ 3 data, however, are computed as a combination of the extrapolation of the LS model for annual and semiannual oscillations and the LS + MAR. The AAM χ 3 predictions are also compared with LS extrapolation and LS + AR prediction. It is shown that the predictions of LOD and UT1-UTC based on LS + MAR taking into account the axial component of AAM are more accurate than the predictions of LOD and UT1-UTC based on LS extrapolation or on LS + AR. In particular, the UT1-UTC predictions based on LS + MAR during El Niño/La Niña events exhibit considerably smaller prediction errors than those calculated by means of LS or LS + AR. The AAM χ 3 time-series is predicted using LS + MAR with higher accuracy than applying LS extrapolation itself in the case of medium-term predictions (up to 100 days in the future). However, the predictions of AAM χ 3 reveal the best accuracy for LS + AR.

Causes of high O3 in the lower free troposphere over the Pacific Northwest as observed at the Mt. Bachelor Observatory

NASA Astrophysics Data System (ADS)

Ambrose, J. L.; Reidmiller, D.; Jaffe, D. A.

2011-12-01

We measured O3, CO, Hg, sub-micron particle scattering of mid-visible light (σsp), and water vapor (WV) at the Mt. Bachelor Observatory (MBO) in central Oregon, USA since 2004. The data were used to identify sources of large ozone enhancements in the lower free troposphere (FT) from 2004-2009. A total of 25 high-ozone events, defined as time periods when the 8-hr averaged O3 mixing ratio was >70.0 ppbv, were recorded. The events occurred between early March and late September. For 18 of the 25 event days we were able to identify sources based on (1) relative enhancements of O3, CO, Hg and WV compared with the corresponding monthly distributions and (2) supporting data from the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model, the Navy Aerosol Analysis and Prediction System (NAAPS) global aerosol model, and Moderate Resolution Imaging Spectroradiometer (MODIS) satellite-derived active fire counts from the Fire Information for Resource Management System (FIRMS). Our analysis suggests that enhanced O3 levels during all the identified events were transported to MBO in the FT and were driven mostly by subsidence of O3-rich air masses from the upper troposphere/lower stratosphere (UT/LS), Asian long range transport (ALRT) and mixed ALRT+UT/LS influences. The UT/LS events were depleted in CO and total atmospheric mercury (TAM) compared to monthly median values. Levels of O3 and CO tended to be anti-correlated during UT/LS events, consistent with transport from clean regions in the UT. Conversely, the ALRT events were characterized by concomitant enhancements in CO and TAM with mean values during each event that were >70th percentile values for the months during which the events occurred. Unlike for UT/LS events, levels of O3 and CO during ALRT events tended to be correlated, consistent with photochemical O3 production in polluted air masses transported across the Pacific. The mixed ALRT+UT/LS events exhibited characteristics that were intermediate between those of the ALRT and UT/LS events. For the classifiable cases the fractional distribution of each event type was: UT/LS, ~44% (n=8); ALRT+UT/LS, ~33% (n=6); ALRT, ~22% (n=4). In terms of the total number of classifiable high-ozone event hours UT/LS, ALRT+UT/LS and ALRT events accounted for ~52% (t=85), ~36% (t=59) and ~13% (t=21), respectively. The results indicate that downward mixing of O3-rich air masses from the UT/LS together with trans-Pacific transport of urban/industrial and biomass burning emissions from the Asian continent are the most important mechanisms for delivering high O3 levels (i.e., 8-hr averages >70.0 ppbv) to the lower FT in the Pacific Northwest. The high-ozone event characterization methodology developed from the 2004-2009 data set is further applied to observations made at MBO during 2010 and 2011.

How the structure of the large subunit controls function in an oxygen-tolerant [NiFe]-hydrogenase

PubMed Central

Bowman, Lisa; Flanagan, Lindsey; Fyfe, Paul K.; Parkin, Alison; Hunter, William N.; Sargent, Frank

2014-01-01

Salmonella enterica is an opportunistic pathogen that produces a [NiFe]-hydrogenase under aerobic conditions. In the present study, genetic engineering approaches were used to facilitate isolation of this enzyme, termed Hyd-5. The crystal structure was determined to a resolution of 3.2 Å and the hydro-genase was observed to comprise associated large and small subunits. The structure indicated that His229 from the large subunit was close to the proximal [4Fe–3S] cluster in the small subunit. In addition, His229 was observed to lie close to a buried glutamic acid (Glu73), which is conserved in oxygen-tolerant hydrogenases. His229 and Glu73 of the Hyd-5 large subunit were found to be important in both hydrogen oxidation activity and the oxygen-tolerance mechanism. Substitution of His229 or Glu73 with alanine led to a loss in the ability of Hyd-5 to oxidize hydrogen in air. Furthermore, the H229A variant was found to have lost the overpotential requirement for activity that is always observed with oxygen-tolerant [NiFe]-hydrogenases. It is possible that His229 has a role in stabilizing the super-oxidized form of the proximal cluster in the presence of oxygen, and it is proposed that Glu73could play a supporting role in fine-tuning the chemistry of His229 to enable this function. PMID:24428762

Architecture and Programming Models for High Performance Intensive Computation

DTIC Science & Technology

2016-06-29

Applications Systems and Large-Scale-Big-Data & Large-Scale-Big-Computing (DDDAS- LS ). ICCS 2015, June 2015. Reykjavk, Ice- land. 2. Bo YT, Wang P, Guo ZL...The Mahali project,” Communications Magazine , vol. 52, pp. 111–133, Aug 2014. 14 DISTRIBUTION A: Distribution approved for public release. Response ID

Large-area landslide susceptibility with optimized slope-units

NASA Astrophysics Data System (ADS)

Alvioli, Massimiliano; Marchesini, Ivan; Reichenbach, Paola; Rossi, Mauro; Ardizzone, Francesca; Fiorucci, Federica; Guzzetti, Fausto

2017-04-01

A Slope-Unit (SU) is a type of morphological terrain unit bounded by drainage and divide lines that maximize the within-unit homogeneity and the between-unit heterogeneity across distinct physical and geographical boundaries [1]. Compared to other terrain subdivisions, SU are morphological terrain unit well related to the natural (i.e., geological, geomorphological, hydrological) processes that shape and characterize natural slopes. This makes SU easily recognizable in the field or in topographic base maps, and well suited for environmental and geomorphological analysis, in particular for landslide susceptibility (LS) modelling. An optimal subdivision of an area into a set of SU depends on multiple factors: size and complexity of the study area, quality and resolution of the available terrain elevation data, purpose of the terrain subdivision, scale and resolution of the phenomena for which SU are delineated. We use the recently developed r.slopeunits software [2,3] for the automatic, parametric delineation of SU within the open source GRASS GIS based on terrain elevation data and a small number of user-defined parameters. The software provides subdivisions consisting of SU with different shapes and sizes, as a function of the input parameters. In this work, we describe a procedure for the optimal selection of the user parameters through the production of a large number of realizations of the LS model. We tested the software and the optimization procedure in a 2,000 km2 area in Umbria, Central Italy. For LS zonation we adopt a logistic regression model implemented in an well-known software [4,5], using about 50 independent variables. To select the optimal SU partition for LS zonation, we want to define a metric which is able to quantify simultaneously: (i) slope-unit internal homogeneity (ii) slope-unit external heterogeneity (iii) landslide susceptibility model performance. To this end, we define a comprehensive objective function S, as the product of three normalized objective functions dealing with the points (i)-(ii)-(iii) independently. We use an intra-segment variance function V, the Moran's autocorrelation index I and the AUCROC function R arising from the application of the logistic regression model. Maximization of the objective function S = f(I,V,R) as a function of the r.slopeunits input parameters provides an objective and reproducible way to select the optimal parameter combination for a proper SU subdivision for LS modelling. We further perform an analysis of the statistical significance of the LS models as a function of the r.slopeunits input parameters, focusing on the degree of coarseness of each subdivision. We find that the LRM, when applied to subdivisions with large average SU size, has a very poor statistical significance, resulting in only few (5%, typically lithological) variables being used in the regression due to the large heterogeneity of all variables within each unit, while up to 35% of the variables are used when SU are very small. This behavior was largely expected and provides further evidence that an objective method to select SU size is highly desirable. [1] Guzzetti, F. et al., Geomorphology 31, (1999) 181-216 [2] Alvioli, M. et al., Geoscientific Model Development 9 (2016), 3975-3991 [3] http://geomorphology.irpi.cnr.it/tools/slope-units [4] Rossi, M. et al., Geomorphology 114, (2010) 129-142 [5] Rossi, M. and Reichenbach, P., Geoscientific Model Development 9 (2016), 3533-3543

Lichen sclerosis: clinicopathological study of 60 cases from Lebanon.

PubMed

Knio, Zeina; Kurban, Mazen; Abbas, Ossama

2016-10-01

Lichen sclerosus (LS) is an uncommon idiopathic chronic inflammatory debilitating disease with predilection for the genital region. Our recent encounter with an LS case exhibiting perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with LS at our institution. All cases of LS diagnosed between 1990 and 2014 were retrospectively reviewed. Diagnosis was confirmed with demonstration of microscopic features typical of LS. Sixty patients (42 women and 18 men) with 65 biopsy specimens of LS were identified, of which 41 were extragenital, 16 genital, and three had both. Histopathologically, significantly higher proportions of follicular plugging, atrophy, and vacuolar interface changes were observed in extragenital LS cases, while angiokeratoma-like, mycosis fungoides-like, and pseudoepitheliomatous changes were only seen in genital LS. Perineural inflammation was observed as a novel finding in 22 cases (33.8%) of LS. Features of patients with LS in this study are generally comparable to those published in the literature, with some differences. In contrast to the literature, extragenital LS was more frequently encountered. Histopathologically, perineural inflammation was not an uncommon feature of LS and thus may serve as a clue in the differentiation of LS from its mimickers. © 2016 The International Society of Dermatology.

Mild clinical manifestation and unusual recovery upon coenzyme Q₁₀ treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.

PubMed

Chen, Zhiting; Zhao, Zhenhua; Ye, Qinyong; Chen, Ying; Pan, Xiaodong; Sun, Bin; Huang, Huapin; Zheng, An

2015-03-01

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one‑year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

Identification of a Kinase in Wheat Germ that Phosphorylates the Large Subunit of Initiation Factor 4F 1

PubMed Central

Humphreys, Jean; Browning, Karen S.; Ravel, Joanne M.

1988-01-01

A kinase has been isolated from wheat (Triticum aestivum) germ that phosphorylates the 220 kilodaltons (kD) subunit of wheat germ initiation factor (eIF) 4F, the 80 kD subunit of eIF-4B (an isozyme form of eIF-4F) and eIF-4G (the functional equivalent to mammalian eIF-4B). The kinase elutes from Sephacryl S-200 slightly in front of ovalbumin. The kinase phosphorylates casein and histone IIA to a small extent, but does not phosphorylate phosvitin. Of the wheat germ initiation factors, elongation factors, and small and large ribosomal subunits, only eIF-4F, eIF-4B, and eIF-4G are phosphorylated to a significant extent. The kinase phosphorylates eIF-4F to the extent of two phosphates per mole of the 220 kD subunit and phosphorylates eIF-4B to the extent of one phosphate per mole of the 80 kD subunit. The 26 kD subunit of eIF-4F and the 28 kD subunit of eIF-4B are not phosphorylated by the kinase. The kinase phosphorylates the 59 kD component of eIF-4G to the extent of 0.25 phosphate per mole of eIF-4G. Phosphorylation of eIF-4F and eIF-4B does not affect their ability to support the binding of mRNA to small ribosomal subunits in vitro. Images Fig. 2 Fig. 3 PMID:16666331

The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities.

PubMed

Shevah, O; Kornreich, L; Galatzer, A; Laron, Z

2005-12-01

The correlation between the molecular defects of the GH receptor (R), psychosocial development and brain abnormalities were evaluated in 10 patients with Laron syndrome (LS), in whom all data were available. The findings revealed that the intelligence quotient (IQ) and abnormalities in the brain of the patients with LS differ with various molecular defects of the GH-receptor. The most severe mental deficits and brain pathology occurred in patients with 3, 5, 6 exon deletion. Patients with point mutations in exons 2, 4 and 7 presented various degrees of medium to mild CNS abnormalities that correlated with the IQ. Notably, the patient with the E180 splice mutation in exon 6 had a normal IQ, which fits the report on normal IQ in a large Ecuadorian cohort with the same mutation. This is the first report to support a correlation between IQ, brain abnormalities and localization of the molecular defects in the GH-R gene. As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.

The Orion Nebula in the Far-Infrared: high-J CO and fine-structure lines mapped by FIFI-LS/SOFIA

NASA Astrophysics Data System (ADS)

Klein, Randolf; Looney, Leslie; Cox, Erin; Fischer, Christian; Iserlohe, Christof; Krabbe, Alfred

2015-08-01

The Orion Nebula is the closest massive star forming region allowing us to study the physical conditions in such a region with high spatial resolution. We used the far infrared integral-field spectrometer, FIFI-LS, on-board the airborne observatory SOFIA to study the atomic and molecular gas in the Orion Nebula at medium spectral resolution.The large maps obtained with FIFI-LS cover the nebula from the BN/KL-object to the bar in several fine structure lines. These spectral maps are the largest and highest spatially resolved to date. They allow us to study the conditions of the photon-dominated region and the interface to the molecular cloud with unprecedented detail.Another investigation targeted the molecular gas in the BN/KL region of the Orion Nebula, which is stirred up by a violent explosion about 500 years ago. The explosion drives a wide angled molecular outflow. We present maps of several high-J CO observations (J in the range of 10 to 30), allowing us to analyse of the heated molecular gas.The observations were taken during the commissioning of FIFI-LS last year and as recent as this March. The results are still preliminary as the data reduction and calibration is still under development.

Reliability Evaluation of Low Power Schottky Clamped Microcircuits.

DTIC Science & Technology

1980-02-01

Temperature 52 15. 54LS191: ICC Versus Temperature 53 16. 54LS181: ICC Versus Temperature 54 17. High Temperature ...Response, Vendor A, 54LS181 56 18. High Temperature Response, Vendor B, 54LS181 57 19. High Temperature Response, Vendor A, 54LS191 58 20. High ... Temperature Response, Vendor B, 54LS191 59 21. High Temperature Response, Vendor A, 54LS251 60 3 LIST OF FIGURES (continued) Figure No. Title Page 22. High

Multiple effects of S13 in modulating the strength of intersubunit interactions in the ribosome during translation.

PubMed

Cukras, Anthony R; Green, Rachel

2005-05-27

The ribosomal protein S13 is found in the head region of the small subunit, where it interacts with the central protuberance of the large ribosomal subunit and with the P site-bound tRNA through its extended C terminus. The bridging interactions between the large and small subunits are dynamic, and are thought to be critical in orchestrating the molecular motions of the translation cycle. S13 provides a direct link between the tRNA-binding site and the movements in the head of the small subunit seen during translocation, thereby providing a possible pathway of signal transduction. We have created and characterized an rpsM(S13)-deficient strain of Escherichia coli and have found significant defects in subunit association, initiation and translocation through in vitro assays of S13-deficient ribosomes. Targeted mutagenesis of specific bridge and tRNA contact elements in S13 provides evidence that these two interaction domains play critical roles in maintaining the fidelity of translation. This ribosomal protein thus appears to play a non-essential, yet important role by modulating subunit interactions in multiple steps of the translation cycle.

Photo anthropometric variations in Japanese facial features: Establishment of large-sample standard reference data for personal identification using a three-dimensional capture system.

PubMed

Ogawa, Y; Wada, B; Taniguchi, K; Miyasaka, S; Imaizumi, K

2015-12-01

This study clarifies the anthropometric variations of the Japanese face by presenting large-sample population data of photo anthropometric measurements. The measurements can be used as standard reference data for the personal identification of facial images in forensic practices. To this end, three-dimensional (3D) facial images of 1126 Japanese individuals (865 male and 261 female Japanese individuals, aged 19-60 years) were acquired as samples using an already validated 3D capture system, and normative anthropometric analysis was carried out. In this anthropometric analysis, first, anthropological landmarks (22 items, i.e., entocanthion (en), alare (al), cheilion (ch), zygion (zy), gonion (go), sellion (se), gnathion (gn), labrale superius (ls), stomion (sto), labrale inferius (li)) were positioned on each 3D facial image (the direction of which had been adjusted to the Frankfort horizontal plane as the standard position for appropriate anthropometry), and anthropometric absolute measurements (19 items, i.e., bientocanthion breadth (en-en), nose breadth (al-al), mouth breadth (ch-ch), bizygomatic breadth (zy-zy), bigonial breadth (go-go), morphologic face height (se-gn), upper-lip height (ls-sto), lower-lip height (sto-li)) were exported using computer software for the measurement of a 3D digital object. Second, anthropometric indices (21 items, i.e., (se-gn)/(zy-zy), (en-en)/(al-al), (ls-li)/(ch-ch), (ls-sto)/(sto-li)) were calculated from these exported measurements. As a result, basic statistics, such as the mean values, standard deviations, and quartiles, and details of the distributions of these anthropometric results were shown. All of the results except "upper/lower lip ratio (ls-sto)/(sto-li)" were normally distributed. They were acquired as carefully as possible employing a 3D capture system and 3D digital imaging technologies. The sample of images was much larger than any Japanese sample used before for the purpose of personal identification. The measurements will be useful as standard reference data for forensic practices and as material data for future studies in this field. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genomic selection for crossbred performance accounting for breed-specific effects.

PubMed

Lopes, Marcos S; Bovenhuis, Henk; Hidalgo, André M; van Arendonk, Johan A M; Knol, Egbert F; Bastiaansen, John W M

2017-06-26

Breed-specific effects are observed when the same allele of a given genetic marker has a different effect depending on its breed origin, which results in different allele substitution effects across breeds. In such a case, single-breed breeding values may not be the most accurate predictors of crossbred performance. Our aim was to estimate the contribution of alleles from each parental breed to the genetic variance of traits that are measured in crossbred offspring, and to compare the prediction accuracies of estimated direct genomic values (DGV) from a traditional genomic selection model (GS) that are trained on purebred or crossbred data, with accuracies of DGV from a model that accounts for breed-specific effects (BS), trained on purebred or crossbred data. The final dataset was composed of 924 Large White, 924 Landrace and 924 two-way cross (F1) genotyped and phenotyped animals. The traits evaluated were litter size (LS) and gestation length (GL) in pigs. The genetic correlation between purebred and crossbred performance was higher than 0.88 for both LS and GL. For both traits, the additive genetic variance was larger for alleles inherited from the Large White breed compared to alleles inherited from the Landrace breed (0.74 and 0.56 for LS, and 0.42 and 0.40 for GL, respectively). The highest prediction accuracies of crossbred performance were obtained when training was done on crossbred data. For LS, prediction accuracies were the same for GS and BS DGV (0.23), while for GL, prediction accuracy for BS DGV was similar to the accuracy of GS DGV (0.53 and 0.52, respectively). In this study, training on crossbred data resulted in higher prediction accuracy than training on purebred data and evidence of breed-specific effects for LS and GL was demonstrated. However, when training was done on crossbred data, both GS and BS models resulted in similar prediction accuracies. In future studies, traits with a lower genetic correlation between purebred and crossbred performance should be included to further assess the value of the BS model in genomic predictions.

Deletion of Marek’s disease virus large subunit of ribonucleotide reductase (RR) impairs virus growth in vitro and in vivo

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV), a highly cell-associated lymphotropic alphaherpesvirus, is the causative agent of a neoplastic disease in domestic chickens, called Marek’s disease (MD). In the unique long region of the MDV genome, open reading frames UL39 and UL40 encode the large and small subunits o...

Marek’s Disease Virus Encoded Ribonucleotide Reductase Large Subunit is not Essential for In Vitro Replication

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV) infected cells express a viral ribonucleotide reductase (RR) that is distinguishable from that present in uninfected cells by monoclonal antibody T81. Open reading frames UL39 and UL40 of the MDV genome encode the large (RR1) and small (RR2) subunits of RR enzyme, respe...

In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans

PubMed Central

Ma, Long; Tan, Zhiping; Teng, Yanling; Hoersch, Sebastian; Horvitz, H. Robert

2011-01-01

The in vivo analysis of the roles of splicing factors in regulating alternative splicing in animals remains a challenge. Using a microarray-based screen, we identified a Caenorhabditis elegans gene, tos-1, that exhibited three of the four major types of alternative splicing: intron retention, exon skipping, and, in the presence of U2AF large subunit mutations, the use of alternative 3′ splice sites. Mutations in the splicing factors U2AF large subunit and SF1/BBP altered the splicing of tos-1. 3′ splice sites of the retained intron or before the skipped exon regulate the splicing pattern of tos-1. Our study provides in vivo evidence that intron retention and exon skipping can be regulated largely by the identities of 3′ splice sites. PMID:22033331

Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

PubMed

Janecka, Anna; Kołodziej-Rzepa, Marta; Biesaga, Beata

2016-01-01

Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Orion Nebula in the Far-Infrared: High-J CO and fine-structure lines mapped by FIFI-LS/SOFIA

NASA Astrophysics Data System (ADS)

Klein, Randolf; Looney, Leslie W.; Cox, Erin; Fischer, Christian; Iserlohe, Christof; Krabbe, Alfred

2017-03-01

The Orion Nebula is the closest massive star forming region allowing us to study the physical conditions in such a region with high spatial resolution. We used the far infrared integral-field spectrometer, FIFI-LS, on-board the airborne observatory SOFIA to study the atomic and molecular gas in the Orion Nebula at medium spectral resolution. The large maps obtained with FIFI-LS cover the nebula from the BN/KL-object to the bar in several fine structure lines. They allow us to study the conditions of the photon-dominated region and the interface to the molecular cloud with unprecedented detail. Another investigation targeted the molecular gas in the BN/KL region of the Orion Nebula, which is stirred up by a violent explosion about 500 years ago. The explosion drives a wide angled molecular outflow. We present maps of several high-J CO observations, allowing us to analyze the heated molecular gas.

Local Time Variation of Water Ice Clouds on Mars as Observed by TES During Aerobraking.

NASA Astrophysics Data System (ADS)

AlJanaahi, A. A.; AlShamsi, M. R.; Smith, M. D.; Altunaiji, E. S.; Edwards, C. S.

2016-12-01

The large elliptical orbit during Mars Global Surveyor aerobraking enabled sampling the martian atmosphere over many local times. The Thermal Emission Spectrometer (TES) aerobraking spectra were taken between Mars Year 23, Ls=180° and Mars Year 24, Ls=30°. These early data from before the main "mapping" part of the mission have been mostly overlooked, and relatively little analysis has been done with them. These datasets have not been used before to study local time variation. Radiative transfer modeling is used to fit the spectra to retrieve surface and atmospheric temperature, and dust and water ice optical depths. Retrievals show significant and systematic variation in water ice cloud optical depth as a function of local time. Cloud optical depth is higher in the early morning (before 9:00) and in the evening (after 17:00) for all seasons observed (Ls=180°-30°). Clouds form consistently in the Tyrrhena region and in the area around Tharsis.

Hour time-scale QPOs in the X-ray and radio emission of LS I +61°303

NASA Astrophysics Data System (ADS)

Nösel, S.; Sharma, R.; Massi, M.; Cimò, G.; Chernyakova, M.

2018-05-01

LS I +61°303 is an X-ray binary with a radio outburst every ˜27 d. Previous studies of the stellar system revealed radio microflares superimposed on the large radio outburst. We present here new radio observations of LS I +61°303 at 2.2 GHz with the Westerbork Synthesis Radio Telescope (WSRT). Using various timing analysis methods, we find significant quasi-periodic oscillations (QPOs) of 55 min stable over the duration of 4 d. We also use archival data obtained from the Suzaku satellite at X-ray wavelengths. We report here for the first time significant X-ray QPOs of about 2 h present over the time span of 21 h. We compare our results with the previously reported QPO observations and we conclude that the QPOs seem to be associated with the radio outburst, independent of the amplitude of the outburst. Finally, the different QPO time-scales are discussed in the context of magnetic reconnection.

Signal-Preserving Erratic Noise Attenuation via Iterative Robust Sparsity-Promoting Filter

DOE PAGES

Zhao, Qiang; Du, Qizhen; Gong, Xufei; ...

2018-04-06

Sparse domain thresholding filters operating in a sparse domain are highly effective in removing Gaussian random noise under Gaussian distribution assumption. Erratic noise, which designates non-Gaussian noise that consists of large isolated events with known or unknown distribution, also needs to be explicitly taken into account. However, conventional sparse domain thresholding filters based on the least-squares (LS) criterion are severely sensitive to data with high-amplitude and non-Gaussian noise, i.e., the erratic noise, which makes the suppression of this type of noise extremely challenging. Here, in this paper, we present a robust sparsity-promoting denoising model, in which the LS criterion ismore » replaced by the Huber criterion to weaken the effects of erratic noise. The random and erratic noise is distinguished by using a data-adaptive parameter in the presented method, where random noise is described by mean square, while the erratic noise is downweighted through a damped weight. Different from conventional sparse domain thresholding filters, definition of the misfit between noisy data and recovered signal via the Huber criterion results in a nonlinear optimization problem. With the help of theoretical pseudoseismic data, an iterative robust sparsity-promoting filter is proposed to transform the nonlinear optimization problem into a linear LS problem through an iterative procedure. The main advantage of this transformation is that the nonlinear denoising filter can be solved by conventional LS solvers. Lastly, tests with several data sets demonstrate that the proposed denoising filter can successfully attenuate the erratic noise without damaging useful signal when compared with conventional denoising approaches based on the LS criterion.« less

Signal-Preserving Erratic Noise Attenuation via Iterative Robust Sparsity-Promoting Filter

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

Zhao, Qiang; Du, Qizhen; Gong, Xufei

Sparse domain thresholding filters operating in a sparse domain are highly effective in removing Gaussian random noise under Gaussian distribution assumption. Erratic noise, which designates non-Gaussian noise that consists of large isolated events with known or unknown distribution, also needs to be explicitly taken into account. However, conventional sparse domain thresholding filters based on the least-squares (LS) criterion are severely sensitive to data with high-amplitude and non-Gaussian noise, i.e., the erratic noise, which makes the suppression of this type of noise extremely challenging. Here, in this paper, we present a robust sparsity-promoting denoising model, in which the LS criterion ismore » replaced by the Huber criterion to weaken the effects of erratic noise. The random and erratic noise is distinguished by using a data-adaptive parameter in the presented method, where random noise is described by mean square, while the erratic noise is downweighted through a damped weight. Different from conventional sparse domain thresholding filters, definition of the misfit between noisy data and recovered signal via the Huber criterion results in a nonlinear optimization problem. With the help of theoretical pseudoseismic data, an iterative robust sparsity-promoting filter is proposed to transform the nonlinear optimization problem into a linear LS problem through an iterative procedure. The main advantage of this transformation is that the nonlinear denoising filter can be solved by conventional LS solvers. Lastly, tests with several data sets demonstrate that the proposed denoising filter can successfully attenuate the erratic noise without damaging useful signal when compared with conventional denoising approaches based on the LS criterion.« less

Reengineering ribosome export.

PubMed

Lo, Kai-Yin; Johnson, Arlen W

2009-03-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages.

Reengineering Ribosome Export

PubMed Central

Lo, Kai-Yin

2009-01-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMID:19144820

Liver stiffness and portal blood flow modifications induced by a liquid meal consumption: pathogenetic mechanisms and clinical relevance.

PubMed

Barone, Michele; Iannone, Andrea; Brunetti, Natale Daniele; Sebastiani, Francesco; Cecere, Onofrio; Berardi, Elsa; Antonica, Gianfranco; Di Leo, Alfredo

2015-05-01

The correlation between liver stiffness (LS) variations and portal blood flow (PBF) modifications induced by a standardized liquid meal consumption and the clinical relevance of this matter are two aspects not yet fully elucidated. Herein, we evaluated the variations of LS and PBF after a standardized liquid meal intake in patients with chronic liver disease. PBF and LS were determined after an overnight fasting period in 54 patients. They were divided in three groups according to baseline LS (absent, moderate, and severe). They consumed 200 ml of water and a standardized liquid meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after water and liquid meal consumption. In all groups, LS and PBF values significantly increased only after meal consumption. A significant correlation between baseline LS values and post-meal increase of LS was observed. Moreover, higher basal stiffness values were associated to a larger increase of LS variation after meal consumption. The effect of the meal on LS remained statistically significant after multiple regression analysis. A significant correlation between increase of LS and PBF was found in patients with absent and moderate baseline LS. Nine patients (17%) switched from a lower to a higher level of LS after meal consumption. A low calories/low-volume meal is capable of significantly increasing LS regardless of the grade of stiffness, determining a reclassification rate of 17%. In presence of minimal or moderate stiffness, the increase of LS is significantly correlated with the augment of PBF.

Recent Advances in Source Localisation Using Range Measurements

DTIC Science & Technology

2015-10-01

Range Weighted SR- LS ............................................................................................ 5 GEOLOCATION USING SEMIDEFINITE... LS ) and the squared range least squares (SR- LS ) [3]. The R- LS -based formulation is of great interest and has been known for its optimal performance...to efficiently compute an R- LS position estimate. A number of optimization tools may be applied to globally solve the R- LS problem and are usually

Glucose metabolism and hepatic Igf1 DNA methylation are altered in the offspring of dams fed a low-salt diet during pregnancy.

PubMed

Siqueira, Flavia R; Furukawa, Luzia N S; Oliveira, Ivone B; Heimann, Joel C

2016-02-01

A low-salt (LS) diet during pregnancy has been linked to insulin resistance in adult offspring, at least in the experimental setting. However, it remains unclear if this effect is due to salt restriction during early or late pregnancy. To better understand this phenomenon, 12-week-old female Wistar rats were fed a LS or normal-salt (NS) diet during gestation or a LS diet during either the first (LS10) or second (LS20) half of gestation. Glucose tolerance test, HOMA-IR, gene expression analysis and DNA methylation measurements were conducted for the Insr, Igf1, Igf1r, Ins1 and Ins2 genes in the livers of neonates and in the liver, white adipose tissue and muscle of 20-week-old male offspring. Birth weight was lower in the LS20 and LS animals compared with the NS and LS10 rats. In the liver, the Igf1 levels in the LS10, LS20 and LS neonates were lower than those in the NS neonates. Methylation of the Insr, Igf1r, Ins1 and Ins2 genes was influenced in a variable manner by low salt intake during pregnancy. Increased liver Igf1 methylation was observed in the LS and LS20 neonates compared with their NS and LS10 counterparts. Glucose intolerance was observed in adult offspring as an effect of low salt intake over the duration of pregnancy. Compared to the NS animals, the HOMA-IR was higher in the 12-week-old LS and 20-week-old LS-10 rats. Based on these results, it appears that the reason a LS diet during pregnancy induces a low birth weight is its negative correlation with Igf1 DNA methylation in neonates. Copyright © 2015 Elsevier Inc. All rights reserved.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

PubMed

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions.

PubMed

Brooks, Benjamin Rix; Crumpacker, David; Fellus, Jonathan; Kantor, Daniel; Kaye, Randall E

2013-01-01

Pseudobulbar affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA. Participating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study-Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient's quality of life (QOL). Presence of PBA symptoms was defined as a CNS-LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded. PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs <13 (6.7 [2.5] vs. 4.7 [3.1], respectively; P<0.0001 two-sample t-test). A greater percentage of patients with CNS-LS ≥13 versus <13 were using antidepressant/antipsychotic medications (53.0% vs 35.4%, respectively; P<0.0001, chi-square test). Data from PRISM, the largest clinic-based study to assess PBA symptom prevalence, showed that PBA symptoms were common among patients with diverse neurological conditions. Higher CNS-LS scores were associated with impaired QOL and greater use of antipsychotic/antidepressant medications. These data underscore a need for greater awareness, recognition, and diagnosis of PBA.

A mononuclear iron(II) complex: cooperativity, kinetics and activation energy of the solvent-dependent spin transition.

PubMed

Bushuev, Mark B; Pishchur, Denis P; Logvinenko, Vladimir A; Gatilov, Yuri V; Korolkov, Ilya V; Shundrina, Inna K; Nikolaenkova, Elena B; Krivopalov, Viktor P

2016-01-07

The system [FeL2](BF4)2 (1)-EtOH-H2O (L is 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-(pyridin-2-yl)-6-methylpyrimidine) shows a complicated balance between the relative stabilities of solvatomorphs and polymorphs of the complex [FeL2](BF4)2. New solvatomorphs, 1(LS)·EtOH·H2O and β-1(LS)·xH2O, were isolated in this system. They were converted into four daughter phases, 1(A/LS), 1(D/LS), 1(E/LS)·yEtOH·zH2O and 1(F/LS). On thermal cycling in sealed ampoules, the phases 1(LS)·EtOH·H2O and β-1(LS)·xH2O transform into the anhydrous phase 1(A/LS). The hysteresis loop width for the (A/LS) ↔ (A/HS) spin transition depends on the water and ethanol contents in the ampoule and varies from ca. 30 K up to 145 K. The reproducible hysteresis loop of 145 K is the widest ever reported one for a spin crossover complex. The phase 1(A/LS) combines the outstanding spin crossover properties with thermal robustness allowing for multiple cycling in sealed ampoules without degradation. The kinetics of the 1(A/LS) → 1(A/HS) transition is sigmoidal which is indicative of strong cooperative interactions. The cooperativity of the 1(A/LS) → 1(A/HS) transition is related to the formation of a 2D supramolecular structure of the phase 1(A/LS). The activation energy for the spin transition is very high (hundreds of kJ mol(-1)). The kinetics of the 1(A/HS) → 1(A/LS) transition can either be sigmoidal or exponential depending on the water and ethanol contents in the ampoule. The phases 1(D/LS) and 1(F/LS) show gradual crossover, whereas the phase 1(E/LS)·yEtOH·yH2O shows a reversible hysteretic transition associated with the solvent molecule release and uptake.

Revisiting the phylogeny of Ocellularieae, the second largest tribe within Graphidaceae (lichenized Ascomycota: Ostropales)

Treesearch

Ekaphan Kraichak; Sittiporn Parnmen; Robert Lücking; Eimy Rivas Plata; Andre Aptroot; Marcela E.S. Caceres; Damien Ertz; Armin Mangold; Joel A. Mercado-Diaz; Khwanruan Papong; Dries Van der Broeck; Gothamie Weerakoon; H. Thorsten Lumbsch; NO-VALUE

2014-01-01

We present an updated 3-locus molecular phylogeny of tribe Ocellularieae, the second largest tribe within subfamily Graphidoideae in the Graphidaceae. Adding 165 newly generated sequences from the mitochondrial small subunit rDNA (mtSSU), the nuclear large subunit rDNA (nuLSU), and the second largest subunit of the DNA-directed RNA polymerase II (RPB2), we currently...

Marek’s disease virus encoded ribonucleotide reductase large subunit is essential for in vivo replication and plays a critical role in viral pathogenesis.

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus encodes a ribonucleotide reductase (RR) that consists of two subunits namely RR1 and RR2, both of which associate to form an active holoenzyme and both subunits are necessary for enzyme activity. It is an essential enzyme for the conversion of ribonucleotides to deoxyribonucleo...

Association between institutional procedural preference and in-hospital outcomes in laparoscopic surgeries; Insights from a retrospective cohort analysis of a nationwide surgical database in Japan.

PubMed

Miyata, Hiroaki; Mori, Masaki; Kokudo, Norihiro; Gotoh, Mitsukazu; Konno, Hiroyuki; Wakabayashi, Go; Matsubara, Hisahiro; Watanabe, Toshiaki; Ono, Minoru; Hashimoto, Hideki; Yamamoto, Hiroyuki; Kumamaru, Hiraku; Kohsaka, Shun; Iwanaka, Tadashi

2018-01-01

To assess the use of laparoscopic surgeries (LS) and the association between its performance and hospitals' preference for LS over open surgeries. LS is increasingly used in many abdominal surgeries, albeit both with and without solid guideline recommendations. To date, the hospitals' preference (LS vs. open surgeries) and its association with in-hospital outcomes has not been evaluated. We enrolled patients undergoing 8 types of gastrointestinal surgeries in 2011-2013 in the Japanese National Clinical Database. We assessed the use of LS and the occurrences of surgery-related morbidity and mortality during the study period. Further, for 4 typical LS procedures, we assessed the hospitals' preference for LS by modeling the propensity to perform LS (over open surgeries) from patient-level factors, and estimating each institution's observed/expected (O/E) ratio for LS use. Institutions with O/E>2 were defined as LS-dominant. Using hierarchical logistic regression models, we assessed the association between LS preference and in-hospital outcomes. Among 1,377,118 patients undergoing gastrointestinal procedures in 2,336 participating hospitals, use of LS increased in all 8 procedures (35.1% to 44.7% for distal gastrectomy (DG), and 27.5% to 43.2% for right hemi colectomy (RHC)). Those operated at LS-dominant hospitals were at an increased risk of operative death (OR 1.83 [95%CI, 1.37-2.45] for DG, 1.79 [95%CI, 1.43-2.25] for RHC) compared to standard O/E level hospitals (0.5≤O/E<2.0). LS use widely increased during 2011-2013 in Japan. Facilities with higher than expected LS use had higher mortality compared to other hospitals, suggesting a need for careful patient selection and dissemination of the procedure.

Biology of Symbioses between Marine Invertebrates and Intracellular Bacteria

DTIC Science & Technology

1990-01-30

bisphosphate carboxylase We designed from published sequence information oligonucleotide primers which are complementary to conserved regions on RubisCO ...large and small subunit genes. These primers were used successfully to amplify using polymerase chain reaction (PCR) specific regions of RubisCO ...for the large subunit of ribulose bisphosphate carboxylase/oxygenase ( RubisCO ) to symbiont DNA shows that the symbionts from both deep-sea and shallow

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

PubMed Central

Torres, Yolima P.; Granados, Sara T.; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above. PMID:25346693

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.

PubMed

Torres, Yolima P; Granados, Sara T; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca(2+) concentration, the large conductance voltage- and Ca(2+)-activated K(+) channel (BK) is unique among the superfamily of K(+) channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K(+) channels) and a large C terminus composed of two regulators of K(+) conductance domains (RCK domains), where the Ca(2+)-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca(2+) sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.

Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

PubMed Central

LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

2012-01-01

Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together define an endocytotic pathway likely used by ameloblasts to remove the enamel matrix during enamel maturation. PMID:23044750

Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis.

PubMed

Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna; Hu, Ping; White, Shane N; Lyngstadaas, S Petter; Okamoto, Curtis T; Smith, Charles E; Paine, Michael L

2013-03-01

Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real-time PCR, we show that the expression of clathrin and adaptor protein subunits are upregulated in maturation stage rodent enamel organ cells. AP complex 2 (AP-2) is the most upregulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts, with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin-dependent endocytosis, thus implying the likelihood of specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also upregulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1); cluster of differentiation 63 and 68 (Cd63 and Cd68); ATPase, H(+) transporting, lysosomal V0 subunit D2 (Atp6v0d2); ATPase, H(+) transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk). Immunohistologic data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain showed upregulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor-regulated pathway for the endocytosis of enamel matrix proteins. These data together define an endocytotic pathway likely used by ameloblasts to remove the enamel matrix during enamel maturation. Copyright © 2013 American Society for Bone and Mineral Research.

Prevalence, incidence and progression of lumbar spondylosis by gender and age strata.

PubMed

Muraki, Shigeyuki; Yoshimura, Noriko; Akune, Toru; Tanaka, Sakae; Takahashi, Ikuno; Fujiwara, Saeko

2014-07-01

To identify the prevalence, incidence and progression of radiographic lumbar spondylosis (LS). From the Adult Health Study conducted by the Radiation Effects Research Foundation, 1,204 participants aged 44-85 years who had lumbar spine radiographs in 1990-1992 were reexamined in 1998-2000 (mean 7.9-year interval). The radiographic severity of LS was determined by Kellgren/Lawrence (KL) grading. In the overall population, the prevalence of radiographic KL ≥ 2 and ≥ 3 LS was 52.9% and 23.6%, respectively. KL ≥ 2 LS was more prevalent in men, whereas KL ≥ 3 LS was more prevalent in women. During the 8-year follow-up, the incidence of KL ≥ 2 LS in men and women was 65.5% and 46.6%, that of KL ≥ 3 LS was 27.3% and 29.5%, that of progressive LS was 31.3% and 34.0%, and multilevel LS was 44.9% and 33.4%, respectively. Body-mass index was a risk factor for both KL ≥ 2 and KL ≥ 3 LS, after adjusting for age and sex. The present longitudinal study revealed the prevalence, incidence and progression of radiographic LS. Prevalence and incidence of KL ≥ 2 LS was higher in men than women, while, those of KL ≥ 3 were similar between men and women.

The Bacillus subtilis Conjugative Plasmid pLS20 Encodes Two Ribbon-Helix-Helix Type Auxiliary Relaxosome Proteins That Are Essential for Conjugation.

PubMed

Miguel-Arribas, Andrés; Hao, Jian-An; Luque-Ortega, Juan R; Ramachandran, Gayetri; Val-Calvo, Jorge; Gago-Córdoba, César; González-Álvarez, Daniel; Abia, David; Alfonso, Carlos; Wu, Ling J; Meijer, Wilfried J J

2017-01-01

Bacterial conjugation is the process by which a conjugative element (CE) is transferred horizontally from a donor to a recipient cell via a connecting pore. One of the first steps in the conjugation process is the formation of a nucleoprotein complex at the origin of transfer ( oriT ), where one of the components of the nucleoprotein complex, the relaxase, introduces a site- and strand specific nick to initiate the transfer of a single DNA strand into the recipient cell. In most cases, the nucleoprotein complex involves, besides the relaxase, one or more additional proteins, named auxiliary proteins, which are encoded by the CE and/or the host. The conjugative plasmid pLS20 replicates in the Gram-positive Firmicute bacterium Bacillus subtilis . We have recently identified the relaxase gene and the oriT of pLS20, which are separated by a region of almost 1 kb. Here we show that this region contains two auxiliary genes that we name aux1 LS20 and aux2 LS20 , and which we show are essential for conjugation. Both Aux1 LS20 and Aux2 LS20 are predicted to contain a Ribbon-Helix-Helix DNA binding motif near their N-terminus. Analyses of the purified proteins show that Aux1 LS20 and Aux2 LS20 form tetramers and hexamers in solution, respectively, and that they both bind preferentially to oriT LS20 , although with different characteristics and specificities. In silico analyses revealed that genes encoding homologs of Aux1 LS20 and/or Aux2 LS20 are located upstream of almost 400 relaxase genes of the Rel LS20 family (MOB L ) of relaxases. Thus, Aux1 LS20 and Aux2 LS20 of pLS20 constitute the founding member of the first two families of auxiliary proteins described for CEs of Gram-positive origin.

Amino acid sequence of the human fibronectin receptor

PubMed Central

1987-01-01

The amino acid sequence deduced from cDNA of the human placental fibronectin receptor is reported. The receptor is composed of two subunits: an alpha subunit of 1,008 amino acids which is processed into two polypeptides disulfide bonded to one another, and a beta subunit of 778 amino acids. Each subunit has near its COOH terminus a hydrophobic segment. This and other sequence features suggest a structure for the receptor in which the hydrophobic segments serve as transmembrane domains anchoring each subunit to the membrane and dividing each into a large ectodomain and a short cytoplasmic domain. The alpha subunit ectodomain has five sequence elements homologous to consensus Ca2+- binding sites of several calcium-binding proteins, and the beta subunit contains a fourfold repeat strikingly rich in cysteine. The alpha subunit sequence is 46% homologous to the alpha subunit of the vitronectin receptor. The beta subunit is 44% homologous to the human platelet adhesion receptor subunit IIIa and 47% homologous to a leukocyte adhesion receptor beta subunit. The high degree of homology (85%) of the beta subunit with one of the polypeptides of a chicken adhesion receptor complex referred to as integrin complex strongly suggests that the latter polypeptide is the chicken homologue of the fibronectin receptor beta subunit. These receptor subunit homologies define a superfamily of adhesion receptors. The availability of the entire protein sequence for the fibronectin receptor will facilitate studies on the functions of these receptors. PMID:2958481

African swine fever virus encodes two genes which share significant homology with the two largest subunits of DNA-dependent RNA polymerases.

PubMed Central

Yáñez, R J; Boursnell, M; Nogal, M L; Yuste, L; Viñuela, E

1993-01-01

A random sequencing strategy applied to two large SalI restriction fragments (SB and SD) of the African swine fever virus (ASFV) genome revealed that they might encode proteins similar to the two largest RNA polymerase subunits of eukaryotes, poxviruses and Escherichia coli. After further mapping by dot-blot hybridization, two large open reading frames (ORFs) were completely sequenced. The first ORF (NP1450L) encodes a protein of 1450 amino acids with extensive similarity to the largest subunit of RNA polymerases. The second one (EP1242L) codes for a protein of 1242 amino acids similar to the second largest RNA polymerase subunit. Proteins NP1450L and EP1242L are more similar to the corresponding subunits of eukaryotic RNA polymerase II than to those of vaccinia virus, the prototype poxvirus, which shares many functional characteristics with ASFV. ORFs NP1450L and EP1242L are mainly expressed late in ASFV infection, after the onset of DNA replication. Images PMID:8506138

Support vector machine regression (LS-SVM)--an alternative to artificial neural networks (ANNs) for the analysis of quantum chemistry data?

PubMed

Balabin, Roman M; Lomakina, Ekaterina I

2011-06-28

A multilayer feed-forward artificial neural network (MLP-ANN) with a single, hidden layer that contains a finite number of neurons can be regarded as a universal non-linear approximator. Today, the ANN method and linear regression (MLR) model are widely used for quantum chemistry (QC) data analysis (e.g., thermochemistry) to improve their accuracy (e.g., Gaussian G2-G4, B3LYP/B3-LYP, X1, or W1 theoretical methods). In this study, an alternative approach based on support vector machines (SVMs) is used, the least squares support vector machine (LS-SVM) regression. It has been applied to ab initio (first principle) and density functional theory (DFT) quantum chemistry data. So, QC + SVM methodology is an alternative to QC + ANN one. The task of the study was to estimate the Møller-Plesset (MPn) or DFT (B3LYP, BLYP, BMK) energies calculated with large basis sets (e.g., 6-311G(3df,3pd)) using smaller ones (6-311G, 6-311G*, 6-311G**) plus molecular descriptors. A molecular set (BRM-208) containing a total of 208 organic molecules was constructed and used for the LS-SVM training, cross-validation, and testing. MP2, MP3, MP4(DQ), MP4(SDQ), and MP4/MP4(SDTQ) ab initio methods were tested. Hartree-Fock (HF/SCF) results were also reported for comparison. Furthermore, constitutional (CD: total number of atoms and mole fractions of different atoms) and quantum-chemical (QD: HOMO-LUMO gap, dipole moment, average polarizability, and quadrupole moment) molecular descriptors were used for the building of the LS-SVM calibration model. Prediction accuracies (MADs) of 1.62 ± 0.51 and 0.85 ± 0.24 kcal mol(-1) (1 kcal mol(-1) = 4.184 kJ mol(-1)) were reached for SVM-based approximations of ab initio and DFT energies, respectively. The LS-SVM model was more accurate than the MLR model. A comparison with the artificial neural network approach shows that the accuracy of the LS-SVM method is similar to the accuracy of ANN. The extrapolation and interpolation results show that LS-SVM is superior by almost an order of magnitude over the ANN method in terms of the stability, generality, and robustness of the final model. The LS-SVM model needs a much smaller numbers of samples (a much smaller sample set) to make accurate prediction results. Potential energy surface (PES) approximations for molecular dynamics (MD) studies are discussed as a promising application for the LS-SVM calibration approach. This journal is © the Owner Societies 2011

Does life satisfaction predict five-year mortality in community-living older adults?

PubMed

St John, Philip D; Mackenzie, Corey; Menec, Verena

2015-01-01

Depression and depressive symptoms predict death, but it is less clear if more general measures of life satisfaction (LS) predict death. Our objectives were to determine: (1) if LS predicts mortality over a five-year period in community-living older adults; and (2) which aspects of LS predict death. 1751 adults over the age of 65 who were living in the community were sampled from a representative population sampling frame in 1991/1992 and followed five years later. Age, gender, and education were self-reported. An index of multimorbidity and the Older American Resource Survey measured health and functional status, and the Terrible-Delightful Scale assessed overall LS as well as satisfaction with: health, finances, family, friends, housing, recreation, self-esteem, religion, and transportation. Cox proportional hazards models examined the influence of LS on time to death. 417 participants died during the five-year study period. Overall LS and all aspects of LS except finances, religion, and self-esteem predicted death in unadjusted analyses. In fully adjusted analyses, LS with health, housing, and recreation predicted death. Other aspects of LS did not predict death after accounting for functional status and multimorbidity. LS predicted death, but certain aspects of LS are more strongly associated with death. The effect of LS is complex and may be mediated or confounded by health and functional status. It is important to consider different domains of LS when considering the impact of this important emotional indicator on mortality among older adults.

Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome.

PubMed

Zhang, Nianhui; Peng, Zechun; Tong, Xiaoping; Lindemeyer, A Kerstin; Cetina, Yliana; Huang, Christine S; Olsen, Richard W; Otis, Thomas S; Houser, Carolyn R

2017-11-01

While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABA A receptors (GABA A Rs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABA A R, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS. Electrophysiological studies of dentate granule cells revealed a marked, nearly four-fold, decrease in tonic inhibition in the Fmr1 KO mice, as well as reduced effects of two δ subunit-preferring pharmacological agents, THIP and DS2, supporting the suggestion that δ subunit-containing GABA A Rs are compromised in the Fmr1 KO mice. Immunohistochemistry demonstrated a small but statistically significant decrease in δ subunit labeling in the molecular layer of the dentate gyrus in Fmr1 KO mice compared to wildtype (WT) littermates. The discrepancy between the large deficits in GABA-mediated tonic inhibition in granule cells in the Fmr1 KO mice and only modest reductions in immunolabeling of the δ subunit led to studies of surface expression of the δ subunit. Cross-linking experiments followed by Western blot analysis demonstrated a small, non-significant decrease in total δ subunit protein in the hippocampus of Fmr1 KO mice, but a four-fold decrease in surface expression of the δ subunit in these mice. No significant changes were observed in total or surface expression of the α4 subunit protein, a major partner of the δ subunit in the forebrain. Postembedding immunogold labeling for the δ subunit demonstrated a large, three-fold, decrease in the number of symmetric synapses with immunolabeling at perisynaptic locations in Fmr1 KO mice. While α4 immunogold particles were also reduced at perisynaptic locations in the Fmr1 KO mice, the labeling was increased at synaptic sites. Together these findings suggest that, in the dentate gyrus, altered surface expression of the δ subunit, rather than a decrease in δ subunit expression alone, could be limiting δ subunit-mediated tonic inhibition in this model of FXS. Finding ways to increase surface expression of the δ subunit of the GABA A R could be a novel approach to treatment of hyperexcitability-related alterations in FXS. Copyright © 2017 Elsevier Inc. All rights reserved.

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B

PubMed Central

Yo, In Ku; Park, Jin Woong; Lee, Jong Joon; Lee, Jung Hyun; Won, In Sik; Na, Sun Young; Jang, Pil Kyu; Park, Pyung Hwa; Choi, Duck Joo; Kim, Yun Soo; Kim, Ju Hyun

2015-01-01

Background/Aims Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. Methods Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared. Results No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. Conclusions A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study. PMID:25834800

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B.

PubMed

Yo, In Ku; Kwon, Oh Sang; Park, Jin Woong; Lee, Jong Joon; Lee, Jung Hyun; Won, In Sik; Na, Sun Young; Jang, Pil Kyu; Park, Pyung Hwa; Choi, Duck Joo; Kim, Yun Soo; Kim, Ju Hyun

2015-03-01

Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared. No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.

Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice

PubMed Central

Fusco, Fernanda B.; Gomes, Diego J.; Bispo, Kely C. S.; Toledo, Veronica P.; Barbeiro, Denise F.; Capelozzi, Vera L.; Furukawa, Luzia N. S.; Velosa, Ana P. P.; Teodoro, Walcy R.; Heimann, Joel C.; Quintao, Eder C. R.; Passarelli, Marisa; Nakandakare, Edna R.; Catanozi, Sergio

2017-01-01

This study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet. PMID:28481921

Ribulose-1,5-bis-phosphate carboxylase/oxygenase accumulation factor1 is required for holoenzyme assembly in maize.

PubMed

Feiz, Leila; Williams-Carrier, Rosalind; Wostrikoff, Katia; Belcher, Susan; Barkan, Alice; Stern, David B

2012-08-01

Most life is ultimately sustained by photosynthesis and its rate-limiting carbon fixing enzyme, ribulose-1,5-bis-phosphate carboxylase/oxygenase (Rubisco). Although the structurally comparable cyanobacterial Rubisco is amenable to in vitro assembly, the higher plant enzyme has been refractory to such manipulation due to poor understanding of its assembly pathway. Here, we report the identification of a chloroplast protein required for Rubisco accumulation in maize (Zea mays), RUBISCO ACCUMULATION FACTOR1 (RAF1), which lacks any characterized functional domains. Maize lines lacking RAF1 due to Mutator transposon insertions are Rubisco deficient and seedling lethal. Analysis of transcripts and proteins showed that Rubisco large subunit synthesis in raf1 plants is not compromised; however, newly synthesized Rubisco large subunit appears in a high molecular weight form whose accumulation requires a specific chaperonin 60 isoform. Gel filtration analysis and blue native gels showed that endogenous and recombinant RAF1 are trimeric; however, following in vivo cross-linking, RAF1 copurifies with Rubisco large subunit, suggesting that they interact weakly or transiently. RAF1 is predominantly expressed in bundle sheath chloroplasts, consistent with a Rubisco accumulation function. Our results support the hypothesis that RAF1 acts during Rubisco assembly by releasing and/or sequestering the large subunit from chaperonins early in the assembly process.

PCR amplification and sequences of cDNA clones for the small and large subunits of ADP-glucose pyrophosphorylase from barley tissues.

PubMed

Villand, P; Aalen, R; Olsen, O A; Lüthi, E; Lönneborg, A; Kleczkowski, L A

1992-06-01

Several cDNAs encoding the small and large subunit of ADP-glucose pyrophosphorylase (AGP) were isolated from total RNA of the starchy endosperm, roots and leaves of barley by polymerase chain reaction (PCR). Sets of degenerate oligonucleotide primers, based on previously published conserved amino acid sequences of plant AGP, were used for synthesis and amplification of the cDNAs. For either the endosperm, roots and leaves, the restriction analysis of PCR products (ca. 550 nucleotides each) has revealed heterogeneity, suggesting presence of three transcripts for AGP in the endosperm and roots, and up to two AGP transcripts in the leaf tissue. Based on the derived amino acid sequences, two clones from the endosperm, beps and bepl, were identified as coding for the small and large subunit of AGP, respectively, while a leaf transcript (blpl) encoded the putative large subunit of AGP. There was about 50% identity between the endosperm clones, and both of them were about 60% identical to the leaf cDNA. Northern blot analysis has indicated that beps and bepl are expressed in both the endosperm and roots, while blpl is detectable only in leaves. Application of the PCR technique in studies on gene structure and gene expression of plant AGP is discussed.

An unusual spliced variant of DELLA protein, a negative regulator of gibberellin signaling, in lettuce.

PubMed

Sawada, Yoshiaki; Umetsu, Asami; Komatsu, Yuki; Kitamura, Jun; Suzuki, Hiroyuki; Asami, Tadao; Fukuda, Machiko; Honda, Ichiro; Mitsuhashi, Wataru; Nakajima, Masatoshi; Toyomasu, Tomonobu

2012-01-01

DELLA proteins are negative regulators of the signaling of gibberellin (GA), a phytohormone regulating plant growth. DELLA degradation is triggered by its interaction with GID1, a soluble GA receptor, in the presence of bioactive GA. We isolated cDNA from a spliced variant of LsDELLA1 mRNA in lettuce, and named it LsDELLA1sv. It was deduced that LsDELLA1sv encodes truncated LsDELLA1, which has DELLA and VHYNP motifs at the N terminus but lacks part of the C-terminal GRAS domain. The recombinant LsDELLA1sv protein interacted with both Arabidopsis GID1 and lettuce GID1s in the presence of GA. A yeast two-hybrid assay suggested that LsDELLA1sv interacted with LsDELLA1. The ratio of LsDELLA1sv to LsDELLA1 transcripts was higher in flower samples at the late reproductive stage and seed samples (dry seeds and imbibed seeds) than in the other organ samples examined. This study suggests that LsDELLA1sv is a possible modulator of GA signaling in lettuce.

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking.

PubMed

Zhou, Ping; Guo, Dongwei; Wang, Hong; Chai, Tianyou

2017-09-29

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVR (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. This indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.

Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome.

PubMed

Schneider, Nayê Balzan; Pastor, Tatiane; Paula, André Escremim de; Achatz, Maria Isabel; Santos, Ândrea Ribeiro Dos; Vianna, Fernanda Sales Luiz; Rosset, Clévia; Pinheiro, Manuela; Ashton-Prolla, Patricia; Moreira, Miguel Ângelo Martins; Palmero, Edenir Inêz

2018-05-01

Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene variants include missense, nonsense, frameshift mutations, large genomic rearrangements and splice-site variants and most of the studies reporting the molecular characterization of LS families have been conducted outside South America. In this study, we analyzed 60 unrelated probands diagnosed with colorectal cancer and LS criteria. Testing for germline mutations and/or rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these, approximately one-third were gene rearrangements. In addition, nine variants of uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands analyzed. Other four novel variants were identified, only in MLH1. Our results suggest that MSH6 pathogenic variants are not common among Brazilian LS probands diagnosed with CRC and that MMR gene rearrangements account for a significant proportion of the germline variants in this population underscoring the need to include rearrangement analysis in the molecular testing of Brazilian individuals with suspected Lynch syndrome. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking

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

Zhou, Ping; Guo, Dongwei; Wang, Hong

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVRmore » (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. In conclusion, this indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.« less

Combinations of early signs of critical illness predict in-hospital death-the SOCCER study (signs of critical conditions and emergency responses).

PubMed

Harrison, Gordon A; Jacques, Theresa; McLaws, Mary-Louise; Kilborn, Gabrielle

2006-12-01

Medical emergency team (MET) call criteria are late signs of a deteriorating clinical condition. Some early signs predict in-hospital death but have a high prevalence so their use as single sign call criteria could be wasteful of resources. This study searched a large database to explore the association of combinations of recordings of early signs (ES), or early with late signs (LS) with in-hospital death. A cross-sectional survey was undertaken of 3046 non-do not attempt resuscitation adult admissions in 5 hospitals without MET over 14 days. The medical records were reviewed for recordings of 26 ES and 21 LS and in-hospital death. Combinations of ES with or without LS were examined as predictors of death. Global modified early warning scores (GMEWS) were calculated. ES with LS, plus LS only, had higher odd ratios than ES alone. Four combinations of ES were strongly associated with death: cardiovascular plus respiratory with decrease in urinary output, cardiovascular plus respiratory with a decrease in consciousness, respiratory with decrease in urinary output, and cardiovascular plus respiratory. In other combinations, recordings of SpO2 90-95%, systolic blood pressure 80-100 mmHg or decrease in urinary output in turn occurring with one or more disturbed blood gas variable were associated with death. Compared with admissions whose GMEWS were 0-2, admissions with GMEWS 5-15 were 27.1 times more likely to die while those with GMEWS 3-4 were 6.5 times more likely. The results support the inclusion of early signs of a deteriorating clinical condition in sets of call criteria.

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking

DOE PAGES

Zhou, Ping; Guo, Dongwei; Wang, Hong; ...

2017-09-29

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVRmore » (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. In conclusion, this indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.« less

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method.

PubMed

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method

PubMed Central

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC. PMID:28005929

Association of lung function and chronic obstructive pulmonary disease with American Heart Association's Life's Simple 7 cardiovascular health metrics.

PubMed

Fan, Wenjun; Lee, Hwa; Lee, Angela; Kieu, Chi; Wong, Nathan D

2017-10-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S. There is a strong association between COPD and cardiovascular (CV) disease; however, the relation between COPD and CV health factors is not well defined. We examined the relation between lung function and CV health factors defined by American Heart Association's (AHA) Life's Simple 7 (LS7). We studied 6352 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Analysis of variance was used to compare mean FEV1% of predicted across levels of each LS7 metric and population attributable risk was calculated based on COPD prevalence. We also conducted linear regression and logistic regression analyses to determine the association between lung function, COPD and LS7 score. Overall 19.9% of subjects were defined as having COPD. Subjects in the highest categories of the LS7 metrics had the highest mean values of FEV1% of predicted (p < 0.0001 except for total cholesterol). Current smoking and hypertension had a population attributed risk of 21.8% and 21.1% of COPD, respectively. Compared to subjects with 0 ideal health factors, the gender and ethnicity-adjusted odds (95% CI) for COPD were 0.45 (0.22-0.93), 0.22 (0.11-0.43) for those with 4 and 5-7 factors, but adjustment for age attenuated this relation. LS7 score is associated with lung function as well as the odds of COPD that is largely explained by age. Studies are needed to show if promotion of CV health will preserve healthy lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model.

PubMed

Schölvinck, D W; Alvarez Herrero, L; Visser, M; Bergman, J J G H M; Weusten, B L A M

2015-10-01

Preliminary data show higher stricture rates after radiofrequency ablation (RFA) for early esophageal squamous neoplasia compared with Barrett's esophagus. We studied the effects of Lugol stain (LS) directly prior to RFA on stricture formation in squamous epithelium. Of 16 pigs, the distal half of the esophagus was LS, followed by circumferential RFA (single application 12 J/cm(2) ) in the unstained and stained esophagus. Pigs were euthanized at day 0 (n = 4), 3 (n = 4), or 28 (n = 8). Histology was evaluated in four areas: blank-control (no RFA, no LS), blank-RFA (no LS), LS+RFA, and LS-control (no RFA). Stenosis severity in LS+RFA and blank-RFA at 28 days was assessed by the ratio of the mucosal diameter at the RFA area to the diameter 2 cm proximal of this zone. Histology showed submucosal edema in 50% of LS+RFA versus 0% in blank-RFA. Severity and depth of inflammation (day 3) was equal in LS+RFA and blank-RFA. Severity and depth of fibrosis (day 28) appeared more severe in LS+RFA. Consequently, stenosis was present in 100% (LS+RFA) versus 12.5% (blank-RFA). The stenosis-severity ratio was 0.40 (interquartile range 0.29-0.45) in LS+RFA versus 0.73 (interquartile range 0.64-0.78) in blank-RFA (P = 0.012). Limitations of this study were the difference in uptake of LS between pigs and humans, the difference in esophageal anatomy between pigs and humans, and between the proximal and distal esophagus within pigs. In conclusion, in the porcine squamous esophagus, stenosis rate and severity after RFA increased when preceded by LS. LS may be contributing in the altered response of squamous epithelium to RFA as compared with Barrett's esophagus. © 2014 International Society for Diseases of the Esophagus.

Association between institutional procedural preference and in-hospital outcomes in laparoscopic surgeries; Insights from a retrospective cohort analysis of a nationwide surgical database in Japan

PubMed Central

Miyata, Hiroaki; Mori, Masaki; Kokudo, Norihiro; Gotoh, Mitsukazu; Konno, Hiroyuki; Wakabayashi, Go; Matsubara, Hisahiro; Watanabe, Toshiaki; Ono, Minoru; Hashimoto, Hideki; Yamamoto, Hiroyuki; Kumamaru, Hiraku; Kohsaka, Shun; Iwanaka, Tadashi

2018-01-01

Objective To assess the use of laparoscopic surgeries (LS) and the association between its performance and hospitals’ preference for LS over open surgeries. Summary background data LS is increasingly used in many abdominal surgeries, albeit both with and without solid guideline recommendations. To date, the hospitals’ preference (LS vs. open surgeries) and its association with in-hospital outcomes has not been evaluated. Methods We enrolled patients undergoing 8 types of gastrointestinal surgeries in 2011–2013 in the Japanese National Clinical Database. We assessed the use of LS and the occurrences of surgery-related morbidity and mortality during the study period. Further, for 4 typical LS procedures, we assessed the hospitals’ preference for LS by modeling the propensity to perform LS (over open surgeries) from patient-level factors, and estimating each institution’s observed/expected (O/E) ratio for LS use. Institutions with O/E>2 were defined as LS-dominant. Using hierarchical logistic regression models, we assessed the association between LS preference and in-hospital outcomes. Results Among 1,377,118 patients undergoing gastrointestinal procedures in 2,336 participating hospitals, use of LS increased in all 8 procedures (35.1% to 44.7% for distal gastrectomy (DG), and 27.5% to 43.2% for right hemi colectomy (RHC)). Those operated at LS-dominant hospitals were at an increased risk of operative death (OR 1.83 [95%CI, 1.37–2.45] for DG, 1.79 [95%CI, 1.43–2.25] for RHC) compared to standard O/E level hospitals (0.5≤O/E<2.0). Conclusions LS use widely increased during 2011–2013 in Japan. Facilities with higher than expected LS use had higher mortality compared to other hospitals, suggesting a need for careful patient selection and dissemination of the procedure. PMID:29505561

Analyses of the Large Subunit Histidine-Rich Motif Expose an Alternative Proton Transfer Pathway in [NiFe] Hydrogenases

PubMed Central

Szőri-Dorogházi, Emma; Maróti, Gergely; Szőri, Milán; Nyilasi, Andrea; Rákhely, Gábor; Kovács, Kornél L.

2012-01-01

A highly conserved histidine-rich region with unknown function was recognized in the large subunit of [NiFe] hydrogenases. The HxHxxHxxHxH sequence occurs in most membrane-bound hydrogenases, but only two of these histidines are present in the cytoplasmic ones. Site-directed mutagenesis of the His-rich region of the T. roseopersicina membrane-attached Hyn hydrogenase disclosed that the enzyme activity was significantly affected only by the replacement of the His104 residue. Computational analysis of the hydrogen bond network in the large subunits indicated that the second histidine of this motif might be a component of a proton transfer pathway including Arg487, Asp103, His104 and Glu436. Substitutions of the conserved amino acids of the presumed transfer route impaired the activity of the Hyn hydrogenase. Western hybridization was applied to demonstrate that the cellular level of the mutant hydrogenases was similar to that of the wild type. Mostly based on theoretical modeling, few proton transfer pathways have already been suggested for [NiFe] hydrogenases. Our results propose an alternative route for proton transfer between the [NiFe] active center and the surface of the protein. A novel feature of this model is that this proton pathway is located on the opposite side of the large subunit relative to the position of the small subunit. This is the first study presenting a systematic analysis of an in silico predicted proton translocation pathway in [NiFe] hydrogenases by site-directed mutagenesis. PMID:22511957

Little evidence for intralocus sexual conflict over the optimal intake of nutrients for life span and reproduction in the black field cricket Teleogryllus commodus

PubMed Central

Rapkin, James; Archer, C. Ruth; Grant, Charles E.; Jensen, Kim; House, Clarissa M.; Wilson, Alastair J.; Hunt, John

2017-01-01

Abstract There is often large divergence in the effects of key nutrients on life span (LS) and reproduction in the sexes, yet nutrient intake is regulated in the same way in males and females given dietary choice. This suggests that the sexes are constrained from feeding to their sex‐specific nutritional optima for these traits. Here, we examine the potential for intralocus sexual conflict (IASC) over optimal protein and carbohydrate intake for LS and reproduction to constrain the evolution of sex‐specific nutrient regulation in the field cricket, Teleogryllus commodus. We show clear sex differences in the effects of protein and carbohydrate intake on LS and reproduction and strong positive genetic correlations between the sexes for the regulated intake of these nutrients. However, the between‐sex additive genetic covariance matrix had very little effect on the predicted evolutionary response of nutrient regulation in the sexes. Thus, IASC appears unlikely to act as an evolutionary constraint on sex‐specific nutrient regulation in T. commodus. This finding is supported by clear sexual dimorphism in the regulated intake of these nutrients under dietary choice. However, nutrient regulation did not coincide with the nutritional optima for LS or reproduction in either sex, suggesting that IASC is not completely resolved in T. commodus. PMID:28640400

Are the major risk/need factors predictive of both female and male reoffending?: a test with the eight domains of the level of service/case management inventory.

PubMed

Andrews, Donald A; Guzzo, Lina; Raynor, Peter; Rowe, Robert C; Rettinger, L Jill; Brews, Albert; Wormith, J Stephen

2012-02-01

The Level of Service/Case Management Inventory (LS/CMI) and the Youth version (YLS/CMI) generate an assessment of risk/need across eight domains that are considered to be relevant for girls and boys and for women and men. Aggregated across five data sets, the predictive validity of each of the eight domains was gender-neutral. The composite total score (LS/CMI total risk/need) was strongly associated with the recidivism of males (mean r = .39, mean AUC = .746) and very strongly associated with the recidivism of females (mean r = .53, mean AUC = .827). The enhanced validity of LS total risk/need with females was traced to the exceptional validity of Substance Abuse with females. The intra-data set conclusions survived the introduction of two very large samples composed of female offenders exclusively. Finally, the mean incremental contributions of gender and the gender-by-risk level interactions in the prediction of criminal recidivism were minimal compared to the relatively strong validity of the LS/CMI risk level. Although the variance explained by gender was minimal and although high-risk cases were high-risk cases regardless of gender, the recidivism rates of lower risk females were lower than the recidivism rates of lower risk males, suggesting possible implications for test interpretation and policy.

Improved Detection of Winter Lightning in the Tohoku Region of Japan using Vaisala’s LS700x Technology

NASA Astrophysics Data System (ADS)

Cummins, Kenneth L.; Honma, Noriyasu; Pifer, Alburt E.; Rogers, Tim; Tatsumi, Masataka

The demand for both data quality and the range of Cloud-to-Ground (CG) lightning parameters is highest for forensic applications within the electric utility industry. For years, the research and operational communities within this industry in Japan have pointed out a limitation of these LLS networks in the detection and location of damaging (high-current and/or large charge transfer) lightning flashes during the winter months (so-called “Winter Lightning”). Most of these flashes appear to be upward-connecting discharges, frequently referred to as “Ground-to-Cloud” (GC) flashes. The basic architecture and design of Vaisala’s new LS700x lightning sensor was developed in-part to improve detection of these unusual and complex flashes. This paper presents our progress-to-date on this effort. We include a review of the winter lightning detection problem, an overview of the LS700x architecture, a discussion of how this architecture was exploited to evaluate and improve performance for winter lightning, and a presentation of results-to-date on performance improvement. A comparison of GC detection performance between Tohoku’s operational 9-sensor IMPACT (ALDF 141-T) LLS and its 6-sensor LS700x research network indicates roughly a factor-of-two improvement for this class of discharges, with an overall detection of 23/24 (96%) of GC flashes.

Source of moist air for the Asian summer monsoon lower stratosphere

NASA Astrophysics Data System (ADS)

Zhang, K.; Fu, R.; Wang, T.

2015-12-01

The Asian monsoon region is the most prominent moist center of lower stratospheric (LS) water vapor during boreal summer. However, the origin of such moist air is still unclear. Using Aura Microwave Limb Sounder (MLS) satellite observations and a domain-filling forward trajectory model, we show that moist air originates mostly from the western Asian Monsoon region where dehydration temperatures are warmer than those on the eastside of the Asian monsoon region. On seasonal scale, a shift of convective and dehydration center from the eastern to western monsoon region from early to late summer may contribute to the increase of LS water vapor over the Asian monsoon region. An increasing convection over the west side of the monsoon region can significantly moisten the LS. Air detrained from convection ascends with enhanced large-scale rising motion and dehydrate mostly within this region under warmer temperature, thus anomalously higher water vapor concentration. After final dehydration, water vapor anomalies show an upper-eastward propagation across the Asian monsoon region. This is primarily due to that air parcels tend to arise across the tropopause layer over the western region (eastern Iranian Plateau and northwestern India) after final dehydration as simulated by the trajectory model. This work highlights the importance of transport pathway shift, induced by the convective regime shift, on both seasonal and intraseasonal variations of water vapor in the Asian monsoon LS.

High-Capacity, Portable Firefighting Pump

NASA Technical Reports Server (NTRS)

Burns, Ralph A.

1988-01-01

Report describes an evaluation of firefighting module that delivers water at 5,000 gal/min (320 L/s). Is compact, self-contained, portable water pump. Besides firefighting, module used for flood control, pumping water into large vessels, and pump water from sinking ships.

Ureteroscopy

MedlinePlus

... obese, or have a blood clotting disorder, ureteroscopy is a good choice. For very large or oddly shaped stones, or stones that are very hard, other treatments such as percutaneous nephrolithotomy or, rarely, open surgery may be needed. ls a basket always used during ureteroscopy? Not always. ...

Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

PubMed

Laron, Z

2001-01-01

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

Physical Performance Measures Associated With Locomotive Syndrome in Middle-Aged and Older Japanese Women.

PubMed

Nakamura, Misa; Hashizume, Hiroshi; Oka, Hiroyuki; Okada, Morihiro; Takakura, Rie; Hisari, Ayako; Yoshida, Munehito; Utsunomiya, Hirotoshi

2015-01-01

The Japanese Orthopaedic Association proposed a concept called locomotive syndrome (LS) to identify middle-aged and older adults at high risk of requiring health care services because of problems with locomotion. It is important to identify factors associated with the development of LS. Physical performance measures such as walking speed and standing balance are highly predictive of subsequent disability and mortality in older adults. However, there is little evidence about the relationship between physical performance measures and LS. To determine the physical performance measures associated with LS, the threshold values for discriminating individuals with and without LS, and the odds ratio of LS according to performance greater than or less than these thresholds in middle-aged and older Japanese women. Participants were 126 Japanese women (mean age = 61.8 years). Locomotive syndrome was defined as a score of 16 or more on the 25-question Geriatric Locomotive Function Scale. Physical performance was evaluated using grip strength, unipedal stance time with eyes open, seated toe-touch, and normal and fast 6-m walk time (6 MWT). Variables were compared between LS and non-LS groups. Fourteen participants (11.1%) were classed as having LS. Unipedal stance time, normal 6 MWT, and fast 6 MWT were significantly different between the 2 groups. The LS group had a shorter unipedal stance time and a longer normal and fast 6 MWT than the non-LS group. For these 3 variables, the area under the receiver operating characteristic curve was greater than 0.7, and the threshold for discriminating the non-LS and LS groups was 15 s for unipedal stance time, 4.8 s for normal 6 MWT and 3.6 s for fast 6 MWT. These variables were entered into a multiple logistic regression analysis, which indicated that unipedal stance time less than 15 s was significantly related to LS (odds ratio = 8.46; P < .01). Unipedal stance time was the physical performance measure that was most strongly associated with LS. This measure may be useful for early detection of LS.

Adapting Logistics Models to a Microcomputer for Interface with Computer-Aided Design Systems.

DTIC Science & Technology

1984-09-01

32654 32654 32654 32654 32654 1 LS AFRRF2 -1 32654 32654 32654 32654 32654 1 LS AFRDII -1 32654 32654 32654 32654 32654 1 LS AFRDI2 -1 32654 ... 32654 32654 32654 32654 1 LS AFRMEI -1 32654 32654 32654 32654 32654 1 LS AFRME2 -1 32654 32654 32654 32654 32654 1

Luminescent threat: toxicity of light stick attractors used in pelagic fishery

PubMed Central

de Oliveira, Tiago Franco; da Silva, Amanda Lucila Medeiros; de Moura, Rafaela Alves; Bagattini, Raquel; de Oliveira, Antonio Anax Falcão; de Medeiros, Marisa Helena Gennari; Di Mascio, Paolo; de Arruda Campos, Ivan Pérsio; Barretto, Fabiano Prado; Bechara, Etelvino José Henriques; de Melo Loureiro, Ana Paula

2014-01-01

Light sticks (LS) are sources of chemiluminescence commonly used in pelagic fishery, where hundreds are discarded and reach the shores. Residents from fishing villages report an improper use of LS contents on the skin. Given the scarce information regarding LS toxicity, the effects of LS solutions in cell cultures were evaluated herein. Loss of viability, cell cycle changes and DNA fragmentation were observed in HepG2 cell line and skin fibroblasts. A non-cytotoxic LS concentration increased the occurrence of the mutagenic lesion 1,N6-εdAdo in HepG2 DNA by three-fold. Additionally, in vitro incubations of spent LS contents with DNA generated dGuo-LS adducts, whose structure elucidation revealed the presence of a reactive chlorinated product. In conclusion, the LS contents were found to be highly cyto- and genotoxic. Our data indicate an urgent need for LS waste management guidelines and for adequate information regarding toxic outcomes that may arise from human exposure. PMID:24942522

Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer

DTIC Science & Technology

2005-04-01

associates with pro- teins that include RBP5, a subunit shared by RNA polymerases I, II , and Ill, an RBP5 binding protein called unconventional prefoldin ...of a large multiprotein complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin ...dithiothreitol; GRIP, glucocorticoid re- ceptor Interacting p rotein; HA, hemagglutinin; MMTV, mouse mamm ary tumor virus ; PAIS, partial AIS; SDS

Lateral septum growth hormone secretagogue receptor affects food intake and motivation for sucrose reinforcement.

PubMed

Terrill, Sarah J; Wall, Kaylee D; Medina, Nelson D; Maske, Calyn B; Williams, Diana L

2018-03-28

The hormone ghrelin promotes eating and is widely considered to be a hunger signal. Ghrelin receptors, growth hormone secretagogue receptors (GHSRs), are found in a number of specific regions throughout the brain, including the lateral septum (LS), an area not traditionally associated with the control of feeding. Here we investigated whether GHSRs in the LS play a role in the control of food intake. We examined the feeding effects of ghrelin and the GHSR antagonists ([D-Lys3]-GHRP-6 and JMV 2959), at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS ghrelin significantly increased chow intake during the mid-light phase, suggesting that pharmacologic activation of LS GHSRs promotes feeding. Conversely, GHSR antagonist delivered to the LS shortly before dark onset significantly reduced chow intake. These data support the hypothesis that exogenous and endogenous stimulation of GHSRs in the LS influence feeding. Ghrelin is known to affect motivation for food, and the dorsal subdivision of LS (dLS) has been shown to play a role in motivation. Thus, we investigated the role of dLS GHSRs in motivation for food reward by examining operant responding for sucrose on a progressive ratio (PR) schedule. Intra-dLS ghrelin increased PR responding for sucrose, while blockade of LS GHSRs did not affect responding in either a fed or fasted state. Together these findings for the first time substantiate the LS as a site of action for ghrelin signaling in the control of food intake.

Pulmonary Toxicity Study of Lunar and Martian Dust Simulants Intratracheally Instilled in Mice

NASA Technical Reports Server (NTRS)

Lam, Chiu-Wing; James, John T.; Latch, John A.; Holian, A.; McCluskey, R.

2000-01-01

NASA is contemplating sending humans to Mars and the Moon for further exploration. The properties of Hawaiian and Californian volcanic ashes allow them to be used to simulate Martian and lunar dusts, respectively. NASA laboratories use these dust simulants to test performance of hardware destined for Martian or lunar environments. Workers in these test facilities are exposed to low levels of these dusts. The present study was conducted to investigate the toxicity of these dust simulants. Particles of respirable-size ranges of lunar simulant (LS), Martian simulant (MS), TiO2 (negative control) and quartz (positive control) were each intratracheally instilled (saline as vehicle) to groups of 4 mice (C57BL, male, 2-3 month old) at a single treatment of 1 (Hi dose) or 0.1 (Lo dose) mg/mouse. The lungs were harvested at the end of 7 days or 90 days for histopathological examination. Lungs of the LS-Lo groups had no evidence of inflammation, edema or fibrosis. The LS-Hi-7d group had mild to moderate acute inflammation, and neutrophilic and lymphocytic infiltration; the LS-Hi-90d group showed signs of chronic inflammation and some fibrosis. Lungs of the MS-Lo-7d group revealed mild inflammation and neutrophilic and lymphocytic infiltration; the MS-Lo-90d group showed mild fibrosis and particle-laden macrophages (PLM). Lungs of the MS-Hi-7d group demonstrated mild to moderate inflammation and large foci of PLM; the MS-Hi-90d group showed chronic mild to moderate inflammation and fibrosis. To mimic the effects of the oxidative and reactive properties of Martian soil surface, groups of mice were exposed to ozone (3 hour at 0.5 ppm) prior to MS dust instillation. Lung lesions in the MS group were more severe with the pretreatment. The results for the negative and positive controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic insults to the lungs were TiO2

Variability of the martian seasonal CO2 cap extent over eight Mars Years

NASA Astrophysics Data System (ADS)

Piqueux, Sylvain; Kleinböhl, Armin; Hayne, Paul O.; Kass, David M.; Schofield, John T.; McCleese, Daniel J.

2015-05-01

We present eight Mars Years of nearly continuous tracking of the CO2 seasonal cap edges from Mars Year (MY) 24 to 31 using Mars Global Surveyor (MGS) Thermal Emission Spectrometer (TES) and Mars Reconnaissance Orbiter (MRO) Mars Climate Sounder (MCS) thermal infrared data. Spatial and temporal resolutions are 1 pixel per degree and 10°Ls (aerocentric longitude of the Sun). The seasonal caps are defined as the regions where the diurnal radiometric temperature variations at ∼32 μm wavelength do not exceed 5 K. With this definition, terrains with small areal fraction of defrosted regolith able to experience measurable diurnal temperature cycles are not mapped as part of the cap. This technique is adequate to distinguish CO2 from H2O ices, and effective during the polar night or under low illumination conditions. The present analysis answers outstanding questions stemming from fragmented observations at visible wavelengths: (1) the previously sparsely documented growth of the North seasonal caps (160° < Ls < 270°) is shown to be repeatable within 1-2° equivalent latitude, and monotonic over the MY 24-31 time period; high repeatability is observed during the retreat of the caps in non-dusty years (∼1° or less equivalent latitude); (2) the MY 25 storm does not seem to have impacted the growth rate, maximal extents, or recession rate of the North seasonal caps, whereas the MY 28 dust storm clearly sped up the recession of the cap (∼2° smaller on average after the storm, during the recession, compared to other years); (3) during non-dusty years, the growth of the South seasonal cap (350° < Ls < 100°) presents noticeable variability (up to ∼4° equivalent latitude near Ls = 20°) with a maximum extent reached near Ls = 90°; (4) the retreat of the Southern seasonal cap (100° < Ls < 310°) exhibits large inter-annual variability, especially near 190° < Ls < 220°; (5) the recession of the MY 25 South seasonal cap is significantly accelerated during the equinox global dust storm, with surface temperatures suggesting increased patchiness or enhanced dust mantling on the CO2 ice. These results suggest that atmospheric temperatures and dust loading are the primary source of variability in an otherwise remarkably repeatable cycle of seasonal cap growth and recession.

Immunohistochemical analyses of alpha1 and alpha3 Na+/K+-ATPase subunit expression in medulloblastomas.

PubMed

Suñol, Mariona; Cusi, Victoria; Cruz, Ofelia; Kiss, Robert; Lefranc, Florence

2011-03-01

The levels of expression of the α1 and α3 subunits of the Na(+)/K(+)-ATPase (the NaK sodium pump) in medulloblastomas are unclear. This study investigated the expression of the NaK subunits using immunohistochemical methods in 29 medulloblastomas including 23 classic, three large-cell/anaplastic and three nodular/desmoplastic medulloblastomas, as well as in three atypical teratoid/rhabdoid tumors (AT/RTs). There was overexpression of the α1 or α3 NaK subunits in more than half of the medulloblastomas and atypical AT/RTs, with about one-third of these tumours displaying overexpression of both subunits. These preliminary data suggest that targeting these subunits in AT/RTs and medulloblastomas that overexpress these proteins may lead to therapeutic benefit. These findings warrant confirmation in larger numbers of patients than those used in this study. Moreover, it should be determined whether inhibition of the α1/α3 NaK subunits can be integrated into the risk stratification schemes already in use for medulloblastoma patients.

DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

PubMed Central

Scornik, Fabiana S.; Bucciero, Ronald S.; Wu, Yuesheng; Selga, Elisabet; Bosch Calero, Cristina; Brugada, Ramon

2013-01-01

The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK) channel activator with selectivity for its β1- or β4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming α-subunit and a smooth muscle-abundant regulatory β1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the β1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its α-subunit. We studied BK channels from wild-type and transgenic β1-knockout mice in excised patches. BK channels from brain arteries, with or without the β1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) (∼30 μM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as −300 mV. This “sweet spot” for persistent activation is independent of Ca2+ and/or the β1–4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. PMID:23542916

Inter-subunit electrostatic interactions in ferritin molecule: comparison with inter-molecular interactions in crystals

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Hogyoku, Michiru; Nagayama, Kuniaki

1996-10-01

We evaluated the contribution of electrostatic interactions to the stability of macromolecular assembly in a horse L ferritin molecule composed of 24 subunits and the three-dimensional crystal of the ferritin molecules with numerical calculation of Poisson-Boltzmann equation based on dielectric model. The calculation showed that the electrostatic energy both favors the assembly of the 24 subunits and the crystalline assembly of the ferritin molecules (i.e., 24-mers). Short-range interactions less than 5 Å such as salt bridges and hydrogen bonds were important for both the subunit assembly and the crystalline assembly. To elucidate the strong stabilization by electrostatic interactions in both the ferritin 24-mer and its crystal, we analyzed the contribution of individual atoms. It revealed that the stabilization was arising from buried salt bridges or hydrogen bonds, which yielded more than 5 kcal/mol in some interactions. These large electrostatic stabilization and also the unexpected small ionic strength dependence was different from those of bovine pancreatic trypsin inhibitor (BPTI) orthorhombic and pig-insulin cubic crystals previously calculated. We also evaluated changes of the accessible surface area (ASA) and hydration free energy in accordance with the process of the subunit assembly. The change of hydration free energy, which was very large (i.e. ˜ + 100 kcal/mol/subunit) and unfavorable for the assembly, was proportional to the electrostatic hydration energy (i.e. Born energy change in hydration process). Hydrophobic groups were likely to appear more frequently than hydrophilic groups at the subunit interfaces. These results suggest that the molecular structure of the ferritin 24-mer and the crystal structure of the 24-mers were both stabilized by local electrostatic interactions, in particular. We view protein crystals as an extension of the protein oligomer to an infinite number of subunits association.

Subunit mass fingerprinting of mitochondrial complex I.

PubMed

Morgner, Nina; Zickermann, Volker; Kerscher, Stefan; Wittig, Ilka; Abdrakhmanova, Albina; Barth, Hans-Dieter; Brutschy, Bernhard; Brandt, Ulrich

2008-10-01

We have employed laser induced liquid bead ion desorption (LILBID) mass spectrometry to determine the total mass and to study the subunit composition of respiratory chain complex I from Yarrowia lipolytica. Using 5-10 pmol of purified complex I, we could assign all 40 known subunits of this membrane bound multiprotein complex to peaks in LILBID subunit fingerprint spectra by comparing predicted protein masses to observed ion masses. Notably, even the highly hydrophobic subunits encoded by the mitochondrial genome were easily detectable. Moreover, the LILBID approach allowed us to spot and correct several errors in the genome-derived protein sequences of complex I subunits. Typically, the masses of the individual subunits as determined by LILBID mass spectrometry were within 100 Da of the predicted values. For the first time, we demonstrate that LILBID spectrometry can be successfully applied to a complex I band eluted from a blue-native polyacrylamide gel, making small amounts of large multiprotein complexes accessible for subunit mass fingerprint analysis even if they are membrane bound. Thus, the LILBID subunit mass fingerprint method will be of great value for efficient proteomic analysis of complex I and its assembly intermediates, as well as of other water soluble and membrane bound multiprotein complexes.

The New Cosmos

ERIC Educational Resources Information Center

McCray, Richard A.

1970-01-01

Discusses areas of modern astronomy that owe their development largely to nonoptical radiation: radio, infrared, ultraviolet, and x-ray radiation. Indicates new observations favor the big-bang" model of the universe, for it is now established that the earth is expanding at a measurable rate. Annotated bibliography. (LS)

Dynamic effect of leachate recirculation on batch mode solid state anaerobic digestion: Influence of recirculated volume, leachate to substrate ratio and recirculation periodicity.

PubMed

Degueurce, Axelle; Trémier, Anne; Peu, Pascal

2016-09-01

Performances of batch mode solid state anaerobic digestion (SSAD) were investigated through several leachate recirculation strategies. Three parameters were shown to particularly influence methane production rates (MPR) and methane yields: the length of the interval between two recirculation events, the leachate to substrate (L:S) ratio and the volume of leachate recirculated. A central composite factor design was used to determine the influence of each parameter on methane production. Results showed that lengthening the interval between two recirculation events reduced methane yield. This effect can be counteracted by recirculating a large volume of leachate at a low L:S ratio. Steady methane production can be obtained by recirculating small amounts of leachate, and by lengthening the interval between two recirculations, regardless of the L:S ratio. However, several combinations of these parameters led to similar performances meaning that leachate recirculation practices can be modified as required by the specific constraints SSAD plants configurations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increasing the starch content and grain weight of common wheat by overexpression of the cytosolic AGPase large subunit gene.

PubMed

Kang, Guozhang; Liu, Guoqin; Peng, Xiaoqi; Wei, Liting; Wang, Chenyang; Zhu, YunJi; Ma, Ying; Jiang, Yumei; Guo, Tiancai

2013-12-01

ADP-glucose pyrophosphorylase (AGPase) catalyzes the first committed step of starch synthesis. AGPase is a heterotetramer composed of two large subunits and two small subunits, has cytosolic and plastidial isoforms, and is detected mainly in the cytosol of endosperm in cereal crops. To investigate the effects of AGPase cytosolic large subunit gene (LSU I) on starch biosynthesis in higher plant, in this study, a TaLSU I gene from wheat was overexpressed under the control of an endosperm-specific promoter in a wheat cultivar (Yumai 34). PCR, Southern blot, and real-time RT-PCR analyses indicated that the transgene was integrated into the genome of transgenic plants and was overexpressed in their progeny. The overexpression of the TaLSU I gene remarkably enhanced AGPase activity, endosperm starch weight, grain number per spike, and single grain weight. Therefore, we conclude that overexpression of the TaLSU I gene enhances the starch biosynthesis in endosperm of wheat grains, having potential applications in wheat breeding to develop a high-yield wheat cultivar with high starch weight and kernel weight. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Adsorption of sophorolipid biosurfactants on their own and mixed with sodium dodecyl benzene sulfonate, at the air/water interface.

PubMed

Chen, Minglei; Dong, Chuchuan; Penfold, Jeff; Thomas, Robert K; Smyth, Thomas J P; Perfumo, Amedea; Marchant, Roger; Banat, Ibrahim M; Stevenson, Paul; Parry, Alyn; Tucker, Ian; Campbell, Richard A

2011-07-19

The adsorption of the lactonic (LS) and acidic (AS) forms of sophorolipid and their mixtures with the anionic surfactant sodium dodecyl benzene sulfonate (LAS) has been measured at the air/water interface by neutron reflectivity, NR. The AS and LS sophorolipids adsorb with Langmuir-like adsorption isotherms. The more hydrophobic LS is more surface active than the AS, with a lower critical micellar concentration, CMC, and stronger surface adsorption, with an area/molecule ∼70 Å(2) compared with 85 Å(2) for the AS. The acidic sophorolipid shows a maximum in its adsorption at the CMC which appears to be associated with a mixture of different isomeric forms. The binary LS/AS and LS/LAS mixtures show a strong surface partitioning in favor of the more surface active and hydrophobic LS component but are nevertheless consistent with ideal mixing at the interface. In contrast, the surface composition of the AS/LAS mixture is much closer to the solution composition, but the surface mixing is nonideal and can be accounted for by regular solution theory, RST. In the AS/LS/LAS ternary mixtures, the surface adsorption is dominated by the sophorolipid, and especially the LS component, in a way that is not consistent with the observations for the binary mixtures. The extreme partitioning in favor of the sophorolipid for the LAS/LS/AS (1:2) mixtures is attributed to a reduction in the packing constraints at the surface due to the AS component. Measurements of the surface structure reveal a compact monolayer for LS and a narrow solvent region for LS, LS/AS, and LS/LAS mixtures, consistent with the more hydrophobic nature of the LS component. The results highlight the importance of the relative packing constraints on the adsorption of multicomponent mixtures, and the impact of the lactonic form of the sophorolipid on the adsorption of the sophorolipid/LAS mixtures.

Investigation of the influence of lineaments, lineament intersections and geology on groundwater yield in the basement complex terrain of Ondo State, Southwestern Nigeria

NASA Astrophysics Data System (ADS)

Akinluyi, Francis O.; Olorunfemi, Martins O.; Bayowa, Oyelowo G.

2018-03-01

The influence of lineaments, lineament intersections and geology on the groundwater yield of the basement terrain of Ondo State was investigated using optical remote sensing data, Aster DEM, geology, and borehole yield data. Landsat-7 ETM+ and Aster DEM were processed to generate composite lineament map. The study area was traversed by five (5) main lineament populations trending N-S, NE-SW, E-W, ENE-WSW, NNW-SSE. Boreholes sited on lineament exhibited a yield range of between 0.8 and 1.28 l/s with an average yield of 1.04 l/s. Boreholes sited close to lineament gave groundwater yield values of between 0.5 and 1.28 l/s and an average yield of 1 l/s, while boreholes located outside lineament gave groundwater yield range of between 0.2 and 1.26 l/s with an average yield of 0.98 l/s. The investigation of the hydrogeological characteristics of the lithologies by superimposing the yield data showed average yield of 0.98 l/s for migmatite gneiss biotite granite undifferentiated (M), 1.01 l/s for porphyritic granite (OGp), 1.03 l/s for medium- to coarse-grained (OGe), 1.17 l/s for pelitic schist undifferentiated (Su), 1.24 l/s for quartz schist and quartzite (Eq), 1.12 l/s for older granite undifferentiated (OGu), 0.5 l/s for slightly migmatised medium-grained granite-gneiss (gg) and 1.23 l/s for fine-grained flaggy quartzite and schists (Sf). The study concluded that borehole data located on or near lineaments or at intersection of lineaments gave higher yields more than those located before lineaments or outside lineaments, while quartz schist and quartzite exhibited the highest average groundwater yield of all the lithological units.

Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome–associated PTPN11 mutation

PubMed Central

Marin, Talita M.; Keith, Kimberly; Davies, Benjamin; Conner, David A.; Guha, Prajna; Kalaitzidis, Demetrios; Wu, Xue; Lauriol, Jessica; Wang, Bo; Bauer, Michael; Bronson, Roderick; Franchini, Kleber G.; Neel, Benjamin G.; Kontaridis, Maria I.

2011-01-01

LEOPARD syndrome (LS) is an autosomal dominant “RASopathy” that manifests with congenital heart disease. Nearly all cases of LS are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11) gene that encodes the SH2 domain-containing PTP-2 (SHP2). RASopathies typically affect components of the RAS/MAPK pathway, yet it remains unclear how PTPN11 mutations alter cellular signaling to produce LS phenotypes. We therefore generated knockin mice harboring the Ptpn11 mutation Y279C, one of the most common LS alleles. Ptpn11Y279C/+ (LS/+) mice recapitulated the human disorder, with short stature, craniofacial dysmorphia, and morphologic, histologic, echocardiographic, and molecular evidence of hypertrophic cardiomyopathy (HCM). Heart and/or cardiomyocyte lysates from LS/+ mice showed enhanced binding of Shp2 to Irs1, decreased Shp2 catalytic activity, and abrogated agonist-evoked Erk/Mapk signaling. LS/+ mice also exhibited increased basal and agonist-induced Akt and mTor activity. The cardiac defects in LS/+ mice were completely reversed by treatment with rapamycin, an inhibitor of mTOR. Our results demonstrate that LS mutations have dominant-negative effects in vivo, identify enhanced mTOR activity as critical for causing LS-associated HCM, and suggest that TOR inhibitors be considered for treatment of HCM in LS patients. PMID:21339643

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.

PubMed

Vaughan, Ashley M; Mikolajczak, Sebastian A; Wilson, Elizabeth M; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H I

2012-10-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.

Topography of succinate dehydrogenase in the mitochondrial inner membrane. A study using limited proteolysis and immunoblotting.

PubMed Central

Clarkson, G H; Neagle, J; Lindsay, J G

1991-01-01

The arrangement of the large (70,000-Mr) and small (30,000-Mr) subunits of succinate dehydrogenase in the mitochondrial inner membrane was investigated by immunoblot analysis of bovine heart mitochondria (right-side-out, outer membrane disrupted) or submitochondrial particles (inside-out) that had been subjected to surface-specific proteolysis. Both subunits were resistant to proteinase treatment provided that the integrity of the inner membrane was preserved, suggesting that neither subunit is exposed at the cytoplasmic surface of the membrane. The bulk of the small subunit appears to protrude into the matrix compartment, since the 30,000-Mr polypeptide is degraded extensively during limited proteolysis of submitochondrial particles without the appearance of an immunologically reactive membrane-associated fragment: moreover, a soluble 27,000-Mr peptide derived from this subunit is observed transiently on incubation with trypsin. Similar data obtained from the large subunit suggest that this polypeptide interacts with the matrix side of the inner membrane via two distinct domains; these are detected as stable membrane-associated fragments of 32,000 Mr and 27,000 Mr after treatment of submitochondrial particles with papain or proteinase K, although the 27,000-Mr fragment can be degraded further to low-Mr peptides with trypsin or alpha-chymotrypsin. A stable 32,000-34,000-Mr fragment is generated by a variety of specific and non-specific proteinases, indicating that it may be embedded largely within the lipid bilayer, or is inaccessible to proteolytic attack owing to its proximity to the surface of the intact membrane, possibly interacting with the hydrophobic membrane anchoring polypeptides of the succinate: ubiquinone reductase complex. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:1996968

Utility of the Lone Star Retractor System in Microsurgical Carotid Endarterectomy.

PubMed

Toyota, Shingo; Kumagai, Tetsuya; Goto, Tetsu; Mori, Kanji; Taki, Takuyu

2017-05-01

The retractor system is an important device in carotid endarterectomy (CEA). We applied the Lone Star (LS) Retractor System, which is a self-retaining retractor originally designed for improved visualization in many other surgical fields, in microsurgical CEA. The LS disposal retractor (14.1 cm × 14.1 cm) and LS elastic stays (5-mm sharp hook) were used as a retractor system in 38 consecutive CEAs. Using the LS retractor system, a shallow operative field could be obtained by lifting up the connective tissue surrounding the deep structures hooked by the LS elastic stays. The LS elastic stays were quick and easy to handle in the microsurgical operative field. There were no complications using the LS retractor system. The application of the LS retractor system in microsurgical CEA is feasible. An additional merit is that it is single use. Copyright © 2017 Elsevier Inc. All rights reserved.

Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations

PubMed Central

Skjaerven, Lars; Grant, Barry; Muga, Arturo; Teigen, Knut; McCammon, J. Andrew; Reuter, Nathalie; Martinez, Aurora

2011-01-01

GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant “opening” of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition. PMID:21423709

Mixing properties of coaxial jets with large velocity ratios and large inverse density ratios

NASA Astrophysics Data System (ADS)

Alexander Schumaker, S.; Driscoll, James F.

2012-05-01

An experimental study was conducted to better understand the mixing properties of coaxial jets as several parameters were systematically varied, including the velocity ratio, density ratio, and the Reynolds number. Diameters of the inner and outer jet were also varied. Coaxial jets are commonly used to mix fluids due to the simplicity of their geometry and the rapid mixing that they provide. A measure of the overall mixing efficiency is the stoichiometric mixing length (Ls), which is the distance along the jet centerline where the two fluids have mixed to some desired concentration, which was selected to be the stoichiometric concentration for H2/O2 and CH4/O2 in this case. For 56 cases, the profiles of mean mixture fraction, rms mixture fraction fluctuations (unmixedness), and Ls were measured using acetone planar laser induced fluorescence diagnostics. Results were compared to three mixing models. The entrainment model of Villermaux and Rehab showed good agreement with the data, indicating that the proper non-dimensional scaling parameter is the momentum flux ratio M. The work extends the existing database of coaxial jet scalar mixing properties because it considers the specific regime of large values of both the velocity ratio and the inverse density ratio, which is the regime in which rocket injectors operate. Also the work focuses on the mixing up to Ls where previous work focused on the mixing up to the end of the inner core. The Reynolds numbers achieved for a number of cases were considerably larger than previous gas mixing studies, which insures that the jet exit boundary conditions are fully turbulent.

X-ray diffraction and reflectivity validation of the depletion attraction in the competitive adsorption of lung surfactant and albumin.

PubMed

Stenger, Patrick C; Wu, Guohui; Miller, Chad E; Chi, Eva Y; Frey, Shelli L; Lee, Ka Yee C; Majewski, Jaroslaw; Kjaer, Kristian; Zasadzinski, Joseph A

2009-08-05

Lung surfactant (LS) and albumin compete for the air-water interface when both are present in solution. Equilibrium favors LS because it has a lower equilibrium surface pressure, but the smaller albumin is kinetically favored by faster diffusion. Albumin at the interface creates an energy barrier to subsequent LS adsorption that can be overcome by the depletion attraction induced by polyethylene glycol (PEG) in solution. A combination of grazing incidence x-ray diffraction (GIXD), x-ray reflectivity (XR), and pressure-area isotherms provides molecular-resolution information on the location and configuration of LS, albumin, and polymer. XR shows an average electron density similar to that of albumin at low surface pressures, whereas GIXD shows a heterogeneous interface with coexisting LS and albumin domains at higher surface pressures. Albumin induces a slightly larger lattice spacing and greater molecular tilt, similar in effect to a small decrease in the surface pressure. XR shows that adding PEG to the LS-albumin subphase restores the characteristic LS electron density profile at the interface, and confirms that PEG is depleted near the interface. GIXD shows the same LS Bragg peaks and Bragg rods as on a pristine interface, but with a more compact lattice corresponding to a small increase in the surface pressure. These results confirm that albumin adsorption creates a physical barrier that inhibits LS adsorption, and that PEG in the subphase generates a depletion attraction between the LS aggregates and the interface that enhances LS adsorption without substantially altering the structure or properties of the LS monolayer.

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences

PubMed Central

Ronninger, Marcus; Shchetynsky, Klementy; Franke, Andre; Nöthen, Markus M.; Müller-Quernheim, Joachim; Schreiber, Stefan; Adrianto, Indra; Karakaya, Bekir; van Moorsel, Coline H. M.; Navratilova, Zdenka; Kolek, Vitezslav; Rybicki, Benjamin A.; Iannuzzi, Michael C.; Petrek, Martin; Grutters, Jan C.; Montgomery, Courtney; Fischer, Annegret; Eklund, Anders; Padyukov, Leonid; Grunewald, Johan

2016-01-01

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren’s syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis. Objectives: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. Methods: An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects. Measurements and Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS–associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated. Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region. PMID:26651848

Prognostic value of the combined use of transient elastography and fibrotest in patients with chronic hepatitis B.

PubMed

Park, Mi Sung; Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Shin, Seung Hwan; Kang, Wonseok; Moon, Chansoo; Han, Kwang-Hyub

2015-02-01

Liver stiffness (LS) measurement using transient elastography and the FibroTest (FT) are alternatives to liver biopsy (LB) in assessing liver fibrosis. We investigated the prognostic role of the combined use of LS and FT in predicting liver-related events (LREs) in patients with chronic hepatitis B (CHB). Consecutive patients with CHB who underwent LB, along with LS and FT on the same day were recruited. LRE was defined as hepatic decompensation, hepatocellular carcinoma (HCC) or liver-related death. A total of 151 patients (86 male) were analyzed. During follow-up (median 59.9 months), overall 18 (11.9%) patients experienced LREs. The areas under receiver-operating characteristic curves of LS, FT, LS + FT and LS × FT in predicting LRE were 0.701, 0.668, 0.702 and 0.741 respectively. After adjusting for age and histological fibrosis staging, significant variables in univariate analysis (both P < 0.05), LS + FT and LS × FT were independent predictors of LREs with hazard ratios (HRs) of 1.080 and 1.126 (all P < 0.05) respectively. When subjects were divided into three groups according to quartile stratification (low quartile, interquartile and high quartile) using LS + FT and LS × FT, cumulative LRE development rate significantly increased with a corresponding increase in value among three groups respectively (log-rank test, all P < 0.05). The combined use of LS and FT significantly predicted forthcoming LRE development, but with only a slight additional benefit compared to LS or FT alone. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Phytochrome Regulates Gibberellin Biosynthesis during Germination of Photoblastic Lettuce Seeds1

PubMed Central

Toyomasu, Tomonobu; Kawaide, Hiroshi; Mitsuhashi, Wataru; Inoue, Yasunori; Kamiya, Yuji

1998-01-01

Germination of lettuce (Lactuca sativa L.) seed is regulated by phytochrome. The requirement for red light is circumvented by the application of gibberellin (GA). We have previously shown that the endogenous content of GA1, the main bioactive GA in lettuce seeds, increases after red-light treatment. To clarify which step of GA1 synthesis is regulated by phytochrome, cDNAs encoding GA 20-oxidases (Ls20ox1 and Ls20ox2, for L. sativa GA 20-oxidase) and 3β-hydroxylases (Ls3h1 and Ls3h2 for L. sativa GA 3β-hydroxylase) were isolated from lettuce seeds by reverse-transcription polymerase chain reaction. Functional analysis of recombinant proteins expressed in Escherichia coli confirmed that the Ls20ox and Ls3h encode GA 20-oxidases and 3β-hydroxylases, respectively. Northern-blot analysis showed that Ls3h1 expression was dramatically induced by red-light treatment within 2 h, and that this effect was canceled by a subsequent far-red-light treatment. Ls3h2 mRNA was not detected in seeds that had been allowed to imbibe under any light conditions. Expression of the two Ls20ox genes was induced by initial imbibition alone in the dark. The level of Ls20ox2 mRNA decreased after the red-light treatment, whereas that of Ls20ox1 was unaffected by light. These results suggest that red light promotes GA1 synthesis in lettuce seeds by inducing Ls3h1 expression via phytochrome action. PMID:9847128

Simultaneous Analysis of the Behavioural Phenotype, Physical Factors, and Parenting Stress in People with Cornelia De Lange Syndrome

ERIC Educational Resources Information Center

Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

2009-01-01

Background: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical…

Subunit interface dynamics in hexadecameric rubisco.

PubMed

van Lun, Michiel; van der Spoel, David; Andersson, Inger

2011-09-02

Ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) plays an important role in the global carbon cycle as a hub for biomass. Rubisco catalyzes not only the carboxylation of RuBP with carbon dioxide but also a competing oxygenation reaction of RuBP with a negative impact on photosynthetic yield. The functional active site is built from two large (L) subunits that form a dimer. The octameric core of four L(2) dimers is held at each end by a cluster of four small (S) subunits, forming a hexadecamer. Each large subunit contacts more than one S subunit. These interactions exploit the dynamic flexibility of Rubisco, which we address in this study. Here, we describe seven different types of interfaces of hexadecameric Rubisco. We have analyzed these interfaces with respect to the size of the interface area and the number of polar interactions, including salt bridges and hydrogen bonds in a variety of Rubisco enzymes from different organisms and different kingdoms of life, including the Rubisco-like proteins. We have also performed molecular dynamics simulations of Rubisco from Chlamydomonas reinhardtii and mutants thereof. From our computational analyses, we propose structural checkpoints of the S subunit to ensure the functionality and/or assembly of the Rubisco holoenzyme. These checkpoints appear to fine-tune the dynamics of the enzyme in a way that could influence enzyme performance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.

PubMed

Hirawake, H; Taniwaki, M; Tamura, A; Kojima, S; Kita, K

1997-01-01

Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms. In this study, the amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome b in human liver complex II were deduced from cDNAs isolated by homology probing with mixed primers for the polymerase chain reaction. The mature cybL and cybS contain 140 and 103 amino acids, respectively, and show little similarity to the amino acid sequences of the subunits from other species in contrast to the highly conserved features of the flavoprotein (Fp) subunit and iron-sulfur protein (Ip) subunit. From hydrophobicity analysis, both cybL and cybS appear to have three transmembrane segments, indicating their role as membrane-anchors for the enzyme complex. Histidine residues, which are possible heme axial ligands in cytochrome b of complex II, were found in the second transmembrane segment of each subunit. The genes for cybL (SDHC) and cybS (SDHD) were mapped to chromosome 1q21 and 11q23, respectively by fluorescent in situ hybridization (FISH).

Tokamak Equilibrium Reconstruction with MSE-LS Data in DIII-D

NASA Astrophysics Data System (ADS)

Lao, L.; Grierson, B.; Burrell, K. H.

2016-10-01

Equilibrium analysis of plasmas in DIII-D using EFIT was upgraded to include the internal magnetic field determined from spectroscopic measurements of motional-Stark-effect line-splitting (MSE-LS). MSE-LS provides measurements of the magnitude of the internal magnetic field, rather than the pitch angle as provided by MSE line-polarization (MSE-LP) used in most tokamaks to date. EFIT MSE-LS reconstruction algorithms and verifications are described. The capability of MSE-LS to provide significant constraints on the equilibrium analysis is evaluated. Reconstruction results with both synthetic and experimental MSE-LS data from 10 DIII-D discharges run over a range of conditions show that MSE-LS measurements can contribute to the equilibrium reconstruction of pressure and safety factor profiles. Adequate MSE-LS measurement accuracy and number of spatial locations are necessary. The 7 available experimental measurements provide useful additional constraints when used with other internal measurements. Using MSE-LS as the only internal measurement yields less current profile information. Work supported by the PPPL Subcontract S013769-F and US DOE under DE-FC02-04ER54698.

Evaluation of high specific-heat ceramic for regenerator use at temperatures between 2-30 K

NASA Technical Reports Server (NTRS)

Lawless, W. N.

1979-01-01

Specific heat, thermal conductivity (both in the range 2-30 K), and microhardness data were measured on the ceramics labelled LS-8, LS-8A, and LS-8A doped with CsI, SnCl2, and AgCl. A work hardened sample of LS-8A was also studied in an effort to determine the feasibility of using these types of LS-8 materials to replace Pb spheres in the regenerator of the JPL cryocooler. The LS-8A materials are all more than an order of magnitude harder than Pb, and the dopants do not significantly improve the hardness. However, the SnCl2 dopant has a remarkable effect in improving the specific heat and thermal conductivity of LS-8A. The SnCl2 doping level which maximized the regenerator enthalpy change in going from an unloaded to a loaded condition was found to be 0.2 percent SnCl2 in LS-8A. It was also found that the enthalpy change for a regenerator employing the LS-8A material is more than three times larger than for the Pb spheres case. The use of rods, rather than spheres, of optimally doped LS-8A in regenerators is discussed.

A protein with an inactive pterin-4a-carbinolamine dehydratase domain is required for Rubisco biogenesis in plants.

PubMed

Feiz, Leila; Williams-Carrier, Rosalind; Belcher, Susan; Montano, Monica; Barkan, Alice; Stern, David B

2014-12-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a critical role in sustaining life by catalysis of carbon fixation in the Calvin-Benson pathway. Incomplete knowledge of the assembly pathway of chloroplast Rubisco has hampered efforts to fully delineate the enzyme's properties, or seek improved catalytic characteristics via directed evolution. Here we report that a Mu transposon insertion in the Zea mays (maize) gene encoding a chloroplast dimerization co-factor of hepatocyte nuclear factor 1 (DCoH)/pterin-4α-carbinolamine dehydratases (PCD)-like protein is the causative mutation in a seedling-lethal, Rubisco-deficient mutant named Rubisco accumulation factor 2 (raf2-1). In raf2 mutants newly synthesized Rubisco large subunit accumulates in a high-molecular weight complex, the formation of which requires a specific chaperonin 60-kDa isoform. Analogous observations had been made previously with maize mutants lacking the Rubisco biogenesis proteins RAF1 and BSD2. Chemical cross-linking of maize leaves followed by immunoprecipitation with antibodies to RAF2, RAF1 or BSD2 demonstrated co-immunoprecipitation of each with Rubisco small subunit, and to a lesser extent, co-immunoprecipitation with Rubisco large subunit. We propose that RAF2, RAF1 and BSD2 form transient complexes with the Rubisco small subunit, which in turn assembles with the large subunit as it is released from chaperonins. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

D1/D2 domain of large-subunit ribosomal DNA for differentiation of Orpinomyces spp.

PubMed

Dagar, Sumit S; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K

2011-09-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation.

Photoinduced reduction of the medial FeS center in the hydrogenase small subunit HupS from Nostoc punctiforme.

PubMed

Raleiras, Patrícia; Hammarström, Leif; Lindblad, Peter; Styring, Stenbjörn; Magnuson, Ann

2015-07-01

The small subunit from the NiFe uptake hydrogenase, HupSL, in the cyanobacterium Nostoc punctiforme ATCC 29133, has been isolated in the absence of the large subunit (P. Raleiras, P. Kellers, P. Lindblad, S. Styring, A. Magnuson, J. Biol. Chem. 288 (2013) 18,345-18,352). Here, we have used flash photolysis to reduce the iron-sulfur clusters in the isolated small subunit, HupS. We used ascorbate as electron donor to the photogenerated excited state of Ru(II)-trisbipyridine (Ru(bpy)3), to generate Ru(I)(bpy)3 as reducing agent. Our results show that the isolated small subunit can be reduced by the Ru(I)(bpy)3 generated through flash photolysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Ribulose-1,5-Bis-Phosphate Carboxylase/Oxygenase Accumulation Factor1 Is Required for Holoenzyme Assembly in Maize[C][W

PubMed Central

Feiz, Leila; Williams-Carrier, Rosalind; Wostrikoff, Katia; Belcher, Susan; Barkan, Alice; Stern, David B.

2012-01-01

Most life is ultimately sustained by photosynthesis and its rate-limiting carbon fixing enzyme, ribulose-1,5-bis-phosphate carboxylase/oxygenase (Rubisco). Although the structurally comparable cyanobacterial Rubisco is amenable to in vitro assembly, the higher plant enzyme has been refractory to such manipulation due to poor understanding of its assembly pathway. Here, we report the identification of a chloroplast protein required for Rubisco accumulation in maize (Zea mays), RUBISCO ACCUMULATION FACTOR1 (RAF1), which lacks any characterized functional domains. Maize lines lacking RAF1 due to Mutator transposon insertions are Rubisco deficient and seedling lethal. Analysis of transcripts and proteins showed that Rubisco large subunit synthesis in raf1 plants is not compromised; however, newly synthesized Rubisco large subunit appears in a high molecular weight form whose accumulation requires a specific chaperonin 60 isoform. Gel filtration analysis and blue native gels showed that endogenous and recombinant RAF1 are trimeric; however, following in vivo cross-linking, RAF1 copurifies with Rubisco large subunit, suggesting that they interact weakly or transiently. RAF1 is predominantly expressed in bundle sheath chloroplasts, consistent with a Rubisco accumulation function. Our results support the hypothesis that RAF1 acts during Rubisco assembly by releasing and/or sequestering the large subunit from chaperonins early in the assembly process. PMID:22942379

Characterization of a Novel Rieske-Type Alkane Monooxygenase System in Pusillimonas sp. Strain T7-7

PubMed Central

Li, Ping; Wang, Lei

2013-01-01

The cold-tolerant bacterium Pusillimonas sp. strain T7-7 is able to utilize diesel oils (C5 to C30 alkanes) as a sole carbon and energy source. In the present study, bioinformatics, proteomics, and real-time reverse transcriptase PCR approaches were used to identify the alkane hydroxylation system present in this bacterium. This system is composed of a Rieske-type monooxygenase, a ferredoxin, and an NADH-dependent reductase. The function of the monooxygenase, which consists of one large (46.711 kDa) and one small (15.355 kDa) subunit, was further studied using in vitro biochemical analysis and in vivo heterologous functional complementation tests. The purified large subunit of the monooxygenase was able to oxidize alkanes ranging from pentane (C5) to tetracosane (C24) using NADH as a cofactor, with greatest activity on the C15 substrate. The large subunit also showed activity on several alkane derivatives, including nitromethane and methane sulfonic acid, but it did not act on any aromatic hydrocarbons. The optimal reaction condition of the large subunit is pH 7.5 at 30°C. Fe2+ can enhance the activity of the enzyme evidently. This is the first time that an alkane monooxygenase system belonging to the Rieske non-heme iron oxygenase family has been identified in a bacterium. PMID:23417490

Sinophysis and Pseudophalacroma are distantly related to typical Dinophysoid dinoflagellates (Dinophysales, Dinophyceae).

PubMed

Gómez, Fernando; Moreira, David; López-García, Purificación

2012-01-01

Dinophysoid dinoflagellates are usually considered a large monophyletic group. Large subunit and small subunit (SSU) rDNA phylogenies suggest a basal position for Amphisoleniaceae (Amphisolenia,Triposolenia) with respect to two sister groups, one containing most Phalacroma species plus Oxyphysis and the other Dinophysis,Ornithocercus, Dinophysoid dinoflagellates are usually considered a large monophyletic group. Large subunit and small subunit (SSU) rDNA phylogenies suggest a basal position for Amphisoleniaceae (Amphisolenia,Triposolenia) with respect to two sister groups, one containing most Phalacroma species plus Oxyphysis and the other Dinophysis,Ornithocercus, Histioneis,Citharistes and some Phalacroma species. We provide here new SSU rDNA sequences of Pseudophalacroma (pelagic) and Sinophysis (the only benthic dinophysoid genus). Molecular phylogenies support that they are very divergent with respect to the main clade of Dinophysales. Additional molecular markers of these two key genera are needed to elucidate the evolutionary relations among the dinophysoid dinoflagellates. Histioneis,Citharistes and some Phalacroma species. We provide here new SSU rDNA sequences of Pseudophalacroma (pelagic) and Sinophysis (the only benthic dinophysoid genus). Molecular phylogenies support that they are very divergent with respect to the main clade of Dinophysales. Additional molecular markers of these two key genera are needed to elucidate the evolutionary relations among the dinophysoid dinoflagellates. © 2011 The Author(s) Journal of Eukaryotic Microbiology © 2011 International Society of Protistologists.

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

Furuta, H.; Imura, A.; Furuta, Y.

Recently, technique of Gadolinium loaded liquid scintillator (Gd-LS) for reactor neutrino oscillation experiments has attracted attention as a monitor of reactor operation and 'nuclear Gain (GA)' for IAEA safeguards. For the practical use, R and D of the 1 ton class compact detector, which is measurable above ground, is necessary. Especially, it is important to reduce much amount of fast neutron background induced by cosmic muons with data analysis for the measurement above ground. We developed a prototype of the Gd-LS detector with 200 L of the target volume, which has Pulse Shape Discrimination (PSD) ability for the fast neutronmore » reduction with data analysis. Usually, it is well known that it is difficult to keep high fast neutron reduction power of PSD with the large volume size such as the neutrino reactor monitor. We evaluated the PSD ability of our prototype with real fast neutrons induced by the muons in our laboratory above ground, and we could confirm to keep the high fast neutron reduction power with even our large detector size. (authors)« less

Structural changes of homodimers in the PDB.

PubMed

Koike, Ryotaro; Amemiya, Takayuki; Horii, Tatsuya; Ota, Motonori

2018-04-01

Protein complexes are involved in various biological phenomena. These complexes are intrinsically flexible, and structural changes are essential to their functions. To perform a large-scale automated analysis of the structural changes of complexes, we combined two original methods. An application, SCPC, compares two structures of protein complexes and decides the match of binding mode. Another application, Motion Tree, identifies rigid-body motions in various sizes and magnitude from the two structural complexes with the same binding mode. This approach was applied to all available homodimers in the Protein Data Bank (PDB). We defined two complex-specific motions: interface motion and subunit-spanning motion. In the former, each subunit of a complex constitutes a rigid body, and the relative movement between subunits occurs at the interface. In the latter, structural parts from distinct subunits constitute a rigid body, providing the relative movement spanning subunits. All structural changes were classified and examined. It was revealed that the complex-specific motions were common in the homodimers, detected in around 40% of families. The dimeric interfaces were likely to be small and flat for interface motion, while large and rugged for subunit-spanning motion. Interface motion was accompanied by a drastic change in contacts at the interface, while the change in the subunit-spanning motion was moderate. These results indicate that the interface properties of homodimers correlated with the type of complex-specific motion. The study demonstrates that the pipeline of SCPC and Motion Tree is useful for the massive analysis of structural change of protein complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

PRISM: A Novel Research Tool to Assess the Prevalence of Pseudobulbar Affect Symptoms across Neurological Conditions

PubMed Central

Brooks, Benjamin Rix; Crumpacker, David; Fellus, Jonathan; Kantor, Daniel; Kaye, Randall E.

2013-01-01

Background Pseudobulbar affect (PBA) is a neurological condition characterized by involuntary, sudden, and frequent episodes of laughing and/or crying, which can be socially disabling. Although PBA occurs secondary to many neurological conditions, with an estimated United States (US) prevalence of up to 2 million persons, it is thought to be under-recognized and undertreated. The PBA Registry Series (PRISM) was established to provide additional PBA symptom prevalence data in a large, representative US sample of patients with neurological conditions known to be associated with PBA. Methods Participating clinicians were asked to enroll ≥20 consenting patients with any of 6 conditions: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI). Patients (or their caregivers) completed the Center for Neurologic Study−Lability Scale (CNS-LS) and an 11-point scale measuring impact of the neurological condition on the patient’s quality of life (QOL). Presence of PBA symptoms was defined as a CNS−LS score ≥13. Demographic data and current use of antidepressant or antipsychotic medications were also recorded. Results PRISM enrolled 5290 patients. More than one third of patients (n = 1944; 36.7%) had a CNS-LS score ≥13, suggesting PBA symptoms. The mean (SD) score measuring impact of neurological condition on QOL was significantly higher (worse) in patients with CNS-LS ≥13 vs <13 (6.7 [2.5] vs. 4.7 [3.1], respectively; P<0.0001 two-sample t-test). A greater percentage of patients with CNS−LS ≥13 versus <13 were using antidepressant/antipsychotic medications (53.0% vs 35.4%, respectively; P<0.0001, chi-square test). Conclusions Data from PRISM, the largest clinic-based study to assess PBA symptom prevalence, showed that PBA symptoms were common among patients with diverse neurological conditions. Higher CNS−LS scores were associated with impaired QOL and greater use of antipsychotic/antidepressant medications. These data underscore a need for greater awareness, recognition, and diagnosis of PBA. PMID:23991068

A Modified LS+AR Model to Improve the Accuracy of the Short-term Polar Motion Prediction

NASA Astrophysics Data System (ADS)

Wang, Z. W.; Wang, Q. X.; Ding, Y. Q.; Zhang, J. J.; Liu, S. S.

2017-03-01

There are two problems of the LS (Least Squares)+AR (AutoRegressive) model in polar motion forecast: the inner residual value of LS fitting is reasonable, but the residual value of LS extrapolation is poor; and the LS fitting residual sequence is non-linear. It is unsuitable to establish an AR model for the residual sequence to be forecasted, based on the residual sequence before forecast epoch. In this paper, we make solution to those two problems with two steps. First, restrictions are added to the two endpoints of LS fitting data to fix them on the LS fitting curve. Therefore, the fitting values next to the two endpoints are very close to the observation values. Secondly, we select the interpolation residual sequence of an inward LS fitting curve, which has a similar variation trend as the LS extrapolation residual sequence, as the modeling object of AR for the residual forecast. Calculation examples show that this solution can effectively improve the short-term polar motion prediction accuracy by the LS+AR model. In addition, the comparison results of the forecast models of RLS (Robustified Least Squares)+AR, RLS+ARIMA (AutoRegressive Integrated Moving Average), and LS+ANN (Artificial Neural Network) confirm the feasibility and effectiveness of the solution for the polar motion forecast. The results, especially for the polar motion forecast in the 1-10 days, show that the forecast accuracy of the proposed model can reach the world level.

Consistency of physicians' legal standard and personal judgments of competency in patients with Alzheimer's disease.

PubMed

Marson, D C; Earnst, K S; Jamil, F; Bartolucci, A; Harrell, L E

2000-08-01

To investigate the consistency of physician judgments of treatment consent capacity (competency) for patients with Alzheimer's disease (AD) when specific legal standards (LS) for competency are used, and to identify the LS most clinically relevant to experienced physicians. Control and AD patient participants were videotaped being administered a measure of capacity to consent to medical treatment. Study physicians viewed videotapes of these assessments individually and made competency judgments for each participant under different LS followed by their own personal judgment of competency. A university medical center. Participants were 10 older controls and 21 patients with AD (10 with mild and 11 with moderate AD). Five physicians with experience assessing the competency of AD patients were recruited from the geriatric psychiatry, geriatric medicine, and neurology services of a university medical center. The 31 participants were videotaped performing on a measure of treatment consent capacity (Capacity to Consent to Treatment Instrument) (CCTI). The CCTI consists of two clinical vignettes (A-neoplasm and B-cardiac) that test competency under five LS. Vignette A and B assessments were videotaped separately for each participant (total videotapes for sample = 62). Each study physician viewed each videotaped vignette individually, made judgments under each of the LS (competent or incompetent), and then made his/her own personal competency judgment. Physicians were blinded to participant diagnosis. Within participant group, consistency of physician judgments was evaluated across LS and personal judgments using percentage agreement and kappa. Agreement between personal and LS judgments for the AD group was evaluated for each physician using logistic regression. As expected, physicians as a group generally demonstrated very high percentage agreement in their LS and personal competency judgments for the control group. For the AD group, mean percentage judgment agreement among physicians ranged from a high of 84% (LS1) (evidencing a treatment choice) to a low of 67% (LS3) (appreciating consequences of treatment choice). Mean percentage agreement for personal competency judgments was 76%. For the AD sample, kappa analyses for physicians as a group demonstrated significant agreement not attributable to chance for LS5 (understanding treatment situation/choices) (k = 0.57, P = .001), LS4 (providing rational reasons for treatment choice) (k = 0.39, P = .04), and also for personal judgments (k = 0.48, P = .009). Analysis of LS judgment agreement within physician indicated that physicians applied the LS as discrete standards. Within-physician and for the AD sample, personal competency judgments were associated significantly with judgments on LS5 (P = .001), LS4 (P = .004), and LS3 (P < .04). Experienced physicians demonstrated significant agreement assessing competency in AD patients when judgments were based upon specific legal standards. Personal competency judgments of physicians showed a substantially higher level of agreement than found in a previous study, where specific LS were not used. These results suggest that consistency of physician competency judgments can be enhanced if they are guided by knowledge of specific LS. Physicians' personal competency judgments were most closely associated with comprehension and reasoning LS, the most conservative and clinically appropriate standards for deciding competency.

LS3MIP (v1.0) Contribution to CMIP6: The Land Surface, Snow and Soil Moisture Model Intercomparison Project Aims, Setup and Expected Outcome.

NASA Technical Reports Server (NTRS)

Van Den Hurk, Bart; Kim, Hyungjun; Krinner, Gerhard; Seneviratne, Sonia I.; Derksen, Chris; Oki, Taikan; Douville, Herve; Colin, Jeanne; Ducharne, Agnes; Cheruy, Frederique;

LS3MIP (v1.0) contribution to CMIP6: the Land Surface, Snow and Soilmoisture Model Intercomparison Project – aims, setup and expected outcome

DOE PAGES

van den Hurk, Bart; Kim, Hyungjun; Krinner, Gerhard; ...

2016-08-24

The Land Surface, Snow and Soil Moisture Model Intercomparison Project (LS3MIP) is designed to provide a comprehensive assessment of land surface, snow and soil moisture feedbacks on climate variability and climate change, and to diagnose systematic biases in the land modules of current Earth system models (ESMs). Furthermore, the solid and liquid water stored at the land surface has a large influence on the regional climate, its variability and predictability, including effects on the energy, water and carbon cycles. Notably, snow and soil moisture affect surface radiation and flux partitioning properties, moisture storage and land surface memory. They both stronglymore » affect atmospheric conditions, in particular surface air temperature and precipitation, but also large-scale circulation patterns. But, models show divergent responses and representations of these feedbacks as well as systematic biases in the underlying processes. LS3MIP will provide the means to quantify the associated uncertainties and better constrain climate change projections, which is of particular interest for highly vulnerable regions (densely populated areas, agricultural regions, the Arctic, semi-arid and other sensitive terrestrial ecosystems). The experiments are subdivided in two components, the first addressing systematic land biases in offline mode (“LMIP”, building upon the 3rd phase of Global Soil Wetness Project; GSWP3) and the second addressing land feedbacks attributed to soil moisture and snow in an integrated framework (“LFMIP”, building upon the GLACE-CMIP blueprint).« less

LS3MIP (v1.0) contribution to CMIP6: the Land Surface, Snow and Soilmoisture Model Intercomparison Project – aims, setup and expected outcome

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

van den Hurk, Bart; Kim, Hyungjun; Krinner, Gerhard

The Land Surface, Snow and Soil Moisture Model Intercomparison Project (LS3MIP) is designed to provide a comprehensive assessment of land surface, snow and soil moisture feedbacks on climate variability and climate change, and to diagnose systematic biases in the land modules of current Earth system models (ESMs). Furthermore, the solid and liquid water stored at the land surface has a large influence on the regional climate, its variability and predictability, including effects on the energy, water and carbon cycles. Notably, snow and soil moisture affect surface radiation and flux partitioning properties, moisture storage and land surface memory. They both stronglymore » affect atmospheric conditions, in particular surface air temperature and precipitation, but also large-scale circulation patterns. But, models show divergent responses and representations of these feedbacks as well as systematic biases in the underlying processes. LS3MIP will provide the means to quantify the associated uncertainties and better constrain climate change projections, which is of particular interest for highly vulnerable regions (densely populated areas, agricultural regions, the Arctic, semi-arid and other sensitive terrestrial ecosystems). The experiments are subdivided in two components, the first addressing systematic land biases in offline mode (“LMIP”, building upon the 3rd phase of Global Soil Wetness Project; GSWP3) and the second addressing land feedbacks attributed to soil moisture and snow in an integrated framework (“LFMIP”, building upon the GLACE-CMIP blueprint).« less

Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome.

PubMed

Bourla, Dan Haim; Laron, Zvi; Snir, Moshe; Lilos, Pearl; Weinberger, Dov; Axer-Siegel, Ruth

2006-07-01

To evaluate the ocular dimensions in patients with primary growth hormone receptor insensitivity (Laron syndrome [LS]) and to study the effect of supplemental insulinlike growth factor I (IGF-I) on ocular growth. Retrospective case series. Twelve patients with LS, 8 untreated (LS group) and 4 treated (LS-T group) with supplemental IGF-I, and 30 healthy controls. Ocular dimensions and refraction were measured, and a full ophthalmologic examination was performed. Differences in the average ocular dimension data among IGF-I-treated patients, untreated ones, and controls. The average axial length of eyes in the LS group was 21.94 mm (standard deviation [SD], 0.81). Corresponding values for the LS-T and control group eyes were 22.53 mm (SD, 1.74) and 23.20 mm (SD, 1.35) respectively. The average anterior chamber depth of eyes in the LS group was 2.55 mm (SD, 0.26). Corresponding values for eyes in the LS-T and control groups were 3.48 mm (SD, 0.09) and 3.84 mm (SD, 0.16) respectively. The average lens thickness of eyes in the LS group was 4.56 mm (SD, 0.36). Corresponding values for the LS-T and control groups were 3.77 mm (SD, 0.23) and 3.51 mm (SD, 0.25), respectively. The average corneal curvature of eyes in the LS group was 46.9 diopters (D) (SD, 2.32). Corresponding values for the LS-T and control groups were 47.6 D (SD, 2.83) and 44.4 D (SD, 1.5), respectively. Insulinlike growth factor I seems to be an important regulator of ocular growth as documented in patients with primary growth hormone insensitivity. The mechanism of this observation should be investigated further.

Chromosome Rearrangements in Cornelia de Lange Syndrome (CdLS): Report of a der(3)t(3;12)(p25.3;p13.3) in Two Half Sibs With Features of CdLS and Review of Reported CdLS Cases With Chromosome Rearrangements

PubMed Central

DeScipio, Cheryl; Kaur, Maninder; Yaeger, Dinah; Innis, Jeffrey W.; Spinner, Nancy B.; Jackson, Laird G.; Krantz, Ian D.

2016-01-01

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited disorder characterized by multisystem involvement, cognitive delay, limb defects, and characteristic facial features. Recently, mutations in NIPBL have been found in ~50% of individuals with CdLS. Numerous chromosomal rearrangements have been reported in individuals with CdLS. These rearrangements may be causative of a CdLS phenotype, result in a phenocopy, or be unrelated to the observed phenotype. We describe two half siblings with a der(3)t(3;12)(p25.3;p13.3) chromosomal rearrangement, clinical features resembling CdLS, and phenotypic overlap with the del(3)(p25) phenotype. Region-specific BAC probes were used to fine-map the breakpoint region by fluorescence in situ hybridization (FISH). FISH analysis places the chromosome 3 breakpoint distal to RP11-115G3 on 3p25.3; the chromosome 12 breakpoint is distal to BAC RP11-88D16 on 12p13.3. A review of published cases of terminal 3p deletions and terminal 12p duplications indicates that the findings in these siblings are consistent with the del(3)(p25) phenotype. Given the phenotypic overlap with CdLS, we have reviewed the reported cases of chromosomal rearrangements involved in CdLS to better elucidate other potential loci that could harbor additional CdLS genes. Additionally, to identify chromosome rearrangements, genome-wide array comparative genomic hybridization (CGH) was performed on eight individuals with typical CdLS and without identifiable deletion or mutation of NIPBL. No pathologic rearrangements were identified. PMID:16075459

LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity

PubMed Central

Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

2014-01-01

LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders. PMID:25288766

Role of lateral septum glucagon-like peptide 1 receptors in food intake.

PubMed

Terrill, Sarah J; Jackson, Christine M; Greene, Hayden E; Lilly, Nicole; Maske, Calyn B; Vallejo, Samantha; Williams, Diana L

2016-07-01

Hindbrain glucagon-like peptide 1 (GLP-1) neurons project to numerous forebrain areas, including the lateral septum (LS). Using a fluorescently labeled GLP-1 receptor (GLP-1R) agonist, Exendin 4 (Ex4), we demonstrated GLP-1 receptor binding throughout the rat LS. We examined the feeding effects of Ex4 and the GLP-1R antagonist Exendin (9-39) (Ex9) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS Ex4 suppressed overnight chow and high-fat diet (HFD) intake, and Ex9 increased chow and HFD intake relative to vehicle. During 2-h tests, intra-LS Ex9 significantly increased 0.25 M sucrose and 4% corn oil. Ex4 can cause nausea, but intra-LS administration of Ex4 did not induce pica. Furthermore, intra-LS Ex4 had no effect on anxiety-like behavior in the elevated plus maze. We investigated the role of LS GLP-1R in motivation for food by examining operant responding for sucrose on a progressive ratio (PR) schedule, with and without a nutrient preload to maximize GLP-1 neuron activation. The preload strongly suppressed PR responding, but blockade of GLP-1R in the intermediate subdivision of the LS did not affect motivation for sucrose under either load condition. The ability of the nutrient load to suppress subsequent chow intake was significantly attenuated by intermediate LS Ex9 treatment. By contrast, blockade of GLP-1R in the dorsal subdivision of the LS increased both PR responding and overnight chow intake. Together, these studies suggest that endogenous activity of GLP-1R in the LS influence feeding, and dLS GLP-1Rs, in particular, play a role in motivation. Copyright © 2016 the American Physiological Society.

LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.

PubMed

Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

2014-10-21

LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders.

Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

PubMed Central

Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Kijun; Han, Kwang-Hyub

2016-01-01

Abstract Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB). Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan–Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves. The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791–0.807 vs 0.691–0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB-4 significantly enhanced the prognostic performance compared with the use of FIB-4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05). LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies. PMID:27196449

Role of lateral septum glucagon-like peptide 1 receptors in food intake

PubMed Central

Jackson, Christine M.; Greene, Hayden E.; Lilly, Nicole; Maske, Calyn B.; Vallejo, Samantha

2016-01-01

Hindbrain glucagon-like peptide 1 (GLP-1) neurons project to numerous forebrain areas, including the lateral septum (LS). Using a fluorescently labeled GLP-1 receptor (GLP-1R) agonist, Exendin 4 (Ex4), we demonstrated GLP-1 receptor binding throughout the rat LS. We examined the feeding effects of Ex4 and the GLP-1R antagonist Exendin (9–39) (Ex9) at doses subthreshold for effect when delivered to the lateral ventricle. Intra-LS Ex4 suppressed overnight chow and high-fat diet (HFD) intake, and Ex9 increased chow and HFD intake relative to vehicle. During 2-h tests, intra-LS Ex9 significantly increased 0.25 M sucrose and 4% corn oil. Ex4 can cause nausea, but intra-LS administration of Ex4 did not induce pica. Furthermore, intra-LS Ex4 had no effect on anxiety-like behavior in the elevated plus maze. We investigated the role of LS GLP-1R in motivation for food by examining operant responding for sucrose on a progressive ratio (PR) schedule, with and without a nutrient preload to maximize GLP-1 neuron activation. The preload strongly suppressed PR responding, but blockade of GLP-1R in the intermediate subdivision of the LS did not affect motivation for sucrose under either load condition. The ability of the nutrient load to suppress subsequent chow intake was significantly attenuated by intermediate LS Ex9 treatment. By contrast, blockade of GLP-1R in the dorsal subdivision of the LS increased both PR responding and overnight chow intake. Together, these studies suggest that endogenous activity of GLP-1R in the LS influence feeding, and dLS GLP-1Rs, in particular, play a role in motivation. PMID:27194565

Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

PubMed

Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Kijun; Han, Kwang-Hyub

2016-05-01

Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB-4 significantly enhanced the prognostic performance compared with the use of FIB-4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies.

Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia.

PubMed

Carlson, J A; Ambros, R; Malfetano, J; Ross, J; Grabowski, R; Lamb, P; Figge, H; Mihm, M C

1998-09-01

The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied. Paraffin sections of vulvar LS, and three controls groups (acute scars, normal vulva, and vulvar lichen simplex chronicus [LSC]) were investigated with a panel of seven tissue markers and for DNA content in areas without vulvar intraepithelial neoplasia (VIN). All published cases to date of vulvar LS associated with SCC were reviewed. Of the cohort of symptomatic vulvar LS patients (mean/median age, 60 years), 9% developed VIN lesions and 21% invasive SCC; symptomatic LS preceded the carcinoma by a mean of 4 years (range, 1 to 23 years). Second and third primary tumors developed in three of these patients. Of the series of 60 patients presenting with vulvar SCCa, the clinical setting and histological features of SCCs associated with LS were significantly distinctive compared with SCCas without LS: SCCs associated with LS occurred in an older age-group (74 v 65 years; P = .01), were located on the clitoris (41% v 5%; P = .003), were of conventional SCCa type (85% v 57%; P = .02), were associated with a prominent fibromyxoid stromal response (46% v 10%; P = .004), were not associated with VIN 3 (SCC in situ) (5% v 67%; P = .02) and diffusely expressed tumor suppressor gene product p53 (43% v 19%; P = .01) and cytokine TGF-beta (33% v 9%; P = .05). The epidermis of vulvar LS was similar to that of acute scars and differed significantly compared with normal vulva with respect to keratinocytic expression of markers to keratin AE 1, involucrin and filaggrin, epidermal thickness (0.13 mm [LS] v 0.05 mm [normal]; P < .03), and proliferative index by PCNA and Mib-1 labeling (53/60 [LS] v 15/19 [normal] per 200 basal cells [bc]; P < .003). Vulvar LS showed significantly higher expression of p53 than all three control groups (80 [LS] v 3 [normal]/44 [acute scar]/28 [LSC] per 200 bc; P < .008), and aneuploidy (33% v diploid controls) in the absence of VIN. Comparing LS with and without associated SCCa found significant increases in age of patients (74 v 66 years; P = .001), and DNA aneuploidy (52% v 11%; P = .0001) and no differences in epidermal thickness, sclerotic thickness, proliferative index, or p53 expression. However, those cases of LS with an aneuploid DNA content showed significantly elevated p53 expression (88 v 60/200 bc; P = .01) and epidermal thickness (0.16 v 0.11 mm; P = .005) compared with LS with a diploid DNA content. Review of published cases supports an association between LS and vulvar SCC. The phenomenon of chronic inflammation and scarring giving rise to carcinoma has been well documented. Vulvar lichen sclerosus (LS) is an inflammatory dermatosis characterized by clinicopathologic persistence and hypocellular fibrosis (sclerosis). A subset of vulvar SCCs is significantly associated with the presence of LS and diffusely express the p53 gene product. Keratinocytes affected by LS show a proliferative phenotype and can exhibit markers of neoplastic progression such as increased p53 expression and DNA aneuploidy. As a chronic scarring inflammatory dermatosis, vulvar LS could act as both "initiator and promoter" of carcinogenesis, explaining the frequent coexistence of these diseases. Because keratinocytes of LS significantly express tumor suppressor gene p53 protein, the p53 gene may be involved early in this proposed pathway of carcinogenesis.

Comparison of complication and conversion rates between robotic-assisted and laparoscopic rectal resection for rectal cancer: which patients and providers could benefit most from robotic-assisted surgery?

PubMed

Ackerman, Stacey J; Daniel, Shoshana; Baik, Rebecca; Liu, Emelline; Mehendale, Shilpa; Tackett, Scott; Hellan, Minia

2018-03-01

To compare (1) complication and (2) conversion rates to open surgery (OS) from laparoscopic surgery (LS) and robotic-assisted surgery (RA) for rectal cancer patients who underwent rectal resection. (3) To identify patient, physician, and hospital predictors of conversion. A US-based database study was conducted utilizing the 2012-2014 Premier Healthcare Data, including rectal cancer patients ≥18 with rectal resection. ICD-9-CM diagnosis and procedural codes were utilized to identify surgical approaches, conversions to OS, and surgical complications. Propensity score matching on patient, surgeon, and hospital level characteristics was used to create comparable groups of RA\\LS patients (n = 533 per group). Predictors of conversion from LS and RA to OS were identified with stepwise logistic regression in the unmatched sample. Post-match results suggested comparable perioperative complication rates (RA 29% vs LS 29%; p = .7784); whereas conversion rates to OS were 12% for RA vs 29% for LS (p < .0001). Colorectal surgeons (RA 9% vs LS 23%), general surgeons (RA 13% vs LS 35%), and smaller bed-size hospitals (RA 14% vs LS 33%) have reduced conversion rates for RA vs LS (p < .0001). Statistically significant predictors of conversion included LS, non-colorectal surgeon, and smaller bed-size hospitals. Retrospective observational study limitations apply. Analysis of the hospital administrative database was subject to the data captured in the database and the accuracy of coding. Propensity score matching limitations apply. RA and LS groups were balanced with respect to measured patient, surgeon, and hospital characteristics. Compared to LS, RA offers a higher probability of completing a successful minimally invasive surgery for rectal cancer patients undergoing rectal resection without exacerbating complications. Male, obese, or moderately-to-severely ill patients had higher conversion rates. While colorectal surgeons had lower conversion rates from RA than LS, the reduction was magnified for general surgeons and smaller bed-size hospitals.

Locomotive syndrome is associated not only with physical capacity but also degree of depression.

PubMed

Ikemoto, Tatsunori; Inoue, Masayuki; Nakata, Masatoshi; Miyagawa, Hirofumi; Shimo, Kazuhiro; Wakabayashi, Toshiko; Arai, Young-Chang P; Ushida, Takahiro

2016-05-01

Reports of locomotive syndrome (LS) have recently been increasing. Although physical performance measures for LS have been well investigated to date, studies including psychiatric assessment are still scarce. Hence, the aim of this study was to investigate both physical and mental parameters in relation to presence and severity of LS using a 25-question geriatric locomotive function scale (GLFS-25) questionnaire. 150 elderly people aged over 60 years who were members of our physical-fitness center and displayed well-being were enrolled in this study. Firstly, using the previously determined GLFS-25 cutoff value (=16 points), subjects were divided into two groups accordingly: an LS and non-LS group in order to compare each parameter (age, grip strength, timed-up-and-go test (TUG), one-leg standing with eye open, back muscle and leg muscle strength, degree of depression and cognitive impairment) between the groups using the Mann-Whitney U-test followed by multiple logistic regression analysis. Secondly, a multiple linear regression was conducted to determine which variables showed the strongest correlation with severity of LS. We confirmed 110 people for non-LS (73%) and 40 people for LS using the GLFS-25 cutoff value. Comparative analysis between LS and non-LS revealed significant differences in parameters in age, grip strength, TUG, one-leg standing, back muscle strength and degree of depression (p < 0.006, after Bonferroni correction). Multiple logistic regression revealed that functional decline in grip strength, TUG and one-leg standing and degree of depression were significantly associated with LS. On the other hand, we observed that the significant contributors towards the GLFS-25 score were TUG and degree of depression in multiple linear regression analysis. The results indicate that LS is associated with not only the capacity of physical performance but also the degree of depression although most participants fell under the criteria of LS. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Overcoming Rapid Inactivation of Lung Surfactant: Analogies Between Competitive Adsorption and Colloid Stability

PubMed Central

Zasadzinski, Joseph A.; Stenger, Patrick C.; Shieh, Ian; Dhar, Prajnaparamita

2009-01-01

Lung surfactant (LS) is a mixture of lipids and proteins that line the alveolar air-liquid interface, lowering the interfacial tension to levels that make breathing possible. In acute respiratory distress syndrome (ARDS), inactivation of LS is believed to play an important role in the development and severity of the disease. This review examines the competitive adsorption of LS and surface-active contaminants, such as serum proteins, present in the alveolar fluids of ARDS patients, and how this competitive adsorption can cause normal amounts of otherwise normal LS to be ineffective in lowering the interfacial tension. LS and serum proteins compete for the air-water interface when both are present in solution either in the alveolar fluids or in a Langmuir trough. Equilibrium favors LS as it has the lower equilibrium surface pressure, but the smaller proteins are kinetically favored over multi-micron LS bilayer aggregates by faster diffusion. If albumin reaches the interface, it creates an energy barrier to subsequent LS adsorption that slows or prevents the adsorption of the necessary amounts of LS required to lower surface tension. This process can be understood in terms of classic colloid stability theory in which an energy barrier to diffusion stabilizes colloidal suspensions against aggregation. This analogy provides qualitative and quantitative predictions regarding the origin of surfactant inactivation. An important corollary is that any additive that promotes colloid coagulation, such as increased electrolyte concentration, multivalent ions, hydrophilic non-adsorbing polymers such as PEG, dextran, etc. or polyelectrolytes such as chitosan, added to LS, also promotes LS adsorption in the presence of serum proteins and helps reverse surfactant inactivation. The theory provides quantitative tools to determine the optimal concentration of these additives and suggests that multiple additives may have a synergistic effect. A variety of physical and chemical techniques including isotherms, fluorescence microscopy, electron microscopy and X-ray diffraction show that LS adsorption is enhanced by this mechanism without substantially altering the structure or properties of the LS monolayer. PMID:20026298

Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

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

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

Variations in risk and protective factors for life satisfaction and mental wellbeing with deprivation: a cross-sectional study.

PubMed

Bellis, Mark A; Lowey, Helen; Hughes, Karen; Deacon, Lynn; Stansfield, Jude; Perkins, Clare

2012-07-02

Improving life satisfaction (LS) and mental wellbeing (MWB) is important for better public health. Like other health issues, LS and MWB are closely related to deprivation (i.e. lack of resources). Developing public health measures that reduce inequalities in wellbeing requires an understanding of how factors associated with high and low LS and MWB vary with deprivation. Here, we examine such variations and explore which public health measures are likely to improve wellbeing while reducing related inequalities. A self-administered questionnaire measuring LS and MWB was used with a cross-sectional sample of adults from the North West of England (n = 15,228). Within deprivation tertiles, analyses examined how demographics, health status, employment, relationships and behaviours (alcohol, tobacco, physical exercise) were associated with LS and MWB. Deprivation was strongly related to low LS and MWB with, for instance, 17.1% of the most deprived tertile having low LS compared to 8.9% in the most affluent. After controlling for confounders, across all deprivation tertiles, better self-assessed health status and being in a relationship were protective against low LS and MWB. Unemployment increased risks of low LS across all tertiles but only risks of low MWB in the deprived tertile. For this tertile, South Asian ethnicity and higher levels of exercise were protective against low MWB. In the middle tertile retired individuals had a reduced risk of low MWB and an increased chance of high LS even in comparison to those in employment. Alcohol's impact on LS was limited to the most deprived tertile where heavy drinkers were at most risk of poor outcomes. In this study, positive outcomes for LS and MWB were strongly associated with lower deprivation and good health status. Public health measures already developed to promote these issues are likely to improve LS and MWB. Efforts to increase engagement in exercise are also likely to have positive impacts, particularly in deprived communities. The development of future initiatives that address LS and MWB must take account of variations in their risk and protective factors at different levels of deprivation.

Little evidence for intralocus sexual conflict over the optimal intake of nutrients for life span and reproduction in the black field cricket Teleogryllus commodus.

PubMed

Rapkin, James; Archer, C Ruth; Grant, Charles E; Jensen, Kim; House, Clarissa M; Wilson, Alastair J; Hunt, John

2017-09-01

There is often large divergence in the effects of key nutrients on life span (LS) and reproduction in the sexes, yet nutrient intake is regulated in the same way in males and females given dietary choice. This suggests that the sexes are constrained from feeding to their sex-specific nutritional optima for these traits. Here, we examine the potential for intralocus sexual conflict (IASC) over optimal protein and carbohydrate intake for LS and reproduction to constrain the evolution of sex-specific nutrient regulation in the field cricket, Teleogryllus commodus. We show clear sex differences in the effects of protein and carbohydrate intake on LS and reproduction and strong positive genetic correlations between the sexes for the regulated intake of these nutrients. However, the between-sex additive genetic covariance matrix had very little effect on the predicted evolutionary response of nutrient regulation in the sexes. Thus, IASC appears unlikely to act as an evolutionary constraint on sex-specific nutrient regulation in T. commodus. This finding is supported by clear sexual dimorphism in the regulated intake of these nutrients under dietary choice. However, nutrient regulation did not coincide with the nutritional optima for LS or reproduction in either sex, suggesting that IASC is not completely resolved in T. commodus. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Energy and cost associated with ventilating office buildings in a tropical climate.

PubMed

Rim, Donghyun; Schiavon, Stefano; Nazaroff, William W

2015-01-01

Providing sufficient amounts of outdoor air to occupants is a critical building function for supporting occupant health, well-being and productivity. In tropical climates, high ventilation rates require substantial amounts of energy to cool and dehumidify supply air. This study evaluates the energy consumption and associated cost for thermally conditioning outdoor air provided for building ventilation in tropical climates, considering Singapore as an example locale. We investigated the influence on energy consumption and cost of the following factors: outdoor air temperature and humidity, ventilation rate (L/s per person), indoor air temperature and humidity, air conditioning system coefficient of performance (COP), and cost of electricity. Results show that dehumidification of outdoor air accounts for more than 80% of the energy needed for building ventilation in Singapore's tropical climate. Improved system performance and/or a small increase in the indoor temperature set point would permit relatively large ventilation rates (such as 25 L/s per person) at modest or no cost increment. Overall, even in a thermally demanding tropical climate, the energy cost associated with increasing ventilation rate up to 25 L/s per person is less than 1% of the wages of an office worker in an advanced economy like Singapore's. This result implies that the benefits of increasing outdoor air ventilation rate up to 25 L/s per person--which is suggested to provide for productivity increases, lower sick building syndrome symptom prevalence, and reduced sick leave--can be much larger than the incremental cost of ventilation.

Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints.

PubMed

Rodríguez, Alexander J; Neeman, Teresa; Giles, Aaron G; Mastronardi, Claudio A; Paz Filho, Gilberto

2014-11-01

The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients. A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints in patients with LS not associated with highly active antiretroviral therapy (HAART) use. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis, lipid profile, and hepatic physiology, using an inverse-variance random-effects model. After screening, 12 studies were included for review. Meta-analysis of results from 226 patients showed that LRT decreased fasting glucose [0.75 SMD units (range 0.36-1.13), p=0.0001], HbA1c [0.49 (0.17-0.81), p=0.003], triglycerides [1.00 (0.69-1.31), p<0.00001], total cholesterol [0.62 (0.21-1.02), p=0.003], liver volume [1.06 (0.51-1.61), p=0.0002] and AST [0.41 (0.10-0.73) p=0.01]. In patients with non-HAART LS, LRT improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.

Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers.

PubMed

Tsai, Hui-Ju; Surkan, Pamela J; Yu, Stella M; Caruso, Deanna; Hong, Xiumei; Bartell, Tami R; Wahl, Anastacia D; Sampankanpanich, Claire; Reily, Anne; Zuckerman, Barry S; Wang, Xiaobin

2017-02-01

Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers.We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers.Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers.Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications.

Fucans, but Not Fucomannoglucuronans, Determine the Biological Activities of Sulfated Polysaccharides from Laminaria saccharina Brown Seaweed

PubMed Central

Ushakova, Natalia A.; Preobrazhenskaya, Marina E.; Piccoli, Antonio; Totani, Licia; Ustyuzhanina, Nadezhda E.; Bilan, Maria I.; Usov, Anatolii I.; Grachev, Alexey A.; Morozevich, Galina E.; Berman, Albert E.; Sanderson, Craig J.; Kelly, Maeve; Di Gregorio, Patrizia; Rossi, Cosmo; Tinari, Nicola; Iacobelli, Stefano; Rabinovich, Gabriel A.; Nifantiev, Nikolay E.

2011-01-01

Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed. PMID:21387013

Diverse Roles for Auxiliary Subunits in Phosphorylation-Dependent Regulation of Mammalian Brain Voltage-Gated Potassium Channels

PubMed Central

Vacher, Helene; Trimmer, James S.

2012-01-01

Voltage-gated ion channels are a diverse family of signaling proteins that mediate rapid electrical signaling events. Among these, voltage-gated potassium or Kv channels are the most diverse, in part due to the large number of principal (or α) subunits and auxiliary subunits that can assemble in different combinations to generate Kv channel complexes with distinct structures and functions. The diversity of Kv channels underlies much of the variability in the active properties between different mammalian central neurons, and the dynamic changes that lead to experience-dependent plasticity in intrinsic excitability. Recent studies have revealed that Kv channel α subunits and auxiliary subunits are extensively phosphorylated, contributing to additional structural and functional diversity. Here we highlight recent studies that show that auxiliary subunits exert some of their profound effects on dendritic Kv4 and axonal Kv1 channels through phosphorylation-dependent mechanisms, either due to phosphorylation on the auxiliary subunit itself, or by influencing the extent and/or impact of α subunit phosphorylation. The complex effects of auxiliary subunits and phosphorylation provide a potent mechanism to generate additional diversity in the structure and function of Kv4 and Kv1 channels, as well as allowing for dynamic reversible regulation of these important ion channels. PMID:21822597

Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

PubMed Central

Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

2012-01-01

Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

PubMed Central

Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

2012-01-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

Loss of visceral pain following colorectal distension in an endothelin-3 deficient mouse model of Hirschsprung's disease

PubMed Central

Zagorodnyuk, Vladimir P; Kyloh, Melinda; Nicholas, Sarah; Peiris, Heshan; Brookes, Simon J; Chen, Bao Nan; Spencer, Nick J

2011-01-01

Abstract Endothelin peptides and their endogenous receptors play a major role in nociception in a variety of different organs. They also play an essential role in the development of the enteric nervous system. Mice with deletions of the endothelin-3 gene (lethal spotted mice, ls/ls) develop congenital aganglionosis. However, little is known about how nociception might be affected in the aganglionic rectum of mice deficient in endothelin-3. In this study we investigated changes in spinal afferent innervation and visceral pain transmission from the aganglionic rectum in ls/ls mice. Electromyogram recordings from anaesthetized ls/ls mice revealed a deficit in visceromotor responses arising from the aganglionic colorectum in response to noxious colorectal distension. Loss of visceromotor responses (VMRs) in ls/ls mice was selective, as no reduction in VMRs was detected after stimulation of the bladder or somatic organs. Calcitonin gene related peptide (CGRP) immunoreactivity, retrograde neuronal tracing and extracellular afferent recordings from the aganglionic rectum revealed decreased colorectal spinal innervation, combined with a reduction in mechanosensitivity of rectal afferents. The sensory defect in ls/ls mice is primarily associated with changes in low threshold wide dynamic range rectal afferents. In conclusion, disruption of endothelin 3 gene expression not only affects development and function of the enteric nervous system, but also specific classes of spinal rectal mechanoreceptors, which are required for visceral nociception from the colorectum. PMID:21320883

Acid mine treatment with open limestone channels

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

Ziemkiewicz, P.F.; Brant, D.L.; Skousen, J.G.

1996-12-31

Acid mine drainage (AMD) is often associated with mining of pyritic coal and metal deposits. Typical AMD associated with coal mines in the eastern US can have acidity and iron concentrations ranging from the teens to the thousands of mg/l. Aluminum and manganese can be present in concentrations ranging from zero to the low hundreds of mg/l. Much attention has been devoted to developing inexpensive, limestone (LS)-based systems for treating AMID with little or no maintenance. However, LS tends to coat with metal hydroxides when exposed to AMID in an oxidized state, a process known as {open_quotes}armoring{close_quotes}. It is generallymore » assumed that once armored, LS ceases to neutralize acid. Another problem is that the hydroxides tend to settle into plug the pore spaces in LS beds forcing water to move around rather than through the LS. While both are caused by the precipitation of metal hydroxides, armoring and plugging are two different problems. Plugging of LS pores can be avoided by maintaining a high flushing rate through the LS bed. Armoring, however, occurs regardless of water velocity. This study investigated the influence of armoring on LS solubility and the implications of armoring and plugging on the construction of open (oxidizing) LS channels for treating AMD. We evaluated the AMID treatment performance of armored and unarmored LS in oxidizing environments both in laboratory and field studies.« less

Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics.

PubMed

Drago, Lorenzo; De Vecchi, Elena; Gabrieli, Arianna; De Grandi, Roberta; Toscano, Marco

2015-07-01

The aim of this study was to evaluate probiotic characteristics of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their immunomodulatory activity in asthmatic subjects. Subjects affected by allergic asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth compatibility by a broth compatibility assay. To study the antimicrobial activity of probiotic strains, an agar diffusion assay was performed. Finally, cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and BR03 was determined by means of specific quantitative enzyme-linked immunosorbent assay (ELISA). The growth of some clinical pathogens were slightly inhibited by LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed promising probiotic properties and beneficial immunomodulatory activity that are increased when the 2 strains are used in combination in the same formulation.

Automated Turn-Key Systems in the Library: Prospects and Perils

ERIC Educational Resources Information Center

Brownrigg, Edwin Blake; Bruer, J. Michael

1976-01-01

Problems, issues, and alternatives in designing individual, stand alone systems for servicing selected library operations, with emphasis on problems of integrating these with major automated systems, a new mode of operation called coupling, and strategies for dealing with large amounts of retrospective data. (Author/LS)

Resistivity Problems in Electrostatic Precipitation

ERIC Educational Resources Information Center

White, Harry J.

1974-01-01

The process of electrostatic precipitation has ever-increasing application in more efficient collection of fine particles from industrial air emissions. This article details a large number of new developments in the field. The emphasis is on high resistivity particles which are a common cause of poor precipitator performance. (LS)

Molecular phylogeny of Laetiporus and other brown rot polypore genera in North America

Treesearch

Daniel L. Lindner; Mark T. Banik

2008-01-01

Phylogenetic relationships were investigated among North American species of Laetiporus, Leptoporus, Phaeolus, Pycnoporellus, and Wolfiporia using ITS, nuclear large subunit and mitochondrial small subunit rDNA sequences. Members of these genera have poroid hymenophores, simple septate hyphae and cause brown rots in a variety of...

D1/D2 Domain of Large-Subunit Ribosomal DNA for Differentiation of Orpinomyces spp.▿

PubMed Central

Dagar, Sumit S.; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K.

2011-01-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation. PMID:21784906

Sequence data for two large-subunit rRNA genes from an Asian strain of Alexandrium catenella.

PubMed Central

Yeung, P K; Kong, K F; Wong, F T; Wong, J T

1996-01-01

PCR generated two distinct products from a toxic isolate of Alexandrium catenella, which had been taken from Dai Ya Bay (southern China), by using primers for large-subunit rRNA. This pattern is distinct from published data for North American Alexandrium species. Sequences of the two products suggest that the smaller was generated by a deletion event. Single-cell PCR generated the same pattern, confirming that the two products were not the results from different individuals. PMID:8900010

A descriptive study of the utilization of physical therapy for postoperative rehabilitation in patients undergoing surgery for lumbar radiculopathy.

PubMed

Louw, Adriaan; Puentedura, Emilio J; Diener, Ina

2016-11-01

To determine the referral patterns, utilization and indications for postoperative physical therapy (PT) for lumbar radiculopathy. At least 50 % of patients following lumbar surgery (LS) for radiculopathy are referred for PT to address postoperative pain and disability. Very little is known regarding factors following LS that predict referral to PT, patient perceptions, satisfaction of postoperative PT and predictors of success for PT following LS for radiculopathy. Sixty-five patients who underwent LS for radiculopathy completed outcome measures on pain and disability prior to, and 1, 3, 6 and 12 months after LS. They also completed a questionnaire regarding postoperative PT at the 12-month follow-up. The majority of patients (59.32 %) attended PT after LS for an average of 14 visits and rated PT favorably. Forty-five percent of the patients who did not attend PT after LS were of the opinion that they would have benefitted from PT after LS, and 62.5 % of these patients reported the surgeon not discussing postoperative PT after LS. Patients with longer duration of symptoms prior to surgery, with greater leg pain scores 1 month after surgery, and who did not feel as well prepared for surgery at the 1 year follow-up were more likely to receive PT, but this did not result in significantly better outcomes on any measure at any follow-up period and did not predict attendance in PT after LS. There is a need to determine if a subgroup of patients following LS exists who will respond favorably to postoperative PT.

LEGO-NMR spectroscopy: a method to visualize individual subunits in large heteromeric complexes.

PubMed

Mund, Markus; Overbeck, Jan H; Ullmann, Janina; Sprangers, Remco

2013-10-18

Seeing the big picture: Asymmetric macromolecular complexes that are NMR active in only a subset of their subunits can be prepared, thus decreasing NMR spectral complexity. For the hetero heptameric LSm1-7 and LSm2-8 rings NMR spectra of the individual subunits of the complete complex are obtained, showing a conserved RNA binding site. This LEGO-NMR technique makes large asymmetric complexes accessible to detailed NMR spectroscopic studies. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons the Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Stopped-flow studies of changes in fluorescence of 8-anilino-1-naphthalene sulfonic acid caused by magnesium and salt binding to yeast enolase.

PubMed

Brewer, J M

1976-12-11

Stopped-flow studies of magnesium and salt (potassium chloride and acetate) effects on yeast enolase were carried out by following 8-anilino-1-naphthalenesulfonic acid fluorescence changes. The fluorescence changes appear to be largely caused by subunit association and dissociation, though there is evidence in some reactions for large changes in fluorescence occurring within the dead time of the stopped-flow measurements. These data are combined with measurements of initial enzyme activity after incubation in various solvents with or without magnesium to obtain subunit association and dissociation rates. From these, it is concluded that magnesium and the salts act by directly changing the affinities of the subunits for each other, apparently by producing a rapid change in protein conformation.

GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors.

PubMed

Has, Ahmad Tarmizi Che; Chebib, Mary

2018-05-15

GABAA receptors (GABAARs) are members of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which includes nicotinic acetylcholine, glycine, and serotonin (5HT3) receptors [1,2,3,4]. LGICs typically mediate fast synaptic transmission via the movement of ions through channels gated by neurotransmitters, such as acetylcholine for nicotinic receptors and GABA for GABAARs [5]. The term Cys-loop receptors originates from the presence of a conserved disulphide bond (or bridge) which holds together two cysteine amino acids of the loop that forms from the structure of polypeptides in the extracellular domain of the receptor's subunit [6]. GABAARs are pentameric transmembrane protein complexes consisting of five subunits from a variety of polypeptide subunits [7,8]. All of these subunits are pseudo-symmetrically organized in the plane of the membrane, with a Cl--selective channel in the middle of the complex. To date, nineteen GABAAR subunits have been identified and categorized into eight classes, α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3, but their variety is further broadened by the existence of several splice forms for certain subunits (e.g., α6, β2 and γ2) [9,10,11,12]. The subunits within each class have an amino acid sequence homology of 70% or more, whereas those with a sequence homology of 30% or less are grouped into different classes [13,14]. A subunit consists of four transmembrane domains (TM1-TM4), each forming an α-helix; a large extracellular N-terminal domain that incorporates part of the orthosteric agonist/antagonist binding site; a large intracellular loop between the TM3 and TM4; a small intracellular loop between TM1 and TM2; a small extracellular loop between TM2 and TM3; and a C-terminal extracellular domain [15,16]. Each subunit is arranged in such a way as to create principal and complementary interfaces with the other subunits, and in a position such that the TM2 of each subunit forms the wall of the channel pore [17,18,19]. The major subunit combination found in the brain comprises α1, β2 and γ2 subunits with the stoichiometry 2α1:2β2:1γ2 [18,20]. For the GABAA α1β2γ2 receptors, the subunits form a specific arrangement in which α1 and β2 subunits alternate with each other and are connected by a γ2 subunit (Figure A) [16,20,21]. For minor subtypes, different α and β subunits have been detected to co-exist as proven by the existence of GABAARs containing α1α2, α1α3, α1α5, α2α3, α3α5, α4α1, α4α2 and α4α3 in the central nervous system [22,23]. Meanwhile, the same pattern has been detected with β and γ subunits, at least the co-occurrence of β in the same GABAAR as well as γ2 with γ3, indicating that these subunits have the capacity to co-exist with each other [24,25,26]. Since different subunits can actually occur in one receptor, GABAARs are considered to exist in a multi-subunit arrangement, leading to ambiguity in the determination of a receptor's stoichiometry. In this review, we first briefly discuss the different subunit arrangements of α1 and β3 subunits in the binary α1β3 receptors. Then we review the GABAA ε-containing receptors predominantly in terms of the ability of ε subunit to present in different position in the ternary α1β3ε receptors, which introduce distinct populations of receptor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A two-step spin crossover mononuclear iron(II) complex with a [HS-LS-LS] intermediate phase.

PubMed

Bonnet, Sylvestre; Siegler, Maxime A; Costa, José Sánchez; Molnár, Gábor; Bousseksou, Azzedine; Spek, Anthony L; Gamez, Patrick; Reedijk, Jan

2008-11-21

The two-step spin crossover of a new mononuclear iron(ii) complex is studied by magnetic, crystallographic and calorimetric methods revealing two successive first-order phase transitions and an ordered intermediate phase built by the repetition of the unprecedented [HS-LS-LS] motif.

Quantitative 3D determination of self-assembled structures on nanoparticles using small angle neutron scattering.

PubMed

Luo, Zhi; Marson, Domenico; Ong, Quy K; Loiudice, Anna; Kohlbrecher, Joachim; Radulescu, Aurel; Krause-Heuer, Anwen; Darwish, Tamim; Balog, Sandor; Buonsanti, Raffaella; Svergun, Dmitri I; Posocco, Paola; Stellacci, Francesco

2018-04-09

The ligand shell (LS) determines a number of nanoparticles' properties. Nanoparticles' cores can be accurately characterized; yet the structure of the LS, when composed of mixture of molecules, can be described only qualitatively (e.g., patchy, Janus, and random). Here we show that quantitative description of the LS' morphology of monodisperse nanoparticles can be obtained using small-angle neutron scattering (SANS), measured at multiple contrasts, achieved by either ligand or solvent deuteration. Three-dimensional models of the nanoparticles' core and LS are generated using an ab initio reconstruction method. Characteristic length scales extracted from the models are compared with simulations. We also characterize the evolution of the LS upon thermal annealing, and investigate the LS morphology of mixed-ligand copper and silver nanoparticles as well as gold nanoparticles coated with ternary mixtures. Our results suggest that SANS combined with multiphase modeling is a versatile approach for the characterization of nanoparticles' LS.

Implications of High Molecular Divergence of Nuclear rRNA and Phylogenetic Structure for the Dinoflagellate Prorocentrum (Dinophyceae, Prorocentrales).

PubMed

Boopathi, Thangavelu; Faria, Daphne Georgina; Cheon, Ju-Yong; Youn, Seok Hyun; Ki, Jang-Seu

2015-01-01

The small and large nuclear subunit molecular phylogeny of the genus Prorocentrum demonstrated that the species are dichotomized into two clades. These two clades were significantly different (one-factor ANOVA, p < 0.01) with patterns compatible for both small and large subunit Bayesian phylogenetic trees, and for a larger taxon sampled dinoflagellate phylogeny. Evaluation of the molecular divergence levels showed that intraspecies genetic variations were significantly low (t-test, p < 0.05), than those for interspecies variations (> 2.9% and > 26.8% dissimilarity in the small and large subunit [D1/D2], respectively). Based on the calculated molecular divergence, the genus comprises two genetically distinct groups that should be considered as two separate genera, thereby setting the pace for major systematic changes for the genus Prorocentrum sensu Dodge. Moreover, the information presented in this study would be useful for improving species identification, detection of novel clades from environmental samples. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Revitalising Mathematics Classroom Teaching through Lesson Study (LS): A Malaysian Case Study

ERIC Educational Resources Information Center

Lim, Chap Sam; Kor, Liew Kee; Chia, Hui Min

2016-01-01

This paper discusses how implementation of Lesson Study (LS) has brought about evolving changes in the quality of mathematics classroom teaching in one Chinese primary school. The Japanese model of LS was adapted as a teacher professional development to improve mathematics teachers' teaching practices. The LS group consisted of five mathematics…

On Least Squares Fitting Nonlinear Submodels.

ERIC Educational Resources Information Center

Bechtel, Gordon G.

Three simplifying conditions are given for obtaining least squares (LS) estimates for a nonlinear submodel of a linear model. If these are satisfied, and if the subset of nonlinear parameters may be LS fit to the corresponding LS estimates of the linear model, then one attains the desired LS estimates for the entire submodel. Two illustrative…

Leigh syndrome: neuropathology and pathogenesis.

PubMed

Lake, Nicole J; Bird, Matthew J; Isohanni, Pirjo; Paetau, Anders

2015-06-01

Leigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.

In vitro and in vivo activity of LS 4477 and LS 4559, novel analogues of the tubulin binder estramustine.

PubMed

Nicholson, K M; Phillips, R M; Shnyder, S D; Bibby, M C

2002-01-01

LS 4477 and LS 4559, two of a series of N-acyl-aminoalkyl phenyl ethers, are rationally designed compounds based on the tubulin binder estramustine. This study investigated their mechanism of action and compared their effectiveness in relation to estramustine in vitro against a panel of human and murine cell lines and in vivo against two murine colon tumour models (MAC). At biologically relevant concentrations, LS 4477 and LS 4559 caused a 59.9 and 56% reduction in tubulin assembly, respectively, compared with a 28.4% reduction in tubulin assembly by estramustine. The analogues were approximately 100 times more potent in chemosensitivity tests in vitro than the parent compound. Both analogues were orally active against the MAC 15A murine tumour model, to a greater extent than estramustine, producing significant growth delays (P<0.01). Significant activity was also shown against the slower growing MAC 26 tumour for LS 4577 (the soluble pro-drug of LS 4559). The results presented in this study suggest these compounds warrant further development with a view to assessing their clinical activity.

Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.

PubMed

Peng, X; Katz, M; Gerzanich, V; Anand, R; Lindstrom, J

1994-03-01

The alpha-bungarotoxin-binding acetylcholine receptors from the human neuroblastoma cell line SH-SY5Y were found to cross-react with some monoclonal antibodies to alpha 7 subunits of nicotinic acetylcholine receptors from chicken brain. The human alpha 7 subunit cDNA from SH-SY5Y was cloned, revealing 94% amino acid sequence identity to rat alpha 7 subunits and 92% identity to chicken alpha 7 subunits. Native human alpha 7 receptors showed affinities for some ligands similar to those previously observed with native chicken alpha 7 receptors, but for other ligands there were large species-specific differences in binding affinity. These results paralleled properties of alpha 7 homomers expressed in Xenopus oocytes. Human alpha 7 homomers exhibited rapidly desensitizing, inwardly rectifying, agonist-induced, cation currents that triggered Ca(2+)-sensitive Cl- channels in the oocytes. A change in efficacy from partial agonist for chicken alpha 7 homomers to full agonist for human alpha 7 homomers was exhibited by 1,1-dimethyl-4-phenylpiperazinium. This result reveals a large species-specific pharmacological difference, despite small differences in alpha 7 sequences. This is important for understanding the effects of these drugs in humans and for identifying amino acids that may contribute to the acetylcholine binding site, for analysis by in vitro mutagenesis. These results also characterize properties of native alpha 7 receptors and alpha 7 homomers that will provide criteria for functional properties expected of structural subunits, when these can be identified, cloned, and coexpressed with alpha 7 subunits.

The Purification of the Chlamydomonas reinhardtii chloroplast ClpP complex: additional subunits and structural features

PubMed Central

Derrien, Benoît; Majeran, Wojciech; Effantin, Grégory; Ebenezer, Joseph; Friso, Giulia; van Wijk, Klaas J.; Steven, Alasdair C.; Maurizi, Michael R.; Vallon, Olivier

2012-01-01

The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero-oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub-complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits PMID:22772861

Stretching position can affect levator scapular muscle activity, length, and cervical range of motion in people with a shortened levator scapulae.

PubMed

Jeong, Hyo-Jung; Cynn, Heon-Seock; Yi, Chung-Hwi; Yoon, Jang-Whon; Lee, Ji-Hyun; Yoon, Tae-Lim; Kim, Bo-Been

2017-07-01

Levator scapulae (LS) muscle stretching exercises are a common method of lengthening a shortened muscle; however, the appropriate stretching position for lengthening the LS in people with a shortened LS remains unclear. The purpose of this study was to compare the effects of different stretching exercise positions on the LS and introduce effective stretching exercise methods to clinicians. Twenty-four university students (12 men, 12 women) with a shortened LS were recruited. LS muscle activity, LS index (LSI), and cervical range of motion (ROM) were measured pre (baseline) and post three different stretching exercise positions (sitting, quadruped, and prone). The LSI and cervical ROM exceeded the minimal detectable change and had significant changes. The LSI was greater in the sitting position than at the baseline (p = 0.01), quadruped position (p < 0.01); the LSI in the prone position presented a higher increase than the quadruped position (p = 0.01). The cervical ROM increased in the sitting position when compared to the baseline (p < 0.01) and quadruped position (p < 0.01). Stretching the LS in the sitting position was the most effective exercise for improving LS muscle length and cervical ROM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Life satisfaction and maladaptive behaviors in early adolescents.

PubMed

Lyons, Michael D; Otis, Kristin L; Huebner, E Scott; Hills, Kimberly J

2014-12-01

This study explored the directionality of the relations between global life satisfaction (LS) and internalizing and externalizing behaviors using a sample of regular education students who were initially enrolled in Grade 7 (n = 470). Self-report measures of internalizing and externalizing behaviors and LS were administered on 2 occasions, 6 months apart, to students from a Southeastern U.S. middle school. Short-term longitudinal analyses revealed that neither externalizing behaviors nor internalizing behaviors at Time 1 predicted LS at Time 2. However, LS at Time 1 predicted externalizing behaviors at Time 2. LS at Time 1 also predicted internalizing behaviors at Time 2, but the results were moderated by student gender. At higher levels of LS, boys reported lower levels of internalizing behaviors at Time 2. The overall results suggested that lower levels of LS are an antecedent of increased maladaptive behaviors among early adolescents. Alternatively, higher levels of LS may be a protective factor against subsequent externalizing behaviors among boys and girls and internalizing behaviors among boys. Furthermore, the results provide further support for the discriminant validity of positive and negative measures of mental health and suggest that LS measures may provide useful information for comprehensive adolescent health screening and monitoring systems. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Serum cystatin C level is associated with locomotive syndrome risk and can be an early predictor in community-living people: The Yakumo study.

PubMed

Tanaka, Satoshi; Ando, Kei; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Tsushima, Mikito; Morozumi, Masayoshi; Machino, Masaaki; Ota, Kyotaro; Seki, Taisuke; Suzuki, Koji; Nishida, Yoshihiro; Ishiguro, Naoki; Hasegawa, Yukiharu; Imagama, Shiro

2018-03-02

The locomotive syndrome (LS) risk has been recently proposed as a criterion for evaluating physical ability. Serum cystatin C level is an early renal function marker and a cardiovascular disease predictor. This study aimed to evaluate the relationship between serum cystatin C level and LS risk. We enrolled 54 participants and conducted the two-step test, stand-up test, 25-question geriatric locomotive function scale, LS risk test, Timed Up and Go test, back muscle strength, grip strength, blood test and serum cystatin C level measurement. A comparative study was conducted in participants with and without LS risk and in subgroups aged <60 and ≥60 years. No significant difference was found in the serum cystatin C level in subgroups aged <60 years and without LS risk. However, it was significantly higher in subjects with LS risk and aged ≥60 years. The area under the curve of the serum cystatin C level for LS risk was 0.824. The serum cystatin C level is significantly related to LS risk and can be an early predictor. In middle-aged and elderly people with high serum cystatin C levels, it is strongly recommended to enforce LS risk test and intervention.

Evaluation of PLS, LS-SVM, and LWR for quantitative spectroscopic analysis of soils

USDA-ARS?s Scientific Manuscript database

Soil testing requires the analysis of large numbers of samples in laboratory that are often time consuming and expensive. Mid-infrared spectroscopy (mid-IR) and near-infrared spectroscopy (NIRS) are fast, non-destructive, and inexpensive analytical methods that have been used for soil analysis, in l...

The Prevalence of Lichen Sclerosus in Patients With Vulvar Squamous Cell Carcinoma.

PubMed

Davick, Jonathan J; Samuelson, Megan; Krone, James T; Stockdale, Colleen K

2017-07-01

Women with vulvar lichen sclerosus (LS) have an increased risk of developing differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma (SCC). Our primary aim was to determine the prevalence of LS among women with vulvar SCC. All patients who underwent excision for invasive SCC of the vulva from January 1, 2009 to December 31, 2013 were identified by searching our institution's electronic laboratory information system (n=111). The vulvar excision specimens from these patients were reviewed for the presence of adjacent LS. The grade of the SCC and clinical data were also documented for each case. The proportion of vulvar SCCs with adjacent LS identified on the excision specimen was 0.29 (95% confidence interval, 0.21-0.38). The proportion of patients in our study population who have ever had a histopathologic diagnosis of LS was 0.36 (95% confidence interval, 0.28-0.45). The presence of LS was not associated with the grade of the adjacent SCC. Patients with synchronous LS on excision were older on average than patients without LS. Tobacco users in our population were more likely to have a history of lower genital tract dysplasia, more likely to be younger, and less likely to have LS identified on the vulvar SCC excision specimen. Given the strong association between LS, differentiated vulvar intraepithelial neoplasia, and vulvar SCC, we recommend careful evaluation of these patients from a clinical and pathologic standpoint.

Diagnostic Accuracy of Full-Body Linear X-Ray Scanning in Multiple Trauma Patients in Comparison to Computed Tomography.

PubMed

Jöres, A P W; Heverhagen, J T; Bonél, H; Exadaktylos, A; Klink, T

2016-02-01

The purpose of this study was to evaluate the diagnostic accuracy of full-body linear X-ray scanning (LS) in multiple trauma patients in comparison to 128-multislice computed tomography (MSCT). 106 multiple trauma patients (female: 33; male: 73) were retrospectively included in this study. All patients underwent LS of the whole body, including extremities, and MSCT covering the neck, thorax, abdomen, and pelvis. The diagnostic accuracy of LS for the detection of fractures of the truncal skeleton and pneumothoraces was evaluated in comparison to MSCT by two observers in consensus. Extremity fractures detected by LS were documented. The overall sensitivity of LS was 49.2 %, the specificity was 93.3 %, the positive predictive value was 91 %, and the negative predictive value was 57.5 %. The overall sensitivity for vertebral fractures was 16.7 %, and the specificity was 100 %. The sensitivity was 48.7 % and the specificity 98.2 % for all other fractures. Pneumothoraces were detected in 12 patients by CT, but not by LS. 40 extremity fractures were detected by LS, of which 4 fractures were dislocated, and 2 were fully covered by MSCT. The diagnostic accuracy of LS is limited in the evaluation of acute trauma of the truncal skeleton. LS allows fast whole-body X-ray imaging, and may be valuable for detecting extremity fractures in trauma patients in addition to MSCT.  The overall sensitivity of LS for truncal skeleton injuries in multiple-trauma patients was < 50 %. The diagnostic reference standard MSCT is the preferred and reliable imaging modality. LS may be valuable for quick detection of extremity fractures. © Georg Thieme Verlag KG Stuttgart · New York.

Nociceptive threshold, blood constituents and physiological values in 213 cows with locomotion scores ranging from normal to severely lame.

PubMed

Tadich, N; Tejeda, C; Bastias, S; Rosenfeld, C; Green, L E

2013-08-01

The aim of this study was to investigate associations between mechanical nociceptive threshold, blood constituents, physiological measurements and locomotion score (LS) in dairy cattle with a range of LS from 1 (normal) to 5 (severely lame). The study used 213 Friesian/Friesian cross dairy cows from 12 farms. There were 40-50 cows each with LS 1-4 and 22 cows with LS 5. Each cow was restrained and her temperature and respiratory and cardiac rates were measured. Nociceptive threshold, plasma concentrations of haptoglobin, β-hydroxybutyrate (β-HB), cortisol, glucose, lactate, creatinine kinase activity, packed cell volume and white blood cell counts were determined. Mixed effect models were used to investigate associations between the variables measured and LS. Parity and stage of lactation were forced into all analyses and the model fit was checked by investigation of residuals. After accounting for parity and stage of lactation, nociceptive threshold was significantly lower in cattle with LS 3-5 compared with LS 1 in a dose response manner, indicating increasing hyperalgesia with increasing LS. Haptoglobin concentration was raised in all cattle with LS>1, demonstrating an inflammatory response with all levels of lameness. Cortisol and glucose concentrations were lower and β-HB concentrations higher in cows with LS 2 compared with cows with other scores, possibly signifying metabolic challenge. Heart and respiratory rate and rectal temperature were significantly higher only in cows with LS 5, suggesting that these measurements were insensitive measures of pain or stress. It was concluded that hyperalgesia increases with increasing severity of lameness and that nociceptive pressure and haptoglobin were sensitive measures of pain from lameness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL).

PubMed

Kaste, S C; Qi, A; Smith, K; Surprise, H; Lovorn, E; Boyett, J; Ferry, R J; Relling, M V; Shurtleff, S A; Pui, C H; Carbone, L; Hudson, M M; Ness, K K

2014-05-01

We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78). Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). © 2014 Wiley Periodicals, Inc.

Arterial pressure suffices to increase liver stiffness.

PubMed

Piecha, Felix; Peccerella, Teresa; Bruckner, Tom; Seitz, Helmut-Karl; Rausch, Vanessa; Mueller, Sebastian

2016-11-01

Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood. Copyright © 2016 the American Physiological Society.

Competency to consent to medical treatment in cognitively impaired patients with Parkinson's disease.

PubMed

Dymek, M P; Atchison, P; Harrell, L; Marson, D C

2001-01-09

To investigate capacity to consent to medical treatment (competency) in cognitively impaired patients with PD. Although competency has been studied empirically in patients with cortical dementia (AD), no empirical studies have examined competency in patients with PD or other subcortical neurodegenerative disorders. Patients with PD with cognitive impairment (n = 20) and older controls (n = 20) were compared using a standardized competency measure (Capacity to Consent to Treatment Instrument [CCTI]) and neuropsychological test measures. The CCTI tests competency performance and assigns outcomes (capable, marginally capable, incapable) under four different legal standards (LS). Patients with PD performed below controls on the four LS: capacity to evidence a treatment choice (LS1) (p < 0.03), capacity to appreciate consequences of a treatment choice (LS3) (p < 0.03), capacity to provide rational reasons for a treatment choice (LS4) (p < 0.0001), and capacity to understand the treatment situation and choices (LS5) (p < 0.0001). With respect to competency outcomes, patients with PD demonstrated increasing compromise (marginally capable or incapable outcomes) across the four standards: LS1 (25%), LS3 (45%), LS4 (55%), and LS5 (80%). In the PD group, simple measures of executive function (the Executive Interview) and to a lesser extent memory/orientation (Dementia Rating Scale, Memory subscale) were key predictors of competency performance and outcome on the LS. Cognitively impaired patients with PD are likely to have impaired consent capacity, and are at risk of losing competency over the course of their neurodegenerative illness. Patients with PD have particular difficulty meeting more stringent, clinically relevant competency standards that tap reasoning skills and comprehension of treatment information. Executive dysfunction appears to be a primary neurocognitive mechanism for competency loss in PD.

Efficacy of probing for children with congenital nasolacrimal duct obstruction: a retrospective study using fluorescein dye disappearance test and lacrimal sac echography.

PubMed

Steindler, Piero; Mantovani, Enrico; Incorvaia, Carlo; Parmeggiani, Francesco

2009-06-01

To evaluate B-scan echography for the assessment of lacrimal sac (LS) in pediatric epiphora secondary to congenital nasolacrimal duct obstruction (CNLDO), and to verify its predictive role in functional efficacy of nasolacrimal duct probing. Thirty-nine eyes of 23 consecutive children, treated with a single probing for persistent CNLDO-related epiphora, were retrospectively studied. These cases were investigated both collectively and considering two sub-groups: group A (ten patients [20 eyes] 13 months. Fluorescein dye disappearance test at 10 minutes (FDDT-10) and ultrasound examination of LS were performed before and after probing. An echographic LS scoring system (grade 0 = no LS enlargement; grade 1 = slight longitudinal LS enlargement; grade 2 = longitudinal and slight transverse LS enlargement; grade 3 = marked longitudinal and transverse LS enlargement) was introduced as a predictor of probing efficacy, estimating FDDT-10 modification between pre- and post-operative checks. Echographic LS evaluation was easily practicable without sedation. In the total cluster and in both age sub-groups, post-probing FDDT-10 decreased with respect to pre-probing value (p < 0.001). Post-probing LS score improved with respect to pre-probing check within the total cluster and group A (p < 0.05). Strong correlation between pre-probing LS alteration and functional probing failure was present in each studied cluster (all p values <0.0001). Within group B, a greater gain of post-probing FDDT-10 was more frequent in patients with a better pre-probing LS score, as well as in younger children (both p values <0.0001). In children with CNLDO-related epiphora, B-scan echography of the LS can represent a reliable and useful examination for a better understanding of the functional prognosis after probing treatment.

Two-dimensional longitudinal strain assessment in the presence of myocardial contrast agents is only feasible with speckle-tracking after microbubble destruction.

PubMed

Cavalcante, João L; Collier, Patrick; Plana, Juan C; Agler, Deborah; Thomas, James D; Marwick, Thomas H

2012-12-01

Longitudinal strain (LS) imaging is an important tool for the quantification of left ventricular function and deformation, but its assessment is challenging in the presence of echocardiographic contrast agents (CAs). The aim of this study was to test the hypothesis that destruction of microbubbles using high mechanical index (MI) could allow the measurement of LS. LS was measured using speckle strain (speckle-tracking LS [STLS]) and Velocity Vector Imaging (VVI) before and after CA administration in 30 consecutive patients. Low MI was used for left ventricular opacification and three-dimensional high MI for microbubble destruction. Four different settings were tested over 60 sec: (1) baseline LS without contrast, (2) LS after CA administration with low MI (0.3), (3) LS after CA administration with high MI (0.9), and (4) LS after microbubble destruction with high MI and three-dimensional imaging. Baseline feasibility of LS assessment (99.3% and 98.2% with STLS and VVI, respectively) was reduced after CA administration using STLS at low (69%, P < .0001) and high (95.4%, P = .0002) MI as well as with VVI (93.8%, P = .004, and 84.7%, P < .0001, respectively). STLS assessment was feasible with high MI after microbubble destruction (1.7% of uninterpretable segments vs 0.7%, P = .26) but not using VVI (7.2% vs 1.8%, P < .001). Regardless of which microbubbles or image settings were used, VVI was associated with significant variability and overestimation of global LS (for low MI, +4.7%, P < .01; for high MI, +3.3%, P < .001; for high MI after microbubble destruction, +1.3%, P = .04). LS assessment is most feasible without contrast. If a CA is necessary, the calculation of LS is feasible using the speckle-tracking method, if three-dimensional imaging is used as a tool for microbubble destruction 1 min after CA administration. Copyright © 2012. Published by Mosby, Inc.

Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach.

PubMed

Hartman, Douglas J; Brand, Randall E; Hu, Huankai; Bahary, Nathan; Dudley, Beth; Chiosea, Simon I; Nikiforova, Marina N; Pai, Reetesh K

2013-11-01

The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas. © 2013.

Patient and provider perspectives on adherence to and care coordination of lynch syndrome surveillance recommendations: findings from qualitative interviews.

PubMed

Schneider, Jennifer L; Goddard, Katrina A B; Muessig, Kristin R; Davis, James V; Rope, Alan F; Hunter, Jessica E; Peterson, Susan K; Acheson, Louise S; Syngal, Sapna; Wiesner, Georgia L; Reiss, Jacob A

2018-01-01

Patients with a genetic variant associated with Lynch syndrome (LS) are recommended to undergo frequent and repeated cancer surveillance activities to minimize cancer-related morbidity and mortality. Little is known about how patients and primary care providers (PCPs) track and manage these recommendations. We conducted a small exploratory study of patient and PCP experiences with recommended LS surveillance activities and communication with family members in an integrated health care system. We used in-depth interviews with patients and providers to understand how surveillance is coordinated and monitored following confirmation of LS. We recruited patients with a range of ages/gender, and providers with at least at least one patient with a molecular diagnosis of LS. All interviews were recorded, transcribed, and content analyzed by a trained qualitative methodologist. Twenty-two interviews were completed with 12 patients and 10 providers. Most patients (10) had detailed knowledge of surveillance recommendations, but were less sure of time intervals. While all patients reported receiving initial education about their surveillance recommendations from a genetic counselor, seven did not follow-up with a genetic counselor in subsequent years. A third of patients described taking sole responsibility for managing their LS surveillance care. Lack of routine communication from the health system (e.g., prompts for surveillance activities), and provider engagement were surveillance barriers. PCPs were generally aware of LS, but had limited familiarity with surveillance recommendations. Most PCPs (7) viewed LS as rare and relied on patient and specialist expertise and support. Providers typically had 1 patient with LS in a panel of 1800 patients overall. Providers felt strongly that management of LS should be coordinated by a dedicated team of specialists. Most patients (92%) had at least one family member that sought LS testing, and common barriers for family members included lack of insurance, affordability, and fear of result. The maximal benefits of screening for confirmation of LS will only be realized with adherence to recommended preventive care. Important factors to ensure patients receive recommended LS care include a comprehensive and coordinated monitoring program that includes reminder prompts, and increased PCP education of LS and associated surveillance recommendations.

Fundamental research on the action mechanism of the 800 nm semiconductor laser on skin blackheads and coarse pores.

PubMed

Lin, Jie; Jing, Li; Zhu, Hao; Dong, Fu-Sheng

2017-01-01

The aim of the study was to determine the mechanism of action of the 800 nm semiconductor laser on skin blackheads and coarse pores. A total of 24 healthy purebred short-haired male guinea pigs, weighing 350-400 g, were selected and smeared with 0.5 ml coal tar suspension evenly by injector once daily. Treatment was continued for 14 days to form an experimental area of 8×3 cm on the back of the guinea pigs. The animals were divided into the following groups: Normal control group (NC), low-dose laser treatment group (L-LS), high-dose laser treatment group (H-LS), and Q-switched Nd:YAG treatment group (QC). Samples were extracted 1, 7 and 14 days after surgery and hematoxylin and eosin staining was used to identify the following: Epidermis, dermis, sebaceous gland change and hair follicle damage; the expression of proliferating cell nuclear antigen (PCNA) of sebaceous gland cells using immunohistochemistry; sebaceous gland cell apoptosis using TUNEL; and the protein expression of caspase-3, Bax and Bcl-2 using western blot analysis. With the extension of time, we observed inflammatory cell infiltration, an increase in hair follicle distortion and necrosis of the surrounding hair follicles. The expression levels of PCNA of the L-LS, H-LS and QC groups decreased with time. Regarding the respective time points, the NC group was highest, the L-LS and H-LS groups were next highest and the H-LS group was lowest. The difference was statistically significant (P<0.05). The apoptotic rate of the L-LS, H-LS and QC groups increased with time. With regard to the respective time points, the NC group was lowest, the L-LS and QC groups were next lowest and the H-LS group was highest. The difference was statistically significant (P<0.05). The protein expression of caspase-3, Bax and Bcl-2 of the L-LS, H-LS and QC groups increased with time. Regarding the respective time points, caspase-3 and Bax protein expression of the NC group was lowest, the L-LS and QC groups were next lowest and the H-LS group was highest. Bcl-2 protein expression of the NC group was highest, protein expression of the NC group was next highest and the H-LS group was lowest. The difference was statistically significant (P<0.05). In conclusion, the low-dose 800 nm semiconductor laser is an effective treatment on skin blackheads and coarse pores, and promotes hair follicle cell apoptosis without reducing the expression of PCNA.

Canopy Nutrient Cycling In Afromontane Tropical Forests At Different Successional Stages

NASA Astrophysics Data System (ADS)

Nyirambangutse, B.; Zibera, E.; Dusenge, M. E.; Nsabimana, D.; Pleijel, H.; Uddling, J.; Wallin, G.

2017-12-01

Canopy nutrient composition and cycling control biogeochemical processes and tree growth in forests. However, the understanding of nutrient limitations and cycling in tropical montane forests (TMF) is currently limited, in particular for Afromontane forests. In this study we investigated leaf nutrient composition and resorption, canopy nutrient cycling and soil carbon and nutrient content in 15 permanent plots at different successional stages in a TMF (elevation 1950 to 2550 m a.s.l.) in Rwanda, Central Africa. Leaf concentrations of 12 elements were analyzed in attached green leaves as well as in shed leaves of 10 early (ES) and 10 late (LS) successional tree species. Leaf nutrient concentrations mostly did not differ between ES and LS species (exception: K was 20% higher in ES), but the ratios of P, K and Mg to N were significantly higher in ES species. Mean resorption efficiencies of N (37%), P (48%) and K (46%) were much higher than for other nutrients. Nutrient resorption efficiency exhibited very large interspecific variation, did not differ between ES and LS species, and was not related to the leaf concentration of the respective element. Total leaf litterfall was on average 4.9 t ha-1 yr-1 (66% of total litterfall) and was independent of the successional stage of the forest. The total content of C, N, P and K in leaf litterfall did not differ between ES and LS stands. Ground litter turnover rates of C and N were 0.98 and 0.78 y-1, respectively. High leaf N concentrations, intermediate N:P ratios and low resorption efficiencies compared to values reported for other TMFs indicate high fertility and likely co-limitation by N and P, however progressively increasing towards P limitation during the course of succession. Our results further demonstrate that resorption efficiency and canopy litterfall inputs to soil mostly do not differ between ES and LS species in Afromontane tropical forests.

Impact of the biorefinery size on the logistics of corn stover supply – A scenario analysis

DOE PAGES

Wang, Yu; Ebadian, Mahmood; Sokhansanj, Shahab; ...

2017-03-23

In this study, three scenarios are considered to quantify the impact of the biorefinery size on the required biomass logistical resources. The biorefinery scenarios include small scale (175 dt/day)-SS, medium scale (520 dt/day)-MS and large scale (860 dt/day)-LS. These scenarios are compared against the following logistical resources (1) harvest area and contracted fields, (2) logistics equipment fleet and the workforce to run this fleet and (3) intermediate storage sites and their biomass inventory levels. To this end, the IBSAL-MC simulation model is applied to a corn stover logistics system in Southwestern Ontario. The obtained results show (1) the harvest areamore » and the number of contracted fields increase by 65% and 78% from the SS scenario to the MS and LS scenarios, respectively, (2) the average biomass delivered costs are estimated to be $82.09, $87.49 and $93.75/dry tonne in the SS, MS and LS scenarios. The increase in the capital costs to develop a dedicated logistics equipment fleet are estimated to be far greater than the increase in the delivered costs as the size of the biorefinery increases. The upfront capital costs are estimated to be 6.72 dollars, 21.83 and 35.51 million in these scenarios. To run the logistics equipment fleet efficiently, 37, 136 and 235 well-trained operators are required in the SS, MS ad LS scenarios, respectively, and (3) the inventory level and the land requirement for storage in the MS and LS scenarios are estimated to be 225% and 425% greater than those of the SS scenario. The sensitivity analysis indicates that the logistical resources are highly sensitive to corn yield and farm participation rate. Overall, this study shows the importance of considering the size of the required logistical resources and the associated level of logistical complexity in evaluating the economic viability of a biorefinery project.« less

Impact of the biorefinery size on the logistics of corn stover supply – A scenario analysis

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

Wang, Yu; Ebadian, Mahmood; Sokhansanj, Shahab

In this study, three scenarios are considered to quantify the impact of the biorefinery size on the required biomass logistical resources. The biorefinery scenarios include small scale (175 dt/day)-SS, medium scale (520 dt/day)-MS and large scale (860 dt/day)-LS. These scenarios are compared against the following logistical resources (1) harvest area and contracted fields, (2) logistics equipment fleet and the workforce to run this fleet and (3) intermediate storage sites and their biomass inventory levels. To this end, the IBSAL-MC simulation model is applied to a corn stover logistics system in Southwestern Ontario. The obtained results show (1) the harvest areamore » and the number of contracted fields increase by 65% and 78% from the SS scenario to the MS and LS scenarios, respectively, (2) the average biomass delivered costs are estimated to be $82.09, $87.49 and $93.75/dry tonne in the SS, MS and LS scenarios. The increase in the capital costs to develop a dedicated logistics equipment fleet are estimated to be far greater than the increase in the delivered costs as the size of the biorefinery increases. The upfront capital costs are estimated to be 6.72 dollars, 21.83 and 35.51 million in these scenarios. To run the logistics equipment fleet efficiently, 37, 136 and 235 well-trained operators are required in the SS, MS ad LS scenarios, respectively, and (3) the inventory level and the land requirement for storage in the MS and LS scenarios are estimated to be 225% and 425% greater than those of the SS scenario. The sensitivity analysis indicates that the logistical resources are highly sensitive to corn yield and farm participation rate. Overall, this study shows the importance of considering the size of the required logistical resources and the associated level of logistical complexity in evaluating the economic viability of a biorefinery project.« less

A reanalysis of ozone on Mars from assimilation of SPICAM observations

NASA Astrophysics Data System (ADS)

Holmes, James A.; Lewis, Stephen R.; Patel, Manish R.; Lefèvre, Franck

2018-03-01

We have assimilated for the first time SPICAM retrievals of total ozone into a Martian global circulation model to provide a global reanalysis of the ozone cycle. Disagreement in total ozone between model prediction and assimilation is observed between 45°S-10°S from LS = 135-180° and at northern polar (60°N-90°N) latitudes during northern fall (LS = 150-195°). Large percentage differences in total ozone at northern fall polar latitudes identified through the assimilation process are linked with excessive northward transport of water vapour west of Tharsis and over Arabia Terra. Modelling biases in water vapour can also explain the underestimation of total ozone between 45°S-10°S from LS = 135-180°. Heterogeneous uptake of odd hydrogen radicals are unable to explain the outstanding underestimation of northern polar total ozone in late northern fall. Assimilation of total ozone retrievals results in alterations of the modelled spatial distribution of ozone in the southern polar winter high altitude ozone layer. This illustrates the potential use of assimilation methods in constraining total ozone where SPICAM cannot observe, in a region where total ozone is especially important for potential investigations of the polar dynamics.

76 FR 253 - Airworthiness Directives; ROLLADEN-SCHNEIDER Flugzeugbau GmbH Model LS6 Gliders

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Airworthiness Directives; ROLLADEN-SCHNEIDER Flugzeugbau GmbH Model LS6 Gliders AGENCY: Federal Aviation... condition does not exist in the Model LS6-c gliders. FAA's Determination We are issuing this AD rescission... Model LS6 glider, and the unsafe condition described previously is not likely to exist or develop in the...

Lunar settlements - A socio-economic outlook

NASA Technical Reports Server (NTRS)

Bluth, B. J.

1986-01-01

Factors in the design and development of a lunar settlement (LS) which affect the performance of the crew members are discussed. Topics examined include LS-program time constraints imposed by decisions made in developing and operating the Space Station; changes to make allowance for the long-term requirements of LSs; the design of the physical, technical, and organic LS environment; and the vital role of group dynamics in assuring LS success. It is suggested that many short-term cost-minimization strategies employed in spacecraft development may be inappropriate for LS programs.

A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome.

PubMed

Lim, Sze Chern; Smith, Katherine R; Stroud, David A; Compton, Alison G; Tucker, Elena J; Dasvarma, Ayan; Gandolfo, Luke C; Marum, Justine E; McKenzie, Matthew; Peters, Heidi L; Mowat, David; Procopis, Peter G; Wilcken, Bridget; Christodoulou, John; Brown, Garry K; Ryan, Michael T; Bahlo, Melanie; Thorburn, David R

2014-02-06

Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic bilateral lesions, typically in the brainstem and basal ganglia. It usually presents in infancy and is genetically heterogeneous, but most individuals with mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals from six families of Lebanese origin. They differed from individuals with SURF1 mutations in having seizures as a prominent feature. Complementation analysis suggested they had mutation(s) in the same gene but targeted massively parallel sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to identify a likely candidate. Linkage and haplotype analyses mapped the location of the gene to chromosome 19 and targeted MPS of the linkage region identified a homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon could potentially still allow initiation at a downstream methionine residue but we showed that this would not result in a functional protein. We confirmed that mutation of this gene was causative by lentiviral-mediated phenotypic correction. C19orf79 was recently renamed PET100 and predicted to encode a complex IV biogenesis factor. We showed that it is located in the mitochondrial inner membrane and forms a ∼300 kDa subcomplex with complex IV subunits. Previous proteomic analyses of mitochondria had overlooked PET100 because its small size was below the cutoff for annotating bona fide proteins. The mutation was estimated to have arisen at least 520 years ago, explaining how the families could have different religions and different geographic origins within Lebanon. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Fly versus man: evolutionary impairment of nucleolar targeting affects the degradome of Drosophila's Taspase1.

PubMed

Wünsch, Désirée; Hahlbrock, Angelina; Heiselmayer, Christina; Bäcker, Sandra; Heun, Patrick; Goesswein, Dorothee; Stöcker, Walter; Schirmeister, Tanja; Schneider, Günter; Krämer, Oliver H; Knauer, Shirley K; Stauber, Roland H

2015-05-01

Human Taspase1 is essential for development and cancer by processing critical regulators, such as the mixed-lineage leukemia protein. Likewise, its ortholog, trithorax, is cleaved by Drosophila Taspase1 (dTaspase1), implementing a functional coevolution. To uncover novel mechanism regulating protease function, we performed a functional analysis of dTaspase1 and its comparison to the human ortholog. dTaspase1 contains an essential nucleophile threonine(195), catalyzing cis cleavage into its α- and β-subunits. A cell-based assay combined with alanine scanning mutagenesis demonstrated that the target cleavage motif for dTaspase1 (Q(3)[F/I/L/M](2)D(1)↓G(1')X(2')X(3')) differs significantly from the human ortholog (Q(3)[F,I,L,V](2)D(1)↓G(1')x(2')D(3')D(4')), predicting an enlarged degradome containing 70 substrates for Drosophila. In contrast to human Taspase1, dTaspase1 shows no discrete localization to the nucleus/nucleolus due to the lack of the importin-α/nucleophosmin1 interaction domain (NoLS) conserved in all vertebrates. Consequently, dTaspase1 interacts with neither the Drosophila nucleoplasmin-like protein nor human nucleophosmin1. The impact of localization on the protease's degradome was confirmed by demonstrating that dTaspase1 did not efficiently process nuclear substrates, such as upstream stimulatory factor 2. However, genetic introduction of the NoLS into dTaspase1 restored its nucleolar localization, nucleophosmin1 interaction, and efficient cleavage of nuclear substrates. We report that evolutionary functional divergence separating vertebrates from invertebrates can be achieved for proteases by a transport/localization-regulated mechanism. © FASEB.

Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.

PubMed

Li, Min; Chang, Shan; Yang, Longjin; Shi, Jingyi; McFarland, Kelli; Yang, Xiao; Moller, Alyssa; Wang, Chunguang; Zou, Xiaoqin; Chi, Chengwu; Cui, Jianmin

2014-02-21

BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.1 that preferentially inhibits BK channels containing the β4 subunit, which is most abundantly expressed in brain and important for neuronal functions. Vt3.1 inhibits the currents by a maximum of 71%, shifts the G-V relation by 45 mV approximately half-saturation concentrations, and alters both open and closed time of single channel activities, indicating that the toxin alters voltage dependence of the channel. Vt3.1 contains basic residues and inhibits voltage-dependent activation by electrostatic interactions with acidic residues in the extracellular loops of the slo1 and β4 subunits. These results suggest a large interaction surface between the slo1 subunit of BK channels and the β4 subunit, providing structural insight into the molecular interactions between slo1 and β4 subunits. The results also suggest that Vt3.1 is an excellent tool for studying β subunit modulation of BK channels and for understanding the physiological roles of BK channels in neurophysiology.

A channel estimation scheme for MIMO-OFDM systems

NASA Astrophysics Data System (ADS)

He, Chunlong; Tian, Chu; Li, Xingquan; Zhang, Ce; Zhang, Shiqi; Liu, Chaowen

2017-08-01

In view of the contradiction of the time-domain least squares (LS) channel estimation performance and the practical realization complexity, a reduced complexity channel estimation method for multiple input multiple output-orthogonal frequency division multiplexing (MIMO-OFDM) based on pilot is obtained. This approach can transform the complexity of MIMO-OFDM channel estimation problem into a simple single input single output-orthogonal frequency division multiplexing (SISO-OFDM) channel estimation problem and therefore there is no need for large matrix pseudo-inverse, which greatly reduces the complexity of algorithms. Simulation results show that the bit error rate (BER) performance of the obtained method with time orthogonal training sequences and linear minimum mean square error (LMMSE) criteria is better than that of time-domain LS estimator and nearly optimal performance.

Subunit architecture and functional modular rearrangements of the transcriptional Mediator complex

PubMed Central

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2014-01-01

SUMMARY The multisubunit Mediator comprising ~30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. PMID:24882805

Intramolecular electron transport in quinoprotein alcohol dehydrogenase of Acetobacter methanolicus: a redox-titration study

PubMed

Frébortova; Matsushita; Arata; Adachi

1998-01-27

Quinohemoprotein-cytochrome c complex alcohol dehydrogenase (ADH) of acetic acid bacteria consists of three subunits, of which subunit I contains pyrroloquinoline quinone (PQQ) and heme c, and subunit II contains three heme c components. The PQQ and heme c components are believed to be involved in the intramolecular electron transfer from ethanol to ubiquinone. To study the intramolecular electron transfer in ADH of Acetobacter methanolicus, the redox potentials of heme c components were determined with ADH complex and the isolated subunits I and II of A. methanolicus, as well as hybrid ADH consisting of the subunit I/III complex of Gluconobacter suboxydans ADH and subunit II of A. methanolicus ADH. The redox potentials of hemes c in ADH complex were -130, 49, 188, and 188 mV at pH 7.0 and 24, 187, 190, and 255 mV at pH 4.5. In hybrid ADH, one of these heme c components was largely changed in the redox potential. Reduced ADH was fully oxidized with potassium ferricyanide, while ubiquinone oxidized the enzyme partially. The results indicate that electrons extracted from ethanol at PQQ site are transferred to ubiquinone via heme c in subunit I and two of the three hemes c in subunit II. Copyright 1998 Elsevier Science B.V.

Prospective association between self-reported life satisfaction and mortality: results from the MONICA/KORA Augsburg S3 survey cohort study.

PubMed

Lacruz, Maria E; Emeny, Rebecca T; Baumert, Jens; Ladwig, Karl H

2011-07-20

To identify factors which determine high life satisfaction (LS) and to analyse the prognostic influence of LS on mortality. Data collection was conducted on 2,675 participants, age 25-74 years, as part of the MONICA Augsburg Project 1994-95. Multivariate logistic regression analyses were used to determine factors associated with high LS (measured with one item, 6-level Likert scale, where "high" = very satisfied/most of the time very satisfied with ones personal life). After 12 years mean follow-up, a total of 245 deaths occurred. We calculated age- and sex-adjusted incident mortality rates per 10,000. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Independent determinants of LS were income, health-perception, and social support, as well as somatisation, anger or depressive symptoms (all p < 0.05). Participants with higher LS (n = 721, 27%) benefited the most with respect to absolute mortality risk reduction (higher LS = 67; mid = 98; low = 140 per 10,000). The sex-stratified analyses indicated an independent association of higher LS and survival for men (HR 0.55; 95% CI 0.37 - 0.81) but not for women. Baseline assessment demonstrated that psychological, social and life-style factors, but not somatic co-morbidities, were relevant determinants of LS. Moreover, the analysis showed that men with higher LS have a substantial long-term survival benefit. The observed association between LS and mortality may be attributed to common underlying causes such as social network integration and/or self-rated health.

Influence of treatments on prognosis for vulvar lichen sclerosus: facts and controversies.

PubMed

Brodrick, Brooks; Belkin, Zoe R; Goldstein, Andrew T

2013-01-01

Lichen sclerosus (LS) is an inflammatory dermatosis with a predilection for the anogential skin. Vulvar LS can be a debilitating disease, causing pruritus and pain, and it carries the potential for atrophy, scarring, and significant functional impairment. Recently, many advances have been made regarding the etiology and natural history of the disease process; however, much debate still exists regarding the most advantageous medical and surgical management of this disorder. In an effort to provide a comprehensive review on current vulvar LS literature, the following three controversies will be discussed: (1) optimal disease treatment, (2) theories behind LS's oncogenicity and treatments for minimizing malignancy, and (3) the value of surgical treatment for LS. Ultra-potent topical corticosteroids (TCSs) are the first-line treatment for vulvar LS, while topical calcineurin inhibitors (TCIs) remain second-line agents for patients for whom TCS treatment resulted in incomplete resolution of symptoms or adverse events. Due to the relapsing nature of the disease, long-term maintenance therapy is often required. In addition, recent advances have contributed to the understanding of the association between LS and squamous cell carcinoma (SCC). While the exact mechanism responsible for LS-associated SCC is not known, immune dysregulation and inflammation may play an important role; therefore, successful treatment of LS should be directed towards alleviation of symptoms and reversal of the underlying histopathologic changes. Patients with LS-associated malignancy, as well as patients who need correction of functionally restrictive, scarring processes, can successfully undergo surgical intervention with tissue conservation. © 2013 Elsevier Inc. All rights reserved.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma.

PubMed

Magee, Kelsey E; Kelsey, Christina E; Kurzinski, Katherine L; Ho, Jonhan; Mlakar, Logan R; Feghali-Bostwick, Carol A; Torok, Kathryn S

2013-01-01

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.

Prospective association between self-reported life satisfaction and mortality: Results from the MONICA/KORA Augsburg S3 survey cohort study

PubMed Central

2011-01-01

Background To identify factors which determine high life satisfaction (LS) and to analyse the prognostic influence of LS on mortality. Methods Data collection was conducted on 2,675 participants, age 25-74 years, as part of the MONICA Augsburg Project 1994-95. Multivariate logistic regression analyses were used to determine factors associated with high LS (measured with one item, 6-level Likert scale, where "high" = very satisfied/most of the time very satisfied with ones personal life). After 12 years mean follow-up, a total of 245 deaths occurred. We calculated age- and sex-adjusted incident mortality rates per 10,000. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results Independent determinants of LS were income, health-perception, and social support, as well as somatisation, anger or depressive symptoms (all p < 0.05). Participants with higher LS (n = 721, 27%) benefited the most with respect to absolute mortality risk reduction (higher LS = 67; mid = 98; low = 140 per 10,000). The sex-stratified analyses indicated an independent association of higher LS and survival for men (HR 0.55; 95% CI 0.37 - 0.81) but not for women. Conclusions Baseline assessment demonstrated that psychological, social and life-style factors, but not somatic co-morbidities, were relevant determinants of LS. Moreover, the analysis showed that men with higher LS have a substantial long-term survival benefit. The observed association between LS and mortality may be attributed to common underlying causes such as social network integration and/or self-rated health. PMID:21774793

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

PubMed Central

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Universal screening for Lynch syndrome among patients with colorectal cancer: Patient perspectives on screening and sharing results with at-risk relatives

PubMed Central

Hunter, Jessica Ezzell; Arnold, Kathleen A.; Cook, Jennifer E.; Zepp, Jamilyn; Gilmore, Marian J.; Rope, Alan F.; Davis, James V.; Bergen, Kellene M.; Esterberg, Elizabeth; Muessig, Kristin R.; Peterson, Susan K.; Syngal, Sapna; Acheson, Louise; Wiesner, Georgia; Reiss, Jacob; Goddard, Katrina A.B.

2018-01-01

Universal screening for Lynch syndrome (LS) among all cases of colorectal cancer (CRC) could increase the diagnosis of LS and reduce morbidity and mortality of LS-associated cancers. Given universal screening includes all patients, irrespective of high risk factors such early age at onset or family history of CRC, it is important to understand perspectives of all patients and not just those at high risk. As part of a study to assess the feasibility and implementation of universal screening, 189 patients newly diagnosed with CRC were surveyed about their interest in screening for LS and communication of results with at-risk family members. Overall, participants responded positively regarding screening for LS, with most wanting to know their genetic risks in general (86%) and risk of hereditary CRC (93%). Prior to receiving screening results, most participants stated they intended to share their screening results with parents (89%), siblings (96%), and children (96%). Of the 28 participants who received a positive LS screening result, 26 (93%) reported sharing their result with at least one first-degree family member. Interest in screening for LS and communication of screening results with family members was not associated with high risk factors. This study indicates that patients are interested in being screened for LS and that sharing information on the risk of LS with at-risk family members is not a significant barrier. These findings provide novel insight into patient perspectives about screening for LS and can guide successful implementation of universal screening programs. PMID:28176204

How can recovery be enhanced after single-stage laparoscopic management of CBD stones? Endoscopic treatment versus laparoscopic surgery.

PubMed

Chapuis-Roux, Emilie; Pellissier, Laurent; Browet, Francois; Berthou, Jean Charles; Hakim, Sami; Brazier, Franck; Cosse, Cyril; Delcenserie, Richard; Regimbeau, Jean Marc

2017-07-01

Single-stage management of CBD stones comprises simultaneous common bile duct (CBD) clearance and cholecystectomy. The CBD can be cleared by using endoscopic treatment (ET) or laparoscopic surgery (LS) alone. To determine the most rapid recovery after the single-stage laparoscopic management of CBD stones. Patients with CBD stones treated at either of two centers (one performing ET only and one performing LS only for single-stage treatment) were included. The primary endpoint was "the textbook outcome". The feasibility rate was 74% for ET and 100% for LS (p≤0.001). The proportion of cases with the textbook outcome was higher in the ET group than in the LS-only group (73% vs. 10%; p<0.001). The CBD clearance rate was similar in the ET and LS-only groups (100% vs. 96.6%, respectively; p=0.17). The overall morbidity rate was lower in the ET group than in the LS-only group (23% vs. 29%, p=0.05). Both ET and LS are feasible, safe and effective for clearance of the CBD. ET was better than LS in terms of a less frequent requirement for drainage and a shorter length of hospital stay. LS was associated with a shorter operating time. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Removing Trypan blue dye using nano-Zn modified Luffa sponge.

PubMed

Nadaroglu, Hayrunnisa; Cicek, Semra; Gungor, Azize Alayli

2017-02-05

This study has presented specific features that are examined to remove the Trypan blue dye from the waste using Luffa sponge (LS) and modified Luffa sponge with zinc nanoparticles (ZnNPs). Peroxidase enzyme was obtained from Euphorbia amygdaloides plant and it was used with the green synthesis of Zn nanoparticles. Luffa sponge was used to be a support material for immobilized nanoparticles and it also used in remediation work. The obtained membrane forms, fibrous materials, (LS, ZnNPs-LS) were characterized with SEM and XRD. LS and ZnNPs-LS were employed as adsorbent to be used for the removal of Trypan blue dye from aqueous via batch studies. Measurements were made for the equilibrium, pH, temperature, concentration of dye with UV-visible spectrometer (590nm; for Trypan blue dye). The optimum removal of Trypan blue dye was found at pH7, the equilibrium was attained within 30min. The thermodynamic properties ΔG 0 , ΔH 0 , and ΔS 0 showed that adsorption of Trypan blue dye onto LS and ZnNPs-LS were spontaneous and endothermic. The equilibrium isotherm data were analyzed using Langmuir and Freundlich models and the sorption process was described by the Langmuir isotherm with maximum monolayer adsorption capacity of 45.32 and 47.3mg/g for LS and LS-ZnNPs at 303±1°K, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Transient micro-elastography: A novel non-invasive approach to measure liver stiffness in mice

PubMed Central

Bastard, Cécile; Bosisio, Matteo R; Chabert, Michèle; Kalopissis, Athina D; Mahrouf-Yorgov, Meriem; Gilgenkrantz, Hélène; Mueller, Sebastian; Sandrin, Laurent

2011-01-01

AIM: To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice. METHODS: A novel transient micro-elastography (TME) device, dedicated to LS measurements in mice with a range of measurement from 1-170 kPa, was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston. The novel probe was validated in a classical fibrosis model (CCl4) and in a transgenic murine model of systemic amyloidosis. RESULTS: TME could be successfully performed in control mice below the xiphoid cartilage, with a mean LS of 4.4 ± 1.3 kPa, a mean success rate of 88%, and an excellent intra-observer agreement (0.98). Treatment with CCl4 over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa). Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88, P < 0.01). In the amyloidosis model, much higher LS values were obtained, reaching maximum values of > 150 kPa. LS significantly correlated with the amyloidosis index (0.93, P < 0.0001) and the plasma concentration of mutant hapoA-II (0.62, P < 0.005). CONCLUSION: Here, we have established the first non-invasive approach to measure LS in mice, and have successfully validated it in two murine models of high LS. PMID:21448348

Women in very low quality marriages gain life satisfaction following divorce.

PubMed

Bourassa, Kyle J; Sbarra, David A; Whisman, Mark A

2015-06-01

Although marital dissolution is associated with increased risk for poor mental and physical health outcomes, many people report improvements in functioning after divorce. To study the hypothesis that women in lower quality marriages would report the best outcomes upon separation/divorce, we investigated the combined effects of marital quality, gender, and marital status for predicting changes in life satisfaction (LS). Participants (N = 1,639; 50.3% men) were drawn from a nationally representative sample (Midlife in the United States Study), which included assessments of marital quality, marital status, and LS, at 2 time points (T1 and T2), roughly 10 years apart. Hierarchical linear regression analyses revealed an interaction between marital quality, marital status, and gender when predicting residual change in LS. Divorced women evidenced a negative association between marital quality and later LS, whereas continuously married women had a positive association between marital quality and later LS. In addition, women in higher quality marriages that become divorced showed the lowest LS, and women in lowest quality marriages show the highest LS among women with similar levels of marital quality. There was no association between marital quality and later LS for divorced or continuously married men. This work extends prior findings regarding gender differences in marital quality to postdivorce well-being, and suggests women in the lowest quality marriages may gain LS following divorce. (c) 2015 APA, all rights reserved).

Containerless Processing of a Lithium Disilicate Glass

NASA Technical Reports Server (NTRS)

Ranasinghe, K. S.; Ray, C. S.; Day, D. E.; Rogers, J. R.; Hyers, R W.; Rathz, T.

2006-01-01

Glasses of Li2O.2SiO2 (LS2) and LS2 doped with 0.001 wt% platinum (LS2 + 0.001 wt% Pt) compositions were melted, cooled and re-heated at controlled rates while levitated (containerless) inside an Electrostatic Levitator (ESL) furnace at NASA Marshall Space Flight Center. The experiments were conducted in vacuum using spherical 2.5 - 3.0 mm diameter glass samples. The measured critical cooling rate for glass formation, Rc, for the LS2 and LS2 + 0.001 wt% Pt glasses processed at ESL were 14 plus or minus 2 C/min and 130 plus or minus 5 C/min, respectively. The values of Rc for the same LS2 and LS2 + 0.001 wt% Pt glasses processed in a container were 62 plus or minus 3 C/min and 162 plus or minus 5 C/min, respectively. The effective activation energy for crystallization, E, for the LS2 glass processed without a container at ESL was higher than that for an identical glass processed in a container. These results suggest that the glass formation tendency for a containerless LS2 melt is significantly increased compared to an identical melt in contact with a container. The absence of heterogeneous nucleation sites that are inherently present in all melts held in containers is believed to be the reason for the increased glass forming tendency of this containerless melt.

Understanding the effects of lignosulfonate on enzymatic saccharification of pure cellulose

Treesearch

Hongming Lou; Haifeng Zhou; Xiuli Li; Mengxia Wang; J.Y. Zhu; Xueqing Qiu

2014-01-01

The effects of lignosulfonate (LS) on enzymatic saccharification of pure cellulose were studied. Four fractions of LS with different molecular weight (MW) prepared by ultrafiltration of a commercial LS were applied at different loadings to enzymatic hydrolysis of Whatman paper under different pH. Using LS fractions with low MW and high degree of sulfonation can enhance...

Biorefinery lignosulfonates from sulfite-pretreated softwoods as dispersant for graphite

Treesearch

Yanlin Qin; Lixuan Yu; Ruchun Wu; Dongjie Yang; Xueqing Qiu; Junyong Zhu

2016-01-01

Two biorefinery lignosulfonates (LSs), Ca-LS-DF and Na-LS-LP were, respectively, isolated from pilot-scale sulfite-pretreated spent liquor of lodgepole pine and fermentation residue of Douglas-fir harvest forest residue. The molecular weights of Na-LS-LP and Ca-LS-DF were approximately 9 000 and 11 000 Da, respectively. The two LSs were applied as dispersant for...

Self-Injurious Behaviour in Cornelia De Lange Syndrome: 2. Association with Environmental Events

ERIC Educational Resources Information Center

Sloneem, J.; Arron, K.; Hall, S. S.; Oliver, C.

2009-01-01

Background: Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods: We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched…

Properties of lotus seed starch-glycerin monostearin complexes formed by high pressure homogenization.

PubMed

Chen, Bingyan; Zeng, Shaoxiao; Zeng, Hongliang; Guo, Zebin; Zhang, Yi; Zheng, Baodong

2017-07-01

Starch-lipid complexes were prepared using lotus seed starch (LS) and glycerin monostearate (GMS) via a high pressure homogenization (HPH) process, and the effect of HPH on the physicochemical properties of LS-GMS complexes was investigated. The results of Fourier transform infrared spectroscopy and complex index analysis showed that LS-GMS complexes were formed at 40MPa by HPH and the complex index increased with the increase of homogenization pressure. Scanning electron microscopy displayed LS-GMS complexes present more nest-shape structure with increasing homogenization pressure. X-ray diffraction and differential scanning calorimetry results revealed that V-type crystalline polymorph was formed between LS and GMS, with higher homogenization pressure producing an increasingly stable complex. LS-GMS complex inhibited starch granules swelling, solubility and pasting development, which further reduced peak and breakdown viscosity. During storage, LS-GMS complexes prepared by 70-100MPa had higher Avrami exponent values and lower recrystallization rates compared with native starch, which suggested a lower retrogradation trendency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mars at Ls 145o: Acidalia/Mare Erythraeum

NASA Technical Reports Server (NTRS)

2005-01-01

11 January 2004 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 145o during a previous Mars year. This month, Mars looks similar, as Ls 145o occurs in mid-January 2005.

This picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day.

Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o--the start of northern spring and southern summer. In January 2005, it is northern summer and southern winter. The seasons on Mars occur according to Ls, described in thefollowing table:

Ls Season 0 - 90 northern spring, southern autumn 90 - 180 northern summer, southern winter 180 - 270 northern autumn, southern spring 270 - 360 northern winter, southern summer

Mars at Ls 145o: Elysium/Mare Cimmerium

NASA Technical Reports Server (NTRS)

2005-01-01

This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 145 during a previous Mars year. This month, Mars looked similar, as Ls 145 occurred in mid-January 2005.

This picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year were posted for MOC Picture of the Day.

Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360 around the Sun in 1 Mars year. The year begins at Ls 0 -- the start of northern spring and southern summer. In January 2005, it is northern summer and southern winter. The seasons on Mars occur according to Ls, described in the following table:

Ls Season 0 - 90 northern spring, southern autumn 90 - 180 northern summer, southern winter 180 - 270 northern autumn, southern spring 270 - 360 northern winter, southern summer

Energy and Cost Associated with Ventilating Office Buildings in a Tropical Climate

PubMed Central

Rim, Donghyun; Schiavon, Stefano; Nazaroff, William W.

2015-01-01

Providing sufficient amounts of outdoor air to occupants is a critical building function for supporting occupant health, well-being and productivity. In tropical climates, high ventilation rates require substantial amounts of energy to cool and dehumidify supply air. This study evaluates the energy consumption and associated cost for thermally conditioning outdoor air provided for building ventilation in tropical climates, considering Singapore as an example locale. We investigated the influence on energy consumption and cost of the following factors: outdoor air temperature and humidity, ventilation rate (L/s per person), indoor air temperature and humidity, air conditioning system coefficient of performance (COP), and cost of electricity. Results show that dehumidification of outdoor air accounts for more than 80% of the energy needed for building ventilation in Singapore’s tropical climate. Improved system performance and/or a small increase in the indoor temperature set point would permit relatively large ventilation rates (such as 25 L/s per person) at modest or no cost increment. Overall, even in a thermally demanding tropical climate, the energy cost associated with increasing ventilation rate up to 25 L/s per person is less than 1% of the wages of an office worker in an advanced economy like Singapore’s. This result implies that the benefits of increasing outdoor air ventilation rate up to 25 L/s per person — which is suggested to provide for productivity increases, lower sick building syndrome symptom prevalence, and reduced sick leave — can be much larger than the incremental cost of ventilation. PMID:25822504

Respiratory Abnormalities among Occupationally Exposed, Non-Smoking Brick Kiln Workers from Punjab, India.

PubMed

Tandon, Supriya; Gupta, Sharat; Singh, Sharanjeet; Kumar, Avnish

2017-07-01

Brick manufacturing industry is one of the oldest and fast-growing industries in India that employs a large section of people. Brick kiln workers are occupationally exposed to air pollutants. Nonetheless, only a few studies have so far been conducted on their respiratory health. To investigate the extent of respiratory impairment in brick kiln workers and to correlate it with the duration of exposure. A cross-sectional study was conducted. Spirometric parameters of 110 non-smoking male brick kiln workers aged 18-35 years in Patiala district, Punjab, India, were compared with an age-matched comparison group of 90 unexposed individuals. Brick kiln workers showed a significant (p<0.05) decline in forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), forced mid-expiratory flow rate (FEF 25-75% ) and peak expiratory flow rate (PEFR) compared with those of the comparison group. The extent of deterioration in lung function of brick kiln workers was associated with the duration of exposure. In workers with >8 years of exposure, the mean values of FEV 1 (1.92 L), FVC (2.01 L), FEF 25-75% (2.19 L/s) and PEFR (4.81 L/s) were significantly (p<0.05) lower than those recorded in workers with <8 years of exposure in whom the values were 2.01 L, 2.68 L, 2.71 L/s, and 5.76 L/s, respectively. There is a significant association between exposure to workplace pollutants and lung function deterioration among brick kiln workers.

Isothermal Analysis of the Crystallization Kinetics in Lithium Disilicate Glass using Trans Temp Furnace

NASA Technical Reports Server (NTRS)

Fuss, T.; Ray, C. S.; Day, D. E.

2006-01-01

Crystallization kinetics for lithium disilicate, Li2O2SiO2, (LS2) glass has been studied extensively by nonisothermal methods, but only a few studies on the isothermal crystallization kinetics of LS2 are available. In the present research, isothermal crystallization experiments or the LS2 glass were conducted in a Trans Temp furnace between 600 and 635 C, and selected properties such as the activation energy for crystallization (E), crystal growth index or Avrami parameter (n), the concentration of quenched-in nuclei in the starting glass (Ni) and the crystal nucleation rate (I) were measured. The crystal nucleation rate (I) was measured at only one selected temperature of 452 C, at this time. This commercial furnace has a 13 cm long isothermal heating zone (+/- 1 C) that allows precise heat treatment of relatively large samples. By placing a thermocouple within approx. 2 mm of the sample, it was possible to detect the heat of crystallization in the form of an isothermal crystallization exotherm during isothermal heat treatment of the sample. The values of E (318 plus or minus 10 kJ/mol), n (3.6 plus or minus 0.l), and N(sub i) (1.6 x 10(exp l2) m(sup -3)) calculated by analyzing these isotherms using the standard Johnson-Mehl-Avrami (JMA) equation were reproducible and in agreement with the literature values. The value of I, 1.9 x 10(exp 10) m(sup -3) s(sup -1) at 452 C, is an order of magnitude higher than the reported value for LS2.

Cognitive models of physicians' legal standard and personal judgments of competency in patients with Alzheimer's disease.

PubMed

Earnst, K S; Marson, D C; Harrell, L E

2000-08-01

To investigate measures of patient cognitive abilities as predictors of physician judgments of medical treatment consent capacity (competency) in patients with Alzheimer's disease (AD). Predictor models of legal standards (LS) and personal competency judgments were developed for each study physician using independent neuropsychological test measures and logistic regression analyses. A university medical center. Five physicians with experience assessing the competency of AD patients were recruited to make competency judgments of videotaped vignettes from 10 older controls and 21 patients with AD (10 with mild and 11 with moderate dementia). The 31 patient and control videotapes of performance on a measure of treatment consent capacity (Capacity to Consent to Treatment Instrument) (CCTI) were rated by the five physicians. The CCTI consists of two clinical vignettes (A-neoplasm and B-cardiac) that test competency under five LS. Each study physician viewed each vignette videotape individually, made judgments of competent or incompetent under each of the LS, and then made his/her own personal competency judgment. Physicians were blinded to participant diagnosis and neuropsychological test performance. Stepwise logistic regression was conducted to identify cognitive predictors of each physician's LS and personal competency judgments for Vignette A using the full sample (n = 31). Classification logistic regression analysis was used to determine how well these cognitive predictor models classified each physician's competency judgments for Vignette A. These classification models were then cross-validated using physician's Vignette B judgments. Cognitive predictor models for Vignette A competency judgments differed across individual physicians, and were related to difficulty of LS and to incompetency outcome rates across LS for AD patients. Measures of semantic knowledge and receptive language predicted judgments under less difficult LS of evidencing a treatment choice (LS1) and making the reasonable treatment choice (LS2). Measures of semantic knowledge, short-term verbal recall, and simple reasoning ability predicted judgments under more difficult and clinically relevant LS of appreciating consequences of a treatment choice (LS3), providing rational reasons for a treatment choice (LS4), and understanding the treatment situation and choices (LSS). Cognitive models for physicians' personal competency judgments were virtually identical to their respective models for LS5 judgments. For AD patients, shortterm memory predictors were associated with high incompetency outcome rates (over 70%), a simple reasoning measure was associated with moderately high incompetency outcome rates (60-70%), and a semantic knowledge measure was associated with lower incompetency outcome rates (30-60%). Overall, single predictor models were relatively robust, correctly classifying an average of 83% of physician judgments for Vignette A and 80% of judgments for Vignette B. Multiple cognitive functions predicted physicians' LS and personal competency judgments. Declines in semantic knowledge, short-term verbal recall, and simple reasoning ability predicted physicians' judgments on the three most difficult and clinically most relevant LS (LS3-LS5), as well as their personal competency judgments. Our findings suggest that clinical assessment of competency should include evaluation of semantic knowledge, verbal recall, and simple reasoning abilities.

Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi

PubMed Central

Schoch, Conrad L.; Seifert, Keith A.; Huhndorf, Sabine; Robert, Vincent; Spouge, John L.; Levesque, C. André; Chen, Wen; Bolchacova, Elena; Voigt, Kerstin; Crous, Pedro W.; Miller, Andrew N.; Wingfield, Michael J.; Aime, M. Catherine; An, Kwang-Deuk; Bai, Feng-Yan; Barreto, Robert W.; Begerow, Dominik; Bergeron, Marie-Josée; Blackwell, Meredith; Boekhout, Teun; Bogale, Mesfin; Boonyuen, Nattawut; Burgaz, Ana R.; Buyck, Bart; Cai, Lei; Cai, Qing; Cardinali, G.; Chaverri, Priscila; Coppins, Brian J.; Crespo, Ana; Cubas, Paloma; Cummings, Craig; Damm, Ulrike; de Beer, Z. Wilhelm; de Hoog, G. Sybren; Del-Prado, Ruth; Dentinger, Bryn; Diéguez-Uribeondo, Javier; Divakar, Pradeep K.; Douglas, Brian; Dueñas, Margarita; Duong, Tuan A.; Eberhardt, Ursula; Edwards, Joan E.; Elshahed, Mostafa S.; Fliegerova, Katerina; Furtado, Manohar; García, Miguel A.; Ge, Zai-Wei; Griffith, Gareth W.; Griffiths, K.; Groenewald, Johannes Z.; Groenewald, Marizeth; Grube, Martin; Gryzenhout, Marieka; Guo, Liang-Dong; Hagen, Ferry; Hambleton, Sarah; Hamelin, Richard C.; Hansen, Karen; Harrold, Paul; Heller, Gregory; Herrera, Cesar; Hirayama, Kazuyuki; Hirooka, Yuuri; Ho, Hsiao-Man; Hoffmann, Kerstin; Hofstetter, Valérie; Högnabba, Filip; Hollingsworth, Peter M.; Hong, Seung-Beom; Hosaka, Kentaro; Houbraken, Jos; Hughes, Karen; Huhtinen, Seppo; Hyde, Kevin D.; James, Timothy; Johnson, Eric M.; Johnson, Joan E.; Johnston, Peter R.; Jones, E.B. Gareth; Kelly, Laura J.; Kirk, Paul M.; Knapp, Dániel G.; Kõljalg, Urmas; Kovács, Gábor M.; Kurtzman, Cletus P.; Landvik, Sara; Leavitt, Steven D.; Liggenstoffer, Audra S.; Liimatainen, Kare; Lombard, Lorenzo; Luangsa-ard, J. Jennifer; Lumbsch, H. Thorsten; Maganti, Harinad; Maharachchikumbura, Sajeewa S. N.; Martin, María P.; May, Tom W.; McTaggart, Alistair R.; Methven, Andrew S.; Meyer, Wieland; Moncalvo, Jean-Marc; Mongkolsamrit, Suchada; Nagy, László G.; Nilsson, R. Henrik; Niskanen, Tuula; Nyilasi, Ildikó; Okada, Gen; Okane, Izumi; Olariaga, Ibai; Otte, Jürgen; Papp, Tamás; Park, Duckchul; Petkovits, Tamás; Pino-Bodas, Raquel; Quaedvlieg, William; Raja, Huzefa A.; Redecker, Dirk; Rintoul, Tara L.; Ruibal, Constantino; Sarmiento-Ramírez, Jullie M.; Schmitt, Imke; Schüßler, Arthur; Shearer, Carol; Sotome, Kozue; Stefani, Franck O.P.; Stenroos, Soili; Stielow, Benjamin; Stockinger, Herbert; Suetrong, Satinee; Suh, Sung-Oui; Sung, Gi-Ho; Suzuki, Motofumi; Tanaka, Kazuaki; Tedersoo, Leho; Telleria, M. Teresa; Tretter, Eric; Untereiner, Wendy A.; Urbina, Hector; Vágvölgyi, Csaba; Vialle, Agathe; Vu, Thuy Duong; Walther, Grit; Wang, Qi-Ming; Wang, Yan; Weir, Bevan S.; Weiß, Michael; White, Merlin M.; Xu, Jianping; Yahr, Rebecca; Yang, Zhu L.; Yurkov, Andrey; Zamora, Juan-Carlos; Zhang, Ning; Zhuang, Wen-Ying; Schindel, David

2012-01-01

Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups. PMID:22454494

Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi.

PubMed

Schoch, Conrad L; Seifert, Keith A; Huhndorf, Sabine; Robert, Vincent; Spouge, John L; Levesque, C André; Chen, Wen

2012-04-17

Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.

Genetic selection for ovulation rate and litter size in rabbits: Estimation of genetic parameters and direct and correlated responses.

PubMed

Ziadi, C; Mocé, M L; Laborda, P; Blasco, A; Santacreu, M A

2013-07-01

The aim of this work was to estimate direct and correlated responses in survival rates in an experiment of selection for ovulation rate (OR) and litter size (LS) in a line of rabbits (OR_LS). From generation 0 to 6 (first selection period), females were selected only for second gestation OR estimated by laparoscopy. From generation 7 to 13 (second selection period), a 2-stage selection for OR and LS was performed. In stage 1, females having the greatest OR at second gestation were selected. In stage 2, selection was for the greatest average LS of the first 2 parities of the females selected in stage 1. Total selection pressure in females was about 30%. The line had approximately 17 males and 75 females per generation. Traits recorded were OR estimated as the number of corpora lutea in both ovaries, number of implanted embryos (IE) estimated as the number of implantation sites, LS estimated as total number of rabbits born recorded at each parity, embryo survival (ES) estimated as IE/OR, fetal survival (FS) estimated as LS/IE, and prenatal survival (PS) estimated as LS/OR. Data were analyzed using Bayesian methodology. The estimated heritabilities of LS, OR, IE, ES, FS, and PS were 0.07, 0.21, 0.10, 0.07, 0.12, and 0.16, respectively. Direct and correlated responses from this study were estimated in each period of selection as the difference between the average genetic values of last and first generation. In the first selection period, OR increased 1.36 ova, but no correlated response was observed in LS due to a decrease on FS. Correlated responses for IE, ES, FS, and PS in the first selection period were 1.11, 0.00, -0.04, and -0.01, respectively. After 7 generations of 2-stage selection for OR and LS, OR increased 1.0 ova and response in LS was 0.9 kits. Correlated responses for IE, ES, FS, and PS in the second selection period were 1.14, 0.02, 0.02, and 0.07, respectively. Two-stage selection for OR and LS can be a promising procedure to improve LS in rabbits.

Three new anascosporic genera of the Saccharomycotina: Danielozyma gen. nov., Deakozyma gen. nov. and Middelhovenomyces gen. nov.

USDA-ARS?s Scientific Manuscript database

Three new non-ascosporic, ascomycetous yeast genera are proposed based on their isolation from currently described species and genera. Phylogenetic placement of the genera was determined from analysis of nuclear gene sequences for D1/D2 large subunit rRNA, small subunit rRNA, translation elongation...

Diet and trophic niche of Antarctic silverfish Pleuragramma antarcticum in the Ross Sea, Antarctica.

PubMed

Pinkerton, M H; Forman, J; Bury, S J; Brown, J; Horn, P; O'Driscoll, R L

2013-01-01

The diet of Antarctic silverfish Pleuragramma antarcticum was evaluated by examining stomach contents of specimens collected in the Ross Sea (71°-77° S; 165°-180° E) in January to March 2008. Pleuragramma antarcticum (50-236 mm standard length, L(S)) and prey items were analysed for stable-isotopic composition of carbon and nitrogen. According to index of relative importance (I(RI) ), which incorporates frequency of occurrence, mass and number of prey items, the most important prey items were copepods (81%I(RI) over all specimens), predominantly Metridia gerlachei and Paraeuchaeta sp., with krill and fishes having low I(RI) (2·2 and 5·6%I(RI) overall). According to mass of prey (M) in stomachs, however, fishes (P. antarcticum and myctophids) and krill dominated overall diet (48 and 22%M, respectively), with copepods being a relatively minor constituent of overall diet by mass (9·9%M). Piscivory by P. antarcticum occurred mainly in the extreme south-west of the region and near the continental slope. Krill identified to species level in P. antarcticum stomachs were predominantly Euphausia superba (14·1%M) with some Euphausia crystallophorias (4·8%M). Both DistLM modelling (PRIMER-permanova+) on stomach contents (by I(RI)) and stepwise generalized linear modelling on stable isotopes showed that L(S) and location were significant predictors of P. antarcticum diet. Postlarval P. antarcticum (50-89 mm L(S)) consumed exclusively copepods. Juvenile P. antarcticum (90-151 mm L(S)) consumed predominantly krill and copepods by mass (46 and 30%M, respectively). Small adult P. antarcticum (152-178 mm L(S)) consumed krill, fishes and copepods (37, 36 and 15%M, respectively). Large adult P. antarcticum (179-236 mm L(S)) consumed predominantly fishes and krill (55 and 17%M, respectively), especially in the north (near the Ross Sea slope) and in the SW Ross Sea. Amphipods were occasionally important prey items for P. antarcticum (western Ross Sea, 39%M). General concordance between stomach contents and trophic level of P. antarcticum and prey based on δ(15) N was demonstrated. Pleuragramma antarcticum trophic level was estimated as 3·7 (postlarval fish) and 4·1 (fish aged 3+ years). © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Multidimensional construct of life satisfaction in older adults in Korea: a six-year follow-up study.

PubMed

Lim, Hyun Ja; Min, Dae Kee; Thorpe, Lilian; Lee, Chel Hee

2016-11-28

Aging raises wide-ranging issues within social, economic, welfare, and health care systems. Life satisfaction (LS) is regarded as an indicator of quality of life which, in turn, is associated with mortality and morbidity in older adults. The objective of this study was to identify the relevant predictors of life satisfaction and to investigate changes in a multidimensional construct of LS over time. This analysis utilized data from the large-scale, nationally representative Korean Retirement and Income Study (KReIS), a longitudinal survey conducted biennially from 2005 to 2011. Outcome measures were degree of satisfaction with health, economic status, housing, neighbor relationships, and family relationships. GEE models were used to investigate changes in satisfaction within each of the five domains. Of a total 3531 individuals aged 65 or older, 2083 (59%) were women, and the mean age was 72 (s.d = ±6) years. The majority had a spouse (60.8%) and lived in a rural area (58%). Analysis showed that physical and mental health were consistently and significantly associated with satisfaction in each of the domains after adjusting for potential confounders. Living in a rural area and living with a spouse were related to satisfaction with economic, housing, family relationships, and neighbor relationships compared to living in urban areas and living without a spouse; the only outcome that did not show relationship to these predictors was health satisfaction. Female and rural residents reported greater economic satisfaction compared to male and urban residents. Living in an apartment was associated with 1.32 times greater odds of economic satisfaction compared to living in a detached house (95% CI: 1.14-1.53; p < 0.0001). Economic satisfaction was also 1.62 times more likely among individuals living with a spouse compared to single households (95% CI: 1.35-1.96; p < 0.0001). Financial stress index value was found to be a significant predictor of satisfaction with family relationships. Our study indicates that a single domain of LS or overall LS will miss many important aspects of LS as age-related LS is multi-faceted and complicated. While most studies focus on overall life satisfaction, considering life satisfaction as multidimensional is essential to gaining a complete picture.

Dietary sodium and nocturnal blood pressure dipping in normotensive men and women.

PubMed

Brian, M S; Dalpiaz, A; Matthews, E L; Lennon-Edwards, S; Edwards, D G; Farquhar, W B

2017-02-01

Impaired nocturnal blood pressure (BP) dipping (i.e., <10% decline in nocturnal BP) is associated with an increased risk of cerebrovascular and cardiovascular diseases. Excess sodium has been shown to impair BP regulation and increase cardiovascular disease risk, yet few studies have assessed the influence of dietary sodium on nocturnal dipping in normotensive adults. The purpose of this study was to determine the effects of dietary sodium on BP dipping in normotensive men and women. Eighty healthy normotensive adults participated in a controlled feeding study (men: n=39, 34±2 years; women: n=41, 41±2 years). Participants consumed a standardized run-in 100 mmol sodium per day diet for 7 days, followed by 7 days of low-sodium (LS; 20 mmol per day) and high-sodium (HS; 300 mmol per day) diets in random order. On the final day of each diet, subjects wore a 24 h ambulatory BP monitor, collected a 24 h urine sample and provided a blood sample. During the run-in diet, 24 h urinary sodium excretion was 79.4±5.1 mmol per 24 h in men and 85.3±5.5 mmol per 24 h in women (P>0.05). Systolic BP dipping was not different between men (11.4±1.0%) and women (11.2±0.9%); (P>0.05). During the HS diet, 24 h urinary sodium excretion increased compared with the LS diet in men (LS=31.7±4.6 mmol per 24 h vs HS=235.0±13.9 mmol per 24 h, P<0.01) and women (LS=25.8±2.2 mmol per 24 h vs HS=234.7±13.8 mmol per 24 h, P<0.01). Despite this large increase in sodium intake and excretion, systolic BP dipping was not blunted in men (LS=8.9±1.0% vs HS=9.4±1.2%, P>0.05) or women (LS=10.3±0.8% vs HS=10.5±0.8%, P>0.05). Among normotensive men and women, HS does not blunt nocturnal BP dipping.

Skeletal development and abnormalities of the vertebral column and of the fins in hatchery-reared turbot Scophthalmus maximus.

PubMed

Tong, X H; Liu, Q H; Xu, S H; Ma, D Y; Xiao, Z Z; Xiao, Y S; Li, J

2012-03-01

To describe the skeletal development and abnormalities in turbot Scophthalmus maximus, samples were collected every day from hatching to 60 days after hatching (DAH). A whole-mount cartilage and bone-staining technique was used. Vertebral ontogeny started with the formation of anterior haemal arches at 5·1 mm standard length (L(S) ) c. 11 DAH, and was completed by the full attainment of parapophyses at 16·9 mm L(S) c. 31 DAH. Vertebral centra started to develop at 6·3 mm L(S) c. 16 DAH and ossification in all centra was visible at 11·0 mm L(S) c. 25 DAH. The caudal fin appeared at 5·1 mm L(S) c. 11 DAH and ossification was visible at 20·6 mm L(S) c. 37 DAH. The onset of dorsal and anal fin elements appeared at 5·8 mm L(S) c. 15 DAH and 6·3 mm L(S) c. 16 DAH, respectively. Ossifications of both dorsal fin and anal fin were visible at 20·6 mm L(S) c. 37 DAH. The pectorals were the only fins present before first feeding, their ossifications were completed at 23·5 mm L(S) c. 48 DAH. Pelvic fins began forming at 7·2 mm L(S) c. 19 DAH and calcification of the whole structure was visible at 19·8 mm L(S) c. 36 DAH. In the present study, 24 types of skeletal abnormalities were observed. About 51% of individuals presented skeletal abnormalities, and the highest occurrence was found in the haemal region of the vertebral column. As for each developmental stage, the most common abnormalities were in the dorsal fin during early metamorphic period (stage 2), vertebral fusion during climax metamorphosis (stage 3) and caudal fin abnormality during both late-metamorphic period (stage 4) and post-metamorphic period (stage 5). Such research will be useful for early detection of skeletal malformations during different growth periods of reared S. maximus. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study.

PubMed

Murbraech, Klaus; Wethal, Torgeir; Smeland, Knut B; Holte, Harald; Loge, Jon Håvard; Holte, Espen; Rösner, Assami; Dalen, Håvard; Kiserud, Cecilie E; Aakhus, Svend

2016-03-01

This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Maternal corticosterone reduces egg fertility and hatchability and increases the numbers of early dead embryos in eggs laid by quail hens selected for exaggerated adrenocortical stress responsiveness.

PubMed

Schmidt, J B; Satterlee, D G; Treese, S M

2009-07-01

Quail hens selected for exaggerated (HS, high stress) rather than reduced (LS, low stress) plasma corticosterone (B) response to brief restraint deposit more B into their egg yolks than do LS hens. Female progeny of HS hens implanted with B also show reduced egg production when compared with female offspring of LS- and HS-control and LS-B-implanted hens. Herein, LS and HS hens were implanted (s.c.) with empty (controls, CON) or B-filled silastic tubes to assess the interactive influences of maternal B-treatment with quail stress line on egg fertility (FERT), total egg hatchability (TOTHATCH) and fertile egg hatchability, and the percentages of embryonic mortality (early dead, ED; late dead) and pipped eggs. Mean FERT was dramatically reduced in eggs of HS compared with LS hens and B-implanted compared with CON-treated hens (P < 0.0001, both cases). Line x implant treatment FERT outcomes partitioned (P < 0.05) as follows: LS-B = LS-CON > HS-CON > HS-B. In addition, TOTHATCH was also affected by line (LS > HS; P < 0.0001) and implant treatment (CON > B-implant; P < 0.0002) and line x implant treatment TOTHATCH means differed (P < 0.05) as follows: LS-CON = LS-B = HS-CON > HS-B. Fertile egg hatchability was reduced (P < 0.05) in HS-B-treated hen eggs when compared with LS-B and HS-CON hen eggs and more (P < 0.05) ED embryos were found in eggs laid by HS-B-implanted hens than in any other treatment group. Late dead and pipped egg percentages were unaffected by any treatment. The findings are important to avian geneticists because they further emphasize the benefits that selection for reduced adrenocortical responsiveness has on hen reproductive performance. The maternal B findings also warn poultry and hatchery managers that unless hen stress during egg formation is avoided, negative consequences in FERT, TOTHATCH, and ED can result, particularly in hens genetically predisposed toward exaggerated adrenal stress responsiveness.

The linearly scaling 3D fragment method for large scale electronic structure calculations

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

Zhao, Zhengji; Meza, Juan; Lee, Byounghak

2009-07-28

The Linearly Scaling three-dimensional fragment (LS3DF) method is an O(N) ab initio electronic structure method for large-scale nano material simulations. It is a divide-and-conquer approach with a novel patching scheme that effectively cancels out the artificial boundary effects, which exist in all divide-and-conquer schemes. This method has made ab initio simulations of thousand-atom nanosystems feasible in a couple of hours, while retaining essentially the same accuracy as the direct calculation methods. The LS3DF method won the 2008 ACM Gordon Bell Prize for algorithm innovation. Our code has reached 442 Tflop/s running on 147,456 processors on the Cray XT5 (Jaguar) atmore » OLCF, and has been run on 163,840 processors on the Blue Gene/P (Intrepid) at ALCF, and has been applied to a system containing 36,000 atoms. In this paper, we will present the recent parallel performance results of this code, and will apply the method to asymmetric CdSe/CdS core/shell nanorods, which have potential applications in electronic devices and solar cells.« less

The Linearly Scaling 3D Fragment Method for Large Scale Electronic Structure Calculations

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

Zhao, Zhengji; Meza, Juan; Lee, Byounghak

2009-06-26

The Linearly Scaling three-dimensional fragment (LS3DF) method is an O(N) ab initio electronic structure method for large-scale nano material simulations. It is a divide-and-conquer approach with a novel patching scheme that effectively cancels out the artificial boundary effects, which exist in all divide-and-conquer schemes. This method has made ab initio simulations of thousand-atom nanosystems feasible in a couple of hours, while retaining essentially the same accuracy as the direct calculation methods. The LS3DF method won the 2008 ACM Gordon Bell Prize for algorithm innovation. Our code has reached 442 Tflop/s running on 147,456 processors on the Cray XT5 (Jaguar) atmore » OLCF, and has been run on 163,840 processors on the Blue Gene/P (Intrepid) at ALCF, and has been applied to a system containing 36,000 atoms. In this paper, we will present the recent parallel performance results of this code, and will apply the method to asymmetric CdSe/CdS core/shell nanorods, which have potential applications in electronic devices and solar cells.« less

Measuring consistent masses for 25 Milky Way globular clusters

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

Kimmig, Brian; Seth, Anil; Ivans, Inese I.

2015-02-01

We present central velocity dispersions, masses, mass-to-light ratios (M/Ls ), and rotation strengths for 25 Galactic globular clusters (GCs). We derive radial velocities of 1951 stars in 12 GCs from single order spectra taken with Hectochelle on the MMT telescope. To this sample we add an analysis of available archival data of individual stars. For the full set of data we fit King models to derive consistent dynamical parameters for the clusters. We find good agreement between single-mass King models and the observed radial dispersion profiles. The large, uniform sample of dynamical masses we derive enables us to examine trendsmore » of M/L with cluster mass and metallicity. The overall values of M/L and the trends with mass and metallicity are consistent with existing measurements from a large sample of M31 clusters. This includes a clear trend of increasing M/L with cluster mass and lower than expected M/Ls for the metal-rich clusters. We find no clear trend of increasing rotation with increasing cluster metallicity suggested in previous work.« less

Cryo-EM structure of the large subunit of the spinach chloroplast ribosome

PubMed Central

Ahmed, Tofayel; Yin, Zhan; Bhushan, Shashi

2016-01-01

Protein synthesis in the chloroplast is mediated by the chloroplast ribosome (chloro-ribosome). Overall architecture of the chloro-ribosome is considerably similar to the Escherichia coli (E. coli) ribosome but certain differences are evident. The chloro-ribosome proteins are generally larger because of the presence of chloroplast-specific extensions in their N- and C-termini. The chloro-ribosome harbours six plastid-specific ribosomal proteins (PSRPs); four in the small subunit and two in the large subunit. Deletions and insertions occur throughout the rRNA sequence of the chloro-ribosome (except for the conserved peptidyl transferase center region) but the overall length of the rRNAs do not change significantly, compared to the E. coli. Although, recent advancements in cryo-electron microscopy (cryo-EM) have provided detailed high-resolution structures of ribosomes from many different sources, a high-resolution structure of the chloro-ribosome is still lacking. Here, we present a cryo-EM structure of the large subunit of the chloro-ribosome from spinach (Spinacia oleracea) at an average resolution of 3.5 Å. High-resolution map enabled us to localize and model chloro-ribosome proteins, chloroplast-specific protein extensions, two PSRPs (PSRP5 and 6) and three rRNA molecules present in the chloro-ribosome. Although comparable to E. coli, the polypeptide tunnel and the tunnel exit site show chloroplast-specific features. PMID:27762343

Evaluations of laparoscopic proctocolectomy versus traditional technique in patients with rectal cancer.

PubMed

Koulas, Spyridon G; Pappas-Gogos, George; Spirou, Spyridon; Roustanis, Evangelos; Tsimogiannis, Konstantinos E; Tsirves, Georgios; Tsimoyiannis, Evangelos C

2009-01-01

This was a retrospective study that evaluated the surgical outcomes of laparoscopic surgery (LS) for rectal cancer, in comparison with a case control series of open surgery (OS), during an 8-year period. Between October 1998 and December 2006, 203 patients with rectal malignancies underwent colectomy; 146 of them had colectomy with the traditional technique (OS), while 57 underwent resection of rectal cancer laparoscopically (LS). The LS group was compared with 60 patients from the OS group (selected from the 146 OS group patients), matched by size, sex, age, anatomical location of the tumor, type, extent of resection, and pathological stage. Data were obtained from patients' medical records. Statistical analysis was performed with the t test and chi-square test. All data are expressed as mean +/- standard error of the mean (SEM). Mean age of the LS group was 63.7+/-12 years versus 69+/-12 years in the OS group. There were more men than women in both the laparoscopic (33 males, 24 females) and OS groups (35 men, 25 women). The mean follow-up period was 38 months and 78 months for LS and OS groups, respectively. The procedure included low anterior resection (43 in LS and 45 in OS), and 13 patients in both groups underwent abdominoperineal resection and 3 transanal resections (2 in OS and 1 in LS). Mean tumor size was 4.2+/-2.12cm in the LS versus 5.2+/-2.02cm in the OS group. Conversion to an open procedure occurred in 4 patients (6.7%), all in the first 20 cases. Postoperative complications developed in 28 patients (11.7%), 13 in the LS group and 15 in the OS group. Median operative time was longer, but median blood loss was significantly lower in the LS group. The length of hospital stay was significantly shorter for the LS group. Laparoscopic surgery is feasible and safe for patients with rectal cancer and provides benefits during the postoperative period without increased morbidity or mortality.

Cognitive-behavioral therapy improves weight loss and quality of life in women with polycystic ovary syndrome: a pilot randomized clinical trial.

PubMed

Cooney, Laura G; Milman, Lauren W; Hantsoo, Liisa; Kornfield, Sara; Sammel, Mary D; Allison, Kelly C; Epperson, C Neill; Dokras, Anuja

2018-06-13

To compare the effects of cognitive-behavioral therapy (CBT) and lifestyle modification (LS) versus LS alone on weight, depressive and anxiety symptoms, and stress response in women with polycystic ovary syndrome (PCOS), overweight/obesity, and depressive symptoms. A 16-week pilot randomized clinical trial. Tertiary-care PCOS center. Overweight/obese women with PCOS and depressive symptoms. Weekly CBT (n = 7) or contact only/no therapy (n = 8) for 8 weeks. Both groups received weekly LS for 16 weeks. Changes in weight, depression (Center for Epidemiologic Studies Depression Scale [CES-D]), anxiety (State-Trait Anxiety Inventory [STAI]), quality of life (Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire [PCOSQ]), laboratory tests, and response to a Trier Social Stress Test (TSST). The CBT+LS group lost more weekly weight (-0.35 kg/wk vs. -0.16 kg/wk) compared with the LS group. Overall, the CBT+LS group lost 3.2 kg versus 1.8 kg for the LS group. The CBT+LS group had greater improvement in PCOSQ at 8 weeks (+3.7 vs. +1.2 points). In the overall cohort, STAI and CES-D decreased by -0.27 points per week and -0.31 points/wk, respectfully, and total and free T decreased at week 8. Heart rate response to TSST was lower at 15 minutes after stressor in the CBT+LS group. Weekly CBT+LS for 8 weeks compared with LS alone resulted in significant weight loss and improved quality of life in overweight/obese women with PCOS and depressive symptoms. These interventions were associated with a decreased autonomic response to a laboratory stressor, suggesting a potential link between CBT, weight loss, and modulation of the stress response. NCT01899001. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

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

Noda, Saori; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba; Takahashi, Atsushi

SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylatedmore » parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.« less

Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients

PubMed Central

Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromistu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro

2016-01-01

Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS-associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing. PMID:26848797

Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients.

PubMed

Kato, Aya; Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromistu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro

2016-06-01

Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS-associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing.

Properties of Two-Variety Natural Luffa Sponge Columns as Potential Mattress Filling Materials

PubMed Central

Chen, Yuxia; Zhang, Kaiting; Yuan, Fangcheng; Zhang, Tingting; Weng, Beibei; Wu, Shanshan; Huang, Aiyue; Su, Na; Guo, Yong

2018-01-01

Luffa sponge (LS) is a resourceful material with fibro-vascular reticulated structure and extremely high porosity, which make it a potential candidate for manufacturing light mattress. In this study, two types of LS columns, namely high-density (HD) and low-density (LD) columns, were investigated as materials for filling the mattress. The results showed that the compressive strength of HD LS columns was significantly greater than that of LD LS columns. However, the densification strains of the two types of LS column were both in the range of 0.6 to 0.7. Besides, HD LS columns separately pressed to the smooth plateau region and the initial densification region exhibited a partial recovery of instant height when they were unloaded, and then both of them showed no more than 4.2% of height recovery after being allowed to rest at a constant temperature and humidity for 24 h. In contrast, when LD LS columns were compressed to the smooth plateau region, the height recovery was less than 1.62% compared to when they were pressed to the initial densification region, and that was more than 15.62%. Similar to other plant fibers used as mattress fillers, the two types of LS columns also showed good water absorption capacity—both of them could absorb water from as much as 2.07 to 3.45 times their own weight. At the same time, the two types of LS columns also showed good water desorption. The water desorption ratio of HD and LD LS columns separately reached 76.86 and 91.44%, respectively, after being let rest at a constant temperature and humidity for 13 h. PMID:29614744

The impact of vulvar lichen sclerosus on sexual dysfunction.

PubMed

Haefner, Hope K; Aldrich, Nely Z; Dalton, Vanessa K; Gagné, Hélène M; Marcus, Stephanie B; Patel, Divya A; Berger, Mitchell B

2014-09-01

Lichen sclerosus (LS) is a chronic inflammatory condition that is known to arise on the vulva. Many women with LS report vulvar pain, often affecting a patient's quality of life. In this study, the sexual function of LS patients, with and without pain, was compared to control populations. A case-control study to examine the relationship between LS and sexual dysfunction was conducted. A total of 335 women presenting to the gynecology clinic were included in the study: 197 women with biopsy confirmed LS were compared to two control groups (95 asymptomatic women were "healthy" controls and 43 women had vulvovaginal candidiasis) on self-reported current health complaints, medical and surgical history and current symptoms such as pain and itching, type and frequency of sexual activity, and satisfaction with sexual activity. Women with LS reported less frequent sexual activity than healthy controls (p=0.007) and Candida controls (p=0.04). Currently sexually active women with LS were significantly less likely to report vaginal intercourse (71.6%) than healthy controls (89.0%, p=0.003) or Candida controls (100%, p=0.0003), even though similar proportions of all three groups reported that vaginal intercourse was important. Satisfaction towards the quality of current sexual activity was significantly lower among women with LS compared with both the healthy and Candida control groups. 23.7% of women with LS reported that sexual activity was rarely or never satisfactory as compared with 0% of healthy controls (p<0.0001) and 6.5% of Candida controls (p=0.03). Women with LS have less frequent sexual activity and less satisfying sexual activity when compared with controls.

Short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy with a very small remnant stomach for cStage I proximal gastric carcinoma.

PubMed

Furukawa, Haruna; Kurokawa, Yukinori; Takiguchi, Shuji; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Yamasaki, Makoto; Nakajima, Kiyokazu; Mori, Masaki; Doki, Yuichiro

2018-05-01

Total or proximal gastrectomy is usually performed for early proximal gastric carcinoma, but the optimal type of gastrectomy is still unknown. We evaluated short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy (LsTG) in comparison with laparoscopic total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG). We analyzed 113 patients who underwent LsTG (n = 38), LTG (n = 48), or LPG (n = 27) for cStage I gastric cancer located in the upper third of the stomach. Postoperative morbidities, nutritional status including body weight, serum albumin, hemoglobin, the prognostic nutritional index (PNI), and endoscopic findings at 1 year after surgery were compared between LsTG and both LTG and LPG. Operation time and intraoperative blood loss were similar among the three groups. The incidence of postoperative morbidities was lower in LsTG than in LTG. The degree of body weight loss was significantly smaller in LsTG than in LTG at 6 and 12 months. At 12 months, LsTG resulted in better serum albumin and PNI than LPG, and better hemoglobin than LTG. Endoscopic examination demonstrated that one LsTG patient and two LPG patients had reflux esophagitis. Remnant gastritis was observed more frequently in LPG than in LsTG. No LsTG patient had bile reflux, although it was observed in four LPG patients. LsTG with a very small remnant stomach had favorable short-term outcomes and nutritional status compared with LTG and LPG, so it may be a better treatment option for cStage I proximal gastric carcinoma.

Containerless Processing of a Lithium Disilicate Glass

NASA Technical Reports Server (NTRS)

Ranasinghe, Kisa; Ray, Chandra S.; Day, Delbert E.; Rogers, Jan R.; Hyers, Robert W.; Rathz, Thomas

2004-01-01

Glasses of Li2O.2SiO2 (LS2), and LS2 doped with 0.001wt% platinum (LS2 + 0.001 wt% Pt) compositions were melted, cooled and reheated at controlled rates while levitated (containerless) inside an Electrostatic Levitator (ESL) furnace at the NASA Marshall Space Flight Center, Huntsville, AL. The experiments were conducted in vacuum (approximately 10(exp -5) Pa) using spherical, 2.5 to 3 millimeter diameter, glass samples. The measured critical cooling rate for glass formation, R(sub c), for the LS2 and LS2+0.001 wt% Pt glasses processed at ESL were 14 plus or minus 2 Celsius per minute and 130 plus or minus 5 Celsius per minute, respectively. The values of R(sub c), for the same LS2 and LS2 + 0.001 wt% Pt glasses processed in a container were 62 plus or minus 3 Celsius per minute and 162 plus or minus 5 Celsius per minute, respectively. The effective activation energy for crystallization, E, for this LS2 glass processed without a container at ESL, 392 plus or minus 15 kiloJoules per mole, was higher than that, 270 plus or minus 15 kiloJoules per mole, for an identical glass processed in a container. These results suggest that the glass formation tendency for a containerless LS2 melt is significantly increased compared to an identical melt in contact with a container. The absence of heterogeneous nucleation sites that are inherently present in all melts held in containers, and or a change in the surface composition due to evaporation of Li2O during processing at ESL are likely reasons for the increased glass forming tendency of this containerless LS2 melt.

Light sensors for objective light measurement in ambulatory polysomnography.

PubMed

Schembri, Rachel; Spong, Jo; Peters, Allison; Rochford, Peter; Wilksch, Philip; O'Donoghue, Fergal J; Greenwood, Kenneth M; Barnes, Maree; Kennedy, Gerard A; Berlowitz, David J

2017-01-01

Ambulatory polysomnography (PSG) does not commonly include an objective measure of light to determine the time of lights off (Loff), and thus cannot be used to calculate important indices such as sleep onset latency and sleep efficiency. This study examined the technical specifications and appropriateness of a prototype light sensor (LS) for use in ambulatory Compumedics Somte PSG.Two studies were conducted. The first examined the light measurement characteristics of the LS when used with a portable PSG device, specifically recording trace range, linearity, sensitivity, and stability. This involved the LS being exposed to varying incandescent and fluorescent light levels in a light controlled room. Secondly, the LS was trialled in 24 home and 12 hospital ambulatory PSGs to investigate whether light levels in home and hospital settings were within the recording range of the LS, and to quantify the typical light intensity reduction at the time of Loff. A preliminary exploration of clinical utility was also conducted. Linearity between LS voltage and lux was demonstrated, and the LS trace was stable over 14 hours of recording. The observed maximum voltage output of the LS/PSG device was 250 mV, corresponding to a maximum recording range of 350 lux and 523 lux for incandescent and fluorescent light respectively. At the time of Loff, light levels were within the recording range of the LS, and on average dropped by 72 lux (9-245) in the home and 76 lux (4-348) in the hospital setting. Results suggest that clinical utility was greatest in hospital settings where patients are less mobile. The LS was a simple and effective objective marker of light level in portable PSG, which can be used to identify Loff in ambulatory PSG. This allows measurement of additional sleep indices and support with clinical decisions.

Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.

PubMed

Fuchs, Gabriele; Petrov, Alexey N; Marceau, Caleb D; Popov, Lauren M; Chen, Jin; O'Leary, Seán E; Wang, Richard; Carette, Jan E; Sarnow, Peter; Puglisi, Joseph D

2015-01-13

Translation initiation can occur by multiple pathways. To delineate these pathways by single-molecule methods, fluorescently labeled ribosomal subunits are required. Here, we labeled human 40S ribosomal subunits with a fluorescent SNAP-tag at ribosomal protein eS25 (RPS25). The resulting ribosomal subunits could be specifically labeled in living cells and in vitro. Using single-molecule Förster resonance energy transfer (FRET) between RPS25 and domain II of the hepatitis C virus (HCV) internal ribosome entry site (IRES), we measured the rates of 40S subunit arrival to the HCV IRES. Our data support a single-step model of HCV IRES recruitment to 40S subunits, irreversible on the initiation time scale. We furthermore demonstrated that after binding, the 40S:HCV IRES complex is conformationally dynamic, undergoing slow large-scale rearrangements. Addition of translation extracts suppresses these fluctuations, funneling the complex into a single conformation on the 80S assembly pathway. These findings show that 40S:HCV IRES complex formation is accompanied by dynamic conformational rearrangements that may be modulated by initiation factors.

Protein Flexibility Facilitates Quaternary Structure Assembly and Evolution

PubMed Central

Marsh, Joseph A.; Teichmann, Sarah A.

2014-01-01

The intrinsic flexibility of proteins allows them to undergo large conformational fluctuations in solution or upon interaction with other molecules. Proteins also commonly assemble into complexes with diverse quaternary structure arrangements. Here we investigate how the flexibility of individual protein chains influences the assembly and evolution of protein complexes. We find that flexibility appears to be particularly conducive to the formation of heterologous (i.e., asymmetric) intersubunit interfaces. This leads to a strong association between subunit flexibility and homomeric complexes with cyclic and asymmetric quaternary structure topologies. Similarly, we also observe that the more nonhomologous subunits that assemble together within a complex, the more flexible those subunits tend to be. Importantly, these findings suggest that subunit flexibility should be closely related to the evolutionary history of a complex. We confirm this by showing that evolutionarily more recent subunits are generally more flexible than evolutionarily older subunits. Finally, we investigate the very different explorations of quaternary structure space that have occurred in different evolutionary lineages. In particular, the increased flexibility of eukaryotic proteins appears to enable the assembly of heteromeric complexes with more unique components. PMID:24866000

Ferromagnetic insulating state in tensile-strained LaCoO3 thin films from LDA + U calculations

NASA Astrophysics Data System (ADS)

Hsu, Han; Blaha, Peter; Wentzcovitch, Renata M.

2012-04-01

With local density approximation+Hubbard U (LDA+U) calculations, we show that the ferromagnetic (FM) insulating state observed in tensile-strained LaCoO3 epitaxial thin films is most likely a mixture of low-spin (LS) and high-spin (HS) Co, namely, a HS/LS mixture state. Compared with other FM states, including the intermediate-spin (IS) state (metallic within LDA+U), which consists of IS Co only, and the insulating IS/LS mixture state, the HS/LS state is the most favorable one. The FM order in the HS/LS state is stabilized via the superexchange interactions between adjacent LS and HS Co. We also show that the Co spin state can be identified by measuring the electric field gradient at the Co nucleus via nuclear magnetic resonance spectroscopy.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

PubMed Central

Torok, Kathryn S.; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N.; Medsger, Thomas; Feghali-Bostwick, Carol A.

2015-01-01

Objective To evaluate peripheral blood T-helper (TH) cell associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. Methods A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Results Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. Conclusion This is the first time that multiple cytokines and chemokines have been examined simultaneously LS. In general, a TH-1 (IFN-γ) and TH-17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN–γ signature with elevated IP-10, MCP-1 and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. PMID:26254121

[A novel approach to NIR spectral quantitative analysis: semi-supervised least-squares support vector regression machine].

PubMed

Li, Lin; Xu, Shuo; An, Xin; Zhang, Lu-Da

2011-10-01

In near infrared spectral quantitative analysis, the precision of measured samples' chemical values is the theoretical limit of those of quantitative analysis with mathematical models. However, the number of samples that can obtain accurately their chemical values is few. Many models exclude the amount of samples without chemical values, and consider only these samples with chemical values when modeling sample compositions' contents. To address this problem, a semi-supervised LS-SVR (S2 LS-SVR) model is proposed on the basis of LS-SVR, which can utilize samples without chemical values as well as those with chemical values. Similar to the LS-SVR, to train this model is equivalent to solving a linear system. Finally, the samples of flue-cured tobacco were taken as experimental material, and corresponding quantitative analysis models were constructed for four sample compositions' content(total sugar, reducing sugar, total nitrogen and nicotine) with PLS regression, LS-SVR and S2 LS-SVR. For the S2 LS-SVR model, the average relative errors between actual values and predicted ones for the four sample compositions' contents are 6.62%, 7.56%, 6.11% and 8.20%, respectively, and the correlation coefficients are 0.974 1, 0.973 3, 0.923 0 and 0.948 6, respectively. Experimental results show the S2 LS-SVR model outperforms the other two, which verifies the feasibility and efficiency of the S2 LS-SVR model.

Impact of age cutoffs on a lynch syndrome screening program.

PubMed

Gudgeon, James M; Belnap, Thomas W; Williams, Janet L; Williams, Marc S

2013-07-01

To determine the impact of applying an age cutoff to tumor-based Lynch syndrome (LS) screening, specifically focusing on changes in relative effectiveness, efficiency, and cost. The project was undertaken to answer questions about implementation of the LS screening program in an integrated health care delivery system. Clinical data extracted from an internal cancer registry, previous modeling efforts, published literature, and gray data were used to populate decision models designed to answer questions about the impact of age cutoffs in LS screening. Patients with colorectal cancer (CRC) were stratified at 10-year intervals from ages 50 to 80 years and compared with no age cutoff. Outcomes are reported for a cohort of 325 patients screened and includes total cost to screen, LS cases present in the cutoff category, number of LS cases expected to be identified by screening, cost per LS case detected, and total number and percentage of LS cases missed. Applying an age cutoff to an LS screening program has considerable potential for decreasing total screening costs and increasing efficiency, but at a loss of effectiveness. Imposing an age cutoff of 50 years reduces the cost of the screening program to 16% of a program with no age cutoff, but at the expense of missing more than half of the cases. Failure to identify LS cases is magnified by a cascade effect in family members. The results of this analysis influenced the final policy in our system.

LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.).

PubMed

Chen, Zijing; Zhao, Wensheng; Ge, Danfeng; Han, Yingyan; Ning, Kang; Luo, Chen; Wang, Shenglin; Liu, Renyi; Zhang, Xiaolan; Wang, Qian

2018-05-17

Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis. Molecular biology, developmental biology, and biochemical tools were combined to investigate the biological function of LsSOC1 in lettuce. LsSOC1 knockdown by RNA interference resulted in a significant delay in the timing of bolting and insensitivity to high temperature, which indicated that LsSOC1 functions as an activator during heat-promoted bolting in lettuce. We determined that two heat-shock transcription factors, HsfA1e and HsfA4c, bound to the promoter of LsSOC1 to confirm that LsSOC1 played an important role in heat-promoted bolting. This study indicates that LsSOC1 plays a crucial role in the heat-promoted bolting process in lettuce. Further investigation of LsSOC1 may be useful for clarification of the bolting mechanism in lettuce. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Structure and Location of the Regulatory β Subunits in the (αβγδ)4 Phosphorylase Kinase Complex* ♦

PubMed Central

Nadeau, Owen W.; Lane, Laura A.; Xu, Dong; Sage, Jessica; Priddy, Timothy S.; Artigues, Antonio; Villar, Maria T.; Yang, Qing; Robinson, Carol V.; Zhang, Yang; Carlson, Gerald M.

2012-01-01

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)4 complex that regulates glycogenolysis in skeletal muscle. Activity of the catalytic γ subunit is regulated by allosteric activators targeting the regulatory α, β, and δ subunits. Three-dimensional EM reconstructions of PhK show it to be two large (αβγδ)2 lobes joined with D2 symmetry through interconnecting bridges. The subunit composition of these bridges was unknown, although indirect evidence suggested the β subunits may be involved in their formation. We have used biochemical, biophysical, and computational approaches to not only address the quaternary structure of the β subunits within the PhK complex, i.e. whether they compose the bridges, but also their secondary and tertiary structures. The secondary structure of β was determined to be predominantly helical by comparing the CD spectrum of an αγδ subcomplex with that of the native (αβγδ)4 complex. An atomic model displaying tertiary structure for the entire β subunit was constructed using chemical cross-linking, MS, threading, and ab initio approaches. Nearly all this model is covered by two templates corresponding to glycosyl hydrolase 15 family members and the A subunit of protein phosphatase 2A. Regarding the quaternary structure of the β subunits, they were directly determined to compose the four interconnecting bridges in the (αβγδ)4 kinase core, because a β4 subcomplex was observed through both chemical cross-linking and top-down MS of PhK. The predicted model of the β subunit was docked within the bridges of a cryoelectron microscopic density envelope of PhK utilizing known surface features of the subunit. PMID:22969083

The Barley Magnesium Chelatase 150-kD Subunit Is Not an Abscisic Acid Receptor1[OA

PubMed Central

Müller, André H.; Hansson, Mats

2009-01-01

Magnesium chelatase is the first unique enzyme of the chlorophyll biosynthetic pathway. It is composed of three gene products of which the largest is 150 kD. This protein was recently identified as an abscisic acid receptor in Arabidopsis (Arabidopsis thaliana). We have evaluated whether the barley (Hordeum vulgare) magnesium chelatase large subunit, XanF, could be a receptor for the phytohormone. The study involved analysis of recombinant magnesium chelatase protein as well as several induced chlorophyll-deficient magnesium chelatase mutants with defects identified at the gene and protein levels. Abscisic acid had no effect on magnesium chelatase activity and binding to the barley 150-kD protein could not be shown. Magnesium chelatase mutants showed a wild-type response in respect to postgermination growth and stomatal aperture. Our results question the function of the large magnesium chelatase subunit as an abscisic acid receptor. PMID:19176716

[Liver stiffness measured by acoustic radiation force impulse imaging in assessing hepatic functional reserve in patients with space-occupying lesions in the liver].

PubMed

Yan, Hui-tong; Luo, Yu-kun; Tang, Wen-bo; Jiao, Zi-yu; Yao, Chun-xiao; Lv, Fa-qin; Tang, Jie

2013-04-01

To investigate the value of liver stiffness measured by acoustic radiation force impulse imaging(ARFI) in assessing hepatic functional reserve in patients with space-occupying lesions in the liver. Sixty-three patients with space-occupying lesions in the liver were enrolled. Liver stiffness (LS) measurements with ARFI and indocyanine green(ICG) retention test were performed in the same day, and plasma clearance rate of indocyanine green(ICG-K), ICG retention at 15 minutes(ICGR15) as well as 10 effective values of LS were recorded. The correlation between Child-Pugh score, ICGR15, ICG-K, and LS were evaluated. The LS measurements with ARFI failed in one patient. A strong correlation between LS and ICGR15(r=0.789, P<0.01) and an inverse correlation between LS and ICG-K(r=-0.738, P<0.01) were observed. Besides, there was a significant correlation between LS measurements and Child-Pugh score(r=0.929, P<0.01) . The LS significantly differed among patients with Child-Pugh class A, B, and C(P<0.01) . ARFI is a simple, feasible and non-invasive method for assessing hepatic functional reserve in patients with space-occupying lesions in the liver.

Biodegradation test of SPS-LS blends as polymer electrolyte membrane fuel cells

NASA Astrophysics Data System (ADS)

Putri, Zufira; Arcana, I. Made

2014-03-01

Sulfonated polystyrene (SPS) can be applied as a proton exchange membrane fuel cell due to its fairly good chemical stability. In order to be applied as polymer electrolyte membrane fuel cells (PEMFCs), membrane polymer should have a good ionic conductivity, high proton conductivity, and high mechanical strength. Lignosulfonate (LS) is a complex biopolymer which has crosslinks and sulfonate groups. SPS-LS blends with addition of SiO2 are used to increase the proton conductivity and to improve the mechanical properties and thermal stability. However, the biodegradation test of SPS-LS blends is required to determine whether the application of these membranes to be applied as an environmentally friendly membrane. In this study, had been done the synthesis of SPS, biodegradability test of SPS-LS blends with variations of LS and SiO2 compositions. The biodegradation test was carried out in solid medium of Luria Bertani (LB) with an activated sludge used as a source of microorganism at incubation temperature of 37°C. Based on the results obtained indicated that SPS-LS-SiO2 blends are more decomposed by microorganism than SPS-LS blends. This result is supported by analysis of weight reduction percentage, functional groups with Fourier Transform Infrared (FTIR) Spectroscopy, and morphological surface with Scanning Electron Microscopy (SEM).

Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

PubMed

Lester, Elizabeth B; Swick, Brian L

2015-01-01

Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spatial emission distribution of InGaN/GaN light-emitting diodes depending on the pattern structures

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

Lee, Kwanjae; Lee, Hyunjung; Lee, Cheul-Ro

2014-10-15

Highlights: • We study carrier lifetimes of InGaN/GaN LEDs fabricated on different PSS. • Spatial EL distribution was investigated depending on the pattern structure. • The carrier lifetime of the LEDs was compared with the spatial EL distribution. - Abstract: We investigated the emission characteristics of InGaN/GaN light-emitting diodes (LEDs) fabricated on lens-shaped (LS) patterned-sapphire substrates (PSS) by using time-resolved photoluminescence (TRPL) and confocal-scanning-electroluminescence microscopy (CSEM). The carrier lifetimes evaluated from the TRPL spectra for the LEDs on the LS-PSS (LS-LEDs) at 10 K were relatively shorter than those of the LEDs on a conventional planar substrate (C-LED). However, themore » carrier lifetimes for the LS-LEDs were relatively long compared to that of the C-LED at room temperature. In the CSEM images of the LS-LEDs, the emission beam around the center region of the LS pattern was relatively weaker than that of the edge region. In addition, the beam profile for the LS-LEDs showed different shapes according to the pattern structures. The emission beam around the boundary region of the LS pattern showed periodic fluctuation with the peak-to-peak distance of 814 nm.« less

Development and use of domain-specific antibodies in a characterization of the large subunits of soybean photosystem 1

NASA Technical Reports Server (NTRS)

Henry, R. L.; Takemoto, L. J.; Murphy, J.; Gallegos, G. L.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

The molecular architecture of the soybean photosystem 1 reaction center complex was examined using a combination of surface labeling and immunological methodology on isolated thylakoid membranes. Synthetic peptides (12 to 14 amino acids in length) were prepared which correspond to the N-terminal regions of the 83 and 82.4 kDa subunits of photosystem 1 (the PsaA and PsaB proteins, respectively). Similarly, a synthetic peptide was prepared corresponding to the C-terminal region of the PsaB subunit. These peptides were conjugated to a carrier protein, and were used for the production of polyclonal antibodies in rabbits. The resulting sera could distinguish between the PsaA and PsaB photosystem 1 subunits by Western blot analysis, and could identify appropriate size classes of cyanogen bromide cleavage fragments as predicted from the primary sequences of these two subunits. When soybean thylakoid membranes were surface-labeled with N-hydroxysuccinimidobiotin, several subunits of the complete photosystem 1 lipid/protein complex incorporated label. These included the light harvesting chlorophyll proteins of photosystem 1, and peptides thought to aid in the docking of ferredoxin to the complex during photosynthetic electron transport. However, the PsaA and PsaB subunits showed very little biotinylation. When these subunits were examined for the domains to which biotin did attach, most of the observed label was associated with the N-terminal domain of the PsaA subunit, as identified using a domain-specific polyclonal antisera.

Characterization and Modeling of a Water-based Liquid Scintillator

DOE PAGES

L. J. Bignell; Beznosko, D.; Diwan, M. V.; ...

2015-12-15

We characterised Water-based Liquid Scintillator (WbLS) using low energy protons, UV-VIS absorbance, and fluorescence spectroscopy. We have also developed and validated a simulation model that describes the behaviour of WbLS in our detector configurations for proton beam energies of 210 MeV, 475 MeV, and 2 GeV and for two WbLS compositions. These results have enabled us to estimate the light yield and ionisation quenching of WbLS, as well as to understand the influence of the wavelength shifting of Cherenkov light on our measurements. These results are relevant to the suitability of WbLS materials for next generation intensity frontier experiments.

Elemental Water Impact Test: Phase 3 Plunge Depth of a 36-Inch Aluminum Tank Head

NASA Technical Reports Server (NTRS)

Vassilakos, Gregory J.

2014-01-01

Spacecraft are being designed based on LS-DYNA water landing simulations. The Elemental Water Impact Test (EWIT) series was undertaken to assess the accuracy of LS-DYNA water impact simulations. Phase 3 featured a composite tank head that was tested at a range of heights to verify the ability to predict structural failure of composites. To support planning for Phase 3, a test series was conducted with an aluminum tank head dropped from heights of 2, 6, 10, and 12 feet to verify that the test article would not impact the bottom of the test pool. This report focuses on the comparisons of the measured plunge depths to LS-DYNA predictions. The results for the tank head model demonstrated the following. 1. LS-DYNA provides accurate predictions for peak accelerations. 2. LS-DYNA consistently under-predicts plunge depth. An allowance of at least 20% should be added to the LS-DYNA predictions. 3. The LS-DYNA predictions for plunge depth are relatively insensitive to the fluid-structure coupling stiffness.

Laparoscopic versus conventional open surgery for immune function in patients with colorectal cancer.

PubMed

Liu, Chuanyuan; Liu, Jungang; Zhang, Sen

2011-11-01

To systematically evaluate the immune function in patients with colorectal cancer after laparoscopic surgery (LS) and conventional open surgery (OS). PUBMED, EMBASE, and the Cochrane library were searched and randomized controlled trials (RCTs) comparing the immunological difference between LS and OS were included. Two authors extracted data and assessed trial quality. Eleven studies including 695 patients were analysed. Immune-competent cells demonstrated no significant differences between LS and OS in six trials. Eight trials assessed various perioperative plasma cytokine concentrations with no significant differences in interleukin-6 (IL-6) and C-reactive protein (CRP) levels between LS and OS. However, meta-analysis showed higher T suppressor lymphocytes (CD8+) counts on postoperative days (POD) 1-3 and lower plasma levels of CRP on POD 0-1 in LS group compared with OS group. Although LS groups displayed higher T suppressor lymphocyte (CD8+) counts on postoperative days (POD) 1-3 and lower plasma levels of CRP on POD 0-1, there is no sufficient evidence to support superior preservation of global immune function with LS compared to OS.

Comparison and applicability of landslide susceptibility models based on landslide ratio-based logistic regression, frequency ratio, weight of evidence, and instability index methods in an extreme rainfall event

NASA Astrophysics Data System (ADS)

Wu, Chunhung

2016-04-01

Few researches have discussed about the applicability of applying the statistical landslide susceptibility (LS) model for extreme rainfall-induced landslide events. The researches focuses on the comparison and applicability of LS models based on four methods, including landslide ratio-based logistic regression (LRBLR), frequency ratio (FR), weight of evidence (WOE), and instability index (II) methods, in an extreme rainfall-induced landslide cases. The landslide inventory in the Chishan river watershed, Southwestern Taiwan, after 2009 Typhoon Morakot is the main materials in this research. The Chishan river watershed is a tributary watershed of Kaoping river watershed, which is a landslide- and erosion-prone watershed with the annual average suspended load of 3.6×107 MT/yr (ranks 11th in the world). Typhoon Morakot struck Southern Taiwan from Aug. 6-10 in 2009 and dumped nearly 2,000 mm of rainfall in the Chishan river watershed. The 24-hour, 48-hour, and 72-hours accumulated rainfall in the Chishan river watershed exceeded the 200-year return period accumulated rainfall. 2,389 landslide polygons in the Chishan river watershed were extracted from SPOT 5 images after 2009 Typhoon Morakot. The total landslide area is around 33.5 km2, equals to the landslide ratio of 4.1%. The main landslide types based on Varnes' (1978) classification are rotational and translational slides. The two characteristics of extreme rainfall-induced landslide event are dense landslide distribution and large occupation of downslope landslide areas owing to headward erosion and bank erosion in the flooding processes. The area of downslope landslide in the Chishan river watershed after 2009 Typhoon Morakot is 3.2 times higher than that of upslope landslide areas. The prediction accuracy of LS models based on LRBLR, FR, WOE, and II methods have been proven over 70%. The model performance and applicability of four models in a landslide-prone watershed with dense distribution of rainfall-induced landslide are interesting and meaningful. Eight landslide-related factors, including elevation, slope, aspect, geology, accumulated rainfall during 2009 Typhoon Morakot, landuse, distance to the fault, and distance to the rivers, were considered in this research. The research builds and compares the difference of the LS maps based on four methods. The average LS value from each method is 0.27 for LRBLR, 0.368 for FR, 0.553 for WOE, and 0.498 for II. The correlation analysis was conducted to identify similarities between the four LS maps. The correlation coefficients are 0.913, 0.829, 0.930, 0.756, 0.729, and 0.652 for the LRBLR vs FR, LRBLR vs WOE, FR vs WOE, LRBLR vs II, FR vs II, and WOE vs II. The research compares the model performance of four LS maps by calculating the AUC value (area under the ROC curve) and ACR value (average correct-predicted ratio). The AUC values of LS maps based on LRBLR, FR, WOE, and II methods are 0.819, 0.819, 0.822 and 0.785. The ACR values of LS maps based on LRBLR, FR, WOE, and II methods are 75.1%, 73.7%, 68.4%, and 64.2%. The results indicate that the model performance based on LRBLR method in an extreme rainfall-landslide event is better than that based on the other three methods.

Copper Tube Compression in Z-Current Geometry, Numerical Simulations and Comparison with Cyclope Experiments

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

Lefrancois, A.; L'Eplattenier, P.; Burger, M.

2006-02-13

Metallic tubes compressions in Z-current geometry were performed at the Cyclope facility from Gramat Research Center in order to study the behavior of metals under large strain at high strain rate. 3D configurations of cylinder compressions have been calculated here to benchmark the new beta version of the electromagnetism package coupled with the dynamics in Ls-Dyna and compared with the Cyclope experiments. The electromagnetism module is being developed in the general-purpose explicit and implicit finite element program LS-DYNA{reg_sign} in order to perform coupled mechanical/thermal/electromagnetism simulations. The Maxwell equations are solved using a Finite Element Method (FEM) for the solid conductorsmore » coupled with a Boundary Element Method (BEM) for the surrounding air (or vacuum). More details can be read in the references.« less

Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature (“FILS syndrome”)

PubMed Central

Pachlopnik Schmid, Jana; Lemoine, Roxane; Nehme, Nadine; Cormier-Daire, Valéry; Revy, Patrick; Debeurme, Franck; Debré, Marianne; Nitschke, Patrick; Bole-Feysot, Christine; Legeai-Mallet, Laurence; Lim, Annick; de Villartay, Jean-Pierre; Picard, Capucine; Durandy, Anne; Fischer, Alain

2012-01-01

DNA polymerase ε (Polε) is a large, four-subunit polymerase that is conserved throughout the eukaryotes. Its primary function is to synthesize DNA at the leading strand during replication. It is also involved in a wide variety of fundamental cellular processes, including cell cycle progression and DNA repair/recombination. Here, we report that a homozygous single base pair substitution in POLE1 (polymerase ε 1), encoding the catalytic subunit of Polε, caused facial dysmorphism, immunodeficiency, livedo, and short stature (“FILS syndrome”) in a large, consanguineous family. The mutation resulted in alternative splicing in the conserved region of intron 34, which strongly decreased protein expression of Polε1 and also to a lesser extent the Polε2 subunit. We observed impairment in proliferation and G1- to S-phase progression in patients’ T lymphocytes. Polε1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. Our results evidence the developmental impact of a Polε catalytic subunit deficiency in humans and its causal relationship with a newly recognized, inherited disorder. PMID:23230001

Multiple forms of ADP-glucose pyrophosphorylase from tomato fruit

NASA Technical Reports Server (NTRS)

Chen, B. Y.; Janes, H. W.

1997-01-01

ADP-glucose pyrophosphorylase (AGP) was purified from tomato (Lycopersicon esculentum Mill.) fruit to apparent homogeneity. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis the enzyme migrated as two close bands with molecular weights of 50,000 and 51,000. Two-dimensional polyacrylamide gel electrophoresis analysis of the purified enzyme, however, revealed at least five major protein spots that could be distinguished by their slight differences in net charge and molecular weight. Whereas all of the spots were recognized by the antiserum raised against tomato fruit AGP holoenzyme, only three of them reacted strongly with antiserum raised against the potato tuber AGP large subunit, and the other two spots (with lower molecular weights) reacted specifically with antisera raised against spinach leaf AGP holoenzyme and the potato tuber AGP small subunit. The results suggest the existence of at least three isoforms of the AGP large subunit and two isoforms of the small subunit in tomato fruit in vivo. The native molecular mass of the enzyme determined by gel filtration was 220 +/- 10 kD, indicating a tetrameric structure for AGP from tomato fruit. The purified enzyme is very sensitive to 3-phosphoglycerate/inorganic phosphate regulation.

Copper coordination in the Glycine receptor by electron spin resonance

NASA Astrophysics Data System (ADS)

Ruthstein, Sharon; Stone, Katherine; Cascio, Michael; Saxena, Sunil

2009-03-01

We describe the use of Electron Spin Resonance (ESR) to identify the coordination environment of copper in the extracellular domain of the protein, as well as the number of copper atoms that bind to Glycine receptor (GlyR). The GlyR channel mediates inhibitory neurotransmission in the central nervous system. It belongs to the superfamily of nicotincoid receptors. These receptors are formed by pentameric arrangement of subunits, each sharing a common topology having a large extracellular domain (ECD) and a transmembrane (TM) domain comprised of four membrane-spanning segments (TM1-TM4). For GlyR, four subunits (1-4) and one subunit have been identified to date, although the homomeric expression of just the α1 subunit of GlyR is sufficient to reconstitute native-like activity. The results are expected to shed light on the role of metals ion in modulating ion permeation in such receptor. In addition, an identification of copper binding sites will allow the measurement of large range distance constraints in the receptor by pulsed ESR. Such structural information on the GlyR in various allosteric states is essential in order to shed light on the gating mechanism of this protein membrane.

[Biological availability of zinc lignosulfonate on calcareous soil of north Guoangdong Province].

PubMed

Wang, Dehan; Lin, Huidong; Peng, Junjie; Xiao, Xiongshi; Liao, Zongwen

2004-07-01

Zinc lignosulfonate (Zn-LS) is a kind of organic fertilizers made from the by-products of paper industry. With leach and plot treatments, this paper studied the difference of the biological availability between Zn-LS and an inorganic Zn-fertilizer on calcareous soil of north Guangdong Province. The results indicated that the Zn of Zn-LS was less absorbed by calcareous soil. In soil B, when applying 10 mg x kg(-1) Zn, the dissolved amount of Zn-LS was 65.2% higher than that of inorganic Zn-fertilizer, corn grew well, and its biomass was higher. In soil A, when applying 10 mg x kg(-1) Zn of Zn-LS, the biomass of corn increased by 16.3%, and its Zn content was 81.2% higher. Therefore, biological availability of Zn-LS was better than that of inorganic Zn fertilizer.

A scoping review of assessment tools for laparoscopic suturing.

PubMed

Bilgic, Elif; Endo, Satoshi; Lebedeva, Ekaterina; Takao, Madoka; McKendy, Katherine M; Watanabe, Yusuke; Feldman, Liane S; Vassiliou, Melina C

2018-05-03

A needs assessment identified a gap in teaching and assessment of laparoscopic suturing (LS) skills. The purpose of this review is to identify assessment tools that were used to assess LS skills, to evaluate validity evidence available, and to provide guidance for selecting the right assessment tool for specific assessment conditions. Bibliographic databases were searched till April 2017. Full-text articles were included if they reported on assessment tools used in the operating room/simulation to (1) assess procedures that require LS or (2) specifically assess LS skills. Forty-two tools were identified, of which 26 were used for assessing LS skills specifically and 26 for procedures that require LS. Tools had the most evidence in internal structure and relationship to other variables, and least in consequences. Through identification and evaluation of assessment tools, the results of this review could be used as a guideline when implementing assessment tools into training programs.

High-frequency ultrasonography (HFUS) as a useful tool in differentiating between plaque morphea and extragenital lichen sclerosus lesions

PubMed Central

Reszke, Radomir; Szepietowski, Jacek C.

2017-01-01

Introduction Morphea and lichen sclerosus (LS) are chronic inflammatory diseases that may pose a diagnostic challenge for a physician. High-frequency ultrasonography (HFUS) is a versatile diagnostic method utilized in dermatologic practice, allowing monitoring the course of the disease, treatment response and differentiation between certain skin disorders. Aim To prove the usefulness of HFUS in differentiating between plaque morphea and extragenital LS lesions. Material and methods We examined 16 patients with plaque morphea and 4 patients with extragenital LS using 20 MHz taberna pro medicum TM (Germany) device. Results Investigations revealed hyperechogenic entrance echo in both morphea and LS lesions, whereas a distinct polycyclic surface of the entrance echo was detected exclusively in LS. Conclusions High-frequency ultrasonography is a current diagnostic modality that may prove useful in differentiating between morphea and LS lesions. PMID:29507565

Differentiating retroperitoneal liposarcoma tumors with optical coherence tomography

NASA Astrophysics Data System (ADS)

Lev, Dina; Baranov, Stepan A.; Carbajal, Esteban F.; Young, Eric D.; Pollock, Raphael E.; Larin, Kirill V.

2011-03-01

Liposarcoma (LS) is a rare and heterogeneous group of malignant mesenchymal neoplasms exhibiting characteristics of adipocytic differentiation. Currently, radical surgical resection represents the most effective and widely used therapy for patients with abdominal/retroperitoneal LS, but the presence of contiguous essential organs, such as the kidney, pancreas, spleen, adrenal glands, esophagus or colon, as well as often reoccurrence of LS in A/RP calls for the enhancement of surgical techniques to minimize resection and avoid LS reoccurrences. Difficulty in detecting the margins of neoplasms due to their affinity to healthy fat tissue accounts for the high reoccurrence of LS within A/RP. Nowadays, the microscopic detection of margins is possible only by use of biopsy, and the minimization of surgical resection of healthy tissues is challenging. In this presentation we'll demonstrate the initial OCT results for the imaging and distinction of LS and normal human fat tissues and clear detection of tumor boundaries.

Liver reserve function assessment by acoustic radiation force impulse imaging

PubMed Central

Sun, Xiao-Lan; Liang, Li-Wei; Cao, Hui; Men, Qiong; Hou, Ke-Zhu; Chen, Zhen; Zhao, Ya-E

2015-01-01

AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse (ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin (ALB), total bilirubin (T-Bil), and other indicators were observed. Liver stiffness (LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green (ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh (CP) scores were carried out based on patient’s preoperative biochemical tests and physical condition. Correlations among CP scores, ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. Kruskal-Wallis test was used to compare LS values of CP scores, and the receiver-operator characteristic (ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B (1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C (1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15 (r = 0.617, P < 0.01) and CP score (r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K (r = -0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively correlated with LS (P < 0.05). The ROC curve revealed that the when the LS value was 2.34 m/s, the Youden index was at its highest point, sensitivity was 69.2% and specificity was 92.1%. CONCLUSION: For patients with liver tumors, ARFI imaging is a useful tool for assessing liver reserve function. PMID:26327773

Quantitative evaluation of longitudinal strain in layer-specific myocardium during normal pregnancy in China.

PubMed

Cong, Juan; Wang, Zhibin; Jin, Hong; Wang, Wugang; Gong, Kun; Meng, Yuanyuan; Lee, Yong

2016-11-10

The myocardial wall of the left ventricle is a complex, multilayered structure and is not homogenous. The aim of this study was to determine longitudinal strain (LS) in the three myocardial layers in normal pregnant women according to gestation proceedings. The advanced two-dimensional speckle tracking echocardiography (2D STE) was performed on 62 women during each pregnancy trimester and 6 to 9 weeks after delivery, while 30 age-matched, healthy, nonpregnant women served as controls. LS on endocardial, mid-myocardial and epicardial layers at 18 cardiac segments were measured. As gestation proceeded, all of layer-specific LS and global LS progressively decreased, which subsequently recovered postpartum (P < 0.05), and the LS gradient between inner and outer myocardium became greater, which reached its maximum in the late pregnancy. Peak systolic LS was the highest at endocardium and the lowest at epicardium, while the highest at the apical level and the lowest at the base (P < 0.05). In the early pregnancy and postpartum, LS at basal level was homogenous, meanwhile layer-specific LS showed significant differences at mid-ventricular and apical level throughout the progress of normal pregnancy (P < 0.05). Using 2D STE, three-layer assessment of LS can be performed in pregnant women and shall give us new insights into the quantitative analysis of global and regional LV function during pregnancy. Future studies on the detection of pregnancy related heart disease would require these parameters as reference values for each time point of a normal pregnancy.

A Land System representation for global assessments and land-use modeling.

PubMed

van Asselen, Sanneke; Verburg, Peter H

2012-10-01

Current global scale land-change models used for integrated assessments and climate modeling are based on classifications of land cover. However, land-use management intensity and livestock keeping are also important aspects of land use, and are an integrated part of land systems. This article aims to classify, map, and to characterize Land Systems (LS) at a global scale and analyze the spatial determinants of these systems. Besides proposing such a classification, the article tests if global assessments can be based on globally uniform allocation rules. Land cover, livestock, and agricultural intensity data are used to map LS using a hierarchical classification method. Logistic regressions are used to analyze variation in spatial determinants of LS. The analysis of the spatial determinants of LS indicates strong associations between LS and a range of socioeconomic and biophysical indicators of human-environment interactions. The set of identified spatial determinants of a LS differs among regions and scales, especially for (mosaic) cropland systems, grassland systems with livestock, and settlements. (Semi-)Natural LS have more similar spatial determinants across regions and scales. Using LS in global models is expected to result in a more accurate representation of land use capturing important aspects of land systems and land architecture: the variation in land cover and the link between land-use intensity and landscape composition. Because the set of most important spatial determinants of LS varies among regions and scales, land-change models that include the human drivers of land change are best parameterized at sub-global level, where similar biophysical, socioeconomic and cultural conditions prevail in the specific regions. © 2012 Blackwell Publishing Ltd.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles.

PubMed

Torok, Kathryn S; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N; Medsger, Thomas; Feghali-Bostwick, Carol A

2015-12-01

To evaluate peripheral blood T-helper (TH) cell-associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS subjects compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α, and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. This is the first time that multiple cytokines and chemokines have been examined simultaneously in LS. In general, a TH1 (IFN-γ) and TH17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN-γ signature with elevated IP-10, MCP-1, and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α, and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Pain evaluation during gynaecological surveillance in women with Lynch syndrome.

PubMed

Helder-Woolderink, Jorien; de Bock, Geertruida; Hollema, Harry; van Oven, Magda; Mourits, Marian

2017-04-01

To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first degree relatives who underwent repetitive annual gynaecological surveillance including endometrial sampling of which 33 were evaluated twice or more and 50 symptomatic women without LS who had single endometrial sampling, were included. Pain intensity was registered with VAS scores. Differences in pain intensities between subsequent visits (in LS) and between the two groups were evaluated. The use of painkillers before endometrial sampling was registered. If women with LS decided for preventive surgery, the reason was recorded. The LS group reported a median VAS score of 5.0 (range 0-10) at the first surveillance (n = 52) and at the second visit (n = 24). Women who repeatedly underwent endometrial sampling more often used painkillers for this procedure. During the study period 7/52 (13 %) women with LS choose for preventive surgery, another 4/52 (8 %) refused further endometrial sampling. Painful endometrial sampling was mentioned as main reason to quit screening. The median VAS score of the 50 symptomatic women was 5.0 (range 1-9). Endometrial sampling, irrespective of indication, is a painful procedure, with a median VAS score of 5.0. During subsequent procedures in women with LS, the median pain score does not aggravate although one in five women chose an alternative for endometrial sampling.

Radon in ground water of the Lower Susqehanna and Potomac River basins

USGS Publications Warehouse

Lindsey, Bruce D.; Ator, Scott W.

1996-01-01

Ground-water samples collected from 267 wells were analyzed for radon as part of a water-quality reconnaissance of subunits of the Lower Susquehanna and Potomac River Basins conducted by the United States Geological Survey (USGS) as part of the National Water-Quality Assessment (NAWQA) program. Radon is a product of the radioactive decay of uranium. Airborne radon has been cited by the Surgeon General of the United States as the second-leading cause of lung cancer and the United States Environmental Protection Agency (USEPA) has identified ground-water supplies as possible contributing sources of indoor radon. Eighty percent of ground-water samples collected for this study were found to contain radon at activities greater than 300 pCi/L (picocuries per liter), the USEPA's proposed Maximum Contaminant Level for radon in drinking water, and 31 percent of samples contained radon at activities greater than 1,000 pCi/L. The 10 subunits where samples were collected were grouped into three classes - median ground-water radon activity less than 300 pCi/L, between 300 pCi/L and 1,000 pCi/L, and greater than 1,000 pCi/L. Subunits underlain by igneous and metamorphic rocks of the Piedmont Physiographic Province typically have the highest median ground-water radon activities (greater than 1,000 pCi/L); although there is a large variation in radon activities within most of the subunits. Lower median radon activities (between 300 pCi/L and 1,000 pCi/L) were found in ground water in subunits underlain by limestone and dolomite. Of three subunits underlain by sandstone and shale, one fell into each of the three radon-activity classes. The large variability within these subunits may be attributed to the fact that the uranium content of sandstone and shale is related to the uranium content of the sediments from which they formed.

A new Em-like protein from Lactuca sativa, LsEm1, enhances drought and salt stress tolerance in Escherichia coli and rice.

PubMed

Xiang, Dian-Jun; Man, Li-Li; Zhang, Chun-Lan; Peng-Liu; Li, Zhi-Gang; Zheng, Gen-Chang

2018-02-07

Late embryogenesis abundant (LEA) proteins are closely related to abiotic stress tolerance of plants. In the present study, we identified a novel Em-like gene from lettuce, termed LsEm1, which could be classified into group 1 LEA proteins, and shared high homology with Cynara cardunculus Em protein. The LsEm1 protein contained three different 20-mer conserved elements (C-element, N-element, and M-element) in the C-termini, N-termini, and middle-region, respectively. The LsEm1 mRNAs were accumulated in all examined tissues during the flowering and mature stages, with a little accumulation in the roots and leaves during the seedling stage. Furthermore, the LsEm1 gene was also expressed in response to salt, dehydration, abscisic acid (ABA), and cold stresses in young seedlings. The LsEm1 protein could effectively reduce damage to the lactate dehydrogenase (LDH) and protect LDH activity under desiccation and salt treatments. The Escherichia coli cells overexpressing the LsEm1 gene showed a growth advantage over the control under drought and salt stresses. Moreover, LsEm1-overexpressing rice seeds were relatively sensitive to exogenously applied ABA, suggesting that the LsEm1 gene might depend on an ABA signaling pathway in response to environmental stresses. The transgenic rice plants overexpressing the LsEm1 gene showed higher tolerance to drought and salt stresses than did wild-type (WT) plants on the basis of the germination performances, higher survival rates, higher chlorophyll content, more accumulation of soluble sugar, lower relative electrolyte leakage, and higher superoxide dismutase activity under stress conditions. The LsEm1-overexpressing rice lines also showed less yield loss compared with WT rice under stress conditions. Furthermore, the LsEm1 gene had a positive effect on the expression of the OsCDPK9, OsCDPK13, OsCDPK15, OsCDPK25, and rab21 (rab16a) genes in transgenic rice under drought and salt stress conditions, implying that overexpression of these genes may be involved in the enhanced drought and salt tolerance of transgenic rice. Thus, this work paves the way for improvement in tolerance of crops by genetic engineering breeding.

Life satisfaction, cardiovascular risk factors, unhealthy behaviours and socioeconomic inequality, 5 years after coronary angiography.

PubMed

Baumann, Michèle; Tchicaya, Anastase; Vanderpool, Kyle; Lorentz, Nathalie; Le Bihan, Etienne

2015-07-15

Five years after coronary angiography, life satisfaction (LS) among patients may be related to incidents of cardiovascular diseases, risk factors and unhealthy behaviours and socioeconomic conditions, but their respective influence remains unclear. Our aim is to analyze LS and its relationships with those factors. Among the 4,391 patients initially contacted, 547 deaths were reported and 209 had an invalid address. In 2013-2014, 3,635 patients who underwent coronary angiography in 2008-2009 at the National Institute of Cardiac Surgery and Cardiological Intervention (INCCI) in Luxembourg were asked to complete a self-administered questionnaire assessing LS [1-10] and other variables. Data were analysed via multiple regression models adjusted initially on age, sex and income, and for a second time with the addition of all CVRF. LS of 1,289 volunteers (69.2 years) was 7.3/10. Most were men, Luxembourgish, employees and manual workers, had secondary education and an income of 36,000 euros or more per year. LS was lowest in female patients, and those with a low to middle income. Patients who lived in a couple had the best LS. Patients with a history in the previous 5 years of physical inactivity (regression coefficient: -0.903), angina pectoris (rc -0.843), obesity (rc -0.512), diabetes, or hypercholesterolemia, were more likely to have lower LS. The previous associations were mostly maintained on the second analysis, with the exceptions of diabetes and obesity. In addition, patients who stopped smoking because of peer pressure (rc -0.011) had a lower LS. The finding that LS was lowest among female patients calls for further research on symptoms, and potential risk factors. Also, certain patient profiles are linked with low LS: 'inclined abstainers' who intended to modify their behaviours, but could not do so, and 'disinclined abstainers' who had no intention of changing and were insufficiently concerned to do so. Patients who stopped smoking and perceived it as unpleasant also had low LS. 'Disinclined actors' were those patients who had to adjust their lifestyles, but were ambivalent about their intentions and the behaviour, which they continued. Health promotion programs would benefit from targeting factors that moderate the unfavourable intention-behaviour relationship and can help enhance LS.

Evidence for an unusual transmembrane configuration of AGG3, a class C Gγ subunit of Arabidopsis

DOE PAGES

Wolfenstetter, Susanne; Chakravorty, David; Kula, Ryan; ...

2014-12-22

Heterotrimeric G proteins are crucial for the perception of external signals and subsequent signal transduction in animal and plant cells. In both model systems, the complex is comprised of one Gα, one Gβ and one Gγ subunit. However, in addition to the canonical Gγ subunits (Class A), plants also possess two unusual, plant-specific classes of Gγ subunits (Classes B and C) not yet found in animals. These include Gγ subunits lacking the C-terminal CaaX motif (Class B) which is important for membrane anchoring of the protein, and thus give rise to a flexible subpopulation of Gβ/γ heterodimers that is notmore » necessarily restricted to the plasma membrane. Even more interesting, plants also contain Class C Gγ subunits which are twice the size of canonical Gγs, with a predicted transmembrane domain, and a large cysteine-rich, extracellular C-terminus. However, neither the presence of the transmembrane domain nor the membrane topology has been unequivocally demonstrated. Finally, we provide compelling evidence that AGG3, a Class C Ggamma subunit of Arabidopsis, contains a functional transmembrane domain, which is sufficient but not essential for plasma membrane localization, and that the cysteine-rich C-terminus is extracellular.« less

LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures.

PubMed

Ryan, Michael; Diekhans, Mark; Lien, Stephanie; Liu, Yun; Karchin, Rachel

2009-06-01

LS-SNP/PDB is a new WWW resource for genome-wide annotation of human non-synonymous (amino acid changing) SNPs. It serves high-quality protein graphics rendered with UCSF Chimera molecular visualization software. The system is kept up-to-date by an automated, high-throughput build pipeline that systematically maps human nsSNPs onto Protein Data Bank structures and annotates several biologically relevant features. LS-SNP/PDB is available at (http://ls-snp.icm.jhu.edu/ls-snp-pdb) and via links from protein data bank (PDB) biology and chemistry tabs, UCSC Genome Browser Gene Details and SNP Details pages and PharmGKB Gene Variants Downloads/Cross-References pages.

Mars at Ls 288°: Syrtis Major

NASA Image and Video Library

2005-09-21

This picture, released 21 September 2005, is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 288° during a previous Mars year. This month, Mars looks similar, as Ls 288° occurred in mid-September 2005. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, are a measure of the time of year on Mars. Mars travels 360° around the Sun in 1 Mars year. The year begins at Ls 0°, the start of northern spring and southern autumn.

A modified JPEG-LS lossless compression method for remote sensing images

NASA Astrophysics Data System (ADS)

Deng, Lihua; Huang, Zhenghua

2015-12-01

As many variable length source coders, JPEG-LS is highly vulnerable to channel errors which occur in the transmission of remote sensing images. The error diffusion is one of the important factors which infect its robustness. The common method of improving the error resilience of JPEG-LS is dividing the image into many strips or blocks, and then coding each of them independently, but this method reduces the coding efficiency. In this paper, a block based JPEP-LS lossless compression method with an adaptive parameter is proposed. In the modified scheme, the threshold parameter RESET is adapted to an image and the compression efficiency is close to that of the conventional JPEG-LS.

Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

PubMed

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2014-06-05

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Highly acidic C-terminal domain of pp32 is required for the interaction with histone chaperone, TAF-Ibeta.

PubMed

Lee, In-Seon; Oh, Sang-Min; Kim, Sung-Mi; Lee, Dong-Seok; Seo, Sang-Beom

2006-12-01

We have previously reported that INHAT (inhibitor of acetyltransferases) complex subunits, TAF (template activating factor)-Ialpha, TAF-Ibeta and pp32 can inhibit histone acetylation and HAT (histone acetyltransferase)-dependent transcription by binding to histones. Evidences are accumulating that INHAT complex subunits have important regulatory roles in various cellular activities such as replication, transcription, and apoptosis etc. However, how these subunits interact each other remains largely unknown. Using immunoprecipitation (IP) and protein-protein interaction assays with TAF-Ibeta and pp32 deletion mutant proteins, we identify INHAT complex subunits, TAF-Ibeta and pp32 interaction requires highly acidic C-terminal domain of pp32. We also show that the interaction between the INHAT complex subunits is stronger in the presence of histones. In this study, we report that the synergistic inhibition of HAT-mediated transcription by TAF-Ibeta and pp32 is dependent on the highly acidic C-terminal domain of pp32.

Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions

PubMed Central

Wasserman, Michael R.; Pulk, Arto; Zhou, Zhou; Altman, Roger B.; Zinder, John C.; Green, Keith D.; Garneau-Tsodikova, Sylvie; Doudna Cate, Jamie H.; Blanchard, Scott C.

2015-01-01

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin—paromomycin, ribostamycin and neamine—each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6′-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6′-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin–ribosome complex, we observe specific contacts between the apical tip of H69 and the 6′-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation. PMID:26224058

Multiple Cis-acting elements modulate programmed -1 ribosomal frameshifting in Pea enation mosaic virus

PubMed Central

Gao, Feng; Simon, Anne E.

2016-01-01

Programmed -1 ribosomal frameshifting (-1 PRF) is used by many positive-strand RNA viruses for translation of required products. Despite extensive studies, it remains unresolved how cis-elements just downstream of the recoding site promote a precise level of frameshifting. The Umbravirus Pea enation mosaic virus RNA2 expresses its RNA polymerase by -1 PRF of the 5′-proximal ORF (p33). Three hairpins located in the vicinity of the recoding site are phylogenetically conserved among Umbraviruses. The central Recoding Stimulatory Element (RSE), located downstream of the p33 termination codon, is a large hairpin with two asymmetric internal loops. Mutational analyses revealed that sequences throughout the RSE and the RSE lower stem (LS) structure are important for frameshifting. SHAPE probing of mutants indicated the presence of higher order structure, and sequences in the LS may also adapt an alternative conformation. Long-distance pairing between the RSE and a 3′ terminal hairpin was less critical when the LS structure was stabilized. A basal level of frameshifting occurring in the absence of the RSE increases to 72% of wild-type when a hairpin upstream of the slippery site is also deleted. These results suggest that suppression of frameshifting may be needed in the absence of an active RSE conformation. PMID:26578603

Energy Logic (EL): a novel fusion engine of multi-modality multi-agent data/information fusion for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2009-04-01

The rapidly advancing hardware technology, smart sensors and sensor networks are advancing environment sensing. One major potential of this technology is Large-Scale Surveillance Systems (LS3) especially for, homeland security, battlefield intelligence, facility guarding and other civilian applications. The efficient and effective deployment of LS3 requires addressing number of aspects impacting the scalability of such systems. The scalability factors are related to: computation and memory utilization efficiency, communication bandwidth utilization, network topology (e.g., centralized, ad-hoc, hierarchical or hybrid), network communication protocol and data routing schemes; and local and global data/information fusion scheme for situational awareness. Although, many models have been proposed to address one aspect or another of these issues but, few have addressed the need for a multi-modality multi-agent data/information fusion that has characteristics satisfying the requirements of current and future intelligent sensors and sensor networks. In this paper, we have presented a novel scalable fusion engine for multi-modality multi-agent information fusion for LS3. The new fusion engine is based on a concept we call: Energy Logic. Experimental results of this work as compared to a Fuzzy logic model strongly supported the validity of the new model and inspired future directions for different levels of fusion and different applications.

HIGH-ENERGY OBSERVATIONS OF PSR B1259–63/LS 2883 THROUGH THE 2014 PERIASTRON PASSAGE: CONNECTING X-RAYS TO THE GeV FLARE

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

Tam, P. H. T.; Li, K. L.; Kong, A. K. H.

2015-01-01

The binary system PSR B1259–63/LS 2883 is well sampled in radio, X-rays, and TeV γ-rays, and shows orbital-phase-dependent variability in these frequencies. The first detection of GeV γ-rays from the system was made around the 2010 periastron passage. In this Letter, we present an analysis of X-ray and γ-ray data obtained by the Swift/XRT, NuSTAR/FPM, and Fermi/LAT, through the recent periastron passage which occurred on 2014 May 4. While PSR B1259–63/LS 2883 was not detected by the Large Area Telescope before and during this passage, we show that the GeV flares occurred at a similar orbital phase as in earlymore » 2011, thus establishing the repetitive nature of the post-periastron GeV flares. Multiple flares each lasting for a few days have been observed and short-term variability is seen as well. We also found X-ray flux variation contemporaneous with the GeV flare for the first time. Strong evidence of the keV-to-GeV connection came from the broadband high-energy spectra, which we interpret as synchrotron radiation from the shocked pulsar wind.« less

Measurement Uncertainty Within the Uniform Engine Test Programme

DTIC Science & Technology

1989-05-01

Design to Cost and l.ifc (.cle Cost to Aircraft Engines AGARD LS 107 (May 1980) Microcomputer Applications in Power and Propulsion Systems AGARD LS...Flows in Propulsion Systems AGARD LS 140 (June 1985) Engine Airframe Integration for Rotorcraft AGARD LS 148 (June 1986) Design Methods Used in Solid...modest nero-thermodynamic design was of no consequence. Two engines were loaned to the proeram by the U.S. Air Force. Due to higher priority test workload

Methods of mesophyll conductance estimation: its impact on key biochemical parameters and photosynthetic limitations in phosphorus-stressed soybean across CO2

USDA-ARS?s Scientific Manuscript database

Photosynthetic potential in C3 plants is largely limited by CO2 diffusion through stomata (Ls) and mesophyll (Lm) and photo-biochemical (Lb) processes. Accurate estimation of mesophyll conductance (gm) using gas exchange (GE) and chlorophyll fluorescence (CF) parameters of the photosynthetic proces...

Biodegradation test of SPS-LS blends as polymer electrolyte membrane fuel cells

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

Putri, Zufira, E-mail: zufira.putri@gmail.com, E-mail: arcana@chem.itb.ac.id; Arcana, I Made, E-mail: zufira.putri@gmail.com, E-mail: arcana@chem.itb.ac.id

Sulfonated polystyrene (SPS) can be applied as a proton exchange membrane fuel cell due to its fairly good chemical stability. In order to be applied as polymer electrolyte membrane fuel cells (PEMFCs), membrane polymer should have a good ionic conductivity, high proton conductivity, and high mechanical strength. Lignosulfonate (LS) is a complex biopolymer which has crosslinks and sulfonate groups. SPS-LS blends with addition of SiO{sub 2} are used to increase the proton conductivity and to improve the mechanical properties and thermal stability. However, the biodegradation test of SPS-LS blends is required to determine whether the application of these membranes tomore » be applied as an environmentally friendly membrane. In this study, had been done the synthesis of SPS, biodegradability test of SPS-LS blends with variations of LS and SiO{sub 2} compositions. The biodegradation test was carried out in solid medium of Luria Bertani (LB) with an activated sludge used as a source of microorganism at incubation temperature of 37°C. Based on the results obtained indicated that SPS-LS-SiO{sub 2} blends are more decomposed by microorganism than SPS-LS blends. This result is supported by analysis of weight reduction percentage, functional groups with Fourier Transform Infrared (FTIR) Spectroscopy, and morphological surface with Scanning Electron Microscopy (SEM)« less

Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation.

PubMed

Suzuki, Maiko; Ikeda, Atsushi; Bartlett, John D

2018-03-01

Low-dose fluoride is an effective caries prophylactic, but high-dose fluoride is an environmental health hazard that causes skeletal and dental fluorosis. Treatments to prevent fluorosis and the molecular pathways responsive to fluoride exposure remain to be elucidated. Previously we showed that fluoride activates SIRT1 as an adaptive response to protect cells. Here, we demonstrate that fluoride induced p53 acetylation (Ac-p53) [Lys379], which is a SIRT1 deacetylation target, in ameloblast-derived LS8 cells in vitro and in enamel organ in vivo. Here we assessed SIRT1 function on fluoride-induced Ac-p53 formation using CRISPR/Cas9-mediated Sirt1 knockout (LS8 Sirt/KO ) cells or CRISPR/dCas9/SAM-mediated Sirt1 overexpressing (LS8 Sirt1/over ) cells. NaF (5 mM) induced Ac-p53 formation and increased cell cycle arrest via Cdkn1a/p21 expression in Wild-type (WT) cells. However, fluoride-induced Ac-p53 was suppressed by the SIRT1 activator resveratrol (50 µM). Without fluoride, Ac-p53 persisted in LS8 Sirt/KO cells, whereas it decreased in LS8 Sirt1/over . Fluoride-induced Ac-p53 formation was also suppressed in LS8 Sirt1/over cells. Compared to WT cells, fluoride-induced Cdkn1a/p21 expression was elevated in LS8 Sirt/KO and these cells were more susceptible to fluoride-induced growth inhibition. In contrast, LS8 Sirt1/over cells were significantly more resistant. In addition, fluoride-induced cytochrome-c release and caspase-3 activation were suppressed in LS8 Sirt1/over cells. Fluoride induced expression of the DNA double strand break marker γH2AX in WT cells and this was augmented in LS8 Sirt1/KO cells, but was attenuated in LS8 Sirt1/over cells. Our results suggest that SIRT1 deacetylates Ac-p53 to mitigate fluoride-induced cell growth inhibition, mitochondrial damage, DNA damage and apoptosis. This is the first report implicating Ac-p53 in fluoride toxicity.

Factors influencing life satisfaction in acute myeloid leukemia survivors following allogeneic stem cell transplantation: a cross-sectional study.

PubMed

Amler, Susanne; Sauerland, Maria Cristina; Deiters, Christian; Büchner, Thomas; Schumacher, Andrea

2015-02-27

Allogeneic stem cell transplantation (alloSCT) is the preferred option of postremission therapy for high-risk patients suffering from acute myeloid leukemia (AML). Therefore, monitoring life satisfaction (LS) of long-term survivors following alloSCT is becoming increasingly important for oncologists. The aim of the study was to evaluate individual survivor priority of various general and health-related domains of life and their satisfaction with these domains. Furthermore, we investigated the impact of general and health-related LS on resilience, anxiety, depression and quality of life in AML survivors following alloSCT. Forty-one AML survivors (median age at time of assessment = 49.0 years) who had undergone alloSCT (median time since transplantation = 3.1 years) were enrolled in the study. Psychosocial parameters were assessed using the following instruments: FLZ(M) (Questions on Life Satisfaction), EORTC QLQ-C30, HADS (Hospital Anxiety and Depression Scale) and the RS-25 (Resilience Scale-25 items). Correlation analyses were computed to reveal the associations between the different questionnaires. Independence from help or care, well-regulated living conditions and financial security contributed positively to LS, whereas being off work due to health-reasons and dissatisfaction with physical aspects were negatively associated to the subjective feelings of overall satisfaction. Moreover, a high quality of life was strongly positively correlated with LS (Spearman's rho general LS: 0.643 and health-related LS: 0.726, both p < 0.001). A high degree of resilience was also strongly positively correlated with better LS (general LS: 0.700, health-related LS: 0.675, both p < 0.001). Symptoms of anxiety and depression were associated with an impaired general LS (anxiety: -0.674, depression: -0.698, both p < 0.001). Our results indicate that LS should be considered an important key contributor to the survivors' well-being following alloSCT. Thus, identifying protective psychological and physical factors that relieve stressors is of high importance in order to support long-term AML survivors with their special needs.

Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus.

PubMed

Chekuri, Sweta; Nickerson, Jillian; Bichoupan, Kian; Sefcik, Roberta; Doobay, Kamini; Chang, Sanders; DelBello, David; Harty, Alyson; Dieterich, Douglas T; Perumalswami, Ponni V; Branch, Andrea D

2016-01-01

To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS). LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant. The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54-64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25-18.60) pre-treatment to 7.60 kPa (IQR: 5.60-12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 --0.38) versus -2.40 kPa (IQR: -7.70 --0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98-0.5) during a median follow-up time of 1.17 (IQR: 0.88-1.63) years, which was not a statistically significant decrease (p = 0.99). LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.

Assessing the Impact of Lesson Study on the Teaching Practice of Middle School Science Teachers

NASA Astrophysics Data System (ADS)

Grove, Michael C.

Despite wave after wave of educational reform in the United States our students continue to lag behind their peers in other industrialized countries on virtually all measures of academic achievement. Effective professional development (PD) is seen as a key to improving instructional practice and therefore student learning, but traditional forms of PD have been wholly unsuccessful in changing teaching practice. Over the last two decades an emerging body of research has identified some key features of effective PD that seem to create meaningful change and improvement in instructional practice. Some of this research highlights the promise of adapting Japanese lesson study (LS) to the American context as a means of incrementally improving instruction. Much of the existing research around LS is descriptive in nature and offers little insight into if and how participation in LS impacts subsequent instructional practice. This study utilized case study methodology to examine the instructional practice of one group of four middle school science teachers before, during, and after participation in LS. The study attempted to identify specific learning outcomes of a LS process, to identify influences on teacher learning during LS, and to identify subsequent changes in the instructional practice of participants resulting from participation in LS. Key findings from the study include significant teacher learning derived from the LS process, the identification of influences that enhanced or inhibited teacher learning, and clear evidence that participants successfully integrated learning from the LS into subsequent instructional practice. Learning outcomes included deepening of subject matter knowledge, increased understanding of student thinking and abilities, clarity of expectations for student performance, recognition of the ineffectiveness of past instructional practice, specific instructional strategies, shared student learning goals, and an increased commitment to future development of student learning. Influences supporting teacher learning were trust and honest dialogue among participants, focused collaboration, examination of student work, and the opportunity to watch other teachers deliver instruction. Influences inhibiting teacher learning related to failure to adhere to key features of the LS protocol. The study offers initial evidence confirming the promise of LS as a model of effective PD.

Pollution potential leaching index as a tool to assess water leaching risk of arsenic in excavated urban soils.

PubMed

Li, Jining; Kosugi, Tomoya; Riya, Shohei; Hashimoto, Yohey; Hou, Hong; Terada, Akihiko; Hosomi, Masaaki

2018-01-01

Leaching of hazardous trace elements from excavated urban soils during construction of cities has received considerable attention in recent years in Japan. A new concept, the pollution potential leaching index (PPLI), was applied to assess the risk of arsenic (As) leaching from excavated soils. Sequential leaching tests (SLT) with two liquid-to-solid (L/S) ratios (10 and 20Lkg -1 ) were conducted to determine the PPLI values, which represent the critical cumulative L/S ratios at which the average As concentrations in the cumulative leachates are reduced to critical values (10 or 5µgL -1 ). Two models (a logarithmic function model and an empirical two-site first-order leaching model) were compared to estimate the PPLI values. The fractionations of As before and after SLT were extracted according to a five-step sequential extraction procedure. Ten alkaline excavated soils were obtained from different construction projects in Japan. Although their total As contents were low (from 6.75 to 79.4mgkg -1 ), the As leaching was not negligible. Different L/S ratios at each step of the SLT had little influence on the cumulative As release or PPLI values. Experimentally determined PPLI values were in agreement with those from model estimations. A five-step SLT with an L/S of 10Lkg -1 at each step, combined with a logarithmic function fitting was suggested for the easy estimation of PPLI. Results of the sequential extraction procedure showed that large portions of more labile As fractions (non-specifically and specifically sorbed fractions) were removed during long-term leaching and so were small, but non-negligible, portions of strongly bound As fractions. Copyright © 2017 Elsevier Inc. All rights reserved.

The Tomato (Solanum Lycopersicum cv. Micro-Tom) Natural Genetic Variation Rg1 and the DELLA Mutant Procera Control the Competence Necessary to Form Adventitious Roots and Shoots

PubMed Central

Peres, Lázaro Eustáquio Pereira

2012-01-01

Despite the wide use of plant regeneration for biotechnological purposes, the signals that allow cells to become competent to assume different fates remain largely unknown. Here, it is demonstrated that the Regeneration1 (Rg1) allele, a natural genetic variation from the tomato wild relative Solanum peruvianum, increases the capacity to form both roots and shoots in vitro; and that the gibberellin constitutive mutant procera (pro) presented the opposite phenotype, reducing organogenesis on either root-inducing medium (RIM) or shoot-inducing medium (SIM). Mutants showing alterations in the formation of specific organs in vitro were the auxin low-sensitivity diageotropica (dgt), the lateral suppresser (ls), and the KNOX-overexpressing Mouse ears (Me). dgt failed to form roots on RIM, Me increased shoot formation on SIM, and the high capacity for in vitro shoot formation of ls contrasted with its recalcitrance to form axillary meristems. Interestingly, Rg1 rescued the in vitro organ formation capacity in proRg1 and dgtRg1 double mutants and the ex vitro low lateral shoot formation in pro and ls. Such epistatic interactions were also confirmed in gene expression and histological analyses conducted in the single and double mutants. Although Me phenocopied the high shoot formation of Rg1 on SIM, it failed to increase rooting on RIM and to rescue the non-branching phenotype of ls. Taken together, these results suggest REGENERATION1 and the DELLA mutant PROCERA as controlling a common competence to assume distinct cell fates, rather than the specific induction of adventitious roots or shoots, which is controlled by DIAGEOTROPICA and MOUSE EARS, respectively. PMID:22915742

The tomato (Solanum lycopersicum cv. Micro-Tom) natural genetic variation Rg1 and the DELLA mutant procera control the competence necessary to form adventitious roots and shoots.

PubMed

Lombardi-Crestana, Simone; da Silva Azevedo, Mariana; e Silva, Geraldo Felipe Ferreira; Pino, Lílian Ellen; Appezzato-da-Glória, Beatriz; Figueira, Antonio; Nogueira, Fabio Tebaldi Silveira; Peres, Lázaro Eustáquio Pereira

2012-09-01

Despite the wide use of plant regeneration for biotechnological purposes, the signals that allow cells to become competent to assume different fates remain largely unknown. Here, it is demonstrated that the Regeneration1 (Rg1) allele, a natural genetic variation from the tomato wild relative Solanum peruvianum, increases the capacity to form both roots and shoots in vitro; and that the gibberellin constitutive mutant procera (pro) presented the opposite phenotype, reducing organogenesis on either root-inducing medium (RIM) or shoot-inducing medium (SIM). Mutants showing alterations in the formation of specific organs in vitro were the auxin low-sensitivity diageotropica (dgt), the lateral suppresser (ls), and the KNOX-overexpressing Mouse ears (Me). dgt failed to form roots on RIM, Me increased shoot formation on SIM, and the high capacity for in vitro shoot formation of ls contrasted with its recalcitrance to form axillary meristems. Interestingly, Rg1 rescued the in vitro organ formation capacity in proRg1 and dgtRg1 double mutants and the ex vitro low lateral shoot formation in pro and ls. Such epistatic interactions were also confirmed in gene expression and histological analyses conducted in the single and double mutants. Although Me phenocopied the high shoot formation of Rg1 on SIM, it failed to increase rooting on RIM and to rescue the non-branching phenotype of ls. Taken together, these results suggest REGENERATION1 and the DELLA mutant PROCERA as controlling a common competence to assume distinct cell fates, rather than the specific induction of adventitious roots or shoots, which is controlled by DIAGEOTROPICA and MOUSE EARS, respectively.

Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major

PubMed Central

Ragab, Seham M.; Badr, Eman A.; Ibrahim, Ahmed S.

2016-01-01

Background Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet. Objectives To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children. Methods Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively). Conclusion Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings. PMID:26740865

High-energy emissions from the gamma-ray binary LS 5039

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

Takata, J.; Leung, Gene C. K.; Cheng, K. S.

2014-07-20

We study mechanisms of multi-wavelength emissions (X-ray, GeV, and TeV gamma-rays) from the gamma-ray binary LS 5039. This paper is composed of two parts. In the first part, we report on results of observational analysis using 4 yr data of the Fermi Large Area Telescope. Due to the improvement of instrumental response function and increase of the statistics, the observational uncertainties of the spectrum in the ∼100-300 MeV bands and >10 GeV bands are significantly improved. The present data analysis suggests that the 0.1-100 GeV emissions from LS 5039 contain three different components: (1) the first component contributes to <1more » GeV emissions around superior conjunction, (2) the second component dominates in the 1-10 GeV energy bands, and (3) the third component is compatible with the lower-energy tail of the TeV emissions. In the second part, we develop an emission model to explain the properties of the phase-resolved emissions in multi-wavelength observations. Assuming that LS 5039 includes a pulsar, we argue that emissions from both the magnetospheric outer gap and the inverse-Compton scattering process of cold-relativistic pulsar wind contribute to the observed GeV emissions. We assume that the pulsar is wrapped by two kinds of termination shock: Shock-I due to the interaction between the pulsar wind and the stellar wind and Shock-II due to the effect of the orbital motion. We propose that the X-rays are produced by the synchrotron radiation at the Shock-I region and the TeV gamma-rays are produced by the inverse-Compton scattering process at the Shock-II region.« less

Procedural virtual reality simulation in minimally invasive surgery.

PubMed

Våpenstad, Cecilie; Buzink, Sonja N

2013-02-01

Simulation of procedural tasks has the potential to bridge the gap between basic skills training outside the operating room (OR) and performance of complex surgical tasks in the OR. This paper provides an overview of procedural virtual reality (VR) simulation currently available on the market and presented in scientific literature for laparoscopy (LS), flexible gastrointestinal endoscopy (FGE), and endovascular surgery (EVS). An online survey was sent to companies and research groups selling or developing procedural VR simulators, and a systematic search was done for scientific publications presenting or applying VR simulators to train or assess procedural skills in the PUBMED and SCOPUS databases. The results of five simulator companies were included in the survey. In the literature review, 116 articles were analyzed (45 on LS, 43 on FGE, 28 on EVS), presenting a total of 23 simulator systems. The companies stated to altogether offer 78 procedural tasks (33 for LS, 12 for FGE, 33 for EVS), of which 17 also were found in the literature review. Although study type and used outcomes vary between the three different fields, approximately 90 % of the studies presented in the retrieved publications for LS found convincing evidence to confirm the validity or added value of procedural VR simulation. This was the case in approximately 75 % for FGE and EVS. Procedural training using VR simulators has been found to improve clinical performance. There is nevertheless a large amount of simulated procedural tasks that have not been validated. Future research should focus on the optimal use of procedural simulators in the most effective training setups and further investigate the benefits of procedural VR simulation to improve clinical outcome.

Rapid-run ionosonde observations of traveling ionospheric disturbances in the auroral ionosphere

NASA Astrophysics Data System (ADS)

Kozlovsky, Alexander; Turunen, Tauno; Ulich, Thomas

2013-08-01

2007, the Sodankylä Geophysical Observatory routinely performs vertical ionosphere soundings once per minute, using a frequency-modulated continuous-wave chirp at the rate of 500 kHz/s from 500 kHz to 16 MHz. We used these data to study traveling ionospheric disturbances (TIDs) during 10-16 local time. The observations were made between April 2007 and June 2012, mostly during low solar activity. The TIDs were studied in five bands of periods corresponding to the following: infrasonic (acoustic) waves and the buoyancy cutoff (periods from 5 to 10 min); small-scale gravity waves (GWs; 10-15 min); medium-scale (MS; 15-30 min) GWs; medium-large scale (MS-LS; 30-60 min) GWs; and large-scale (LS; 60-120 min) GWs. Relative contribution (with respect to LS TIDs) of the short-period (5-15 min) and MS (15-30 min) TIDs shows minima in winter and maxima in summer. These annual variations anticorrelate with variations of true height, namely, the largest relative amplitudes occur in summer, when TIDs were observed at minimal heights. We suggest that the summer increase of shorter-period TIDs is due to lowering reflection to the height where the Brunt-Väisälä period is smaller and, hence, shorter-period gravity waves exist. The summer maxima were most prominent during the 3 years of minimal solar activity (2008-2010). In 2011, when solar activity increased, the annual variation seems less prominent. Annual variations of the longer-period (30-120 min) TIDs are essentially less significant. For all TIDs, no obvious dependences on the AE and Ap indices of magnetic activity were found.

Predictors of weight loss in early treated Parkinson's disease from the NET-PD LS-1 cohort.

PubMed

Wills, Anne-Marie; Li, Ruosha; Pérez, Adriana; Ren, Xuehan; Boyd, James

2017-08-01

Weight loss is a common symptom of Parkinson's disease and is associated with impaired quality of life. Predictors of weight loss have not been studied in large clinical cohorts. We previously observed an association between change in body mass index and change in Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores. In this study, we performed a secondary analysis of longitudinal data (1-6 years) from 1619 participants in the NINDS Exploratory Trials in PD Long-term Study-1 (NET-PD LS1) to explore predictors of weight loss in a large prospective clinical trial cohort of early treated Parkinson's disease. The NET-PD LS1 study was a double-blind randomized placebo controlled clinical trial of creatine monohydrate 10 gm/day in early treated PD (within 5 years of diagnosis and within 2 years of starting dopaminergic medications). Linear mixed models were used to estimate the effect of baseline clinical covariates on weight change over time. On average, participants lost only 0.6 kg per year. Higher age, baseline weight, female gender, higher baseline UPDRS scores, greater postural instability, difficulty eating and drinking, lower cognitive scores and baseline levodopa use (compared to dopamine agonists) were all associated with weight loss. Surprisingly baseline difficulty swallowing, dyskinesia, depression, intestinal hypomotility (constipation) and self-reported nausea/vomiting/anorexia were not significantly associated with weight loss in this cohort of early treated Parkinson's disease patients. On average, participants with Parkinson's disease experience little weight loss during the first 1-6 years after starting dopaminergic replacement therapy, however levodopa use and postural instability were both predictors of early weight loss. Trial Registration clinicaltrials.gov identifier# NCT00449865.

Manual for LS-DYNA Wood Material Model 143

DOT National Transportation Integrated Search

2007-08-01

An elastoplastic damage model with rate effects was developed for wood and was implemented into LS-DYNA, a commercially available finite element code. This manual documents the theory of the wood material model, describes the LS-DYNA input and output...

Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels

PubMed Central

Neely, Alan; Hidalgo, Patricia

2014-01-01

Openings of high-voltage-activated (HVA) calcium channels lead to a transient increase in calcium concentration that in turn activate a plethora of cellular functions, including muscle contraction, secretion and gene transcription. To coordinate all these responses calcium channels form supramolecular assemblies containing effectors and regulatory proteins that couple calcium influx to the downstream signal cascades and to feedback elements. According to the original biochemical characterization of skeletal muscle Dihydropyridine receptors, HVA calcium channels are multi-subunit protein complexes consisting of a pore-forming subunit (α1) associated with four additional polypeptide chains β, α2, δ, and γ, often referred to as accessory subunits. Twenty-five years after the first purification of a high-voltage calcium channel, the concept of a flexible stoichiometry to expand the repertoire of mechanisms that regulate calcium channel influx has emerged. Several other proteins have been identified that associate directly with the α1-subunit, including calmodulin and multiple members of the small and large GTPase family. Some of these proteins only interact with a subset of α1-subunits and during specific stages of biogenesis. More strikingly, most of the α1-subunit interacting proteins, such as the β-subunit and small GTPases, regulate both gating and trafficking through a variety of mechanisms. Modulation of channel activity covers almost all biophysical properties of the channel. Likewise, regulation of the number of channels in the plasma membrane is performed by altering the release of the α1-subunit from the endoplasmic reticulum, by reducing its degradation or enhancing its recycling back to the cell surface. In this review, we discuss the structural basis, interplay and functional role of selected proteins that interact with the central pore-forming subunit of HVA calcium channels. PMID:24917826

Th17-lineage cells in pulmonary sarcoidosis and Löfgren's syndrome: Friend or foe?

PubMed

Miedema, Jelle R; Kaiser, Ylva; Broos, Caroline E; Wijsenbeek, Marlies S; Grunewald, Johan; Kool, Mirjam

2018-02-01

Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressive mechanisms may account for differences in clinical presentation as well as prognosis compared to non-LS sarcoidosis. In contrast with LS, up to 20% of non-LS sarcoidosis patients may progress to irreversible pulmonary fibrosis. In non-LS sarcoidosis patients, IFN-γ-producing Th17.1-cells appear to be more pathogenic and possibly linked to disease progression, while a broader range of cytokines is found in bronchoalveolar lavage fluid (BALF) in LS patients. Differences in Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression on Th17-cells and regulatory T-cells (Treg) could contribute to Th17-cell pathogenicity and consequently to either disease resolution or ongoing inflammation in sarcoidosis. Furthermore, several genes and SNPs are associated with disease susceptibility and outcome in sarcoidosis, the majority of which are involved in antigen presentation, T-cell activation or regulation of T-cell survival. Novel insights into the role of Th17-cells in the pathogenesis of both LS and non-LS sarcoidosis will unravel pathogenic and benign Th17-lineage cell function and drivers of Th17-cell plasticity. This will also help identify new treatment strategies for LS and non-LS sarcoidosis patients by altering Th17-cell activation, suppress conversion into more pathogenic subtypes, or influence cytokine signaling towards a beneficial signature of Th17-lineage cells. In this review, we summarize new insights into Th17-cell plasticity in the complex pathogenesis of sarcoidosis and connect these cells to the different disease phenotypes, discuss the role of genetic susceptibility and autoimmunity and focus on possible treatment strategies. Copyright © 2017. Published by Elsevier Ltd.

The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice.

PubMed

Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H; Luedtke, Robert R

2016-09-01

Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. Copyright © 2016. Published by Elsevier Inc.

Assessing performance of Bayesian state-space models fit to Argos satellite telemetry locations processed with Kalman filtering.

PubMed

Silva, Mónica A; Jonsen, Ian; Russell, Deborah J F; Prieto, Rui; Thompson, Dave; Baumgartner, Mark F

2014-01-01

Argos recently implemented a new algorithm to calculate locations of satellite-tracked animals that uses a Kalman filter (KF). The KF algorithm is reported to increase the number and accuracy of estimated positions over the traditional Least Squares (LS) algorithm, with potential advantages to the application of state-space methods to model animal movement data. We tested the performance of two Bayesian state-space models (SSMs) fitted to satellite tracking data processed with KF algorithm. Tracks from 7 harbour seals (Phoca vitulina) tagged with ARGOS satellite transmitters equipped with Fastloc GPS loggers were used to calculate the error of locations estimated from SSMs fitted to KF and LS data, by comparing those to "true" GPS locations. Data on 6 fin whales (Balaenoptera physalus) were used to investigate consistency in movement parameters, location and behavioural states estimated by switching state-space models (SSSM) fitted to data derived from KF and LS methods. The model fit to KF locations improved the accuracy of seal trips by 27% over the LS model. 82% of locations predicted from the KF model and 73% of locations from the LS model were <5 km from the corresponding interpolated GPS position. Uncertainty in KF model estimates (5.6 ± 5.6 km) was nearly half that of LS estimates (11.6 ± 8.4 km). Accuracy of KF and LS modelled locations was sensitive to precision but not to observation frequency or temporal resolution of raw Argos data. On average, 88% of whale locations estimated by KF models fell within the 95% probability ellipse of paired locations from LS models. Precision of KF locations for whales was generally higher. Whales' behavioural mode inferred by KF models matched the classification from LS models in 94% of the cases. State-space models fit to KF data can improve spatial accuracy of location estimates over LS models and produce equally reliable behavioural estimates.

Assessing Performance of Bayesian State-Space Models Fit to Argos Satellite Telemetry Locations Processed with Kalman Filtering

PubMed Central

Silva, Mónica A.; Jonsen, Ian; Russell, Deborah J. F.; Prieto, Rui; Thompson, Dave; Baumgartner, Mark F.

2014-01-01

Argos recently implemented a new algorithm to calculate locations of satellite-tracked animals that uses a Kalman filter (KF). The KF algorithm is reported to increase the number and accuracy of estimated positions over the traditional Least Squares (LS) algorithm, with potential advantages to the application of state-space methods to model animal movement data. We tested the performance of two Bayesian state-space models (SSMs) fitted to satellite tracking data processed with KF algorithm. Tracks from 7 harbour seals (Phoca vitulina) tagged with ARGOS satellite transmitters equipped with Fastloc GPS loggers were used to calculate the error of locations estimated from SSMs fitted to KF and LS data, by comparing those to “true” GPS locations. Data on 6 fin whales (Balaenoptera physalus) were used to investigate consistency in movement parameters, location and behavioural states estimated by switching state-space models (SSSM) fitted to data derived from KF and LS methods. The model fit to KF locations improved the accuracy of seal trips by 27% over the LS model. 82% of locations predicted from the KF model and 73% of locations from the LS model were <5 km from the corresponding interpolated GPS position. Uncertainty in KF model estimates (5.6±5.6 km) was nearly half that of LS estimates (11.6±8.4 km). Accuracy of KF and LS modelled locations was sensitive to precision but not to observation frequency or temporal resolution of raw Argos data. On average, 88% of whale locations estimated by KF models fell within the 95% probability ellipse of paired locations from LS models. Precision of KF locations for whales was generally higher. Whales’ behavioural mode inferred by KF models matched the classification from LS models in 94% of the cases. State-space models fit to KF data can improve spatial accuracy of location estimates over LS models and produce equally reliable behavioural estimates. PMID:24651252

Results of Li-Tho trial: a prospective randomized study on effectiveness of LigaSure® in lung resections.

PubMed

Bertolaccini, Luca; Viti, Andrea; Cavallo, Antonio; Terzi, Alberto

2014-04-01

The role of electro-thermal bipolar tissue sealing system (LigaSure(®), (LS); Covidien, Inc., CO, USA) in thoracic surgery is still undefined. Reports of its use are still limited. The objective of the trial was to evaluate the cost and benefits of LS in major lung resection surgery. A randomized blinded study of a consecutive series of 100 patients undergoing lobectomy was undertaken. After muscle-sparing thoracotomy and classification of lung fissures according to Craig-Walker, patients with fissure Grade 2-4 were randomized to Stapler group or LS group fissure completion. Recorded parameters were analysed for differences in selected intraoperative and postoperative outcomes. Statistical analysis was performed with the bootstrap method. Pearson's χ(2) test and Fisher's exact test were used to calculate probability value for dichotomous variables comparison. Cost-benefit evaluation was performed using Pareto optimal analysis. There were no significant differences between groups, regarding demographic and baseline characteristics. No patient was withdrawn from the study; no adverse effect was recorded. There was no mortality or major complications in both groups. There were no statistically significant differences as to operative time or morbidity between patients in the LS group compared with the Stapler group. In the LS group, there was a not statistically significant increase of postoperative air leaks in the first 24 postoperative hours, while a statistically significant increase of drainage amount was observed in the LS group. No statistically significant difference in hospital length of stay was observed. Overall, the LS group had a favourable multi-criteria analysis of cost/benefit ratio with a good 'Pareto optimum'. LS is a safe device for thoracic surgery and can be a valid alternative to Staplers. In this setting, LS allows functional lung tissue preservation. As to costs, LS seems equivalent to Staplers.

Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.

PubMed

Terrill, Sarah J; Maske, Calyn B; Williams, Diana L

2018-03-03

Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 min of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4-6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline.

PubMed

Weissman, Scott M; Burt, Randall; Church, James; Erdman, Steve; Hampel, Heather; Holter, Spring; Jasperson, Kory; Kalady, Matt F; Haidle, Joy Larsen; Lynch, Henry T; Palaniappan, Selvi; Wise, Paul E; Senter, Leigha

2012-08-01

Identifying individuals who have Lynch syndrome (LS) involves a complex diagnostic work up that includes taking a detailed family history and a combination of various genetic and immunohistochemical tests. The National Society of Genetic Counselors (NSGC) and the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) have come together to publish this clinical practice testing guideline for the evaluation of LS. The purpose of this practice guideline is to provide guidance and a testing algorithm for LS as well as recommendations on when to offer testing. This guideline does not replace a consultation with a genetics professional. This guideline includes explanations in support of this and a summary of background data. While this guideline is not intended to serve as a review of LS, it includes a discussion of background information on LS, and cites a number of key publications which should be reviewed for a more in-depth understanding of LS. These guidelines are intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses and other healthcare providers who evaluate patients for LS.

Safety and Efficacy of Topical Lime Sulfur in Mice Infested with Myocoptes musculinus

PubMed Central

Wood, Jennifer S; Courtney, Cynthia L; Lieber, Karen A; Lee, Vanessa K

2013-01-01

Current treatment options for murine fur mites have limitations in safety and efficacy. This study evaluated whether topical lime sulfur (LS) is an adjunct or alternative to traditional treatment options for Myocoptes musculinus. To evaluate the safety of topical LS, mice were dipped in a 3% LS solution at 34 and 41 d of age. Mice were observed daily for side effects and mortality, with blood work and necropsy at 42 d of age to evaluate for pathologic changes. To determine the efficacy of topical LS, postweanling mice infested with M. musculinus were treated with LS once weekly for 2 wk and then housed with uninfested sentinel mice for 4 wk. Weekly tape tests and postmortem tape tests and skin scrapings were performed on all mice. Treated postweanling mice had significantly lower Hgb levels and higher BUN levels than did control animals. In mite-infested mice, the number of positive cages at euthanasia was the same between treated and control animals. Although topical LS did not cause gross or microscopic changes to organ systems, it may cause clinicopathologic changes, and topical LS is not effective as a sole treatment for M. musculinus infestation of postweanling mice. PMID:23849408

Trends in life satisfaction in European and North-American adolescents from 2002 to 2010 in over 30 countries.

PubMed

Cavallo, Franco; Dalmasso, Paola; Ottová-Jordan, Veronika; Brooks, Fiona; Mazur, Joanna; Välimaa, Raili; Gobina, Inese; Gaspar de Matos, Margarida; Raven-Sieberer, Ulrike

2015-04-01

Life satisfaction (LS) is an indicator which is widely used for assessing the perception of a child's feeling about his life. LS is assessed in Health Behaviour in School-aged Children via the Cantril ladder with 10 steps indicating the worst and best possible life. This range of values (0-10) was dichotomized into 'low' (0-5) vs. 'high' (6-10). Countries, age groups and genders were compared based on the odds ratio (OR) of declaring a higher LS in 2010 with respect to 2002. Analyzing the difference between 2002 and 2010, six countries from Western Europe show decreasing LS: Austria, Canada, Switzerland, Denmark, Finland and Greenland. In contrast, a group of Eastern European Countries, that is, Estonia, Croatia, Lithuania, Latvia, Russia and Ukraine, show a significant increase in LS. Data on gender and age differences confirm the lower rating of LS in girls and a decreasing rating with age. The LS scale appears to be a tool capable of discriminating the level of wellbeing of adolescent population among countries. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

PubMed

Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

2015-01-01

The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Lactosucrose attenuates intestinal inflammation by promoting Th2 cytokine production and enhancing CD86 expression in colitic rats.

PubMed

Zhou, Yan; Ruan, Zheng; Zhou, Xiaoli; Huang, Xiaoliu; Li, Hua; Wang, Ling; Zhang, Cui; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

2015-01-01

Some oligosaccharides have immunoregulatory and anti-inflammatory functions in the intestine. This study investigated the immunoregulatory effect of lactosucrose (LS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic rats. Alkaline phosphatase activity was increased but myeloperoxidase activity was decreased in the LS-TNBS group, as compared with the TNBS group (colitis rats without receiving LS). LS supplementation stimulated IL-4 and IL-10 production, while up-regulating CD86 expression in dendritic cells. LS supplementation reduced the ratio of CD80/CD86 and the ratio of IFN-γ/IL-4 compared to the TNBS group. Moreover, IFN-γ was significantly correlated with CD80 (r = 0.764, p < 0.01), whereas IL-4 was significantly correlated with CD86 (r = 0.489, p < 0.05). These results indicated that LS attenuated colitis by promoting the production of Th2-type cytokines and rebalancing the ratio of Th1/Th2 and that enhanced IL-4 production is correlated with enhanced CD86 expression in the gut. Therefore, LS is a functional food for patients with inflammatory bowel disease.

Symmetric and anti-symmetric LS hyperon potentials from lattice QCD

NASA Astrophysics Data System (ADS)

Ishii, Noriyoshi; Murano, Keiko; Nemura, Hidekatsu; Sasaki, Kenji; Inoue, Takashi; HAL QCD Collaboration

2014-09-01

We present recent results of odd-parity hyperon-hyperon potentials from lattice QCD. By using HAL QCD method, we generate hyperon-hyperon potentials from Nambu-Bethe-Salpeter (NBS) wave functions generated by lattice QCD simulation in the flavor SU(3) limit. Potentials in the irreducible flavor SU(3) representations are combined to make a Lambda-N potential which has a strong symmetric LS potential and a weak anti-symmetric LS potential. We discuss a possible cancellation between symmetric and anti-symmetric LS (Lambda-N) potentials after the coupled Sigma-N sector is integrated out. We present recent results of odd-parity hyperon-hyperon potentials from lattice QCD. By using HAL QCD method, we generate hyperon-hyperon potentials from Nambu-Bethe-Salpeter (NBS) wave functions generated by lattice QCD simulation in the flavor SU(3) limit. Potentials in the irreducible flavor SU(3) representations are combined to make a Lambda-N potential which has a strong symmetric LS potential and a weak anti-symmetric LS potential. We discuss a possible cancellation between symmetric and anti-symmetric LS (Lambda-N) potentials after the coupled Sigma-N sector is integrated out. This work is supported by JSPS KAKENHI Grant Number 25400244.

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

PubMed Central

Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa

2017-01-01

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient’s tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR. PMID:29184699

Virtual interface substructure synthesis method for normal mode analysis of super-large molecular complexes at atomic resolution.

PubMed

Chen, Xuehui; Sun, Yunxiang; An, Xiongbo; Ming, Dengming

2011-10-14

Normal mode analysis of large biomolecular complexes at atomic resolution remains challenging in computational structure biology due to the requirement of large amount of memory space and central processing unit time. In this paper, we present a method called virtual interface substructure synthesis method or VISSM to calculate approximate normal modes of large biomolecular complexes at atomic resolution. VISSM introduces the subunit interfaces as independent substructures that join contacting molecules so as to keep the integrity of the system. Compared with other approximate methods, VISSM delivers atomic modes with no need of a coarse-graining-then-projection procedure. The method was examined for 54 protein-complexes with the conventional all-atom normal mode analysis using CHARMM simulation program and the overlap of the first 100 low-frequency modes is greater than 0.7 for 49 complexes, indicating its accuracy and reliability. We then applied VISSM to the satellite panicum mosaic virus (SPMV, 78,300 atoms) and to F-actin filament structures of up to 39-mer, 228,813 atoms and found that VISSM calculations capture functionally important conformational changes accessible to these structures at atomic resolution. Our results support the idea that the dynamics of a large biomolecular complex might be understood based on the motions of its component subunits and the way in which subunits bind one another. © 2011 American Institute of Physics

Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.

PubMed

Mirzakhanyan, Yeva; Gershon, Paul D

2017-09-01

The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. The first half of this review surveys the recently determined structural biology of cellular RNA polymerases for a microbiology readership. The second half discusses a reannotation of MSDDRP subunits from NCLDV families and the apparent specialization of these enzymes by virus family and by subunit with regard to subunit or domain loss, subunit dissociability, endogenous control of polymerase arrest, and the elimination/customization of regulatory interactions that would confer higher-order cellular control. Some themes are apparent in linking subunit function to structure in the viral world: as with cellular RNA polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes seem to opt for speed and processivity and seem to have eliminated domains associated with higher-order regulation. The adoption/loss of viral RNA polymerase proofreading functions may have played a part in matching intrinsic mutability to genome size. Copyright © 2017 American Society for Microbiology.

Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy.

PubMed Central

Rubin, H; Salem, J S; Li, L S; Yang, F D; Mama, S; Wang, Z M; Fisher, A; Hamann, C S; Cooperman, B S

1993-01-01

Malaria remains a leading cause of morbidity and mortality worldwide, accounting for more than one million deaths annually. We have focused on the reduction of ribonucleotides to 2'-deoxyribonucleotides, catalyzed by ribonucleotide reductase, which represents the rate-determining step in DNA replication as a target for antimalarial agents. We report the full-length DNA sequence corresponding to the large (PfR1) and small (PfR2) subunits of Plasmodium falciparum ribonucleotide reductase. The small subunit (PfR2) contains the major catalytic motif consisting of a tyrosyl radical and a dinuclear Fe site. Whereas PfR2 shares 59% amino acid identity with human R2, a striking sequence divergence between human R2 and PfR2 at the C terminus may provide a selective target for inhibition of the malarial enzyme. A synthetic oligopeptide corresponding to the C-terminal 7 residues of PfR2 inhibits mammalian ribonucleotide reductase at concentrations approximately 10-fold higher than that predicted to inhibit malarial R2. The gene encoding the large subunit (PfR1) contains a single intron. The cysteines thought to be involved in the reduction mechanism are conserved. In contrast to mammalian ribonucleotide reductase, the genes for PfR1 and PfR2 are located on the same chromosome and the accumulation of mRNAs for the two subunits follow different temporal patterns during the cell cycle. Images Fig. 2 Fig. 4 Fig. 5 PMID:8415692

Constitutive Gαi coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein.

PubMed

Hu, Qiao-Xia; Dong, Jun-Hong; Du, Hai-Bo; Zhang, Dao-Lai; Ren, Hong-Ze; Ma, Ming-Liang; Cai, Yuan; Zhao, Tong-Chao; Yin, Xiao-Lei; Yu, Xiao; Xue, Tian; Xu, Zhi-Gang; Sun, Jin-Peng

2014-08-29

The very large G protein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 β-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 β-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 β-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independent Gαi signaling pathway of the VLGR1 β-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Catalytic Subunit 1 of Protein Phosphatase 2A Is a Subunit of the STRIPAK Complex and Governs Fungal Sexual Development.

PubMed

Beier, Anna; Teichert, Ines; Krisp, Christoph; Wolters, Dirk A; Kück, Ulrich

2016-06-21

The generation of complex three-dimensional structures is a key developmental step for most eukaryotic organisms. The details of the molecular machinery controlling this step remain to be determined. An excellent model system to study this general process is the generation of three-dimensional fruiting bodies in filamentous fungi like Sordaria macrospora Fruiting body development is controlled by subunits of the highly conserved striatin-interacting phosphatase and kinase (STRIPAK) complex, which has been described in organisms ranging from yeasts to humans. The highly conserved heterotrimeric protein phosphatase PP2A is a subunit of STRIPAK. Here, catalytic subunit 1 of PP2A was functionally characterized. The Δpp2Ac1 strain is sterile, unable to undergo hyphal fusion, and devoid of ascogonial septation. Further, PP2Ac1, together with STRIPAK subunit PRO22, governs vegetative and stress-related growth. We revealed in vitro catalytic activity of wild-type PP2Ac1, and our in vivo analysis showed that inactive PP2Ac1 blocks the complementation of the sterile deletion strain. Tandem affinity purification, followed by mass spectrometry and yeast two-hybrid analysis, verified that PP2Ac1 is a subunit of STRIPAK. Further, these data indicate links between the STRIPAK complex and other developmental signaling pathways, implying the presence of a large interconnected signaling network that controls eukaryotic developmental processes. The insights gained in our study can be transferred to higher eukaryotes and will be important for understanding eukaryotic cellular development in general. The striatin-interacting phosphatase and kinase (STRIPAK) complex is highly conserved from yeasts to humans and is an important regulator of numerous eukaryotic developmental processes, such as cellular signaling and cell development. Although functional insights into the STRIPAK complex are accumulating, the detailed molecular mechanisms of single subunits are only partially understood. The first fungal STRIPAK was described in Sordaria macrospora, which is a well-established model organism used to study the formation of fungal fruiting bodies, three-dimensional organ-like structures. We analyzed STRIPAK subunit PP2Ac1, catalytic subunit 1 of protein phosphatase PP2A, to study the importance of the catalytic activity of this protein during sexual development. The results of our yeast two-hybrid analysis and tandem affinity purification, followed by mass spectrometry, indicate that PP2Ac1 activity connects STRIPAK with other signaling pathways and thus forms a large interconnected signaling network. Copyright © 2016 Beier et al.

Genetic and Physiological Studies of Bacillus anthracis Related to Development of an Improved Vaccine

DTIC Science & Technology

1987-07-01

nontransformable Bacillus species such as B. anthracis. Our results suggest that plasmid pLS20 of Bacillus subtilis ( natto ), which promotes transfer of the...mobilizing pBC16, pLS20 mediates transfer of the B. subtills ( natto ) plasmid pLS19 and the Staphylococcus aureus plasmid pUB110. To facilitate direct...and (v) transformation of B. cereus and B. anthracis with plasmid DNA. The 55-kb plasmid, pLS20, of Bacillus subtilis ( natto ) 3335 promotes tr msfer

Phylogenetic relationships of the Gomphales based on nuc-25S-rDNA, mit-12S-rDNA, and mit-atp6-DNA combined sequences

Treesearch

Admir J. Giachini; Kentaro Hosaka; Eduardo Nouhra; Joseph Spatafora; James M. Trappe

2010-01-01

Phylogenetic relationships among Geastrales, Gomphales, Hysterangiales, and Phallales were estimated via combined sequences: nuclear large subunit ribosomal DNA (nuc-25S-rDNA), mitochondrial small subunit ribosomal DNA (mit-12S-rDNA), and mitochondrial atp6 DNA (mit-atp6-DNA). Eighty-one taxa comprising 19 genera and 58 species...

The ribosomes of Drosophila. II. Studies on intraspecific variation.

PubMed

Berger, E M; Weber, L

1974-12-01

Electrophoretic comparisons of 40S and 55S ribosomal subunit proteins from 18 strains of Drosophila melanogaster revealed the virtual absence of allelic variation. More detailed two-dimensional studies on the large subunit proteins in 6 of the strains demonstrated additional complexity but still no interstrain variation. The significance of these results is discussed with respect to present estimates of genic heterozygosity in natural populations.

Dynamic contact network between ribosomal subunits enables rapid large-scale rotation during spontaneous translocation

PubMed Central

Bock, Lars V.; Blau, Christian; Vaiana, Andrea C.; Grubmüller, Helmut

2015-01-01

During ribosomal translation, the two ribosomal subunits remain associated through intersubunit bridges, despite rapid large-scale intersubunit rotation. The absence of large barriers hindering rotation is a prerequisite for rapid rotation. Here, we investigate how such a flat free-energy landscape is achieved, in particular considering the large shifts the bridges undergo at the periphery. The dynamics and energetics of the intersubunit contact network are studied using molecular dynamics simulations of the prokaryotic ribosome in intermediate states of spontaneous translocation. Based on observed occupancies of intersubunit contacts, residues were grouped into clusters. In addition to the central contact clusters, peripheral clusters were found to maintain strong steady interactions by changing contacts in the course of rotation. The peripheral B1 bridges are stabilized by a changing contact pattern of charged residues that adapts to the rotational state. In contrast, steady strong interactions of the B4 bridge are ensured by the flexible helix H34 following the movement of protein S15. The tRNAs which span the subunits contribute to the intersubunit binding enthalpy to an almost constant degree, despite their different positions in the ribosome. These mechanisms keep the intersubunit interaction strong and steady during rotation, thereby preventing dissociation and enabling rapid rotation. PMID:26109353

Polypeptide composition of fraction 1 protein of the somatic hybrid between Petunia parodii and Petunia parviflora.

PubMed

Kumar, A; Wilson, D; Cocking, E C

1981-04-01

The analysis of the subunit polypeptide composition of Fraction 1 protein provides information on the expression of both chloroplast and nuclear genomes. Fraction 1 protein, isolated from leaves of the somatic hybrid plants derived form the fusion of protoplasts of Petunia parodii and P. parviflora, was analyzed for its subunit polypeptide composition by isoelectric focusing in 8 M urea. The fraction 1 protein enzyme oligomer in the somatic hybrid plants contained small subunits resulting from the expression of both parental nuclear genomes, but probably only one of the parental large subunits, namely that of P. parodii. The relevance of such somatic hybrid material for the study of nucleocytoplasmic interrelationship is discussed, as well as the use of these fraction 1 protein isoelectric focusing patterns for the analysis of taxonomic relationships in Petunia.

Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in glucocorticoid-induced osteoporosis in Wistar rats.

PubMed

Elshal, Mohamed F; Almalki, Abdulrahman L; Hussein, Hussein K; Khan, Jalal A

2013-01-01

Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.

Total and high molecular weight adiponectin are elevated in patients with Laron syndrome despite marked obesity.

PubMed

Kanety, Hannah; Hemi, Rina; Ginsberg, Shira; Pariente, Clara; Yissachar, Eleanor; Barhod, Ehud; Funahashi, Tohru; Laron, Zvi

2009-12-01

Patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene, are characterized by dwarfism, profound obesity, and hyperlipidemia. The aim of the current study was to evaluate adiponectin levels in LS, as obesity is known to be associated with low adiponectin. We studied nine untreated LS adult patients (5 males, 4 females) and six girls with LS receiving once-daily treatment by IGF1. Total and high molecular weight (HMW) adiponectin levels, adiponectin multimers distribution, and metabolic indices were analyzed in serum samples obtained during several years of follow-up. Adiponectin levels in the severely obese adult LS patients (percent body fat; females 61.0+/-2.5%, males 40.6+/-8.1%) were two- to three-fold higher than those reported for subjects of corresponding age, gender and degree of adiposity. Total adiponectin was significantly higher in females compared with males (21.4+/-3.5 vs 10.2+/-4.6 microg/ml, P<0.001). The elevated adiponectin in LS subjects was associated with an increased abundance of the HMW isoform, and positively correlated with body fat percentage (r=0.65, P=0.017) and leptin (r=0.65, P=0.012). There was no correlation between adiponectin levels (total and HMW) and the degree of insulin resistance in LS subjects or their blood lipids levels. Adiponectin was also high in young girls with LS (22.9+/-7.4 microg/ml) and did not change during long-term IGF1 replacement therapy. Adiponectin hypersecretion in LS, despite profound obesity, suggests that GH activity may negatively impact adiponectin secretion from adipocytes.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

PubMed

Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

Serotoninergic neuronal systems and ethanol sensitivity in long-sleep (LS) and short-sleep (SS) mice

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

French, T.A.; Weiner, N.

LS and SS mice selectively bred for differences in CNS sensitivity to ethanol (EtOH) exhibit markedly different sleep times (LS = 120 min; SS = 13 min) and differ considerably in hypothermic response following EtOH< 4 g/kg i.p. Basal levels of serotonin (5HT), 5-hydroxyindole acetic acid and 5HT turnover (defined as 5-hydroxy-tryptophan accumulation after inhibition of aromatic L-amino acid decarboxylase) in 6 brain regions (hypthalamus (HYP), dorsal raphe (DR), pontine-medullary raphe (PMR), striatum (STR), hippocampus (HIP) and cortex (CTX)) differ minimally between the two lines. 5 HT turnover in STR, HIP, CTX and PMR of either LS or SS micemore » or in HYP or DR of SS mice was not altered at either 20 or 120 min after EtOH, 4 g/kg. However, in LS mice, 5HT turnover was decreased 23% in HYP at 20 min and 30-34% in HYP and DR at 120 min. LS mice become 1.2 and 2.2/sup 0/ more hypothermic than SS mice at 20 and 120 min after EtOH, 4 g/kg. When approximately equi-effective hypothermic doses of EtOH were administered to LS (3.5 g/kg) and SS (5.0 g/kg) mice, differences in 5HT turnover were still apparent. Pentobarbital administration (65 mg/kg) both decreased brain 5HT turnover 30-60% and produced comparable degrees of hypothermia in LS and SS mice. These data suggest that the apparent increase in sensitivity to inhibition by EtOH of 5HT neurons of HYP and DR of LS mice may contribute to the greater degree of hypothermia induced in this line.« less

Patterns of care and treatment outcomes of patients with Craniopharyngioma in the national cancer database.

PubMed

Rao, Yuan J; Hassanzadeh, Comron; Fischer-Valuck, Benjamin; Chicoine, Michael R; Kim, Albert H; Perkins, Stephanie M; Huang, Jiayi

2017-03-01

To investigate the patterns of care and outcomes in patients with craniopharyngioma in the National Cancer Data Base (NCDB). This study included 697 patients (166 pediatric and 531 adult cases) treated for craniopharyngioma between 2004 and 2012 in the NCDB. Adjuvant radiotherapy (RT) was defined if within 6 months of surgery. Limited surgery (LS) was defined as biopsy or subtotal resection. Proportional-hazards models were used to evaluate associations between covariates and overall survival (OS). A time-dependent analysis of RT was performed to account for early deaths after surgery. Median follow-up was 46 months. Overall, 21% of patients received adjuvant RT. Of patients with known surgical extent (n = 195), 71% had LS. Utilization of adjuvant RT increased from 18% in 2004-2007 to 24% in 2008-2012. Patterns of care regarding adjuvant RT or LS were not significantly different between adult and pediatric patients. Tumor size, low comorbidity, and LS were associated with increased utilization of adjuvant RT. The 5-year OS among patients treated with LS, LS+RT, and gross total resection were 75, 85, and 82% (p = 0.02). On multivariate analysis of the 195 patients with known surgical extent, LS+RT was associated with improved OS compared to LS (HR 0.22, 95% CI 0.05-0.99, p = 0.04), but was not significant when early deaths (<2 months from surgery) were removed to adjust for immortal-time bias. Medical practice regarding surgical approach and adjuvant RT are similar for pediatric and adult craniopharyngiomas. Immortal-time bias may confound assessment of OS for adjuvant RT. Prospective studies comparing adjuvant RT versus observation after LS are warranted.

Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCα, and the renin-angiotensin-aldosterone system.

PubMed

Deliyanti, Devy; Armani, Roksana; Casely, David; Figgett, William A; Agrotis, Alex; Wilkinson-Berka, Jennifer L

2014-09-01

Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin-angiotensin-aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin-angiotensin-aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin-angiotensin-aldosterone system in ischemic retinopathy. Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood-retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor-sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression. An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin-angiotensin-aldosterone system. © 2014 American Heart Association, Inc.

Prevalence and Risk Factors for Lumbar Spondylosis and Its Association with Low Back Pain among Rural Korean Residents.

PubMed

Lee, Sung Yeon; Cho, Nam H; Jung, Young Ok; Seo, Young Il; Kim, Hyun Ah

2017-01-01

The purpose of this study was to investigate the prevalence of and the relevant risk factors for lumbar spondylosis (LS) among middle-aged and elderly rural Korean residents and to explore the association between radiographic LS and lower back pain (LBP) in relation to age and gender. This community-based, cross-sectional study evaluated 1512 subjects with available radiograph. The prevalence of LBP was obtained using a questionnaire and disability resulting from LBP was measured using a validated Korean version of the Oswestry disability index (ODI). In lumbar spine radiographs, vertebral levels from L1/2 to L4/5 were evaluated for the presence of osteophytes and joint-space narrowing (JSN), and Kellgren-Lawrence (KL) grading was applied. Of 4261 subjects aged 40-79 years, data from 1512 subjects were included. The prevalence of radiographic LS indicated by grade ≥2 osteophytes and JSN were 53.9 and 15.8%, respectively. Seventy-three percent of subjects had KL grade ≥2 spondylosis and LBP was present in 36.5% of subjects. Although LS was more common among males, the prevalence of LBP was higher among females. Age, male gender and history of hand or knee arthritis were risk factors for LS. LS was significantly associated with LBP mostly among females over 60 years old and correlated with the ODI after adjusting for age and gender. Our study among rural Korean residents revealed a high prevalence of LS and LBP. The association between LS and LBP was observed mostly among females and LS was significantly correlated with the severity of back pain.

Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome.

PubMed

Binder, Hans; Hopp, Lydia; Schweiger, Michal R; Hoffmann, Steve; Jühling, Frank; Kerick, Martin; Timmermann, Bernd; Siebert, Susann; Grimm, Christina; Nersisyan, Lilit; Arakelyan, Arsen; Herberg, Maria; Buske, Peter; Loeffler-Wirth, Henry; Rosolowski, Maciej; Engel, Christoph; Przybilla, Jens; Peifer, Martin; Friedrichs, Nicolaus; Moeslein, Gabriela; Odenthal, Margarete; Hussong, Michelle; Peters, Sophia; Holzapfel, Stefanie; Nattermann, Jacob; Hueneburg, Robert; Schmiegel, Wolff; Royer-Pokora, Brigitte; Aretz, Stefan; Kloth, Michael; Kloor, Matthias; Buettner, Reinhard; Galle, Jörg; Loeffler, Markus

2017-10-01

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses. Our data support two subgroups of LS-CRCs, G1 and G2, whereby G1 tumours show a higher number of somatic mutations, a higher amount of microsatellite slippage, and a different mutation spectrum. The gene expression phenotypes support this difference. Reference mucosa of G1 shows a strong immune response associated with the expression of HLA and immune checkpoint genes and the invasion of CD4+ T cells. Such an immune response is not observed in LS tumours, G2 reference and normal (non-Lynch) mucosa, and sporadic CRC. We hypothesize that G1 tumours are edited for escape from a highly immunogenic microenvironment via loss of HLA presentation and T-cell exhaustion. In contrast, G2 tumours seem to develop in a less immunogenic microenvironment where tumour-promoting inflammation parallels tumourigenesis. Larger studies on non-neoplastic mucosa tissue of mutation carriers are required to better understand the early phases of emerging tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Quality professional development for secondary science teachers

NASA Astrophysics Data System (ADS)

Mchazlett, Dwight Henry, Jr.

This record of study (ROS) explores the perceptions of three high school biology teachers who implemented a form of the Japanese originated Lesson Study Professional Development (LS PD) model. Additionally, this ROS reports on the perceptions of the internal stakeholders with regard to the model's viability as a potential solution to a proposed problem of practice where there was a lack of quality professional development for secondary biology teachers. The audience of internal stakeholders includes district administrators, high school teachers, and science teachers from the elementary and middle school grade levels. Participants of this study collaboratively explored the problem of practice in the fall semester of 2015, then implemented the LS PD model in the spring semester. The participants completed three cycles of LS that focused on collaboratively designing research-based lessons, teaching the lessons with peer observations, revising and re-teaching the lessons with peer observations, and reflecting on the participants' growth experiences. Four research questions were addressed: (a) What are the perceptions of the participants in regard to their own professional growth as a result of participating in the LS initiative? (b) What improvements to the LS PD model might facilitate future implementation? and (c) What are the perceptions of the LS dissemination audience toward LS as a viable solution to a lack of quality PD for secondary biology teachers? Results of the study suggested that LS PD may be a viable solution to the proposed problem of practice where there is a lack of quality professional development for secondary biology teachers. Long-term implications posit that LS PD can be adapted and scaled up to benefit all content areas and grade levels.

Boletus edulis ribonucleic acid - a potent apoptosis inducer in human colon adenocarcinoma cells.

PubMed

Lemieszek, Marta Kinga; Ribeiro, Miguel; Guichard Alves, Helena; Marques, Guilhermina; Nunes, Fernando Milheiro; Rzeski, Wojciech

2016-07-13

Despite the large popularity of the Boletus edulis mushroom, little is known about its influence on human health and the possibilities of its therapeutic use. Nevertheless, several reports revealed the usefulness of biopolymers isolated from it in cancer treatment. Our previous studies have shown that B. edulis water soluble biopolymers are not toxic against normal colon epithelial cells (CCD841 CoTr) and at the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells (LS180) which was accompanied with cell cycle arrest in the G0/G1 phase. The purpose of the present study was to verify the proapoptotic properties of a selected fraction from B. edulis - BE3, as well as determine its chemical nature. The BE3 fraction was extracted with hot water and purified by anion-exchange chromatography. Further chemical examinations revealed that BE3 consists mainly of ribonucleic acid (59.1%). The ability of BE3 to induce programmed cell death was examined in human colon cancer cell lines LS180 and HT-29 by measuring caspase activation, DNA fragmentation and expression of BAX, BCL2, TP53 and CDKN1A genes. The sensitivity of colon cancer cells with silenced BAX, TP53 and CDKN1A expression to BE3 treatment was also evaluated. We have demonstrated for the first time that the BE3 fraction is a potent apoptosis inducer in human colon cancer cells. The revealed mechanism of apoptosis triggering was dependent on the presence of functional p53 and consequently was a little different in investigated cell lines. Our results indicated that BE3 stimulated proapoptotic genes BAX (LS180, HT-29), TP53 (LS180) and CDKN1A (HT-29) while at the same time silenced the expression of the key prosurvival gene BCL2 (LS180, HT-29). The obtained results indicate the high therapeutic potential of the BE3 fraction against colon cancer, yet it is necessary to further confirm fraction efficacy and safety in animal and clinical studies.